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Bactrim DS
Classes
Sulfonamide and Trimethoprim Antibiotic Combinations
Administration
NOTE: The doses below are expressed in terms of the trimethoprim content of the fixed combination, which consists of 5 mg sulfamethoxazole: 1 mg trimethoprim.
May be administered without regard to meals. Administer with food, water, or milk to minimize gastric irritation.
Suspension: Shake well before using.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Rapid or direct IV injection must be avoided.
Dilute 5 ml of the concentrate for injection in 125 ml of D5W. For fluid-restricted patients, 75 ml of D5W may be used. Use diluted solution within 2 hours of preparation and do not refrigerate.
If using Septra ADD-Vantage vials, dilute each 10 ml vial in ADD-Vantage diluent containers containing 250 ml of D5W.
Infuse over a period of 60—90 minutes. Change infusion site every 48—72 hours.
Adverse Reactions
hyperkalemia / Delayed / 10.0
megaloblastic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
methemoglobinemia / Early / Incidence not known
angioedema / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
serum sickness / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
periarteritis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
acute febrile neutrophilic dermatosis / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
anuria / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
oliguria / Early / Incidence not known
seizures / Delayed / Incidence not known
aseptic meningitis / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
torsade de pointes / Rapid / Incidence not known
myocarditis / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
uveitis / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
eosinophilic pneumonia / Delayed / Incidence not known
crystalluria / Delayed / 10.0
eosinophilia / Delayed / Incidence not known
bone marrow suppression / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
hypoprothrombinemia / Delayed / Incidence not known
hemolysis / Early / Incidence not known
leukopenia / Delayed / Incidence not known
depression / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
hallucinations / Early / Incidence not known
neuritis / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
glossitis / Early / Incidence not known
hypoglycemia / Early / Incidence not known
phlebitis / Rapid / Incidence not known
hyponatremia / Delayed / Incidence not known
QT prolongation / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
metabolic acidosis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
interstitial lung disease / Delayed / Incidence not known
dyspnea / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hyperthyroidism / Delayed / Incidence not known
hypothyroidism / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
rash / Early / Incidence not known
chills / Rapid / Incidence not known
fever / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
pallor / Early / Incidence not known
purpura / Delayed / Incidence not known
tinnitus / Delayed / Incidence not known
insomnia / Early / Incidence not known
vertigo / Early / Incidence not known
headache / Early / Incidence not known
weakness / Early / Incidence not known
fatigue / Early / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
anorexia / Delayed / Incidence not known
vomiting / Early / Incidence not known
nausea / Early / Incidence not known
abdominal pain / Early / Incidence not known
diarrhea / Early / Incidence not known
diuresis / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
pharyngitis / Delayed / Incidence not known
cough / Delayed / Incidence not known
Common Brand Names
Bacter-Aid DS, Bactrim, Bactrim DS, Septra, Septra DS, Sulfatrim, Sulfatrim Pediatric, Sultrex Pediatric
Dea Class
Rx
Description
Combination product of trimethoprim and sulfamethoxazole in a fixed 1:5 ratio; both are synthetic folate antagonists.
Dosage And Indications
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times daily for 21 days then chronic suppressive therapy.
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times daily for 21 days then chronic suppressive therapy.
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 hours (Max: 1,600 mg trimethoprim/day) for 21 days then chronic suppressive therapy.
15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 21 days then chronic suppressive therapy.
15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 21 days then chronic suppressive therapy.
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times daily for 14 to 21 days.
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times daily for 14 to 21 days.
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) for 14 to 21 days.
15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 14 to 21 days. May consider the addition of caspofungin for salvage therapy.
15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 14 to 21 days. May consider the addition of caspofungin for salvage therapy.
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) for 14 to 21 days.
15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 hours (Max: 1,600 mg trimethoprim/day) for 14 to 21 days.
15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 14 to 21 days. May consider the addition of caspofungin for salvage therapy.
15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 14 to 21 days. May consider the addition of caspofungin for salvage therapy.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily. Alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily. Alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.
2.5 to 5 mg/kg/dose (trimethoprim component) PO twice daily or 2 or 3 times weekly or 5 to 10 mg/kg/dose (trimethoprim component) PO once daily (Max: 320 mg trimethoprim/day). Recommended for patients with CD4 count less than 200 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.
2.5 to 5 mg/kg/dose (trimethoprim component) PO twice daily or 2 or 3 times weekly or 5 to 10 mg/kg/dose (trimethoprim component) PO once daily. Recommended for patients with CD4 count less than 500 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.
2.5 to 5 mg/kg/dose (trimethoprim component) PO twice daily or 2 or 3 times weekly or 5 to 10 mg/kg/dose (trimethoprim component) PO once daily. Recommended for all HIV-infected or HIV-indeterminate infants younger than 12 months regardless of CD4 count or percentage. Consider prophylaxis for infants born to HIV-infected mothers beginning at 4 to 6 weeks. Discontinue prophylaxis in infants with indeterminate HIV infection status when they are determined to be definitively ore presumptively HIV-uninfected. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily. Alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.[34362]
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily. Alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.
2.5 to 5 mg/kg/dose (trimethoprim component) PO twice daily or 2 or 3 times weekly or 5 to 10 mg/kg/dose (trimethoprim component) PO once daily (Max: 320 mg trimethoprim/day). May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.
2.5 to 5 mg/kg/dose (trimethoprim component) PO twice daily or 2 or 3 times weekly or 5 to 10 mg/kg/dose (trimethoprim component) PO once daily. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.
2.5 to 5 mg/kg/dose (trimethoprim component) PO twice daily or 2 or 3 times weekly or 5 to 10 mg/kg/dose (trimethoprim component) PO once daily. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
150 mg/m2/day (trimethoprim component) PO once daily on 3 consecutive days/week or divided twice daily on 3 or 7 days/week (Max: 320 mg trimethoprim/day) starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
5 to 10 mg/kg/day (trimethoprim component) PO once daily on 7 days/week or divided twice daily on 2 or 3 days/week (Max: 320 mg trimethoprim/day) for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily. Recommended for patients receiving alemtuzumab, fludarabine/cyclophosphamide/rituximab, corticosteroids at doses equivalent to more than 20 mg/day of prednisone for 4 weeks, nucleoside or purine analogs, radiotherapy for brain tumors/metastasis plus high-dose steroids as well as for patients with acute lymphoblastic leukemia (ALL) and lymphoma treated with R-CHOP14 or escalated BEACOPP. Duration of prophylaxis for ALL is from induction to the end of maintenance. Prophylaxis for alemtuzumab-associated treatment and fludarabine/cyclophosphamide/rituximab treatment is suggested for at least 6 months after treatment completion.
150 mg/m2/day (trimethoprim component) PO once or twice daily, 2 or 3 times weekly, or once weekly (Max: 320 mg trimethoprim/day). Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.[55864] [64855] [64857]
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily or 3 times weekly. Recommended for patients receiving corticosteroids at doses equivalent to 20 mg/day or more of prednisone for 4 weeks or more, particularly if an additional risk factor is present.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours.
8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days is recommended in FDA-approved labeling. The American Academy of Pediatrics (AAP) does not recommend sulfamethoxazole; trimethoprim as a treatment option in patients with type I penicillin allergy due to the low rates of cross sensitivity between penicillin and second and third generation cephalosporins, which are the recommended alternative agents. Sulfamethoxazole; trimethoprim is also not recommended as second-line therapy for children who have failed amoxicillin therapy due to high rates of pneumococcal resistance.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 5 to 7 days. The FDA-approved treatment duration is 14 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 8 to 12 hours for 7 to 14 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 14 days.
8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 7 to 14 days.
8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 960 mg trimethoprim/day) for 7 to 14 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 3 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 14 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 14 days.
8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 14 days.
8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 960 mg trimethoprim/day). Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 10 to 14 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 7 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 3 to 5 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 3 days.
40 mg trimethoprim/200 mg sulfamethoxazole PO every 24 hours or 3 times weekly. The duration of prophylaxis is variable and should be assessed routinely. Generally 3 to 12 months is suggested; however, longer durations have been used.
2 mg/kg/dose (trimethoprim component) PO every 24 hours or 5 mg/kg/dose (trimethoprim component) PO 2 times weekly.[31857] [39033] [41141]
40 mg trimethoprim/200 mg sulfamethoxazole or 80 mg trimethoprim/400 mg sulfamethoxazole as a single dose as needed.
NOTE: Routine antimicrobial prophylaxis for patients aged 2 to 24 months with vesicoureteral reflux is not supported by currently available data; however, antimicrobial prophylaxis is still utilized and has biological plausibility.
Oral dosage Infants and Children 2 months to 2 years
2 mg/kg/dose (trimethoprim component) PO every 24 hours or 5 mg/kg/dose (trimethoprim component) PO 2 times weekly. Prophylaxis is recommended in high-risk patients, which includes infants and children with recurrent febrile UTI and infants and children with reflux grade of III or higher.[51831] Guidelines recommend antibiotic prophylaxis for all grades of vesicoureteral reflux in all patients younger than 1 year.
150 mg/m2/day (trimethoprim component) PO divided every 12 hours. Secondary prophylaxis is only recommended for infants and children with more than 2 serious bacterial infections in a 1-year period who are unable to take antiretroviral therapy. Secondary prophylaxis may be discontinued for sustained (3 months or more) immune reconstitution (CD4 at least 25% if 6 years or younger; CD4 at least 20% or CD4 count more than 350 cells/mm3 if older than 6 years). Secondary prophylaxis should be restarted for more than 2 serious bacterial infections in a 1-year period despite antiretroviral therapy.
150 mg/m2/day (trimethoprim component) PO divided every 12 hours may be considered an alternative treatment to decrease the rate of serious bacterial infections in HIV-infected infants and children unable to take antiretroviral therapy; however, guidelines do not recommend routine primary prophylaxis of bacterial infections, when not indicated for PCP or MAC prophylaxis or other specific reasons. A randomized, double-blind, placebo-controlled study in Zambian children aged 1 to 14 years (n = 541) with clinical features of HIV-infection evaluated the efficacy of sulfamethoxazole; trimethoprim (SMX-TMP) in reducing opportunistic infections in an area with high levels of in vitro bacterial resistance to SMX-TMP. Children younger than 5 years received 240 mg (5 mL of suspension) PO daily and those 5 years and older received 480 mg (10 mL suspension) PO daily or matching placebo. SMX-TMP reduced mortality by 43% and hospitalization by 23% compared to placebo. It was concluded that children of all ages with clinical features of HIV infection receive SMX-TMP prophylaxis in resource-poor areas, regardless of local resistance to the antibiotic.
5 mg/kg/dose (trimethoprim component) PO every 12 hours as an alternative regimen, then chronic maintenance therapy. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
5 mg/kg/dose (trimethoprim component) PO every 12 hours as an alternative regimen, then chronic maintenance therapy. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
5 mg/kg/dose (trimethoprim component) PO every 12 hours has been used as an alternative regimen in adults; however, this regimen has not been evaluated in children.
5 mg/kg/dose (trimethoprim component) IV every 12 hours as an alternative regimen, then chronic maintenance therapy. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
5 mg/kg/dose (trimethoprim component) IV every 12 hours as an alternative regimen, then chronic maintenance therapy. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
5 mg/kg/dose (trimethoprim component) IV every 12 hours has been used as an alternative regimen in adults; however, this regimen has not been evaluated in children.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily in patients with an IgG antibody to Toxoplasma and a CD4+ count less than 100 cells/mm3. As an alternative, may give 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times per week or 80 mg trimethoprim/400 mg sulfamethoxazole PO daily. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral therapy with an increase in CD4 count to more than 200 cells/mm3 for at least 3 months. Prophylaxis should be reintroduced if CD4 count decreases to less than 100 to 200 cells/mm3.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily in patients with an IgG antibody to Toxoplasma and a CD4+ count less than 100 cells/mm3. As an alternative, may give 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times per week or 80 mg trimethoprim/400 mg sulfamethoxazole PO daily. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral therapy with an increase in CD4 count to more than 200 cells/mm3 for at least 3 months. Prophylaxis should be reintroduced if CD4 count decreases to less than 100 to 200 cells/mm3.
150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO once daily (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/day) in patients with an IgG antibody to Toxoplasma and severe immunosuppression (i.e., infants and children younger than 6 years of age with a CD4 percentage less than 15% or children 6 years and older with a CD4 count less than 100 cells/mm3). Acceptable alternative regimens include 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO once daily for 3 consecutive days each week, 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO per day in 2 divided doses given every day, or 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO per day in 2 divided doses given 3 times per week on alternate days (e.g., Monday, Wednesday, Friday). Prophylaxis should not be discontinued in infants younger than 1 year of age. For children 1 to 5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if CD4 percentage is at least 15% for more than 3 consecutive months. For children 6 years and older, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if CD4 count is more than 200 cells/mm3 for more than 3 consecutive months. Primary prophylaxis should be restarted if CD4 counts fall below these thresholds.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or twice daily is recommended as an alternative in the HIV guidelines. Once daily therapy may be associated with an increased risk of relapse; therefore, a gradual transition from acute therapy may be beneficial, utilizing the twice daily dose for 4 to 6 weeks before switching to once daily dosing. Chronic maintenance therapy may be discontinued if initial therapy is successfully completed, patient remains free of signs and symptoms of encephalitis, and has a CD4 count more than 200 cells/mm3 for more than 6 months in response to antiretroviral therapy. Restart chronic maintenance therapy if the CD4 count drops below 200 cells/mm3.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or twice daily is recommended as an alternative in the HIV guidelines. Once daily therapy may be associated with an increased risk of relapse; therefore, a gradual transition from acute therapy may be beneficial, utilizing the twice daily dose for 4 to 6 weeks before switching to once daily dosing. Chronic maintenance therapy may be discontinued if initial therapy is successfully completed, patient remains free of signs and symptoms of encephalitis, and has a CD4 count more than 200 cells/mm3 for more than 6 months in response to antiretroviral therapy. Restart chronic maintenance therapy if the CD4 count drops below 200 cells/mm3.
150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO once daily (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/day) is recommended as an alternative by guidelines. There are very limited data for alternative regimens in children and trimethoprim/sulfamethoxazole is only recommended in patients who are intolerant to other preferred regimens. Chronic maintenance therapy may be discontinued in patients who have received antiretroviral therapy for at least 6 months, have successfully completed initial therapy and remain free of signs and symptoms of encephalitis, and have a CD4 count of at least 15% (1 to 5 years of age) or more than 200 cells/mm3 (6 years and older) for more than 6 months. Restart chronic maintenance therapy if the CD4 count drops below these thresholds.
NOTE: Prophylaxis should be started after engraftment and given as long as the patient remains on immunosuppressant therapy (i.e., usually until 6 months after HSCT).
Oral dosage Adults
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily; or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily; or 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times per week.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily; or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily; or 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times per week.
150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole per day PO in 1 of the following regimens: 2 divided doses 3 times weekly on consecutive days, a single dose 3 times weekly on consecutive days, 2 divided doses daily, or 2 divided doses 3 times weekly on alternate days (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/day).
160 mg trimethoprim/800 mg sulfamethoxazole IV every 8 hours.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours.
23 mg/kg/day PO of sulfamethoxazole and 4.6 mg/kg/day of trimethoprim PO in two divided doses in combination with streptomycin.
45 mg/kg/day PO of sulfamethoxazole and 9 mg/kg/day of trimethoprim PO in two divided doses in combination with dapsone or amikacin.
Uncertainty exists regarding the dose of co-trimoxazole for this condition. A retrospective review of 19 patients at Duke University who received co-trimoxazole for treatment of documented Nocardia infection revealed that patients received an average of 8.2 regular strength tablets/day for an average of 7.2 months. Resolution was achieved in 17/19 patients and in 9/19, co-trimoxazole was the only form of therapy given.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 14 days is recommended as an alternative to a macrolide. For postexposure prophylaxis, administer to asymptomatic close contacts within 3 weeks of exposure, especially patients at high risk for pertussis-related complications (e.g., pregnant women in third trimester). Symptomatic contacts (coughing) should be treated as if they have pertussis.
8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 14 days is recommended as an alternative to a macrolide. For postexposure prophylaxis, administer to asymptomatic close contacts within 3 weeks of exposure, especially patients at high risk for pertussis-related complications (e.g., infants younger than 12 months). Symptomatic contacts (coughing) should be treated as if they have pertussis.
3 to 5 mg/kg/dose (trimethoprim component) IV every 8 hours.
6 to 12 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 960 mg trimethoprim/day) for mild-to-moderate infections and 15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for certain serious catheter-associated infections.
5 mg/kg/dose (trimethoprim component) IV every 12 hours in combination plus high dose daptomycin in patients with persistent MRSA bacteremia and vancomycin treatment failures. If there is reduced susceptibility to vancomycin and daptomycin, sulfamethoxazole; trimethoprim may be administered as a single agent or in combination with other antibiotics.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 8 to 12 hours (Max: 320 mg/dose trimethoprim component).
8 to 10 mg/kg/day (trimethoprim component) IV divided every 8 to 12 hours.
160 mg trimethoprim/800 mg sulfamethoxazole PO once daily.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 10 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO 4 times daily for 10 days, then 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 3 weeks.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 10 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO 4 times daily for 10 days or 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days; may start with twice-daily dosing and increase dose and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with a CD4 count less than 200/mm3.
160 mg trimethoprim/800 mg sulfamethoxazole PO 4 times daily for 10 days or 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days; may start with twice-daily dosing and increase dose and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with a CD4 count less than 200/mm3.
10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days; may increase dose to 20 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 640 mg trimethoprim/3,200 mg sulfamethoxazole/day) and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with severe immunosuppression.
160 mg trimethoprim/800 mg sulfamethoxazole IV 4 times daily for 10 days or 160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 10 days; may start with twice-daily dosing and increase dose and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with a CD4 count less than 200/mm3.
160 mg trimethoprim/800 mg sulfamethoxazole IV 4 times daily for 10 days or 160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 10 days; may start with twice-daily dosing and increase dose and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with a CD4 count less than 200/mm3.
10 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days; may increase dose to 20 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 640 mg trimethoprim/3,200 mg sulfamethoxazole/day) and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with severe immunosuppression.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 48 to 72 hours or until the patient becomes afebrile. Routine use is not recommended; reserve for patients at high risk for invasive infection.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 48 to 72 hours or until the patient becomes afebrile. Routine use is not recommended; reserve for patients at high risk for invasive infection.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 14 days as an alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 14 days as an alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.
160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 14 days as an alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.
160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 14 days as an alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 5 days.
8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 5 days.
8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 5 days.
8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 5 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days as an alternative; treat for at least 14 days if concurrent bacteremia. Treat for up to 6 weeks for recurrent infections.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days as an alternative; treat for at least 14 days if concurrent bacteremia. Treat for up to 6 weeks for recurrent infections.
160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 10 days as an alternative; treat for at least 14 days if concurrent bacteremia. Treat for up to 6 weeks for recurrent infections.
160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 10 days as an alternative; treat for at least 14 days if concurrent bacteremia. Treat for up to 6 weeks for recurrent infections.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 3 to 5 days. Guidelines do not include trimethoprim; sulfamethoxazole.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 7 to 14 days as first-line therapy; treat for 14 days if concurrent bacteremia.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 14 days as first-line therapy; treat for 14 days if concurrent bacteremia.
160 mg trimethoprim/800 mg sulfamethoxazole PO 2 or 4 times daily for 14 days as an alternative.
8 to 12 mg/kg/day (trimethoprim component) PO divided 2 or 4 times daily (Max: 640 mg trimethoprim/day) for 14 days as an alternative.
160 mg trimethoprim/800 mg sulfamethoxazole IV 2 or 4 times daily for 14 days as an alternative.
8 to 12 mg/kg/day (trimethoprim component) IV divided 2 or 4 times daily (Max: 640 mg trimethoprim/day) for 14 days as an alternative.
In a prospective, randomized, double-blind trial, SMX-TMP dosed as 320 mg trimethoprim IV every 12 hours was compared to vancomycin in IV drug abusers with infections due to Staphylococcus aureus. Although the cure rate was significantly higher with vancomycin after roughly 3 weeks of therapy (e.g., 98% for vancomycin vs. 86% for SMX-TMP), the authors concluded that SMX-TMP could be considered an alternative in patients who cannot receive vancomycin if infection is due to methicillin-sensitive S. aureus. Clinical practice guidelines do not recommend SMX-TMP for endocarditis but acknowledge occasional use as salvage therapy.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
5 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 6 hours for incisional surgical site infections of the trunk or extremity away from the axilla or perineum.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO every 12 hours for 5 to 7 days.
4 to 6 mg/kg/dose (trimethoprim component) (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) PO every 12 hours for 5 to 7 days.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO every 12 hours for 5 to 14 days.
57437Infants, Children, and Adolescents 2 months to 17 years
4 to 6 mg/kg/dose (trimethoprim component) (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) PO every 12 hours for 5 to 14 days.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO every 12 hours for 5 to 10 days plus incision and drainage.
4 to 6 mg/kg/dose (trimethoprim component) (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) PO every 12 hours for 5 to 10 days plus incision and drainage.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO every 12 hours for 7 days.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole IV every 12 hours for 7 days.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO every 12 hours for 7 to 14 days for mild infections due to methicillin-resistant S. aureus (MRSA) or other staphylococci or streptococci in patients allergic or intolerant to beta-lactams or moderate or severe infections in patients with risk factors for MRSA. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole IV every 12 hours for 7 to 14 days for mild infections due to methicillin-resistant S. aureus (MRSA) or other staphylococci or streptococci in patients allergic or intolerant to beta-lactams or moderate or severe infections in patients with risk factors for MRSA. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 8 to 12 hours (Max: 320 mg/dose trimethoprim component).
8 to 10 mg/kg/day (trimethoprim component) IV divided every 8 to 12 hours.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy. For pregnant and lactating patients, use erythromycin or azithromycin.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.
80 mg trimethoprim/400 mg sulfamethoxazole to 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 3 days has been used. Retreat after 7 to 10 days.
5 mg/kg/dose (trimethoprim component) PO every 12 hours for 10 days has been used. Oral sulfamethoxazole/trimethoprim either alone or combined with topical 1% permethrin was effective; however, it was recommended that combination therapy be reserved for cases of lice resistance or multiple treatment failures.
320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 12 hours for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in setting of persistent bacteremia.
240 mg trimethoprim/1,200 mg sulfamethoxazole PO every 12 hours for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in setting of persistent bacteremia.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in setting of persistent bacteremia.
8 mg/kg/dose (trimethoprim component) PO every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in the setting of persistent bacteremia.
This rapid protocol was studied in HIV infected patients who required SMX-TMP therapy. Increasing doses of SMX-TMP are given every 15 minutes for 31 doses; then, if protocol tolerated, begin sulfonamide therapy as indicated. The protocol is as follows:
Doses 1 to 3 (10 ng/mL SMX-TMP): 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.00007 mg of the SMX component.
Doses 4 to 7 (100 ng/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.00075 mg of the SMX component.
Doses 8 to 11 (1 mcg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.0075 mg of the SMX component.
Doses 12 to 15 (10 mcg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.075 mg of the SMX component.
Doses 16 to 19 (100 mcg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.75 mg of the SMX component.
Doses 20 to 23 (1 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 7.5 mg of the SMX component.
Doses 24 to 27 (10 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 75 mg of the SMX component.
Doses 28 to 30 (40 mg/mL SMX-TMP): 2 mL, 4 mL, and 8 mL PO given 15 minutes apart for a total dose of 560 mg of the SMX component.
Dose 31: 1 double strength tablet (800 mg of the SMX component) PO.
Data on sulfonamide desensitization protocols are lacking in pediatric patients. In 1 rapid, 4-hour oral protocol in HIV-infected children (n = 5), sulfamethoxazole; trimethoprim suspension was diluted in sterile water, and doses were given every 15 minutes at the following proportions of the final dose: 1:10,000, 1:1,000, 1:500, 1:250, 1:125, 1:62, 1:30, 1:15, 1:7.5, 1:5, 1:2.5, and full strength. After desensitization, maintenance sulfamethoxazole; trimethoprim therapy was begun at a dosage of 150 mg/m2/day PO divided twice daily. The desensitization protocol was successful in 4 of the 5 patients. Another protocol in HIV-infected patients, 4 of whom were pediatric patients, used sulfamethoxazole; trimethoprim suspension administered orally every 8 hours beginning with 1:10,000 of the desired total daily dose and progressing through serial dilutions of 1:5,000, 1:1,000, 1:500, 1:100, 1:50, and 1:10. Subsequently, the desired dosage was administered orally twice per day. The desensitization protocol was successful in 6 of the 7 patients.
This ambulatory desensitization protocol was studied in HIV infected patients who required SMX-TMP prophylaxis. Increasing doses of SMX-TMP given PO 3 times daily were used for 8 days. On the ninth day and if protocol tolerated, the patients received 1 double-strength tablet (800 mg/160mg SMX-TMP) PO once daily.[27465] The protocol is as follows:
Day 1 (0.00002 mg/mL SMX-TMP): 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.00007 mg of the SMX component.
Day 2 (0.0002 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.00075 mg of the SMX component.
Day 3 (0.002 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.0075 mg of the SMX component.
Day 4 (0.02 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.075 mg of the SMX component.
Day 5 (0.2 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 0.75 mg of the SMX component.
Day 6 (2 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 7.5 mg of the SMX component.
Day 7 (20 mg/mL SMX-TMP): 0.5 mL, 1 mL, 2 mL, and 4 mL PO given 15 minutes apart for a total dose of 75 mg of the SMX component.
Day 8 (40 mg/mL SMX-TMP): 2 mL, 4 mL, and 8 mL PO given 15 minutes apart for a total dose of 560 mg of the SMX component.
Day 9: Give 1 double strength tablet (800 mg of the SMX component) PO.
Data on ambulatory sulfonamide desensitization protocols are lacking in pediatric patients. In 1 successful protocol in HIV-infected children (n = 4), 1 mL of sulfamethoxazole; trimethoprim oral suspension (8 mg/mL trimethoprim) was diluted with 19 mL of distilled water for a concentration of 0.4 mg/mL (used for Days 1 to 4 of the desensitization regimen). The following desensitization regimen was used (all doses represent trimethoprim component): Day 1: 0.4 mg; Day 2: 0.8 mg; Day 3: 1.6 mg; Day 4: 3.2 mg; Day 5: 4.8 mg; Day 6: 9.6 mg; Day 7: 20 mg; Day 8: 40 mg; Day 9: 80 mg; Days 10 to 17: 40 mg; Days 18 onward: dose increased every 3 days to 5 mg/kg/day PO.
4 mg/kg/dose (trimethoprim component) IV every 8 to 12 hours (Max: 960 mg trimethoprim/day) for at least 8 weeks, which may be followed by long-term suppressive therapy. May consider the addition of rifampin; for patients with concurrent bacteremia, add rifampin after bacteremia clearance.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 640 mg trimethoprim/day). Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 8 to 12 hours for at least 8 weeks, which may be followed by long-term suppressive therapy. May consider the addition of rifampin; for patients with concurrent bacteremia, add rifampin after bacteremia clearance.
8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) as step-down therapy after initial parenteral therapy. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
2 to 4 mg/kg/dose (trimethoprim component) IV every 12 hours (Max: 960 mg trimethoprim/day). Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 640 mg trimethoprim/day). Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
160 mg trimethoprim/800 mg sulfamethoxazole or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 3 to 6 weeks (parenteral plus oral).
8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) as step-down therapy after initial parenteral therapy. Treat for a total duration of 2 to 3 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours as step-down therapy after initial parenteral therapy.
66745]68646 Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.For the treatment of prosthetic joint infections† due to methicillin-resistant S. aureus. Intravenous dosage Adults
4 mg/kg/dose (trimethoprim component) IV every 8 to 12 hours (Max: 960 mg trimethoprim/day) in combination with rifampin for 2 to 6 weeks, followed by oral step-down therapy, which may be followed by long-term suppressive therapy.
320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 8 to 12 hours in combination with rifampin as oral step-down therapy for 3 to 6 months; then 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours may be used as long-term suppressive therapy if needed.
4 mg/kg/dose (trimethoprim component) IV every 8 to 12 hours (Max: 960 mg trimethoprim/day) in combination with rifampin followed by long-term suppressive therapy.
320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 8 to 12 hours in combination with rifampin followed by 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours as long-term suppressive therapy.
2 to 4 mg/kg/dose (trimethoprim component) IV every 12 hours (Max: 960 mg trimethoprim/day) for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
160 mg trimethoprim/800 mg sulfamethoxazole or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
2 to 4 mg/kg/dose (trimethoprim component) IV every 12 hours (Max: 960 mg trimethoprim/day) for 6 weeks.
160 mg trimethoprim/800 mg sulfamethoxazole or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 12 hours for 6 weeks.
2 to 4 mg/kg/dose (trimethoprim component) IV every 12 hours (Max: 960 mg trimethoprim/day) for 4 to 6 weeks.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 640 mg trimethoprim/day). Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
160 mg trimethoprim/800 mg sulfamethoxazole or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 12 hours for 4 to 6 weeks.
8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) as step-down therapy after initial parenteral therapy. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
160 mg trimethoprim/800 mg sulfamethoxazole PO as single dose 1 hour before transrectal biopsy of the prostate or 320 mg trimethoprim/1600 mg sulfamethoxazole PO as single dose 1 to 3 hours before transurethral resection of the prostate. No intraoperative redosing and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. Clinical practice guidelines recommend sulfamethoxazole; trimethoprim for urologic procedures involving lower tract instrumentation with risk factors for infection, including transrectal prostate biopsy.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for at least 21 days.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for at least 21 days.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 10 to 14 days.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 10 to 14 days.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 4 to 6 weeks; consider the addition of oral rifampin.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 4 to 6 weeks; considering the addition of oral rifampin.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 21 days.
10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 21 days.
160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO twice daily for 10 to 14 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 21 to 28 days.
5 to 10 mg/kg/dose (trimethoprim component) PO every 24 hours (Max: 80 mg trimethoprim/400 mg sulfamethoxazole/day) for 21 days.
80 mg trimethoprim/400 mg sulfamethoxazole PO every 24 hours to 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 14 to 21 days.
5 to 10 mg/kg/dose (trimethoprim component) PO every 24 hours (Max: 80 mg trimethoprim/400 mg sulfamethoxazole/day) for 14 to 28 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours in combination with doxycycline for 6 to 8 weeks is recommended as an alternative therapy. For serious infections or complications (i.e., endocarditis, meningitis, and osteomyelitis), the addition of streptomycin or gentamicin for the first 14 to 21 days of therapy is recommended.
8 to 12 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 6 to 8 weeks. Give in combination with rifampin or doxycycline (pediatric patients older than 8 years) to reduce the incidence of relapse. For serious infections or complications (i.e., endocarditis, meningitis, and osteomyelitis), the addition of streptomycin or gentamicin for the first 14 to 21 days of therapy is recommended.
Doxycycline is the treatment of choice in adults; however, 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours throughout pregnancy is recommended for all pregnant women.
Doxycycline is the treatment of choice.
4 mg/kg/dose (trimethoprim component) PO every 12 hours (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/dose) for 14 days. Trimethoprim/sulfamethoxazole may be considered as an alternative therapy to doxycycline in children with mild or uncomplicated illness or as an option in patients who remain febrile after a 5-day course of doxycycline. Children with high-risk criteria (e.g., hospitalized or who have severe illness, children with preexisting heart valvulopathy, immunocompromised children, or children with delayed Q fever diagnosis who have experienced illness for more than 14 days without resolution of symptoms) should receive doxycycline treatment for 14 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly, or alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times weekly in patients with CD4 count less than 200 cells/mm3. Discontinuation may be considered in patients without evidence of active infection who have sustained increase in CD4 count to more than 200 cells/mm3 for more than 6 months in response to antiretroviral therapy.
160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly, or alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times weekly in patients with CD4 count less than 200 cells/mm3. Discontinuation may be considered in patients without evidence of active infection who have sustained increase in CD4 count to more than 200 cells/mm3 for more than 6 months in response to antiretroviral therapy.
2.5 mg/kg/dose (trimethoprim component) PO twice daily 3 times weekly (Max: 160 mg trimethoprim/day) in patients with severe immunosuppression (CDC immunologic category 3). Discontinuation may be considered in patients without evidence of active infection who have sustained improvement in immunologic status (CDC immunologic category 1 or 2) for longer than 6 months in response to ART.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 6 weeks.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 14 days as second-line therapy.
10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 14 days as second-line therapy.
5 mg/kg/dose (trimethoprim component) PO every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) PO every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) IV every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) IV every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) PO every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) PO every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) IV every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) IV every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
5 mg/kg/dose (trimethoprim component) PO every 12 hours until 48 hours after the last perceived exposure as an alternative therapy.
5 mg/kg/dose (trimethoprim component) PO every 12 hours until 48 hours after the last perceived exposure as an alternative therapy.
5 mg/kg/dose (trimethoprim component) PO every 12 hours for 7 days as an alternative therapy.
5 mg/kg/dose (trimethoprim component) PO every 12 hours for 7 days as an alternative therapy.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours in persons with recurrent bacteremia or gastroenteritis with a CD4 count of less than 200 cells/mm3 and severe diarrhea as an alternative. Discontinuation may be considered after resolution of infection in persons with a response to antiretroviral therapy with sustained viral suppression and CD4 count more than 200 cells/mm3.
160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours in persons with recurrent bacteremia or gastroenteritis with a CD4 count of less than 200 cells/mm3 and severe diarrhea as an alternative. Discontinuation may be considered after resolution of infection in persons with a response to antiretroviral therapy with sustained viral suppression and CD4 count more than 200 cells/mm3.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) in combination with gentamicin for 7 to 14 days.
8 to 10 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) in combination with gentamicin for 7 to 14 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 10 days.
NOTE: For CNS disease, see meningitis indication.
For the treatment of invasive listeriosis† with bacteremia. Intravenous dosage Adults
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 14 days.
8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 14 days.
160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 3 to 7 days.
8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 3 to 7 days.
†Indicates off-label use
Dosing Considerations
Both sulfamethoxazole and trimethoprim are metabolized by the liver. Dosage adjustments may be necessary in patients with hepatic impairment; however, specific dosage adjustment guidelines are not available.
Renal ImpairmentAdults
General renal dosage adjustment:
CrCl more than 30 mL/minute: No dosage adjustment needed.[28344] [42298] Alternatively, full daily dose divided every 12 hours (i.e., 8 to 12 mg/kg/day of trimethoprim component IV/PO divided every 12 hours) for 14 days, then one-half of the daily dose every 24 hours (i.e., 4 to 6 mg/kg/day of trimethoprim component IV/PO once daily).[42300] [42332]
CrCl 15 to 30 mL/minute: Reduce dose to one-half of the usual dosage regimen.[28344] [42298] Alternatively, full daily dose divided every 12 hours (i.e., 8 to 12 mg/kg/day of trimethoprim component IV/PO divided every 12 hours) for 24 to 48 hours, then one-half of the daily dose every 24 hours (i.e., 4 to 6 mg/kg/day of trimethoprim component IV/PO once daily).[42300] [42332]
CrCl less than 15 mL/minute: Use not recommended.[28344] [42298] Alternatively, full daily dose (i.e., 8 to 12 mg/kg/dose of trimethoprim component IV/PO) every 48 hours or one-half of the daily dose in 1 or 2 divided doses (i.e., 4 to 6 mg/kg/day of trimethoprim component IV/PO divided every 12 to 24 hours).[42300] [42332]
Pneumocystis pneumonia (PCP) renal dosage adjustment:
CrCl more than 30 mL/minute: No dosage adjustment needed.[34362] [42300] [42332]
CrCl 15 to 30 mL/minute: For treatment, 5 mg/kg/dose of trimethoprim component IV every 12 hours or 2 double-strength tablets PO every 12 hours.[34362] Alternatively, 15 to 20 mg/kg/day of trimethoprim component IV/PO divided every 6 to 8 hours for 48 hours, then 7 to 10 mg/kg/day of trimethoprim component IV/PO divided every 12 hours. For prophylaxis, 5 mg/kg/dose of trimethoprim component IV/PO every 24 to 48 hours for 3 to 7 doses/week.[42332]
CrCl 10 to 14 mL/minute: For treatment, 5 mg/kg/dose of trimethoprim component IV every 12 hours or 2 double-strength tablets PO every 12 hours.[34362] Alternatively, 15 to 20 mg/kg/dose of trimethoprim component IV/PO every 48 hours or 7 to 10 mg/kg/day divided every 12 to 24 hours. For prophylaxis, 5 mg/kg/dose of trimethoprim component IV/PO every 48 to 72 hours.[42332]
CrCl less than 10 mL/minute: For treatment, 5 mg/kg/dose of trimethoprim component IV every 24 hours, 1 double-strength tablet PO every 12 hours, or 2 double-strength tablets PO every 24 hours.[34362] Alternatively, 15 to 20 mg/kg/dose of trimethoprim component IV/PO every 48 hours or 7 to 10 mg/kg/day divided every 12 to 24 hours. For prophylaxis, 5 mg/kg/dose of trimethoprim component IV/PO every 48 to 72 hours.[42332]
Pediatrics
Off-label dose adjustments
The following dose adjustments are based on a usual recommended dose in pediatric patients of 5 to 20 mg/kg/day (trimethoprim component) divided every 6 to 12 hours [32569]:
CrCl more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 30 to 50 mL/minute/1.73 m2: 5 to 7.5 mg/kg/dose every 8 hours.
CrCl 10 to 29 mL/minute/1.73 m2: 5 to 10 mg/kg/dose every 12 hours.
CrCl less than 10 mL/minute/1.73 m2: Use not recommended; if used, 5 to 10 mg/kg/dose every 24 hours.
FDA-approved dose adjustments
CrCl more than 30 mL/minute: No dosage adjustment needed.
CrCl 15 to 30 mL/minute: Reduce the recommended dose by 50%.
CrCl less than 15 mL/minute: Use not recommended.[43889]
Intermittent hemodialysis
Adults
General hemodialysis dosage adjustment:
Use not recommended.[28344] [42298] Alternatively, full daily dose (i.e., 8 to 12 mg/kg/day of trimethoprim component IV/PO) before dialysis, then one-half of the daily dose (i.e., 4 to 6 mg/kg/day of trimethoprim component IV/PO) after dialysis.[42300] [42332] A pharmacokinetic study demonstrated that 44% of the administered trimethoprim and 57% of the administered sulfamethoxazole dose was removed during hemodialysis, suggesting that 50% of the usual dose be administered after the dialysis session.[42301]
Pneumocystis pneumonia (PCP) hemodialysis dosage adjustment:
For treatment, 5 mg/kg/day of trimethoprim component IV or 2 double-strength tablets PO after dialysis on dialysis days. Consider therapeutic drug monitoring with a target trimethoprim concentration of 5 to 8 mcg/mL.[34362] Alternatively, 15 to 20 mg/kg/dose of the trimethoprim component IV/PO before dialysis with 7 to 10 mg/kg/dose of trimethoprim component IV/PO after dialysis. For prophylaxis, 5 mg/kg/dose of trimethoprim component IV/PO after each dialysis.[42332]
Pediatrics
Generally, use is not recommended in patients receiving hemodialysis. If used, 5 to 10 mg/kg/dose of trimethoprim component every 24 hours.[32569]
Peritoneal dialysis
Adults: 160 mg trimethoprim; 800 mg sulfamethoxazole PO twice daily.[61676]
Pediatrics: Generally, use is not recommended in patients receiving peritoneal dialysis. If used, 5 to 10 mg/kg/dose of trimethoprim component every 24 hours.[32569]
Continuous renal replacement therapy
Adults: 2.5 to 7.5 mg/kg/dose of trimethoprim component IV/PO twice daily has been recommended for CVVH, CVVHD, and CVVHDF.[42303]
Pediatrics: 5 mg/kg/dose of trimethoprim component every 8 hours.[32569]
Drug Interactions
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use. (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Acarbose: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Acetaminophen; Aspirin: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alpha-glucosidase Inhibitors: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Amantadine: (Major) Avoid concurrent use of amantadine and trimethoprim. A single case of toxic delirium has been reported after coadministration of trimethoprim and amantadine. Amantadine is an OCT2 substrate and trimethoprim is an OCT2 inhibitor.
Amiloride: (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Aminosalicylate sodium, Aminosalicylic acid: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Amitriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Amlodipine; Benazepril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Amlodipine; Olmesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Amlodipine; Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Amoxicillin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Amoxicillin; Clavulanic Acid: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Ampicillin: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Ampicillin; Sulbactam: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Angiotensin II receptor antagonists: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Aprepitant, Fosaprepitant: (Minor) Use caution if sulfamethoxazole and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of sulfamethoxazole. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Sulfamethoxazole is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
Articaine; Epinephrine: (Moderate) Coadministration of articaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Aspirin, ASA: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Caffeine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Carisoprodol: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Dipyridamole: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Omeprazole: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Aspirin, ASA; Oxycodone: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Atenolol; Chlorthalidone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Atovaquone: (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs by 16% and 10%, respectively, in a small number of HIV-positive subjects. No difference was observed in atovaquone pharmacokinetics. The effect of the interaction of atovaquone with TMP-SMX is minor and unlikely to be of clinical significance. (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs in a small number of HIV-positive subjects. This may not be of any clinical significance but should be used with caution.
Atovaquone; Proguanil: (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs by 16% and 10%, respectively, in a small number of HIV-positive subjects. No difference was observed in atovaquone pharmacokinetics. The effect of the interaction of atovaquone with TMP-SMX is minor and unlikely to be of clinical significance. (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs in a small number of HIV-positive subjects. This may not be of any clinical significance but should be used with caution.
Azathioprine: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive. Drugs that may affect the production of leukocytes, including sulfamethoxazole; trimethoprim, SMX-TMP, may lead to exaggerated leukopenia, especially in patients who have received a renal transplant.
Azilsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Azilsartan; Chlorthalidone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Benazepril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Benazepril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Benzalkonium Chloride; Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzocaine; Butamben; Tetracaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly. (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Bismuth Subsalicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Bosentan: (Moderate) Sulfamethoxazole potently inhibits CYP2C9 and may theoretically lead to elevated plasma concentrations of bosentan when coadministered. Monitor for potential adverse effects of bosentan during coadministration. Excessive bosentan dosage may result in hypotension or elevated hepatic enzymes.
Bromocriptine: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., sulfonamides), which may alter their effectiveness and risk for side effects.
Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with sulfamethoxazole is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and sulfamethoxazole is a moderate CYP2C9 inhibitor.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Candesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Candesartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Captopril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Chloramphenicol: (Major) The risk for developing leukopenia and/or thrombocytopenia can be increased if other bone marrow depressants are used with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include chloramphenicol. If these agents are used concomitantly, close observation of blood counts is warranted.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Chloroprocaine: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chlorothiazide: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Chlorpropamide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Chlorthalidone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Chlorthalidone; Clonidine: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received sulfamethoxazole; trimethoprim within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as sulfamethoxazole; trimethoprim, may diminish vaccine efficacy and result in suboptimal immune response. A duration of fewer than 14 days between stopping antibiotics and vaccination might also be acceptable in some clinical settings if travel cannot be avoided before 14 days have elapsed after stopping antibiotics.
Choline Salicylate; Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Clomipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Cyclosporine: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and cyclosporine. There have been reports of significant, but reversible nephrotoxicity with coadministration in renal transplant patients. In addition, there are case reports of reduced exposure to cyclosporine in patients receiving concomitant sulfonamides. Monitor renal function and cyclosporine concentrations if concomitant use is required.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Daprodustat: (Major) Reduce the initial daprodustat dose by half during concomitant use of sulfamethoxazole unless the daprodustat dose is already 1 mg. Monitor hemoglobin and further adjust the daprodustat dose as appropriate. Concomitant use may increase daprodustat exposure and the risk for daprodustat-related adverse reactions. Daprodustat is a CYP2C8 substrate and sulfamethoxazole is a moderate CYP2C8 inhibitor. Concomitant use with a moderate CYP2C8 inhibitor is expected to increase daprodustat overall exposure by approximately 4-fold.
Dapsone: (Major) Agranulocytosis has been reported in the second to third month of weekly concomitant treatment with dapsone and other hemolytic agents such as folic acid antagonists (e.g., trimethoprim, sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole). These combinations increase the likelihood of adverse hematologic events. Concurrent administration of dapsone with trimethoprim increases the plasma concentrations of both drugs. The efficacy of dapsone is increased, which may provide a therapeutic advantage in the treatment of Pneumocystis pneumonia; however, an increase in the frequency and severity of dapsone toxicity (methemoglobinemia, hemolytic anemia) also has been noted. (Moderate) Coadministration of dapsone with sulfonamides may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Desipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Dicloxacillin: (Minor) Sulfonamides may compete with dicloxacillin for renal tubular secretion, increasing dicloxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Dienogest; Estradiol valerate: (Moderate) Anti-infectives that disrupt the normal GI flora, including sulfonamides, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Digoxin: (Major) Monitor serum digoxin concentrations before initiating concomitant trimethoprim. Reduce digoxin concentrations by decreasing the dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. Concomitant use increased digoxin concentrations by 22% to 28%.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Diphenhydramine; Naproxen: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Disulfiram: (Major) The ingestion of ethanol by patients receiving disulfiram causes an extremely unpleasant reaction that can last from 30 minutes to several hours. Intravenous sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole contains ethanol and should not be co-administered with disulfiram. This reaction would not be expected to occur with oral sulfamethoxazole; trimethoprim.
Dofetilide: (Contraindicated) Concomitant use of dofetilide with trimethoprim is contraindicated due to increased plasma concentrations of dofetilide, which may cause serious ventricular arrhythmias associated with QT prolongation, including torsade de pointes (TdP). Trimethoprim is an inhibitor of the renal cation transport system and decreases the active tubular secretion of dofetilide. The combination of trimethoprim 160 mg and 800 mg sulfamethoxazole co-administered twice daily with dofetilide 500 mcg for 4 days has been shown to increase dofetilide AUC by 93% and Cmax by 103%.
Donepezil; Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as trimethoprim, may decrease memantine elimination by competing for common renal tubular transport systems. Although this interaction is theoretical, careful patient monitoring and dose adjustment of memantine and/or trimethoprim is recommended.
Doxepin: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as sulfamethoxazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Dronabinol: (Major) Use caution if coadministration of dronabinol with sulfamethoxazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; sulfamethoxazole is a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elexacaftor; tezacaftor; ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sulfamethoxazole; trimethoprim, SMX-TMP. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering inhibitors of CYP2C8, such as trimethoprim, on the systemic exposure of eltrombopag has not been established. Monitor pat
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when elvitegravir is administered with sulfamethoxazole; trimethoprim, SMX-TMP as there is a potential for decreased sulfamethoxazole concentrations. Sulfamethoxazole is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when elvitegravir is administered with sulfamethoxazole; trimethoprim, SMX-TMP as there is a potential for decreased sulfamethoxazole concentrations. Sulfamethoxazole is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Enalapril, Enalaprilat: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Enalapril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Entecavir: (Moderate) Both entecavir and trimethoprim are secreted by active tubular secretion. In theory, coadministration of entecavir with trimethoprim may increase the serum concentrations of either drug due to competition for the drug elimination pathway.
Eplerenone: (Major) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Trimethoprim should be used with caution with other drugs known to cause significant hyperkalemia such as eplerenone.
Eprosartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Eprosartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and sulfamethoxazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If sulfamethoxazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP2C9 substrate and sulfamethoxazole is a moderate CYP2C9 inhibitor.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Estradiol: (Moderate) Anti-infectives that disrupt the normal GI flora, including sulfonamides, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) Anti-infectives which disrupt the normal GI flora, including sulfonamides, may potentially decrease the effectiveness of estrogen containing oral contraceptives. Alternative or additional contraception may be advisable.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as sulfamethoxazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of sulfamethoxazole during coadministration with fenofibric acid.
Fenoprofen: (Minor) An interaction may occur between fenoprofen and sulfonamides. Fenoprofen is 99% bound to albumin. Thus, fenoprofen may displace other highly protein bound drugs from albumin or vice versa. If fenoprofen is used concurrently with sulfonamides, monitor patients for toxicity from any of the drugs.
Finerenone: (Moderate) Monitor serum potassium concentrations closely if finerenone and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia. High doses of trimethoprim may increase the risk for hyperkalemia especially in patients with additional risk factors such as renal insufficiency.
Fluorouracil, 5-FU: (Major) Use of other folate antagonists should be avoided during therapy with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Hematologic toxicity, such as leukopenia and/or thrombocytopenia, can be increased by concurrent use of fluorouracil, 5-FU or other bone marrow depressants. (Major) Use of other folate antagonists should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of fluorouracil, 5-FU.
Fluvastatin: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as sulfonamides, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity.
Folic Acid, Vitamin B9: (Minor) Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9.
Food: (Major) Advise patients to avoid cannabis use during sulfamethoxazole treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoid delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP2C9 substrates and sulfamethoxazole is a moderate CYP2C9 inhibitor.
Fosinopril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Fosphenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with fosphenytoin and sulfamethoxazole due to risk for phenytoin toxicity. Concomitant use may increase phenytoin concentrations. Phenytoin is a CYP2C9 substrate and sulfamethoxazole is a CYP2C9 inhibitor. (Moderate) Monitor phenytoin concentrations during concomitant therapy with fosphenytoin and trimethoprim due to risk for phenytoin toxicity. Concomitant use may increase phenytoin concentrations. Trimethoprim may inhibit the hepatic metabolism of phenytoin. Trimethoprim, given at a common clinical dosage, increased the phenytoin half-life by 51% and decreased the phenytoin metabolic clearance rate by 30%.
Ganciclovir: (Moderate) Use ganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Glimepiride: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Glipizide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Glyburide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Hydrochlorothiazide, HCTZ; Moexipril: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly. (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Ibritumomab Tiuxetan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia. (Moderate) Use potassium phosphate cautiously with trimethoprim (especially high dose), as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Monitor serum potassium concentrations at periodic intervals.
Imipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Indinavir: (Minor) Concomitant administration of indinavir and trimethoprim should be done with caution. Administration of indinavir and sulfamethoxazole; trimethoprim, SMX-TMP significantly increased the AUC of trimethoprim. There was no effect on the AUC of indinavir or sulfamethoxazole.
Indomethacin: (Major) Avoid the concomitant use of sulfamethoxazole and indomethacin as coadministration may result in increased serum concentrations of sulfamethoxazole. Coadministration may increase the risk of sulfamethoxazole toxicity.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulins: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Iodine; Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Irbesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Irbesartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy. (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15% to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Additionally, sulfamethoxazole; trimethoprim may increase the serum concentration of rifampin. The drugs are often given together for certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy and increased rifampin toxicity.
Isoniazid, INH; Rifampin: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy. (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15% to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Additionally, sulfamethoxazole; trimethoprim may increase the serum concentration of rifampin. The drugs are often given together for certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy and increased rifampin toxicity.
Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sulfamethoxazole; trimethoprim, SMX-TMP. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use. (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Lesinurad: (Moderate) Use lesinurad and sulfamethoxazole together with caution; sulfamethoxazole may increase the systemic exposure of lesinurad. Sulfamethoxazole is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Lesinurad; Allopurinol: (Moderate) Use lesinurad and sulfamethoxazole together with caution; sulfamethoxazole may increase the systemic exposure of lesinurad. Sulfamethoxazole is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Leucovorin: (Minor) Racemic leucovorin may be used to offset the toxicity of folate antagonists such as trimethoprim; however, the concomitant use of leucovorin with sulfamethoxazole; trimethoprim for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect. (Minor) The concomitant use of leucovorin with sulfamethoxazole; trimethoprim, for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levoleucovorin: (Minor) Racemic leucovorin may be used to offset the toxicity of folate antagonists such as trimethoprim; however, the concomitant use of leucovorin with sulfamethoxazole; trimethoprim for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect. (Minor) The concomitant use of leucovorin with sulfamethoxazole; trimethoprim, for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect.
Levomefolate: (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Lidocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lisinopril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Lisinopril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and sulfamethoxazole; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, closely monitor patients for lonafarnib-related adverse reactions. Lonafarnib is a CYP2C9 substrate and sulfamethoxazole is a CYP2C9 inhibitor.
Losartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperk alemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors. (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as sulfonamides, have potential to inhibit the conversion of losartan to its active metabolite. Monitor therapeutic response to individualize losartan dosage.
Losartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors. (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as sulfonamides, have potential to inhibit the conversion of losartan to its active metabolite. Monitor therapeutic response to individualize losartan dosage.
Lumacaftor; Ivacaftor: (Minor) Concomitant use of sulfamethoxazole; trimethoprim and lumacaftor; ivacaftor may alter sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole exposure. Sulfamethoxazole is a substrate of CYP2C9; in vitro data suggest it is also a substrate for the P-glycoprotein (P-gp) drug transporter. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C9 and P-gp. The net effect of lumacaftor; ivacaftor on CYP2C9-mediated metabolism and P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events.
Lumacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sulfamethoxazole; trimethoprim, SMX-TMP. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Mefenamic Acid: (Moderate) Mefenamic acid is a substrate for CYP450 2C9. Inhibitors of the 2C9 isoenzyme, such as trimethoprim, may lead to increased serum concentrations of mefenamic acid. If administered concurrently with mefenamic acid, monitor for NSAID related side effects.
Meglitinides: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with sulfamethoxazole is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and sulfamethoxazole is a moderate CYP2C9 inhibitor.
Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as trimethoprim, may decrease memantine elimination by competing for common renal tubular transport systems. Although this interaction is theoretical, careful patient monitoring and dose adjustment of memantine and/or trimethoprim is recommended.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Mercaptopurine, 6-MP: (Moderate) Increased bone marrow suppression may occur if mercaptopurine is coadministered with trimethoprim sulfamethoxazole. If concomitant use is necessary, monitor complete blood counts and adjust the dose of mercaptopurine if severe neutropenia or thrombocytopenia occur.
Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Repaglinide: (Major) Coadministration of trimethoprim and repaglinide increases the AUC of repaglinide by 61%; if coadministration is necessary, consider a dose reduction of repaglinide and increased frequency of glucose monitoring. Trimethoprim is a CYP2C8 inhibitor and repaglinide is a CYP2C8 substrate. The possibility of an increased risk of hypoglycemia should be considered during concomitant use of trimethoprim and repaglinide. (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Rosiglitazone: (Moderate) It is possible that an increase in the exposure of rosiglitazone may occur when coadministered with drugs that inhibit CYP2C8 such as trimethoprim. Patients should be monitored for changes in glycemic control if any CYP2C8 inhibitors are coadministered with rosiglitazone. (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Methenamine: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly.
Methenamine; Sodium Acid Phosphate: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly.
Methenamine; Sodium Salicylate: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly. (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Methotrexate: (Major) Avoid concomitant use of methotrexate and sulfamethoxazole due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Increased bone marrow suppression has been reported in patients receiving methotrexate and sulfamethoxazole; trimethoprim. Methotrexate is approximately 50% protein bound; sulfamethoxazole is highly protein-bound. Sulfamethoxazole may displace methotrexate from its protein binding sites and compete with the renal transport of methotrexate, increasing methotrexate plasma concentrations. (Major) Avoid concomitant use of methotrexate and trimethoprim due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Increased bone marrow suppression has been reported in patients receiving methotrexate and sulfamethoxazole; trimethoprim.
Methoxsalen: (Moderate) Use methoxsalen and sulfonamides together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Methyclothiazide: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Metolazone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Miglitol: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Moexipril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with trimethoprim is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and trimethoprim is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Naproxen: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Naproxen; Esomeprazole: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Naproxen; Pseudoephedrine: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Nebivolol; Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Nortriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Olmesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Olmesartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Sulfamethoxazole; trimethoprim, SMX-TMP did not alter the pharmacokinetics of rifabutin. (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oritavancin: (Moderate) Sulfamethoxazole is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated sulfamethoxazole plasma concentrations. If these drugs are administered concurrently, monitor for sulfamethoxazole toxicity such as diarrhea, anorexia, or nausea.
Oxacillin: (Minor) Sulfonamides may compete with oxacillin for renal tubular secretion, increasing oxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Paclitaxel: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trimethoprim is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. This interaction may also be applicable to combination products containing trimethoprim, including sulfamethoxazole; trimethoprim (also known as SMX-TMP or cotrimoxazole).
Penicillin G Benzathine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. Sulfonamides may also compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects. (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. Sulfonamides may also compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin G: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin V: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Perindopril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Perindopril; Amlodipine: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Perphenazine; Amitriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with sulfamethoxazole. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Phenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with sulfamethoxazole due to risk for phenytoin toxicity. Concomitant use may increase phenytoin concentrations. Phenytoin is a CYP2C9 substrate and sulfamethoxazole is a CYP2C9 inhibitor. (Moderate) Monitor phenytoin concentrations during concomitant therapy with trimethoprim due to risk for phenytoin toxicity. Concomitant use may increase phenytoin concentrations. Trimethoprim may inhibit the hepatic metabolism of phenytoin. Trimethoprim, given at a common clinical dosage, increased the phenytoin half-life by 51% and decreased the phenytoin metabolic clearance rate by 30%.
Photosensitizing agents (topical): (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Pioglitazone; Glimepiride: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Piperacillin; Tazobactam: (Minor) Sulfonamides may compete with piperacillin for renal tubular secretion, increasing piperacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Porfimer: (Major) Avoid coadministration of porfimer with sulfonamides due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like sulfonamides may increase the risk of a photosensitivity reaction.
Posaconazole: (Major) Posaconazole and sulfamethoxazole should be coadministered with caution due to an increased potential for sulfamethoxazole-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of sulfamethoxazole. These drugs used in combination may result in elevated sulfamethoxazole plasma concentrations, causing an increased risk for sulfamethoxazole-related adverse events.
Potassium Acetate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Bicarbonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Citrate; Citric Acid: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Gluconate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Phosphate: (Moderate) Use potassium phosphate cautiously with trimethoprim (especially high dose), as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Monitor serum potassium concentrations at periodic intervals.
Potassium Phosphate; Sodium Phosphate: (Moderate) Use potassium phosphate cautiously with trimethoprim (especially high dose), as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Monitor serum potassium concentrations at periodic intervals.
Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium-sparing diuretics: (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Pralatrexate: (Major) Renal elimination accounts for approximately 34% of the overall clearance of pralatrexate. Concomitant administration of drugs that undergo substantial renal clearance, such as sulfamethoxazole; trimethoprim, SMX-TMP, may result in delayed clearance of pralatrexate.
Pramlintide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Pretomanid: (Major) Avoid coadministration of pretomanid with sulfamethoxazole, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Probenecid: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Probenecid; Colchicine: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Procainamide: (Moderate) Monitor procainamide plasma concentrations, if available, and for clinical and ECG signs of procainamide toxicity with concomitant trimethoprim use. Trimethoprim increases the plasma concentrations of procainamide and its active N-acetyl metabolite (NAPA). The increased procainamide and NAPA plasma concentrations are associated with further prolongation of the QTc interval.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Protriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Pyrimethamine: (Major) Avoid concurrent use of sulfamethoxazole and pyrimethamine. Reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses more than 25 mg/week may develop megaloblastic anemia with concurrent sulfamethoxazole; trimethoprim. Additionally, the concomitant use of other antifolic drugs associated with myelosuppression, including sulfamethoxazole; trimethoprim, may increase the risk of bone marrow suppression. (Major) Avoid concurrent use of trimethoprim and pyrimethamine. Reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses more than 25 mg/week may develop megaloblastic anemia with concurrent sulfamethoxazole; trimethoprim. Additionally, the concomitant use of other antifolic drugs associated with myelosuppression, including sulfamethoxazole; trimethoprim, may increase the risk of bone marrow suppression.
Quinapril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Ramelteon: (Moderate) Ramelteon should be administered with caution to patients taking CYP2C9 inhibitors, such as sulfamethoxazole. The AUC and Cmax of ramelteon have been elevated > 150% when administered with other CYP2C9 inhibitors. The patient should be monitored closely for toxicity even though ramelteon has a wide therapeutic index.
Ramipril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Repaglinide: (Major) Coadministration of trimethoprim and repaglinide increases the AUC of repaglinide by 61%; if coadministration is necessary, consider a dose reduction of repaglinide and increased frequency of glucose monitoring. Trimethoprim is a CYP2C8 inhibitor and repaglinide is a CYP2C8 substrate. The possibility of an increased risk of hypoglycemia should be considered during concomitant use of trimethoprim and repaglinide.
Rifabutin: (Moderate) Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Sulfamethoxazole; trimethoprim, SMX-TMP did not alter the pharmacokinetics of rifabutin.
Rifampin: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy. (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15% to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Additionally, sulfamethoxazole; trimethoprim may increase the serum concentration of rifampin. The drugs are often given together for certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy and increased rifampin toxicity.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and sulfamethoxazole. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rosiglitazone: (Moderate) It is possible that an increase in the exposure of rosiglitazone may occur when coadministered with drugs that inhibit CYP2C8 such as trimethoprim. Patients should be monitored for changes in glycemic control if any CYP2C8 inhibitors are coadministered with rosiglitazone.
Sacubitril; Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Salicylates: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Salsalate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Sapropterin: (Moderate) Drugs that inhibit folate metabolism, such as trimethoprim, should be used with caution in patients taking sapropterin. More frequent monitoring of blood phenylalanine concentrations is warranted in patients receiving these agents concurrently. An increased dosage of sapropterin may be necessary to achieve a biochemical response. Trimethoprim may decrease the bioavailability of endogenous tetrahydrobiopterin (BH4) by inhibiting the enzyme dihydrofolate reductase. Reduction of BH4 could make management of hyperphenylalaninemia with sapropterin more difficult.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Selexipag: (Major) Consider a less frequent dosing regimen (e.g., once daily) when initiating selexipag in patients receiving trimethoprim. Reduce the selexipag dose when trimethoprim is initiated in patients already taking selexipag. Coadministration can be expected to increase exposure to selexipag and its active metabolite. Selexipag is a substrate of CYP2C8; trimethoprim is a moderate CYP2C8 inhibitor.
Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Siponimod: (Moderate) Concomitant use of siponimod and sulfamethoxazole may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate or strong CYP3A4 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; sulfamethoxazole is a moderate CYP2C9 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sodium Iodide: (Moderate) Sulfonamides may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administrations.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sodium Sulfate; Magnesium Sulfate; Potassium Chlori de: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with trimethoprim. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 substrate; trimethoprim is an inhibitor of CYP2C8.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with trimethoprim. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 substrate; trimethoprim is an inhibitor of CYP2C8.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sparsentan: (Moderate) Monitor potassium during concomitant use of sparsentan and trimethoprim. Concomitant use increases the risk for hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Spironolactone: (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Sulfonylureas: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Sumatriptan; Naproxen: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Telmisartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Telmisartan; Amlodipine: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Telmisartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering sulfamethoxazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; sulfamethoxazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering trimethoprim. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP2C8; trimethoprim is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Tetracaine: (Major) Coadministration of tetracaine with sulfonamides may antagonize the effect of sulfonamides. Tetracaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of tetracaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Tezacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sulfamethoxazole; trimethoprim, SMX-TMP. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Thiazide diuretics: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tolazamide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides.
Tolbutamide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. (Minor) Trimethoprim has been shown to reduce the clearance of unbound tolbutamide and prolong tolbutamide half-life. The reductions in tolbutamide clearance are relatively small. While the risk of enhanced hypoglycemic effects appears low, closely monitor blood glucose during concomitant therapy.
Trandolapril: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Trandolapril; Verapamil: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Triamterene: (Major) Avoid use of other folate antagonists, such as triamterene, with sulfamethoxazole; trimethoprim as an increased risk of megaloblastic anemia may occur due to folate deficiency. (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Triamterene; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid use of other folate antagonists, such as triamterene, with sulfamethoxazole; trimethoprim as an increased risk of megaloblastic anemia may occur due to folate deficiency. (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Tricyclic antidepressants: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Trimipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant sulfamethoxazole; trimethoprim use; adjust the tricyclic antidepressant dose if needed. The efficacy of tricyclic antidepressants can decrease during concomitant use. (Moderate) Monitor therapeutic response and adjust the tricyclic antidepressant dose, if needed, when use sulfamethoxazole; trimethoprim concomitantly. The efficacy of tricyclic antidepressants can decrease when administered with sulfamethoxazole; trimethoprim.
Trospium: (Moderate) Both trospium and trimethoprim are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or trimethoprim due to competition for the drug elimination pathway. Careful patient monitoring is recommended. For trospium, monitor for anticholinergic effects, such as dry mouth, constipation, blurred vision, urinary retention, or increased CNS effects which are not frequent when the drug is used alone. Trimethoprim dose-related side effects include nausea, vomiting, dizziness, headaches, mental depression/confusion, palpitations, and bone marrow depression. In some patients, a dosage reduction may be required.
Typhoid Vaccine: (Major) Avoid use of sulfonamides and other antibiotics during the oral typhoid vaccination series at concurrent administration may result in a reduced immune response. In order to provided immunity, the oral typhoid vaccine requires initiation of a limited infection localized within the gastrointestinal tract. Antibiotics prevent this bacterial infection from occurring, thereby, reducing the vaccines protective immune response.
Valganciclovir: (Moderate) Use valganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Valproic Acid, Divalproex Sodium: (Minor) The risk for developing leukopenia and/or thrombocytopenia can be increased if other bone marrow depressants are used with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include: valproic acid, divalproex sodium. If these agents are used concomitantly, close observation of blood counts is warranted. (Minor) Use of other folate antagonists should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of divalproex or valproic acid.
Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Valsartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with sulfonamides is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like sulfonamides may increase the risk of a photosensitivity reaction.
Vigabatrin: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as sulfamethoxazole, may occur during concurrent use of vigabatrin.
Vonoprazan; Amoxicillin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Voriconazole: (Moderate) Monitor for increased voriconazole-related adverse reactions if coadministered with sulfamethoxazole. Elevated voriconazole concentrations and, thus, adverse reactions may result. Voriconazole is a CYP2C9 substrate and sulfamethoxazole is a CYP2C9 inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with sulfonamides is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Warfarin doses may need to be adjusted when sulfonamide therapy is discontinued. Sulfonamides, including sulfathiazole, sulfamethoxazole, and sulfisoxazole, potentiate the anticoagulant effect of warfarin. Sulfonamides are known to inhibit the hepatic metabolism of S-warfarin and have, in some cases, doubled the hypoprothrombinemic effect of warfarin. A protein-binding interaction also may be possible, with sulfonamides displacing warfarin from protein binding sites.
Zidovudine, ZDV: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use. (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Ziprasidone: (Major) Concomitant use of ziprasidone and sulfamethoxazole; trimethoprim should be avoided if possible due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
How Supplied
Bacter-Aid DS/Bactrim/Bactrim DS/Septra/Septra DS/Sulfamethoxazole, Trimethoprim Oral Tab: 400-80mg, 800-160mg
Septra/Sulfamethoxazole, Trimethoprim/Sulfatrim/Sulfatrim Pediatric/Sultrex Pediatric Oral Susp: 5mL, 200-40mg
Sulfamethoxazole, Trimethoprim Intravenous Inj Sol: 1mL, 80-16mg
Maximum Dosage
All doses are based on trimethoprim component.
Adults20 mg/kg/day PO (Max: 1,600 mg/day); 20 mg/kg/day IV (Max: 960 mg/day).
Geriatric20 mg/kg/day PO (Max: 1,600 mg/day); 20 mg/kg/day IV (Max: 960 mg/day).
Adolescents20 mg/kg/day PO (Max: 1,600 mg/day); 20 mg/kg/day IV (Max: 960 mg/day).
Children20 mg/kg/day PO (Max: 1,600 mg/day); 20 mg/kg/day IV (Max: 960 mg/day).
Infants2 to 11 months: 20 mg/kg/day PO/IV.
younger than 2 months: Contraindicated in infants younger than 2 months of age; however, doses up to 10 mg/kg/day PO are used off-label for PCP prophylaxis in HIV-infected/exposed infants as young as 4 weeks of age.
Contraindicated in infants younger than 2 months of age; however, doses up to 10 mg/kg/day PO are used off-label for PCP prophylaxis in HIV-infected/exposed infants as young as 4 weeks of age.
Mechanism Of Action
Sulfamethoxazole; trimethoprim is usually bactericidal and acts by inhibiting sequential enzymes of the folic acid synthesis pathway. Sulfamethoxazole is a structural analog of p-aminobenzoic acid (PABA), and it inhibits the formation of dihydrofolic acid by competing with PABA for binding to bacterial dihydropteroate synthase. This action interferes with the conversion of PABA into folic acid, an essential component of bacterial development. Trimethoprim binds to and reversibly inhibits the enzyme dihydrofolate reductase, which prevents the formation of tetrahydrofolic acid from dihydrofolic acid. Tetrahydrofolic acid, or THF, is the metabolically active form of folic acid. Without THF, bacteria cannot synthesize thymidine, which leads to interference with bacterial nucleic acid and protein formation. The combination of trimethoprim with sulfamethoxazole is synergistic against some bacteria.[43890] [51808] [55864] [63994]
The susceptibility interpretive criteria for sulfamethoxazole; trimethoprim are delineated by pathogen. The MICs are defined for Enterobacterales, B. cepacia complex, Acinetobacter sp., S. maltophilia, other non-Enterobacterales, and Staphylococcus sp. as susceptible at 2/38 mcg/mL or less and resistant at 4/76 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, and S. pneumoniae as susceptible at 0.5/9.5 mcg/mL or less, intermediate at 1/19 to 2/38 mcg/mL, and resistant at 4/76 mcg/mL or more. The MICs are defined for N. meningitidis as susceptible at 0.12/2.4 mcg/mL or less, intermediate at 0.25/4.75 mcg/mL, and resistant at 0.5/9.5 mcg/mL or more; sulfamethoxazole; trimethoprim may only be appropriate for prophylaxis of meningococcal case contacts.[63320] [63321]
Differences in toxicity between healthy individuals and certain patient populations have been documented with sulfonamides. Sulfonamides are metabolized mainly by acetylation. Patients who are slow acetylators (50% of the US population) metabolize more sulfonamide drug by the cytochrome P450 system than fast acetylators. Metabolism via the cytochrome P450 system produces reactive metabolites, usually detoxified by scavengers, such as glutathione. Some patient populations, however, have low amounts of glutathione (i.e., AIDS patients) and toxic metabolites accumulate, leading to a higher incidence of severe toxicities such as hypersensitivity reactions.[63993] [63994]
Pharmacokinetics
Sulfamethoxazole; trimethoprim is administered orally and intravenously. Both sulfamethoxazole and trimethoprim are widely distributed throughout all body tissues and fluids, including sputum, vaginal fluid, and middle ear fluid. CSF concentrations are 20% and 30% to 50% of serum concentrations, respectively, for sulfamethoxazole and trimethoprim. Trimethoprim also reaches high concentrations in the liver, kidney, pulmonary tissue, and prostatic fluid. Both also cross the placenta and enter breast milk. Protein-binding is 44% for trimethoprim and 70% for sulfamethoxazole. In circulation, CYP2C9 metabolizes sulfamethoxazole to form the N4-hydroxy metabolite. Four other sulfamethoxazole metabolites have also been identified: N4-acetyl-, 5-methylhydroxy-, N4-acetyl-5-methylhydroxy-, and the N-glucuronide conjugate. The acetylated metabolites of sulfamethoxazole are more highly bound to protein than is the free drug. Trimethoprim is metabolized into 11 different metabolites, with the major metabolites being the 1- and 3-oxides and the 3- and 4-hydroxy derivatives. Of note, only the free forms of sulfamethoxazole and trimethoprim are considered to be therapeutically active. The kidney and liver are both important in the elimination of trimethoprim and sulfamethoxazole. Up to 80% of trimethoprim and roughly 20% of sulfamethoxazole are eliminated unchanged in the urine. Both compounds are removed by glomerular filtration, with some tubular secretion. Sulfamethoxazole is also reabsorbed, and its excretion is increased in alkaline urine. Trimethoprim's excretion is increased in acid urine and decreased in alkaline urine. In patients with normal renal function, sulfamethoxazole's half-life ranges from 6 to 12 hours, and trimethoprim's half-life ranges from 8 to 10 hours. Small amounts of both trimethoprim and sulfamethoxazole are excreted in feces and bile.[42300] [43888] [43890] [51808] [51809]
Affected cytochrome P450 isoenzymes and drug transporter: CYP2C9, CYP2C8, P-gp, OCT1, OCT2
Sulfamethoxazole is a substrate and inhibitor of CYP2C9. In vitro data suggest trimethoprim is a substrate for the drug transporters P-glycoprotein (P-gp), OCT1, and OCT2. Trimethoprim also inhibits both OCT2 and the hepatic isoenzyme CYP2C8.[43888]
Sulfamethoxazole; trimethoprim is rapidly and well absorbed (90% to 100%) from the GI tract. Peak serum concentrations of 1 to 2 mcg/mL and 40 to 60 mcg/mL are achieved 1 to 4 hours after a single oral dose of 160 mg trimethoprim and 800 mg sulfamethoxazole, respectively. At steady state, the serum ratio of trimethoprim to sulfamethoxazole is 1:20. [51809]
Intravenous RouteAfter IV infusion of 160 mg trimethoprim and 800 mg sulfamethoxazole, peak steady-state serum concentrations are roughly 9 mcg/mL and 105 mcg/mL, and troughs are 6 mcg/mL and 70 mcg/mL, respectively.
Pregnancy And Lactation
Sulfamethoxazole; trimethoprim may cause fetal harm if administered during pregnancy. Use sulfamethoxazole; trimethoprim during pregnancy only if the potential benefit justifies the potential risk to the fetus. In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, sulfonamide use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 2.01; 95% CI: 1.36 to 2.97; 30 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. Limited data have also linked first trimester exposure to sulfamethoxazole; trimethoprim to an increased risk for congenital malformations (i.e., cardiovascular malformations, neural tube defects, oral cleft, urinary tract defects, club foot). However, other studies such as the Collaborative Perinatal Project, which included 1,455 mothers with first trimester sulfonamide exposure and 5,689 with exposure anytime during pregnancy, found no evidence to suggest a relationship between sulfonamide use and fetal malformations. Sulfonamides should generally be avoided near term due to the potential for jaundice, hemolytic anemia, and kernicterus in the newborn; sulfonamides readily cross the placenta with fetal concentrations averaging 70% to 90% of maternal concentrations. If sulfamethoxazole; trimethoprim is used during pregnancy, the patient should be advised of the potential risk to the fetus and supplemental multivitamins should be administered. Use of the drug is recommended for prophylaxis of pneumocystis pneumonia (PCP) in HIV-infected pregnant women.
Both sulfamethoxazole and trimethoprim are excreted into human breast milk at concentrations of approximately 2% to 5% of the recommended daily dose for infants over 2 months of age. Because of the potential risk of bilirubin displacement and kernicterus, avoid breast-feeding during treatment with sulfamethoxazole; trimethoprim. However, previous American Academy of Pediatrics (AAP) recommendations considered sulfamethoxazole; trimethoprim as usually compatible with breast-feeding. An extensive review in HIV-infected women suggested that the risk of kernicterus in the breast-feeding infant is very low. In a study of 12 newborn infants of less than 3 days postnatal age receiving systemic sulfamethoxazole; trimethoprim, the authors noted that despite therapeutic serum concentrations, there was no displacement of bilirubin from albumin in the newborns. If sulfamethoxazole; trimethoprim is administered to the mother of a young infant, monitor the infant for signs of increased bilirubin and jaundice. Ciprofloxacin, amoxicillin, and nitrofurantoin (cautioned in the infant with glucose-6-phosphate dehydrogenase deficiency) may be potential alternatives to consider during breast-feeding as generally considered compatible by previous AAP recommendations.