Zithromax

Macrolide Antibiotics
Ophthalmological Anti-infectives

Oral Administration Oral Solid Formulations

May be taken with or without food; however, increased tolerability has been observed when the tablets are taken with food.

Oral Liquid Formulations

Oral suspension (immediate-release, bottles for reconstitution):
Review the reconstitution instructions for the particular product and package size, as the amount of water required for reconstitution may vary from manufacturer to manufacturer.
Tap the bottle to loosen the powder. Add water in 2 portions and shake well after each portion.
Azithromycin for oral suspension (100 mg/5 mL or 200 mg/5 mL strengths) may be taken with or without food.
Measure dosage with a calibrated spoon, cup, or oral syringe.
Storage after reconstitution: Store at 5 to 30 degrees C (41 to 86 degrees F). Discard any unused portion per manufacturer recommendations.[28855]
 
Oral suspension (1 gram single-dose packet):
Do not use for administration of doses other than 1 gram.
Zithromax for oral suspension (1-g single-dose packet) may be taken with or without food; however, administration with food may increase tolerability.
Mix the entire contents of the packet in 60 mL (approximately 2 ounces) of water. Administer the entire contents immediately, then add an additional 60 mL of water, mix and administer to assure complete administration of the dosage.[43975]
 
Oral suspension (extended-release, bottles for reconstitution):
Extended-release oral suspension (2 grams azithromycin) should be taken as a single dose at least 1 hour before or 2 hours after a meal.
If a patient vomits within 5 minutes of the dose, the manufacturer recommends additional antibiotic treatment due to minimal absorption of the azithromycin dose. If a patient vomits between 5 to 60 minutes following the dose, consider alternate therapy. In patients with normal gastric emptying, if vomiting occurs 60 minutes or later after the dose, no additional antibiotic therapy is warranted. In patients with delayed gastric emptying, consider alternative therapy.
Constitute with 60 mL of water, replace cap, and shake bottle well.
Storage after reconstitution: Do not refrigerate. Use within 12 hours.[34473]

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Reconstitution:
Add 4.8 mL of Sterile Water Injection to a concentration of 100 mg/mL.
Because the vial is supplied under vacuum, it is recommended that a standard 5 mL (non-automated) syringe be used to ensure that the exact amount of 4.8 mL of sterile water is dispensed.
Shake until all of the drug is dissolved.
Further dilution is required.
Storage: The reconstituted solution is stable for 24 hours when stored below 30 degrees C (86 degrees F).[43974]
 
Dilution:
Dilute by transferring 5 mL of the reconstituted solution into a compatible diluent; use 500 mL of diluent for a concentration of 1 mg/mL and 250 mL of diluent for a concentration of 2 mg/mL.
Compatible diluents include: 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, 5% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose and 0.45% Sodium Chloride Injection with 20 mEq KCl, 5% Dextrose and Lactated Ringer's Injection, 5% Dextrose and 0.3% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, Normosol-M and 5% Dextrose Injection, and Normosol-R and 5% Dextrose Injection.
Storage: Diluted solutions are stable for 24 hours at or below room temperature (30 degrees C or 86 degrees F) or for 7 days if stored under refrigeration (5 degrees C or 41 degrees F).[43974]
 
Intravenous infusion:
Do not administer intramuscularly or via IV bolus.
Other intravenous substances, additives, or medications should not be added to azithromycin or infused simultaneously through the same IV line.
For a dose of 500 mg in 250 mL (concentration = 2 mg/mL), infuse over 1 hour. For a dose of 500 mg in 500 mL (concentration = 1 mg/mL), infuse over 3 hours.[43974]

Ophthalmic Administration

For ophthalmic use only. Apply topically only to the eye.
Instruct patient on proper instillation of eye solution.
Avoid contamination of the eye solution; do not touch the tip of the eye dropper to the eye, fingertips, or other surface.
Due to the difficulty of administering eye drops to pediatric patients, consider a 2 person administration approach to ensure proper installation of the drops (1 person to hold the eyelids open and 1 person to administer the drops).
To avoid contamination, do not share an opened bottle among patients.[43976]

Severe

hyperkalemia / Delayed / 1.0-2.0
pleural effusion / Delayed / 0-1.0
uveitis / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
keratitis / Delayed / 0-1.0
corneal erosion / Delayed / 0-1.0
visual impairment / Early / 0-1.0
lymphoma / Delayed / 0-1.0
leukemia / Delayed / 0-1.0
azotemia / Delayed / 0-1.0
pancreatitis / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
seizures / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
torsade de pointes / Rapid / Incidence not known
hearing loss / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
pyloric stenosis / Delayed / Incidence not known

Moderate

elevated hepatic enzymes / Delayed / 1.0-6.0
erythema / Early / 3.1-3.1
hyperbilirubinemia / Delayed / 0-3.0
vaginitis / Delayed / 0-2.8
stomatitis / Delayed / 1.9-1.9
dyspnea / Early / 0-1.9
melena / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
constipation / Delayed / 0-1.0
cholestasis / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
superinfection / Delayed / 0-1.0
anemia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
neutropenia / Delayed / 0-1.0
chest pain (unspecified) / Early / 0-1.0
palpitations / Early / 0-1.0
conjunctivitis / Delayed / 0-1.0
contact dermatitis / Delayed / 0-1.0
blurred vision / Early / 0-1.0
hyponatremia / Delayed / 0-1.0
hypokalemia / Delayed / 0-1.0
dysuria / Early / 0-1.0
lymphocytosis / Delayed / 1.0
eosinophilia / Delayed / 1.0
lymphopenia / Delayed / 1.0
hypoglycemia / Early / 1.0
hyperglycemia / Delayed / 1.0
hepatitis / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
edema / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known

Mild

nausea / Early / 0.4-18.0
diarrhea / Early / 1.8-14.0
abdominal pain / Early / 1.2-14.0
vomiting / Early / 0-14.0
injection site reaction / Rapid / 1.9-12.0
rash / Early / 0-8.1
flatulence / Early / 0-5.0
headache / Early / 0-5.0
fatigue / Early / 0-3.9
dizziness / Early / 0-3.9
pruritus / Rapid / 0-3.9
tinnitus / Delayed / 0.9-3.4
arthralgia / Delayed / 0-3.0
fever / Early / 0-2.1
anorexia / Delayed / 0-2.0
ocular irritation / Rapid / 1.0-2.0
dysgeusia / Early / 0-1.3
malaise / Early / 0-1.1
dyspepsia / Early / 0-1.0
pharyngitis / Delayed / 0-1.0
cough / Delayed / 0-1.0
sinusitis / Delayed / 0-1.0
rhinitis / Early / 0-1.0
nasal congestion / Early / 0-1.0
paresthesias / Delayed / 0-1.0
chills / Rapid / 0-1.0
asthenia / Delayed / 0-1.0
agitation / Early / 0-1.0
vertigo / Early / 0-1.0
insomnia / Early / 0-1.0
drowsiness / Early / 0-1.0
hyperkinesis / Delayed / 0-1.0
emotional lability / Early / 0-1.0
irritability / Delayed / 0-1.0
maculopapular rash / Early / 0-1.0
diaphoresis / Early / 0-1.0
vesicular rash / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
photosensitivity / Delayed / 0-1.0
ocular pruritus / Rapid / 0-1.0
xerophthalmia / Early / 0-1.0
ocular pain / Early / 0-1.0
ocular discharge / Delayed / 0-1.0
tongue discoloration / Delayed / Incidence not known
candidiasis / Delayed / Incidence not known
syncope / Early / Incidence not known
anxiety / Delayed / Incidence not known
dysosmia / Delayed / Incidence not known
anosmia / Delayed / Incidence not known
Jarisch-Herxheimer reaction / Early / Incidence not known

Azasite, Zithromax, Zithromax Powder, Zithromax Single-Dose, Zithromax Tri-Pak, Zithromax Z-Pak, Zmax

Rx

Macrolide antibiotic similar in structure to erythromycin, but can be dosed systemically once daily
Used systemically for otitis media, pharyngitis, community-acquired pneumonia, sexually transmitted diseases, and Mycobacterium avium complex (MAC) prophylaxis and treatment in patients with advanced HIV disease; an ophthalmic solution is used for bacterial conjunctivitis
Produces less GI intolerance and reaches higher intracellular concentrations than erythromycin

For the treatment of community-acquired pneumonia (CAP). Oral dosage (immediate-release) Outpatient Adults

500 mg PO on day 1, followed by 250 mg PO once daily for at least 5 days as monotherapy for patients without comorbidities or risk factors for MRSA or P. aeruginosa and as part of combination therapy for patients with comorbidities. Guide treatment duration by clinical stability.[28855] [34362] [64669] FDA-approved labeling recommends a 5-day treatment course.[28855]

Hospitalized Adults

500 mg PO once daily for at least 5 days as part of combination therapy. Guide treatment duration by clinical stability.[34362] [64669]

Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.[28855] Guidelines recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for persons living with HIV.[34362] [46963]

Infants and Children 6 months to 12 years

10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.[28855] Guidelines recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized persons living with HIV.[34361] [46963]

Infants 1 to 5 months†

10 mg/kg/dose PO for 1 day, followed by 5 mg/kg/dose PO once daily for 4 days. Guidelines in older pediatric patients recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized persons living with HIV.[34361] [46963]

Neonates†

10 mg/kg/dose PO for 1 day, followed by 5 mg/kg/dose PO once daily for 4 days. Guidelines in older pediatric patients recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized persons living with HIV.[34361] [46963]

Oral dosage (extended-release) Adults

2 g PO as a single dose. This dosage form is not recommended for patients with moderate or severe illness or those with other underlying risk factors for which oral therapy is inappropriate.[34473]

Infants, Children, and Adolescents 6 months to 17 years

60 mg/kg/dose (Max: 2 g/dose) PO as a single dose. This dosage form is not recommended for patients with moderate or severe illness or those with other underlying risk factors for which oral therapy is inappropriate.[34473]

Intravenous dosage Adults

500 mg IV once daily for at least 5 days as part of combination therapy for hospitalized patients. Guide treatment duration by clinical stability.[34362] [64669] FDA-approved labeling recommends IV therapy for at least 2 days then step-down to oral therapy to complete a 7- to 10-day treatment course. The switch to oral therapy should be done at the discretion of the physician and based on the clinical response of the patient.[43974]

Adolescents 16 to 17 years

500 mg IV once daily for at least 2 days, followed by oral therapy to complete a 5-day treatment course.[46963] Guidelines recommend azithromycin as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected.[34362] [46963] FDA-approved labeling recommends IV therapy for at least 2 days then step-down to oral therapy to complete a 7- to 10-day treatment course. The switch to oral therapy should be done at the discretion of the physician and based on the clinical response of the patient.[43974]

Infants, Children, and Adolescents 4 months to 15 years†

10 mg/kg/dose (Max: 500 mg/dose) IV once daily for 2 days, followed by oral therapy to complete a 5-day treatment course. Guidelines recommend azithromycin as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected.[34361] [34362] [46963]

Infants 1 to 3 months†

10 mg/kg/dose IV once daily. Guidelines in older pediatric patients generally recommend IV therapy for 2 days, followed by oral step-down therapy to complete a 5-day treatment course. Azithromycin is recommended as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected.

Neonates†

10 mg/kg/dose IV once daily. Guidelines in older pediatric patients generally recommend IV therapy for 2 days, followed by oral step-down therapy to complete a 5-day treatment course. Azithromycin is recommended as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected.

For the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis. Oral dosage (immediate-release) Adults

500 mg PO once daily for 5 days as an alternative in patients allergic to penicillin. The FDA-approved dose is 500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days.

Children and Adolescents 2 to 17 years

12 mg/kg/dose (Max: 500 mg/dose) PO once daily for 5 days as an alternative in patients allergic to penicillin.[28855] [35507] [52889]

Infants† and Children 1 year†

12 mg/kg/dose PO once daily for 5 days as an alternative in patients allergic to penicillin.

For the treatment of acute bacterial sinusitis. Oral dosage (immediate-release) Adults

500 mg PO once daily for 3 days.[28855] Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy.[49853]

Infants, Children, and Adolescents 6 months to 17 years

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days.[28855] Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy.[49853]

Oral dosage (extended-release) Adults

2 g PO as a single dose. Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy.

For the treatment of acute otitis media. Oral dosage (immediate-release) Infants, Children, and Adolescents 6 months to 17 years

30 mg/kg/dose (Max: 1,500 mg/dose) PO as a single dose, or 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days, or 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.[28855] Because macrolides have limited efficacy against both H. influenzae and S. pneumoniae, these agents are not included in guidelines.[53345]

For the treatment of bacterial conjunctivitis. Ophthalmic dosage Adults

1 drop in the affected eye(s) twice daily (8 to 12 hours apart) for 2 days, then 1 drop in the affected eye(s) once daily for 5 days.[43976]

Children and Adolescents

1 drop in the affected eye(s) twice daily (8 to 12 hours apart) for 2 days, then 1 drop in the affected eye(s) once daily for 5 days.[43976]

For the treatment of uncomplicated skin and skin structure infections. Oral dosage (immediate-release) Adults

500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days.

For the treatment of pelvic inflammatory disease (PID). Intravenous dosage Adults

500 mg IV once daily for 1 to 2 days, followed by oral therapy for a total of 7 days in combination with metronidazole as an alternative.

Adolescents 16 to 17 years

500 mg IV once daily for 1 to 2 days, followed by oral therapy for a total of 7 days in combination with metronidazole as an alternative.

Adolescents 13 to 15 years†

500 mg IV once daily for 1 to 2 days, followed by oral therapy for a total of 7 days in combination with metronidazole as an alternative.

Oral dosage (immediate-release) Adults

250 mg PO once daily to complete a total of 7 days after IV therapy in combination with metronidazole as an alternative.[43974]

Adolescents 16 to 17 years

250 mg PO once daily to complete a total of 7 days after IV therapy in combination with metronidazole as an alternative.[43974]

Adolescents 13 to 15 years†

250 mg PO once daily to complete a total of 7 days after IV therapy in combination with metronidazole as an alternative.

For the treatment of uncomplicated gonorrhea, including cervicitis, urethritis, and proctitis†. Oral dosage (immediate-release) Adults

2 g PO as a single dose plus gentamicin as an alternative in patients with a cephalosporin allergy or when ceftriaxone is not available.

Children weighing more than 45 kg† and Adolescents†

2 g PO as a single dose plus gentamicin as an alternative in patients with a cephalosporin allergy or when ceftriaxone is not available.

For the treatment of chancroid. Oral dosage (immediate-release) Adults

1 g PO as a single dose. Data are limited in HIV-infected patients.

Adolescents†

1 g PO as a single dose. Data are limited in HIV-infected patients.

Infants† and Children†

20 mg/kg/dose (Max: 1 g/dose) PO as a single dose. Data are limited in HIV-infected patients.

For the treatment of Mycobacterium avium complex infection (MAC) in HIV-infected patients. Oral dosage (immediate-release) Adults

500 to 600 mg PO once daily as part of combination therapy as an alternative.[34362] [43975] Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

Adolescents†

500 to 600 mg PO once daily as part of combination therapy as an alternative. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

Infants† and Children†

10 to 12 mg/kg/dose (Max: 500 mg/dose) PO once daily as part of combination therapy as an alternative. Duration of treatment depends on clinical response but should continue for at least 12 months.[34361]

For Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients. For primary Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients. Oral dosage (immediate-release) Adults

1,200 mg PO once weekly or 600 mg PO twice weekly as preferred therapy.[34362] [43975] Discontinue primary prophylaxis upon initiation of effective antiretroviral therapy (ART). Restart primary prophylaxis if the CD4 count decreases to less than 50 cells/mm3 and not on fully suppressive ART.[34362]

Adolescents†

1,200 mg PO once weekly or 600 mg PO twice weekly as preferred therapy. Primary prophylaxis is only recommended for patients not on fully suppressive antiretroviral therapy (ART) with CD4 counts less than 50 cells/mm3 after ruling out disseminated MAC. Discontinue primary prophylaxis upon initiation of effective ART. Restart primary prophylaxis if the CD4 count decreases to less than 50 cells/mm3 and not on fully suppressive ART.[34362]

Children 6 to 12 years†

20 mg/kg/dose (Max: 1,200 mg/dose) PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose (Max: 250 mg/dose) PO once daily. Primary prophylaxis is recommended in children 6 years and older with a CD4 count less than 50 cells/mm3. Primary prophylaxis may be discontinued after 6 months or more of antiretroviral therapy (ART) and a CD4 count more than 100 cells/mm3 for more than 3 consecutive months. Restart primary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34361]

Children 2 to 5 years†

20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in children 2 to 5 years with a CD4 count less than 75 cells/mm3. Primary prophylaxis may be discontinued after 6 months or more of antiretroviral therapy (ART) and a CD4 count more than 200 cells/mm3 for more than 3 consecutive months. Restart primary prophylaxis if the CD4 count decreases to less than 200 cells/mm3.[34361]

Children 1 year†

20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in children 1 to 2 years with a CD4 count less than 500 cells/mm3. Do not discontinue primary prophylaxis for children younger than 2 years.[34361]

Infants†

20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in infants with a CD4 count less than 750 cells/mm3. Do not discontinue primary prophylaxis for children younger than 2 years.[34361]

For secondary Mycobacterium avium complex (MAC) prophylaxis† (i.e., long-term suppressive therapy) in HIV-infected patients. Oral dosage (immediate-release) Adults

500 to 600 mg PO once daily as part of combination therapy and preferred therapy. Consider discontinuing secondary prophylaxis in patients who have completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for more than 6 months in response to antiretroviral therapy (ART). Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34362]

Adolescents

500 to 600 mg PO once daily as part of combination therapy and preferred therapy. Consider discontinuing secondary prophylaxis in patients who have completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for more than 6 months in response to antiretroviral therapy (ART). Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34362]

Children 6 to 12 years

5 mg/kg/dose (Max: 250 mg/dose) PO once daily as part of combination therapy as an alternative. Consider discontinuing secondary prophylaxis in patients who have completed 6 months or more of antiretroviral therapy (ART), completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for 6 consecutive months or more. Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34361]

Children 2 to 5 years

5 mg/kg/dose PO once daily as part of combination therapy as an alternative. Consider discontinuing secondary prophylaxis in children who have completed 6 months or more of antiretroviral therapy (ART), completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 200 cells/mm3 for 6 consecutive months or more. Restart secondary prophylaxis if the CD4 count decreases to less than 200 cells/mm3.[34361]

Infants and Children 1 year

5 mg/kg/dose PO once daily as part of combination therapy as an alternative. Do not discontinue secondary prophylaxis for children younger than 2 years.[34361]

For the treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD)†, including chronic bronchitis or emphysema†, as well as for maintenance treatment of COPD†. For the treatment of acute bacterial exacerbations of COPD, including chronic bronchitis or emphysema†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 3 days, or 500 mg PO once daily for 1 day followed by 250 mg PO once daily for 4 days.  

For maintenance treatment of COPD† to reduce risk for COPD exacerbations†. Oral dosage (immediate release) Adults

250 to 500 mg PO 3 days per week or 250 mg PO once daily has been recommended to reduce exacerbation rates in patients with more than 3 exacerbations requiring steroid therapy and at least 1 exacerbation requiring hospitalization per year. Consider treatment for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations; stop if no symptomatic improvement. According to guidelines, long-term azithromycin therapy reduces exacerbations over 1 year; however, there are no data showing efficacy or safety of chronic azithromycin treatment to prevent COPD exacerbations beyond 1 year of treatment. Use was associated with an increased incidence of bacterial resistance, prolongation of QTc interval, and impaired hearing tests. Azithromycin prophylaxis can be considered for former smokers with COPD exacerbations despite appropriate therapy; a post-hoc analysis suggests lesser benefit in active smokers. It is not necessary to stop prophylactic azithromycin during acute exacerbations of COPD.

For the treatment of non-gonococcal urethritis (NGU) and cervicitis and chlamydia infection, including urethritis, cervicitis, trachoma†, and chlamydial conjunctivitis†. For the treatment of urethritis and cervicitis due to C. trachomatis. Oral dosage (immediate-release) Adults

1 g PO as a single dose as an alternative.

Children weighing 45 kg† or more and Adolescents†

1 g PO as a single dose as an alternative.

For the treatment of pneumonia caused by C. trachomatis in neonates and infants†. Oral dosage (immediate-release) Infants

20 mg/kg/dose PO once daily for 3 days as an alternative.

Neonates

20 mg/kg/dose PO once daily for 3 days as an alternative.

For the treatment of recurrent or persistent non-gonococcal urethritis (NGU) due to M. genitalium†. Oral dosage (immediate-release) Adults

1 g PO on day 1, followed by 500 mg PO once daily for 3 days (2.5 g total), following initial treatment with doxycycline in persons with macrolide-sensitive M. genitalium or as an alternative when resistance testing is not possible and moxifloxacin cannot be used.

Children weighing 45 kg or more and Adolescents

1 g PO on day 1, followed by 500 mg PO once daily for 3 days (2.5 g total), following initial treatment with doxycycline in persons with macrolide-sensitive M. genitalium or as an alternative when resistance testing is not possible and moxifloxacin cannot be used.

For the treatment of nonspecified non-gonococcal urethritis (NGU)†. Oral dosage (immediate-release) Adults

1 g PO as a single dose or 500 mg PO on day 1, followed by 250 mg PO once daily for 4 days as an alternative. For recurrent or persistent urethritis due to noncompliance or reexposure, may consider retreatment with the initial regimen.

Children weighing 45 kg or more and Adolescents

1 g PO as a single dose or 500 mg PO on day 1, followed by 250 mg PO once daily for 4 days as an alternative. For recurrent or persistent urethritis due to noncompliance or reexposure, may consider retreatment with the initial regimen.

For the treatment of trachoma†. Oral dosage (immediate-release) Adults

1 g PO as a single dose.

Infants, Children, and Adolescents

20 mg/kg/dose (Max: 1 g/dose) PO as a single dose.

For the treatment of chlamydial conjunctivitis†. Oral dosage (immediate-release) Adults

1 g PO as a single dose.

Adolescents

1 g PO as a single dose.

For the treatment of lymphogranuloma venereum† caused by C. trachomatis. Oral dosage (immediate-release) Adults

1 g PO once weekly for 3 weeks as an alternative.

Adolescents

1 g PO once weekly for 3 weeks as an alternative.

For the treatment of granuloma inguinale† (Donovanosis). Oral dosage (immediate-release) Adults

1 g PO once weekly or 500 mg PO once daily 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. Azithromycin is recommended for pregnant and lactating patients.

Adolescents

1 g PO once weekly or 500 mg PO once daily 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.

Children weighing 45 kg or more

1 g PO once weekly or 500 mg PO once daily 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 the treatment of bartonellosis†, including cat scratch disease†, neuroretinitis†, bacillary angiomatosis†, bacillary peliosis† (peliosis hepatis†), bacteremia†, osteomyelitis†, and chronic verruga peruana†. For the treatment of typical cat scratch disease in immunocompetent patients†. Oral dosage (immediate-release) Adults

500 mg PO on day 1, followed by 250 mg PO once daily for 4 days. Most cases resolve without treatment; however, consider treating patients with extensive lymphadenopathy.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. Most cases resolve without treatment; however, consider treating patients with extensive lymphadenopathy.

For the treatment of atypical hepatosplenic or bony cat scratch disease in immunocompetent patients†. Oral dosage (immediate-release) Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 to 6 weeks plus rifampin as first-line therapy.

Intravenous dosage Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) IV on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) IV once daily for 4 to 6 weeks plus rifampin as first-line therapy.

For the treatment of Bartonella infections, including cat scratch disease, bacillary angiomatosis, bacillary peliosis (peliosis hepatis), bacteremia, and osteomyelitis, in immunocompromised patients†. Oral dosage (immediate-release) Adults

500 mg PO once daily for at least 3 months as an alternative.

Adolescents

500 mg PO once daily for at least 3 months as an alternative.

Infants and Children

10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for at least 3 months as an alternative.

For the treatment of severe Bartonella infections, including multifocal disease or with clinical decompensation, in immunocompromised patients†. Oral dosage (immediate-release) Adults

500 mg PO once daily for at least 3 months plus rifampin as an alternative.

Adolescents

500 mg PO once daily for at least 3 months plus rifampin as an alternative.

For the treatment of Bartonella-related neuroretinitis in immunocompetent patients†. Oral dosage (immediate-release) Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily plus rifampin for 4 to 6 weeks with or without corticosteroids as first-line therapy.

For the treatment of chronic verruga peruana†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 7 to 14 days as first-line therapy.

Pregnant or Breast-feeding Persons

500 mg PO once daily for 7 to 14 days, or 1 g PO once weekly for 3 weeks.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 7 to 14 days.

For secondary bartonellosis prophylaxis† (i.e., long-term suppressive therapy†) in persons living with HIV. Oral dosage (immediate-release) Adults

500 mg PO once daily if a relapse occurs after at least 3 months of treatment. Discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing suppressive therapy.[34362]

Adolescents

500 mg PO once daily if a relapse occurs after at least 3 months of treatment. Discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing suppressive therapy.[34362]

For the treatment of infectious diarrhea† and gastroenteritis†, including campylobacteriosis†, cholera†, salmonellosis†, shigellosis†, and traveler's diarrhea†. For the empiric treatment of infectious diarrhea†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 3 days or 1,000 mg PO as a single dose. Routine use is not recommended.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days or 30 mg/kg/dose (Max: 1,000 mg/dose) as a single dose. Routine use is not recommended.

For the treatment of campylobacteriosis† in persons without HIV. Oral dosage (immediate-release) Adults

500 mg PO once daily for 3 days or 1,000 mg PO as a single dose as first-line therapy.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days or 30 mg/kg/dose (Max: 1,000 mg/dose) as a single dose as first-line therapy.

For the treatment of campylobacteriosis† in persons living with HIV. Oral dosage (immediate-release) Adults

500 mg PO once daily for 5 days as first-line therapy. Azithromycin is not recommended for Campylobacter bacteremia.

Adolescents

500 mg PO once daily for 5 days as first-line therapy. Azithromycin is not recommended for Campylobacter bacteremia.

For the treatment of cholera†. Oral dosage (immediate-release) Adults

1,000 mg PO as a single dose as an alternative.

Infants, Children, and Adolescents

20 mg/kg/dose (Max: 1,000 mg/dose) PO as a single dose as an alternative.

For the treatment of shigellosis† in persons without HIV. Oral dosage (immediate-release) Adults

500 mg PO once daily for 3 days.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days.

For the treatment of shigellosis† in persons living with HIV. Oral dosage (immediate-release) Adults

500 mg PO once daily for 5 days as an alternative. Treat for up to 6 weeks for recurrent infections. Azithromycin is not recommended for Shigella bacteremia.

Adolescents

500 mg PO once daily for 5 days as an alternative. Treat for up to 6 weeks for recurrent infections. Azithromycin is not recommended for Shigella bacteremia.

For the treatment of traveler's diarrhea†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 3 days or 1,000 mg PO as a single dose; if symptoms are not resolved after single dose, continue treatment for up to 3 days. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.

For the treatment of salmonellosis†. Oral dosage (immediate-release) Adults

500 mg PO daily for 48 to 72 hours or until patient becomes afebrile; treat for 7 to 14 days if concurrent bacteremia. Routine use is not recommended; reserve for patients at high risk for invasive infection.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 48 to 72 hours or the patient becomes afebrile; treat for 7 to 14 days if concurrent bacteremia. Routine use is not recommended; reserve for patients at high risk for invasive infection. 

For the treatment of typhoid fever†. For the treatment of multidrug-resistant uncomplicated typhoid fever† or quinolone-resistant uncomplicated typhoid fever†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 7 days or 1 g PO once daily PO once daily for 5 to 7 days. 

Infants, Children, and Adolescents

8 to 20 mg/kg/dose (Max: 1 g/dose) PO once daily for 5 to 7 days.

For the treatment of extensively drug-resistant typhoid fever†. Oral dosage (immediate-release) Adults

1 g PO once daily for 1 day, followed by 500 mg to 1 g PO once daily for 5 to 10 days. Use as a single agent for uncomplicated disease or in combination with a carbapenem for complicated disease.

Infants, Children, and Adolescents

20 mg/kg/dose (Max: 1 g/dose) PO once daily for 1 day, followed by 8 to 20 mg/kg/dose (Max: 1 g/dose) PO once daily for 5 to 10 days. Use as a single agent for uncomplicated disease or in combination with a carbapenem for complicated disease.

For the treatment of early Lyme disease† (erythema migrans†), including solitary and multiple erythema migrans† as second line therapy. For the treatment of early Lyme disease† (erythema migrans†) in adults as second line therapy. Oral dosage (immediate-release) Adults

500 mg PO once daily for 7 days. Due to lower efficacy, reserve macrolides for patients in whom other antibiotic classes are contraindicated.

For the treatment of early Lyme disease† (erythema migrans†) in pediatric patients as second line therapy. Oral dosage (immediate-release) Infants, Children, and Adolescents

10 mg/kg/day (Max: 500 mg/day) PO once daily for 7 days. Due to lower efficacy, reserve macrolides for patients in whom other antibiotic classes are contraindicated.

For the treatment of babesiosis†. For the treatment of babesiosis† in immunocompetent ambulatory patients with mild to moderate disease in combination with atovaquone. Oral dosage (immediate-release) Adults

500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 7 to 10 days.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 7 to 10 days.

For the treatment of babesiosis† in immunocompromised ambulatory patients with mild to moderate disease in combination with atovaquone. Oral dosage (immediate-release) Adults

500 mg PO once daily for 1 day, followed by 250 mg PO once daily for at least 7 to 10 days; duration may need to be extended in these patients.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for at least 7 to 10 days; duration may need to be extended in these patients.

For the initial treatment of babesiosis† in immunocompetent hospitalized patients with acute, severe disease in combination with atovaquone. Intravenous dosage Adults

500 mg IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of 7 to 10 days.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of 7 to 10 days.

For the initial treatment of babesiosis† in immunocompromised hospitalized patients with acute, severe disease in combination with atovaquone. Intravenous dosage Adults

500 to 1,000 mg IV once then 500 mg IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

For oral stepdown treatment of babesiosis† in immunocompetent hospitalized patients in combination with atovaquone after initial IV therapy. Oral dosage (immediate-release) Adults

250 to 500 mg PO once daily for a total treatment duration of 7 to 10 days.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total treatment duration of 7 to 10 days.

For oral stepdown treatment of babesiosis† in immunocompromised hospitalized patients in combination with atovaquone after initial IV therapy. Oral dosage (immediate-release) Adults

500 to 1,000 mg PO once daily for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

For oral stepdown treatment of babesiosis† in highly immunocompromised patients in combination with atovaquone after initial IV therapy. Oral dosage (immediate-release) Adults

500 to 1,000 mg PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

Adolescents

10 mg/kg/dose (Max: 1,000 mg/dose) PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

Infants and Children

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

For oral stepdown treatment of refractory or relapsed babesiosis† as part of combination therapy after initial IV therapy. Oral dosage (immediate-release) Adults

500 to 1,000 mg PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

Adolescents

10 mg/kg/dose (Max: 1,000 mg/dose) PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

Infants and Children

10 mg/kg/dose (Max: 500 mg/dose) PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

For the initial treatment of babesiosis† in highly immunocompromised patients in combination with atovaquone. Intravenous dosage Adults

500 to 1,000 mg IV once then 500 mg IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

Adolescents

10 mg/kg/dose (Max: 1,000 mg/dose) IV once then 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

Infants and Children

10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

For the initial treatment of refractory or relapsed babesiosis† as part of combination therapy. Intravenous dosage Adults

500 to 1,000 mg IV once then 500 mg IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

Adolescents

10 mg/kg/dose (Max: 1,000 mg/dose) IV once then 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

Infants and Children

10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

For the treatment of dental infection† or dentoalveolar infection†, including periodontitis†, acute dental abscess (apical)†, and dental abscess (periapical)†. For the treatment of chronic periodontitis† after scaling and root planing. Oral dosage (immediate-release) Adults

500 mg PO once daily for 4 to 7 days.

For the treatment of acute dental abscess in combination with surgical incision and drainage in patients with beta-lactam allergy. Oral dosage (immediate-release) Adults

1 g PO once daily for 1 day, followed by 500 mg PO once daily for 2 days.

For bacterial endocarditis prophylaxis†. Oral dosage (immediate-release) Adults

500 mg PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.[61833]

Children and Adolescents

15 mg/kg/dose (Max: 500 mg/dose) PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.[61833]

For the treatment of cystic fibrosis† to improve pulmonary function and reduce exacerbations. Oral dosage (immediate-release) Adults

250 mg PO once daily or 500 mg PO 3 times weekly. Consider an initial 6-month trial.

Children and Adolescents weighing 40 kg or more

500 mg PO 3 times weekly. Consider an initial 6-month trial.

Infants, Children, and Adolescents weighing less than 40 kg

10 mg/kg/dose (Max: 250 mg/dose) PO 3 times weekly. Consider an initial 6-month trial.

For the treatment of pertussis (whooping cough)†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days.

Infants, Children, and Adolescents 6 months to 17 years

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.

Infants 1 to 5 months

10 mg/kg/dose PO once daily for 5 days.

iv> Neonates

10 mg/kg/dose PO once daily for 5 days.

For asthma maintenance† treatment in uncontrolled or severe asthma as an adjunct. Oral dosage (immediate-release) Adults

250 to 500 mg PO 3 times weekly has been recommended to reduce the incidence of asthma exacerbations in persons with severe asthma who are optimized on inhaled corticosteroids/long-acting beta agonist therapy but who continue to have exacerbations. Consider treatment for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations; stop if no symptomatic improvement. Breaks in therapy may be considered to reduce treatment burden. Fewer asthma exacerbations and improved quality of life were reported in persons (n = 213) treated with azithromycin 500 mg PO 3 times weekly for 48 weeks. The rate of severe exacerbations and lower respiratory tract infections were not reduced in persons (n = 55) with severe asthma treated with azithromycin 250 mg PO 3 times weekly.

For postexposure pertussis prophylaxis†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days. Administer to close contacts within 3 weeks of exposure.

Infants, Children, and Adolescents 6 months to 17 years

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. Administer to close contacts within 3 weeks of exposure.

Infants 1 to 5 months

10 mg/kg/dose PO once daily for 5 days. Administer to close contacts within 3 weeks of exposure.

Neonates

10 mg/kg/dose PO once daily for 5 days. Administer to close contacts within 3 weeks of exposure.

For the treatment of bronchiectasis† to reduce exacerbations in patients with high exacerbation rates. Oral dosage (immediate-release) Adults

250 to 500 mg PO 3 days per week has been recommended to reduce exacerbation rates. Consider treatment for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations; stop if no symptomatic improvement. Breaks in therapy may be considered to reduce treatment burden.

Children and Adolescents

30 mg/kg PO once weekly has been studied.

For the treatment of bronchiolitis obliterans† in lung transplant recipients.. Oral dosage (immediate-release) Adults

250 mg PO 3 days per week for a trial period of 3 months has been recommended.

For bronchiolitis obliterans prevention after transplantation† in lung transplant patients. Oral dosage (immediate-release) Adults

250 mg PO 3 days per week has been recommended to prevent occurrence of bronchiolitis obliterans.

For the adjunctive treatment of diphtheria† and to prevent establishment of carrier state†. Oral dosage (immediate-release) Adults

500 mg PO once daily for 14 days or 1,000 mg once daily for 1 day, then 500 mg PO once daily for a total of 7 to 10 days as an adjunct to diphtheria antitoxin.

Infants, Children, and Adolescents

10 to 20 mg/kg/dose (Max: 500 mg/dose) PO once daily for 14 days as an adjunct to diphtheria antitoxin.

For the post-exposure diphtheria prophylaxis† of close contacts of persons with diphtheria. Oral dosage (immediate-release) Adults

500 mg PO once daily for 5 to 7 days.

Infants, Children, and Adolescents

10 to 20 mg/kg/dose (Max: 500 mg/dose) PO once daily for 7 days.

For post-exposure meningococcal infection prophylaxis†. Oral dosage (immediate-release) Adults

500 mg PO as a single dose. Not recommended for first-line use; use in the rare circumstance of sustained ciprofloxacin-resistance in a community. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value. 

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO as a single dose. Not recommended for first-line use; use in the rare circumstance of sustained ciprofloxacin-resistance in a community. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

For the treatment of leptospirosis†. Oral dosage (immediate-release) Adults

1,000 mg PO once daily for 1 day, then 500 mg PO once daily for 2 days or 500 mg PO once daily for 3 days as alternative therapy for mild or moderate disease.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, then 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 2 days as alternative therapy for mild or moderate disease.

For the treatment of psittacosis†. Oral dosage (immediate-release) Pregnant Persons

500 mg PO once daily on day 1, followed by 250 mg PO once daily for 4 days.

Infants, Children, and Adolescents

10 mg/kg/dose (Max: 500 mg/dose) PO once daily on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.

For diphtheria carriage eradication†. Oral dosage (immediate-release) Adults

1,000 mg once daily for 1 day, then 500 mg PO once daily for a total of 7 to 10 days.

For the prolongation of latency and reduction of maternal and neonatal infections and neonatal morbidity in persons with preterm premature rupture of membranes† (PROM). Oral dosage (immediate-release) Adults

1 g PO as a single dose in combination with IV ampicillin for 48 hours followed by oral step-down therapy with amoxicillin for 5 days. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant persons with preterm PROM who are less than 34 0/7 weeks gestation. Persons with preterm PROM who are candidates for Group B streptococcal (GBS) intrapartum prophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.

Adolescents

1 g PO as a single dose in combination with IV ampicillin for 48 hours followed by oral step-down therapy with amoxicillin for 5 days. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant persons with preterm PROM who are less than 34 0/7 weeks gestation. Persons with preterm PROM who are candidates for Group B streptococcal (GBS) intrapartum prophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.

For the prevention of ophthalmia neonatorum (i.e., ophthalmia neonatorum prophylaxis†) as an alternative therapy. Ophthalmic dosage Neonates

1 to 2 drops placed in each conjunctival sac immediately after birth (i.e., within 1 hour) as an alternative if erythromycin ointment is unavailable.

†Indicates off-label use

Hepatic Impairment

Dosage adjustment recommendations are not available; azithromycin has not been studied in patients with impaired hepatic function.

Renal Impairment

CrCl more than 80 mL/min: No dosage adjustment is needed.
CrCl 10 to 80 mL/min: No dosage adjustment is recommended.
CrCl less than 10 mL/min: No dosage adjustment is recommended; however, the manufacturer recommends caution in patients with severe renal impairment since mean AUC is increased roughly 35%.

Adagrasib: (Major) Concomitant use of adagrasib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfuzosin: (Major) Avoid coadministration of azithromycin with alfuzosin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Alfuzosin may prolong the QT interval in a dose-dependent manner.
Aluminum Hydroxide: (Moderate) Separate administration of immediate-release azithromycin and aluminum- and magnesium-containing antacids by 2 hours. Coadministration may decrease the absorption of azithromycin which may decrease its efficacy. The extended-release suspension may be taken without regard to antacids containing aluminum or magnesium.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of immediate-release azithromycin and aluminum- and magnesium-containing antacids by 2 hours. Coadministration may decrease the absorption of azithromycin which may decrease its efficacy. The extended-release suspension may be taken without regard to antacids containing aluminum or magnesium.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate administration of immediate-release azithromycin and aluminum- and magnesium-containing antacids by 2 hours. Coadministration may decrease the absorption of azithromycin which may decrease its efficacy. The extended-release suspension may be taken without regard to antacids containing aluminum or magnesium.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of immediate-release azithromycin and aluminum- and magnesium-containing antacids by 2 hours. Coadministration may decrease the absorption of azithromycin which may decrease its efficacy. The extended-release suspension may be taken without regard to antacids containing aluminum or magnesium.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of immediate-release azithromycin and aluminum- and magnesium-containing antacids by 2 hours. Coadministration may decrease the absorption of azithromycin which may decrease its efficacy. The extended-release suspension may be taken without regard to antacids containing aluminum or magnesium.
Amiodarone: (Major) Concomitant use of azithromycin and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Avoid coadministration of azithromycin with amisulpride due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Amisulpride causes dose- and concentration- dependent QT prolongation.
Anagrelide: (Major) Avoid coadministration of azithromycin with anagrelide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TdP and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects.
Antacids: (Moderate) Separate administration of immediate-release azithromycin and aluminum- and magnesium-containing antacids by 2 hours. Coadministration may decrease the absorption of azithromycin which may decrease its efficacy. The extended-release suspension may be taken without regard to antacids containing aluminum or magnesium.
Apomorphine: (Major) Avoid coadministration of azithromycin with apomorphine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) Concomitant use of azithromycin and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) Avoid coadministration of azithromycin with arsenic trioxide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Artemether; Lumefantrine: (Major) Avoid coadministration of azithromycin with artemether; lumefantrine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Artemether; lumefantrine is associated with prolongation of the QT interval.
Asenapine: (Major) Avoid coadministration of azithromycin with asenapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Asenapine has been associated with QT prolongation.
Atomoxetine: (Major) Concomitant use of azithromycin and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Avoid coadministration of azithromycin with bedaquiline due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 ms. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Bedaquiline prolongs the QT interval.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine: (Major) Concomitant use of azithromycin and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of azithromycin and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cabotegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Ceritinib: (Major) Avoid coadministration of azithromycin with ceritinib if possible due to the risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
Chloroquine: (Major) Avoid coadministration of chloroquine with azithromycin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances (See Therapeutic Drug Monitoring for recommendations specific to COVID-19). Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
Chlorpromazine: (Major) Avoid coadministration of azithromycin with chlorpromazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Chlorpromazine is associated with an established risk of QT prolongation and TdP.
Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received azithromycin within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as azithromycin, 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.
Ciprofloxacin: (Major) Concomitant use of azithromycin and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Avoid concomitant use of cisapride and azithromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of azithromycin and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clofazimine: (Major) Concomitant use of clofazimine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Avoid coadministration of azithromycin with clozapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of azithromycin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of azithromycin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Colchicine: (Moderate) Monitor for colchicine toxicity during concomitant azithromycin use. Concurrent use resulted in an increase in colchicine Cmax of 21.6% and an increase in the AUC of 57.1%.
Conjugated Estrogens; Bazedoxifene: (Moderate) Coadministration of azithromycin and bazedoxifene increased the Cmax of bazedoxifene by 6% and decreased AUC of bazedoxifene by 15%. The clinical effect of these changes is not described.
Crizotinib: (Major) Avoid coadministration of crizotinib with azithromycin due to the risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Prolongation of the QT interval and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
Cyclosporine: (Moderate) Caution is warranted with the concomitant use of azithromycin and cyclosporine as increased cyclosporine concentrations may occur. Dose adjustment of cyclosporine may be necessary; monitor cyclosporine serum concentrations during use with azithromycin and after discontinuation of azithromycin.
Dasatinib: (Major) Avoid coadministration of azithromycin with dasatinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
Degarelix: (Major) Avoid coadministration of azithromycin with degarelix due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
Desflurane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
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.
Deutetrabenazine: (Major) Avoid coadministration of azithromycin with deutetrabenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Quinidine: (Major) Concomitant use of quinidine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dienogest; Estradiol valerate: (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: (Moderate) Monitor digoxin concentrations before and during concomitant use of azithromycin and reduce the digoxin dose if necessary. Elevated digoxin concentrations have been observed when azithromycin has been coadministered with digoxin.
Disopyramide: (Major) Avoid coadministration of azithromycin with disopyramide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Disopyramide is associated with QT prolongation and TdP.
Dofetilide: (Major) Avoid coadministration of azithromycin with dofetilide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP.
Dolasetron: (Major) Avoid coadministration of azithromycin with dolasetron due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Major) Avoid coadministration of azithromycin with donepezil due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Donepezil; Memantine: (Major) Avoid coadministration of azithromycin with donepezil due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Dronedarone: (Contraindicated) Avoid concomitant use of dronedarone and azithromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) Avoid coadministration of azithromycin with droperidol due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Droperidol administration is associated with an established risk for QT prolongation and TdP. Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.
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.
Efavirenz: (Major) Avoid coadministration of azithromycin with efavirenz due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QTc prolongation has been observed with the use of efavirenz.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of azithromycin with efavirenz due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QTc prolongation has been observed with the use of efavirenz.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of azithromycin with efavirenz due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QTc prolongation has been observed with the use of efavirenz.
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.
Eliglustat: (Major) Avoid coadministration of azithromycin with eliglustat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concomitant use of rilpivirine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of rilpivirine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Avoid coadministration of azithromycin with encorafenib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Encorafenib is associated with dose-dependent prolongation of the QT interval. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
Entrectinib: (Major) Avoid coadministration of azithromycin with entrectinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Entrectinib has been associated with QT prolongation.
Eribulin: (Major) Avoid coadministration of azithromycin with eribulin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Eribulin has been associated with QT prolongation.
Escitalopram: (Major) Concomitant use of azithromycin and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Etrasimod: (Major) Concomitant use of etrasimod and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fexinidazole: (Major) Concomitant use of fexinidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fingolimod: (Major) Avoid coadministration of azithromycin with fingolimod due to the increased risk of QT prolongation. If concomitant use is unavoidable, overnight monitoring with continuous ECG in a medical facility is advised after the first dose of fingolimod; monitor ECG closely throughout therapy, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of azithromycin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Major) Concomitant use of azithromycin and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of azithromycin and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Major) Avoid coadministration of azithromycin with fluphenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Fluvoxamine: (Major) Avoid coadministration of azithromycin with fluvoxamine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation and TdP have been reported during fluvoxamine postmarketing use.
Foscarnet: (Major) Concomitant use of azithromycin and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosphenytoin: (Minor) Until more data are available, the manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin with fosphenytoin. Azithromycin was not implicated in clinical trials with drug interactions with fosphenytoin. However, specific drug interaction studies have not been performed with the combination of azithromycin and fosphenytoin.
Fostemsavir: (Major) Avoid coadministration of azithromycin with fostemsavir due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Avoid coadministration of azithromycin with gemifloxacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Avoid coadministration of azithromycin with gemtuzumab due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Major) Avoid coadministration of azithromycin with gilteritinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Gilteritinib has been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of azithromycin with glasdegib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia.
Goserelin: (Major) Avoid coadministration of azithromycin with goserelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval.
Granisetron: (Major) Avoid coadministration of azithromycin with granisetron due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Granisetron has been associated with QT prolongation.
Halogenated Anesthetics: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
Haloperidol: (Major) Avoid coadministration of azithromycin with haloperidol due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Major) Avoid coadministration of azithromycin with histrelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of azithromycin and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibutilide: (Major) Avoid coadministration of azithromycin with ibutilide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Concomitant use of iloperidone and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with azithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Avoid any non-essential QT prolonging drugs and correct electrolyte imbalances. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance.
Isoflurane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
Itraconazole: (Major) Concomitant use of itraconazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ivosidenib: (Major) Avoid coadministration of azithromycin with ivosidenib due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and azithromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. If use together is medically necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances.
Lapatinib: (Major) Avoid coadministration of azithromycin with lapatinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
Lefamulin: (Major) Avoid coadministration of azithromycin with lefamulin as concurrent use may increase the risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
Lenvatinib: (Major) Avoid coadministration of azithromycin with lenvatinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Prolongation of the QT interval has been reported with lenvatinib therapy.
Leuprolide: (Major) Concomitant use of leuprolide and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Leuprolide; Norethindrone: (Major) Concomitant use of leuprolide and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (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.
Levofloxacin: (Major) Concomitant use of azithromycin and levofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and azithromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. If use together is medically necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances.
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.
Lithium: (Major) Concomitant use of azithromycin and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Concomitant use of lofexidine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loperamide: (Major) Concomitant use of azithromycin and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loperamide; Simethicone: (Major) Concomitant use of azithromycin and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lopinavir; Ritonavir: (Major) Avoid coadministration of azithromycin with lopinavir; ritonavir due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Lopinavir; ritonavir is associated with QT prolongation.
Macimorelin: (Major) Avoid coadministration of azithromycin with macimorelin due to the increased risk of QT prolongation and torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval.
Magnesium Hydroxide: (Moderate) Separate administration of immediate-release azithromycin and aluminum- and magnesium-containing antacids by 2 hours. Coadministration may decrease the absorption of azithromycin which may decrease its efficacy. The extended-release suspension may be taken without regard to antacids containing aluminum or magnesium.
Maprotiline: (Major) Avoid coadministration of azithromycin with maprotiline due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Major) Avoid coadministration of azithromycin with mefloquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Methadone: (Major) Concomitant use of azithromycin and methadone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Metronidazole: (Major) Concomitant use of metronidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) Concomitant use of midostaurin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of azithromycin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Major) Concomitant use of azithromycin and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mobocertinib: (Major) Concomitant use of mobocertinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Concomitant use of azithromycin with moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nelfinavir: (Moderate) Coadministration of nelfinavir and azithromycin results in increased azithromycin concentrations. Dosage adjustments are not necessary, although patients should be monitored for azithromycin related adverse effects such as increased hepatic enzymes and hearing impairment.
Nilotinib: (Major) Concomitant use of azithromycin and nilotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Ofloxacin: (Major) Concomitant use of azithromycin and ofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Concomitant use of olanzapine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Fluoxetine: (Major) Concomitant use of azithromycin and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Concomitant use of olanzapine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Samidorphan: (Major) Concomitant use of olanzapine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ondansetron: (Major) Concomitant use of azithromycin and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
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.
Osilodrostat: (Major) Concomitant use of osilodrostat and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osimertinib: (Major) Concomitant use of osimertinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of oxaliplatin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ozanimod: (Major) Avoid coadministration of azithromycin with ozanimod due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Pacritinib: (Major) Concomitant use of pacritinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Concomitant use of paliperidone and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Panobinostat: (Major) Concomitant use of panobinostat and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pasireotide: (Major) Concomitant use of pasireotide and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pazopanib: (Major) Concomitant use of pazopanib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pentamidine: (Major) Concomitant use of pentamidine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Perphenazine: (Major) Concomitant use of perphenazine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Perphenazine; Amitriptyline: (Major) Concomitant use of perphenazine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Phenytoin: (Minor) Until more data are available, the manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin with phenytoin. Azithromycin was not implicated in clinical trials with drug interactions with phenytoin. However, specific drug interaction studies have not been performed with the combination of azithromycin and phenytoin.
Pimavanserin: (Major) Concomitant use of pimavanserin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Pitolisant: (Major) Concomitant use of pitolisant and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) Avoid coadministration of azithromycin with ponesimod due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Posaconazole: (Major) Concomitant use of posaconazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pravastatin: (Moderate) Azithromycin has the potential to increase pravastatin exposure when used concomitantly. Coadminister pravastatin and azithromycin cautiously due to a potential increased risk of myopathies.
Primaquine: (Major) Concomitant use of primaquine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Probenecid; Colchicine: (Moderate) Monitor for colchicine toxicity during concomitant azithromycin use. Concurrent use resulted in an increase in colchicine Cmax of 21.6% and an increase in the AUC of 57.1%.
Procainamide: (Major) Concomitant use of procainamide and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Prochlorperazine: (Major) Concomitant use of prochlorperazine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine: (Major) Concomitant use of azithromycin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of azithromycin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of azithromycin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of azithromycin and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of azithromycin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Concomitant use of quinidine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinine: (Major) Concomitant use of quinine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quizartinib: (Major) Concomitant use of quizartinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Concomitant use of ranolazine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Relugolix: (Major) Concomitant use of relugolix and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Relugolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of relugolix and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (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.
Ribociclib: (Major) Concomitant use of ribociclib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ribociclib; Letrozole: (Major) Concomitant use of ribociclib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rilpivirine: (Major) Concomitant use of rilpivirine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Major) Concomitant use of risperidone and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Romidepsin: (Major) Concomitant use of romidepsin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Saquinavir: (Major) Avoid coadministration of azithromycin with saquinavir boosted with ritonavir due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP.
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.
Selpercatinib: (Major) Concomitant use of selpercatinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sertraline: (Major) Concomitant use of azithromycin and sertraline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
Siponimod: (Major) Concomitant use of siponimod and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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 Stibogluconate: (Major) Concomitant use of sodium stibogluconate and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Concomitant use of solifenacin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sorafenib: (Major) Concomitant use of sorafenib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of azithromycin and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sunitinib: (Major) Concomitant use of sunitinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tacrolimus: (Major) Concomitant use of tacrolimus and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tamoxifen: (Major) Concomitant use of azithromycin and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Concomitant use of telavancin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and azithromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Tolterodine: (Major) Avoid coadministration of azithromycin with tolterodine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Concomitant use of toremifene and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trazodone: (Major) Concomitant use of azithromycin and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Major) Concomitant use of trifluoperazine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triptorelin: (Major) Concomitant use of triptorelin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vandetanib: (Major) Concomitant use of vandetanib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Major) Concomitant use of azithromycin and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Avoid coadministration of azithromycin with vemurafenib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Vemurafenib has been associated with QT prolongation.
Venlafaxine: (Major) Concomitant use of azithromycin and venlafaxine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voclosporin: (Major) Concomitant use of voclosporin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Voriconazole: (Major) Avoid coadministration of azithromycin with voriconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP.
Vorinostat: (Major) Concomitant use of vorinostat and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Warfarin: (Moderate) Carefully monitor the PT/INR in patients who receive warfarin and azithromycin concomitantly. Postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin.
Ziprasidone: (Major) Concomitant use of ziprasidone and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.

Azasite Ophthalmic Drops: 1%
Azithromycin/Zithromax/Zithromax Powder Intravenous Inj Pwd F/Sol: 2.5g, 500mg
Azithromycin/Zithromax/Zithromax Powder/Zithromax Single-Dose Oral Pwd F/Recon: 1g, 5mL, 100mg, 200mg
Azithromycin/Zithromax/Zithromax Tri-Pak/Zithromax Z-Pak Oral Tab: 250mg, 500mg, 600mg
Zmax Oral Susp ER: 2g

Adults

500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose; 500 mg/day IV infusion.

Geriatric

500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose; 500 mg/day IV infusion.

Adolescents

16 to 17 years: 500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose; 500 mg/day IV infusion.
13 to 15 years: For the immediate-release oral suspension or tablets, 12 mg/kg/day PO (Max: 500 mg/dose) and single doses up to 30 mg/kg PO (Max: 1.5 g/dose) are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO (Max: 1,000 mg/day) or 1,200 mg/day are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO (Max: 2 g/dose). Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day (Max: 500 mg/dose) have been used off-label.

Children

2 to 12 years: For the immediate-release oral suspension or tablets, 12 mg/kg/day PO (Max: 500 mg/dose) and single doses up to 30 mg/kg PO (Max: 1.5 g/dose) are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO (Max: 1,000 mg/day) are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO (Max: 2 g/dose). Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day (Max: 500 mg/dose) have been used off-label.
1 year: For the immediate-release oral suspension or tablets, 10 mg/kg/day PO and single doses up to 30 mg/kg PO are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO. Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day have been used off-label.

Infants

6 to 11 months: For the immediate-release oral suspension or tablets, 10 mg/kg/day PO and single doses up to 30 mg/kg PO are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO. Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day have been used off-label.
3 to 5 months: Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO or 10 mg/kg/day IV have been used off-label.
1 to 2 months: Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO have been used off-label.

Neonates

Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO have been used off-label.

Azithromycin inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action is generally bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms. Azithromycin is more active against gram-negative organisms but has less activity against streptococci and staphylococci than does erythromycin; erythromycin-resistant gram-positive isolates demonstrate cross-resistance to azithromycin.[34473] [50470] Azithromycin concentrates in phagocytes and fibroblasts leading to high intracellular concentrations. Drug distribution to inflamed tissues is thought to occur from the concentration in phagocytes.[43975]
 
The susceptibility interpretive criteria for azithromycin are delineated by pathogen. The MICs are defined for beta-hemolytic streptococci, S. viridans group, and S. pneumoniae as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for S. enterica ser. Typhi as susceptible at 16 mcg/mL or less and resistant at 32 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, Aggregatibacter sp., Cardiobacterium sp., E. corrodens, and Kingella sp. as susceptible at 4 mcg/mL or less. The MICs are defined for N. meningitidis as susceptible at 2 mcg/mL or less, which may be only appropriate for prophylaxis of meningococcal case contacts and does not apply to treatment of invasive disease. The MICs are defined for N. gonorrhoeae as susceptible at 1 mcg/mL or less, presuming use of a 1 g single dose regimen that includes an additional antimicrobial agent. The MICs are defined for M. catarrhalis as susceptible at 0.25 mcg/mL or less. The MICs are defined for V. cholerae as susceptible at 2 mcg/mL or less. The MICs are defined for Pasteurella sp. as susceptible at 1 mcg/mL or less. Erythromycin-susceptible Campylobacter jejuni/coli may be considered susceptible to azithromycin.[63320] [63321]
 
Macrolides have been reported to have immunomodulatory properties in pulmonary inflammatory disorders. They may downregulate inflammatory responses and reduce the excessive cytokine production associated with respiratory viral infections; however, their direct effects on viral clearance are uncertain. Immunomodulatory mechanisms may include reducing chemotaxis of neutrophils (PMNs) to the lungs by inhibiting cytokines (i.e., IL-8), inhibition of mucus hypersecretion, decreased bacterial adhesion to the epithelium, decreased production of reactive oxygen species, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors.[65149] [65150] [65151] [65152] [65153]

Azithromycin is administered orally, intravenously, and topically to the eye. Following systemic administration, it is widely distributed to body tissues and fluids including bone, prostate, ovary, uterus, stomach, liver, middle ear, lung, tonsils and adenoids, and sputum. Azithromycin exhibits significant intracellular penetration and concentrates within fibroblasts and phagocytes. As a result, tissue concentrations are significantly higher than are plasma concentrations. Azithromycin is distributed widely into brain tissue but not into cerebrospinal fluid or the aqueous humor of the eye. Protein binding varies with plasma concentration; 51% of the drug is bound at low concentrations (0.02 mcg/ml) and this binding decreases to 7% at higher concentrations (2 mcg/ml). Azithromycin has a long half-life in both adults (40 to 68 hours) and children (32 to 64 hours), which is partially explained by its extensive tissue uptake and slow release. Elimination is largely in the feces, following excretion into the bile, with less than 14% excreted in the urine.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Oral Route

Immediate-release suspension
Peak concentrations of azithromycin occur approximately 2 hours after administration.[51753] Food increases the Cmax by approximately 56%, but the extent of absorption is unaltered.[28855]
 
Single-dose (1 g) immediate-release suspension
Administration with food increased the Cmax by 46% and the AUC by 14%.[43975]
 
250 mg and 500 mg immediate-release tablets
The absolute bioavailability is approximately 38%. The Cmax for a 5-day regimen of 250 mg PO ranged from 0.24 to 0.43 mcg/mL and the AUC was 14.9 mcg x hour/mL. The Cmax for 3-day regimen of 500 mg PO ranged from 0.44 to 0.54 mcg/mL and the AUC was 17.4 mcg x hour/mL. Food increases the Cmax by approximately 23%, but the extent of absorption is unaltered.[28855]
 
600 mg immediate-release tablets
The absolute bioavailability is 34%. For a 1,200 mg dose, the Cmax is 0.33 mcg/mL, the Tmax is 2.5 hours, and the AUC is 6.8 mcg x hour/mL. Administration with food increased the Cmax by 31%; however, the AUC was unchanged.[43975]
 
Extended-release suspension
The bioavailability of the extended-release suspension compared to the immediate-release suspension is 83%. Food increases absorption. Administration with a high-fat meal increased the Cmax by 115% and the AUC by 23% compared to the fasted state. Administration with a standard meal increased the Cmax by 119% and the AUC by 12%.[34473] Peak concentrations occur approximately 3 hours (range 2 to 8 hours) after administration.[51753] Extended-release suspension and immediate-release formulations are not bioequivalent and cannot be interchanged.[34473]

Intravenous Route

Azithromycin doses of 500 mg IV daily administered over 1 hour for 2 to 5 days resulted in a mean Cmax +/- SD of 3.63 +/- 1.60 mcg/mL, a 24-hour trough of 0.20 +/- 0.15 mcg/mL, and an AUC24 of 9.60 +/- 4.80 mcg x hour/mL. Doses of 500 mg IV administered over 3 hours resulted in a mean Cmax of 1.14 +/- 0.14 mcg/mL, a 24-hour trough of 0.18 +/- 0.02 mcg/mL, and an AUC24 of 8.03 +/- 0.86 mcg x hour/mL. Similar pharmacokinetic values were obtained in patients that received the same 3-hour IV infusion regimen for 2 to 5 days. A comparison of the pharmacokinetics after the first and fifth daily doses showed an increase in AUC24 of 61%, reflecting a 3-fold rise in trough concentrations. Cmax increased by 8%.[43974]

Other Route(s)

Ophthalmic Route
The systemic concentration of azithromycin after ocular administration is estimated to be below quantifiable limits (10 ng/mL or less).

Pregnancy

Available data over several decades with systemic azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Developmental toxicity studies in animals showed no drug-induced fetal malformations at doses up to 4 times the adult human daily dose of 500 mg based on body surface area; however, decreased viability and delayed development were observed in the offspring of pregnant rats given azithromycin at a dose equivalent to 4 times the adult human daily dose from day 6 of pregnancy through weaning.[28855] In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, systemic azithromycin use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 1.65, 95% CI 1.34 to 2.02, 110 exposed cases); residual confounding by severity of infection may be a potential limitation of this study.[62176] In a large population-based cohort study (n = 104,605 live births) assessing systemic macrolide (n = 8,632) or penicillin (n = 95,973) use during pregnancy and the risk of major malformations, macrolide use in the first trimester was associated with increased risk of any malformation (27.7 vs. 17.7 per 1,000 live births; adjusted risk ratio 1.55, 95% CI 1.19 to 2.03), and in particular, cardiovascular malformations (10.6 vs. 6.6 per 1,000 live births; adjusted risk ratio 1.62, 95% CI 1.05 to 2.51). Specific findings for azithromycin use during the first trimester were precluded due to few events. Macrolide use during the second and third trimesters showed no increased risk of any major malformation (19.5 vs. 17.3 per 1,000 live births; adjusted risk ratio 1.13, 95% CI 0.94 to 1.36); however, a borderline association with gastrointestinal malformations was observed (adjusted risk ratio 1.89, 95% CI 1 to 3.58). Macrolide use in any trimester was associated with an increased risk of genital malformations (adjusted risk ratio 1.58, 95% CI 1.14 to 2.19), mainly hypospadias.[65012] Additionally, in another large population-based cohort study (n = 139,938 live births) assessing systemic antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, macrolide exposure was associated with an increased risk of digestive system malformations (adjusted odds ratio (aOR) 1.46, 95% CI 1.04 to 2.06, 35 exposed cases).[62177]

Azithromycin is present in human breast milk. Non-serious adverse reactions have been reported in breast-fed infants after maternal administration of azithromycin. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for azithromycin and any potential adverse effects on the breast-fed infant from azithromycin or the underlying maternal condition. Monitor the breast-fed infant for diarrhea, vomiting, or rash. There are no available data on the effects of azithromycin on milk production. Azithromycin breast milk concentrations were measured in 20 women receiving a single 2 g oral dose during labor. Azithromycin was present in breast milk up to 4 weeks after dosing. Another study of 8 women receiving azithromycin IV before incision of cesarean section showed azithromycin was present in breast milk up to 48 hours later.[28855] A prospective observational study assessing the safety of macrolide antibiotics during lactation found that 12.7% (n = 55) of babies exposed to macrolides via breast milk experienced adverse events including rash, diarrhea, loss of appetite, and somnolence. The adverse event rate was similar to that seen in babies in a control group whose mothers were treated with amoxicillin (8.3%). Only 10 mothers in the study received azithromycin, 6 received clarithromycin, 2 received erythromycin, and the remainder were treated with roxythromycin.[45767] A population-based cohort study found that babies diagnosed with infantile hypertrophic pyloric stenosis were 2.3 to 3 times more likely to have been exposed to a macrolide antibiotic through breast milk during the first 90 days of life than babies not exposed during that same time period. The study did not specify which antibiotic the mothers of affected babies were prescribed; however, the majority of macrolide prescriptions were for erythromycin (72%), with 7% for azithromycin and 1.7% for clarithromycin.[45779] Previous American Academy of Pediatrics (AAP) recommendations consider erythromycin to be usually compatible with breast-feeding; azithromycin has not been evaluated by the AAP.[27500]