Unasyn

Penicillin and Beta-Lactamase Inhibitor Combination Antibiotics

Injectable Administration

Ampicillin; sulbactam is administered intravenously or intramuscularly.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Ampicillin; sulbactam 1.5 g corresponds to 1 g ampicillin and 0.5 g sulbactam, while ampicillin; sulbactam 3 g corresponds to 2 g ampicillin and 1 g sulbactam.

Intravenous Administration

Reconstitution
Vials: Reconstitute 1.5 g (1 g ampicillin and 0.5 g sulbactam) vial with 3.2 mL or 3 g (2 g ampicillin and 1 g sulbactam) vial with 6.4 mL of Sterile Water for Injection to give a solution containing 375 mg/mL ampicillin; sulbactam (250 mg ampicillin and 125 mg sulbactam per mL). Immediately further dilute.[29888]
Pharmacy bulk vial: Reconstitute 15 g (10 g ampicillin and 5 g sulbactam) vial with 92 mL of Sterile Water for Injection or 0.9% Sodium Chloride Injection for a resultant concentration of 150 mg/mL ampicillin; sulbactam (100 mg ampicillin and 50 mg sulbactam per mL). The diluent should be added in two aliquots; first add 50 mL and shake to dissolve, then add 42 mL and shake. Use contents of pharmacy bulk vial within 2 hours if stored at room temperature and 4 hours if stored under refrigeration.[54630]
Piggyback bottles: Reconstitute with up to 100 mL of a compatible IV solution (i.e., 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Lactated Ringer's Injection).
ADD-Vantage vials: For IV infusion only. Reconstitute with 0.9% Sodium Chloride Injection only using the appropriate ADD-Vantage diluent containers. 1.5 g (1 g ampicillin and 0.5 g sulbactam) ADD-Vantage vials should be used with 50 mL, 100 mL, or 250 mL diluent container; 3 g (2 g ampicillin and 1 g sulbactam) ADD-Vantage vials should be used with 100 mL or 250 mL diluent containers.[29888]
Dilution
Vials: Further dilute vials with compatible IV solution (i.e., 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Lactated Ringer's Injection) to a usual concentration of 3 to 45 mg/mL of ampicillin; sulbactam (i.e., 2 to 30 mg/mL ampicillin and 1 to 15 mg/mL of sulbactam).
Piggyback bottles: Following reconstitution, no further dilution is required.
ADD-Vantage vials: Following reconstitution, no further dilution is required.
Storage: Diluted solutions are stable for the following time periods in the following diluents: [29888]
0.9% Sodium Chloride Injection: Stable for 8 hours at room temperature or 48 hours refrigerated at a maximum concentration of 45 mg/mL ampicillin; sulbactam (i.e., 30 mg/mL ampicillin and 15 mg/mL sulbactam); stable for 72 hours refrigerated at a maximum concentration of 30 mg/mL ampicillin; sulbactam (i.e., 20 mg/mL ampicillin and 10 mg/mL sulbactam).
5% Dextrose Injection: Stable for 2 hours at room temperature or 4 hours refrigerated at a maximum concentration of 30 mg/mL ampicillin; sulbactam (i.e., 20 mg/mL ampicillin and 10 mg/mL sulbactam); stable for 4 hours at room temperature at a maximum concentration of 3 mg/mL of ampicillin; sulbactam (i.e., 2 mg/mL ampicillin and 1 mg/mL sulbactam).
Lactated Ringer's Injection: Stable for 8 hours at room temperature or 24 hours refrigerated at a maximum concentration of 45 mg/mL ampicillin; sulbactam (i.e., 30 mg/mL ampicillin and 15 mg/mL sulbactam).
ADD-Vantage vials: Diluted in 0.9% Sodium Chloride Injection are stable for 8 hours at room temperature at a maximum concentration of 30 mg/mL ampicillin; sulbactam (i.e., 20 mg/mL ampicillin and 10 mg/mL sulbactam).
Solutions prepared from reconstituted Pharmacy bulk vials stored for less than 1 hour at room temperature: The above storage conditions apply.
Solutions prepared from reconstituted Pharmacy bulk vials stored for 1 to 2 hours at room temperature: Solutions diluted in 0.9% Sodium Chloride Injection are stable for 4 hours at room temperature or 24 hours refrigerated at a maximum concentration of 45 mg/mL ampicillin; sulbactam (i.e., 30 mg/mL ampicillin and 15 mg/mL sulbactam).[54630]
Intermittent IV Infusion
Infuse via slow IV injection over 10 to 15 minutes or as an IV infusion over 15 to 30 minutes.[29888]

Intramuscular Administration

Use only freshly prepared solutions and administer within 1 hour after preparing.
Vials: reconstitute 1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) with 3.2 or 6.4 mL, respectively, of Sterile Water for Injection or 0.5% or 2% lidocaine to give a solution containing 250 mg of ampicillin and 125 mg of sulbactam per mL.
Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh).

Severe

C. difficile-associated diarrhea / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
acute myocardial ischemia / Early / Incidence not known
seizures / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known

Moderate

phlebitis / Rapid / 1.2-3.0
glossitis / Early / 0-1.0
candidiasis / Delayed / 0-1.0
erythema / Early / 0-1.0
chest pain (unspecified) / Early / 0-1.0
edema / Delayed / 0-1.0
dysuria / Early / 0-1.0
urinary retention / Early / 0-1.0
gastritis / Delayed / Incidence not known
melena / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
lymphocytosis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hypoalbuminemia / Delayed / Incidence not known
dyspnea / Early / Incidence not known

Mild

injection site reaction / Rapid / 3.0-16.0
diarrhea / Early / 3.0-3.0
rash / Early / 0-2.0
flatulence / Early / 0-1.0
nausea / Early / 0-1.0
vomiting / Early / 0-1.0
pruritus / Rapid / 0-1.0
headache / Early / 0-1.0
epistaxis / Delayed / 0-1.0
fatigue / Early / 0-1.0
malaise / Early / 0-1.0
chills / Rapid / 0-1.0
tongue discoloration / Delayed / Incidence not known
dyspepsia / Early / Incidence not known
abdominal pain / Early / Incidence not known
urticaria / Rapid / Incidence not known
dizziness / Early / Incidence not known

Unasyn

Rx

Parenteral antibiotic combining ampicillin with sulbactam (a beta-lactamase inhibitor); sulbactam enhances ampicillin's spectrum to include many beta-lactamase-producing bacteria; similar coverage to oral amoxicillin-clavulanic acid combination; main uses of ampicillin-sulbactam: intra-abdominal infections, gynecologic infections, and skin and soft-tissue infection; not indicated for meningitis.

For the treatment of skin and skin structure infections, including cellulitis, animal or human bite wounds, diabetic foot ulcer, pyomyositis, and surgical incision site infections. For the treatment of diabetic foot ulcer. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 7 to 14 days for mild infections in patients with recent antibiotic exposure or moderate or severe infections with no complicating features or with ischemic limb/necrosis/gas forming. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

For the treatment of unspecified skin and skin structure infections. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours.

Children and Adolescents weighing 40 kg or more

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours.

Children and Adolescents weighing less than 40 kg

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. The FDA-approved dosage is 200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.

Infants†

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.   Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.

Neonates†

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications.

Premature Neonates†

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.

Intramuscular dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IM every 6 hours.

For the treatment of surgical incision site infections. Intravenous dosage Adults

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours plus gentamicin or tobramycin for incisional surgical site infections of the intestinal or genitourinary tract.

For the treatment of animal bite wounds. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 to 8 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

For the treatment of pyomyositis. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

Children and Adolescents weighing 40 kg or more

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

Children and Adolescents weighing less than 40 kg

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 14 to 21 days plus vancomycin in patients with underlying conditions. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. The FDA-approved dosage is 200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.

Infants†

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.   Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.

For the treatment of human bite wounds. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours.

For the treatment of cellulitis. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 5 to 14 days.

Children and Adolescents weighing 40 kg or more

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 5 to 14 days.

Children and Adolescents weighing less than 40 kg

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 5 to 14 days. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. The FDA-approved dosage is 200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.

Infants†

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours for 5 to 14 days. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.

Neonates†

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours for 5 to 14 days based on limited data in neonates for other indications.

For the treatment of gynecologic infections, including postpartum endometritis, pelvic inflammatory disease (PID)† and tubo-ovarian abscess†. For the treatment of pelvic inflammatory disease (PID)† and tubo-ovarian abscess†. Intravenous dosage Adults

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours in combination with doxycycline as an alternative. Ampicillin; sulbactam should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral doxycycline and metronidazole for a total of 14 days of therapy.

Adolescents

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours in combination with doxycycline as an alternative. Ampicillin; sulbactam should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral doxycycline and metronidazole for a total of 14 days of therapy.

For the general treatment of gynecologic infections. Intravenous or Intramuscular dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV or IM every 6 hours.

Adolescents†

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]).

For the treatment of postpartum endometritis. Intravenous dosage Adults

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours in combination with gentamicin. Continue treatment until clinical improvement and afebrile for 24 to 48 hour.

For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, and peritoneal dialysis-related peritonitis†. For the treatment of complicated intraabdominal infections with adequate source control. Intravenous or Intramuscular dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV or IM every 6 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

Infants†, Children†, and Adolescents†

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 3 to 7 days. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

Neonates†

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours for 7 to 10 days based on limited data in neonates for other indications.

Premature Neonates†

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours for 7 to 10 days has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.

For the treatment of peritoneal dialysis-related peritonitis†. Intermittent Intraperitoneal dosage† Adults

3 g (2 g ampicillin and 1 g sulbactam) intraperitoneally every 12 hours for 21 days.

Continuous Intraperitoneal dosage† Adults

0.75 to 1 g/L intraperitoneal loading dose, followed by 100 mg/L in each dialysate exchange. Treat for 21 days.

For the treatment of community-acquired pneumonia (CAP)† and pleural empyema†. For the treatment of community-acquired pneumonia (CAP)†. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) to 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for at least 5 days as part of combination therapy for hospitalized patients.[34362] [64669]

Infants, Children, and Adolescents

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 5 to 7 days.[34362] [54666] Doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have rarely been reported for serious infections.[44462] [54682] In persons living with HIV, ampicillin; sulbactam is recommended as part of combination therapy for hospitalized patients.[34362]

Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications.

Premature neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.

For the treatment of community-acquired pleural empyema†. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours. Treat for at least 2 weeks after drainage and defervescence.

Infants, Children, and Adolescents

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Treat for at least 2 weeks after drainage and defervescence.

For the treatment of acute epiglottitis†. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours.

Infants†, Children†, and Adolescents†

200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). In a clinical study, 31 patients (15 months to 8 years) were treated with ampicillin; sulbactam (200 mg/kg/day ampicillin and 30 mg/kg/day sulbactam divided every 6 hours) for acute epiglottitis; the average number of doses received was 9.4 doses (over 3 days). Of the patients enrolled in the study, 84% had Haemophilus influenzae type b (Hib) isolated from a blood culture and 27% of those isolates were beta-lactamase producing strains. Twenty-five of the 31 patients showed a prompt response to therapy, including all of the patients with beta-lactamase positive strains of Hib.

For surgical infection prophylaxis†. Intravenous dosage Adults

3 g (2 g ampicillin and 1 g sulbactam) IV as a single dose within 60 minutes prior to the surgical incision. Intraoperative redosing 2 hours from the first preoperative dose and duration of prophylaxis less than 24 hours for most procedures are suggested by clinical practice guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Clinical practice guidelines recommend ampicillin; sulbactam for certain thoracic, biliary tract, colorectal, head and neck, urogynecology, and plastic surgery procedures.

Infants, Children, and Adolescents

50 mg/kg/dose ampicillin component (75 mg/kg/dose ampicillin; sulbactam) IV as a single dose (Max: 2 g ampicillin component [3 g ampicillin; sulbactam] per dose) within 60 minutes prior to the surgical incision. Intraoperative redosing 2 hours from the first preoperative dose and duration of prophylaxis less than 24 hours for most procedures are suggested by clinical practice guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Clinical practice guidelines recommend ampicillin; sulbactam for certain thoracic, biliary tract, colorectal, head and neck, urogynecology, and plastic surgery procedures.

For the treatment of infective endocarditis†. Intravenous dosage Adults

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours. Guidelines recommend ampicillin; sulbactam in combination with an aminoglycoside for beta-lactamase producing penicillin-resistant enterococcal infections; treat for 6 weeks. Ampicillin; sulbactam may be an alternate option for endocarditis due to HACEK microorganisms; treat for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis. For patients with subacute culture-negative NVE, ampicillin; sulbactam plus vancomycin could be reasonable empiric therapy; treat for 4 to 6 weeks.

Children and Adolescents

133 to 200 mg/kg/day ampicillin component (200 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 4 to 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Guidelines recommend ampicillin; sulbactam plus gentamicin with or without vancomycin for culture-negative, community-acquired native valve endocarditis (NVE) or late (more than 1 year after surgery) prosthetic valve endocarditis (PVE); treat for 4 to 6 weeks for NVE and for 6 weeks with rifampin for PVE. Ampicillin; sulbactam for 4 weeks is recommended for endocarditis due to HACEK microorganisms.

Infants

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.

For the treatment of acute bacterial sinusitis† in patients with severe infection requiring hospitalization. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 5 to 10 days.

Infants, Children, and Adolescents

200 to 400 mg/kg/day ampicillin component (300 to 600 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 10 to 14 days.

For the treatment of bone and joint infections†, including osteomyelitis† and infectious arthritis†. For the treatment of osteomyelitis†. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 4 to 6 weeks.    

Infants, Children, and Adolescents 3 months to 17 years

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.

Infants 1 to 2 months

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

Premature Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

For the treatment of infectious arthritis†. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.

Infants, Children, and Adolescents 3 months to 17 years

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

Infants 1 to 2 months

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

Premature Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

For the treatment of suppurative sialadenitis† or parotitis†. Intravenous dosage Adults

1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours is the usual adult dosage.

Infants, Children, and Adolescents

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.

Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam; frequency not specified) IV for 9 days was successfully used in a case report of a 17-day-old neonate with submandibular sialadenitis. Other limited data in neonates suggest dividing the daily dose and administering every 8 hours.

For the treatment of bacteremia† and sepsis†. Intravenous dosage Adults

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

Infants, Children, and Adolescents

100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

Premature Neonates

100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.

For the treatment of chorioamnionitis† or intraamniotic infection†. Intravenous dosage Adults

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

Adolescents

3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

†Indicates off-label use

Hepatic Impairment

No dosage adjustment is needed.

Renal Impairment

Adults
CrCl more than 30 mL/min: No dosage adjustment needed.
CrCl 15 to 30 mL/min: Extend dosing interval of the selected dosage to every 12 hours.
CrCl 5 to 15 mL/min: Extend dosing interval of the selected dosage to every 24 hours.
 
Pediatrics
The following dosage adjustments are based on a usual dose in pediatric patients of 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours :
CrCl 30 to 50 mL/min/1.73 m2: 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 8 hours.
CrCl 10 to 29 mL/min/1.73 m2: 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 12 hours.
CrCl less than 10 mL/min/1.73 m2: 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 24 hours.
 
Intermittent hemodialysis
For adult patients, a dose of 1.5 to 3 g IV every 12 to 24 hours has been recommended. For pediatric patients, a dose of 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 24 hours has been recommended.
 
Peritoneal dialysis
For adult patients, a dose of 1.5 to 3 g IV every 12 to 24 hours has been recommended. For pediatric patients, a dose of 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 24 hours has been recommended.
 
Continuous renal replacement therapy (CRRT)
For adult patients, the following are the recommended doses: 1.5 to 3 g IV every 8 to 12 hours for CVVH, 1.5 to 3 g IV every 8 hours for CVVHD, and 1.5 to 3 g IV every 6 to 8 hours for CVVHDF. For pediatric patients, a dose of 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 8 hours has been recommended (method of CRRT not specified).

Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Allopurinol: (Minor) Use of ampicillin with allopurinol can increase the incidence of drug-related skin rash.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Aspirin, ASA: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Dipyridamole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Omeprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption. (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Oxycodone: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Atenolol: (Major) Ampicillin has been reported to reduce the bioavailability of single-dose atenolol, and to increase the tachycardic response to exercise compared to atenolol monotherapy. Monitor clinical response, and adjust atenolol dosage if needed to attain therapeutic goals.
Atenolol; Chlorthalidone: (Major) Ampicillin has been reported to reduce the bioavailability of single-dose atenolol, and to increase the tachycardic response to exercise compared to atenolol monotherapy. Monitor clinical response, and adjust atenolol dosage if needed to attain therapeutic goals.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Caffeine; Sodium Benzoate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Carbidopa; Levodopa; Entacapone: (Moderate) As entacapone is primarily excreted in the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidation, such as ampicillin, are given concurrently with entacapone.
Choline Salicylate; Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
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.
Dexlansoprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Dichlorphenamide: (Moderate) Use dichlorphenamide and ampicillin together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including ampicillin. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
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: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
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.
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.
Entacapone: (Moderate) As entacapone is primarily excreted in the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidation, such as ampicillin, are given concurrently with entacapone.
Esomeprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
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.
Ethacrynic Acid: (Minor) Ethacrynic acid may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
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.
Furosemide: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Indomethacin: (Minor) Indomethacin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Lansoprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Lesinurad; Allopurinol: (Minor) Use of ampicillin with allopurinol can increase the incidence of drug-related skin rash.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
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.
Mafenide: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Methotrexate: (Major) Avoid concomitant use of methotrexate with penicillins due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions.
Naproxen; Esomeprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
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 pharmacok

inetics 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.
Omeprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Omeprazole; Amoxicillin; Rifabutin: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Omeprazole; Sodium Bicarbonate: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
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.
Pantoprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Probenecid: (Moderate) Monitor for an increase in sulbactam-related adverse effects if concomitant use with probenecid is necessary. Concomitant use may increase sulbactam exposure. Sulbactam is an OAT1 substrate and probenecid is an OAT1 inhibitor. (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Probenecid; Colchicine: (Moderate) Monitor for an increase in sulbactam-related adverse effects if concomitant use with probenecid is necessary. Concomitant use may increase sulbactam exposure. Sulbactam is an OAT1 substrate and probenecid is an OAT1 inhibitor. (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Proton pump inhibitors: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Rabeprazole: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Salsalate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins. An enhanced effect of the displaced drug may occur.
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.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in sulbactam-related adverse effects if concomitant use with taurusodiol is necessary. Concomitant use may increase sulbactam exposure. Sulbactam is an OAT1 substrate and taurusodiol is an OAT1 inhibitor.
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.
Sulfadiazine: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfasalazine: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfonamides: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Tetracyclines: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Typhoid Vaccine: (Major) Antibiotics which possess bacterial activity against salmonella typhi organisms may interfere with the immunological response to the live typhoid vaccine. Allow 24 hours or more to elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.

Ampicillin Sodium, Sulbactam Sodium/Ampicillin, Sulbactam/Unasyn Intramuscular Inj Pwd F/Sol: 1-0.5g, 10-5g, 2-1g
Ampicillin Sodium, Sulbactam Sodium/Ampicillin, Sulbactam/Unasyn Intravenous Inj Pwd F/Sol: 1-0.5g, 10-5g, 2-1g

Adults

12 g/day (8 g ampicillin and 4 g sulbactam) IV/IM.

Geriatric

12 g/day (8 g ampicillin and 4 g sulbactam) IV/IM.

Adolescents

200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV is recommended in the FDA-approved labeling; however, doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) IV have been used off-label (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]).

Children

200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV is recommended in the FDA-approved labeling; however, doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) IV have been used off-label (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]).

Infants

Safety and efficacy have not been established; however, doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) IV have been used off-label.

Neonates

Safety and efficacy have not been established; however, doses up to 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV have been used off-label.

Beta-lactam antibiotics, such as ampicillin, are mainly bactericidal. Like other penicillins, ampicillin inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of ampicillin, as well as the other penicillins, against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, ampicillin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.[51465]
 
Sulbactam is an irreversible inhibitor of beta-lactamases. Like clavulanic acid, sulbactam inhibits the activity of beta-lactamase Richmond types II, III, IV, V, and VI but not chromosomally mediated type I. Sulbactam has little useful antibacterial activity if used alone. Sulbactam does not alter the actions of ampicillin or the sensitivity of organisms to ampicillin if they are sensitive to ampicillin alone.[54638]
 
The susceptibility interpretive criteria for ampicillin; sulbactam are delineated by pathogen. The MICs are defined for Enterobacterales, Acinetobacter sp., anaerobes, and Vibrio sp. (excluding V. cholerae) as susceptible at 8/4 mcg/mL or less, intermediate at 16/8 mcg/mL, and resistant at 32/16 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 2/1 mcg/mL or less and resistant at 4/2 mcg/mL or more. The breakpoints for H. influenzae and H. parainfluenzae are based on a dosage regimen of 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours. Non-meningitis S. pneumoniae that are susceptible to penicillin are predictably sensitive to ampicillin; sulbactam. Similarly, a Streptococcus sp. beta-hemolytic group organism that is susceptible to penicillin can be considered susceptible to ampicillin; sulbactam. Considering site of infection and appropriate ampicillin; sulbactam dosing, oxacillin-susceptible Staphylococcus sp. can be considered susceptible to ampicillin; sulbactam. The results of ampicillin or penicillin susceptibility tests may be used to predict susceptibility to ampicillin; sulbactam for non-beta-lactamase producing enterococci.

Ampicillin; sulbactam is administered intravenously or intramuscularly. Protein binding is approximately 15—25% for ampicillin and 38% for sulbactam. Both drugs are distributed into the lungs, liver, gallbladder, appendix, maxillary sinus, prostate, and other tissues. The drug also distributes very well into various body fluids, such as skin blisters, middle ear effusions, bronchial secretions, urine, and pleural, peritoneal, and synovial fluids. Therapeutic levels are attained within the CSF in the presence of inflammation; however, ampicillin; sulbactam is not indicated for meningitis. The drug does cross the placenta. Approximately 15—25% of both drugs are metabolized. The drug and its metabolites are excreted into the urine primarily via tubular secretion and glomerular filtration. A small percentage of ampicillin; sulbactam is excreted in breast milk. In patients with normal renal function, the elimination half-life of both ampicillin and sulbactam is 1—1.5 hours.

Intravenous Route

Peak serum levels of both ampicillin and sulbactam occur immediately after a 15-minute intravenous (IV) infusion. After a 2000 mg ampicillin dose with 1000 mg sulbactam, peak ampicillin serum levels ranging from 109 to 150 mcg/mL and peak sulbactam concentrations ranging from 48 to 88 mcg/mL are attained. Peak ampicillin levels of 40 to 71 mcg/mL and peak sulbactam levels of 21 to 40 mcg/mL attained after administration of 1000 mg ampicillin plus 500 mg sulbactam.

Intramuscular Route

Peak serum levels of both ampicillin and sulbactam occur within 1 hour following an intramuscular (IM) dose. After an IM injection of 1000 mg ampicillin plus 500 mg sulbactam, peak ampicillin serum levels ranging from 8 to 37 mcg/mL and peak sulbactam serum levels ranging from 6 to 24 mcg/mL are attained.

Pregnancy

There are no adequate and well-controlled studies in human pregnancy. Both ampicillin and sulbactam readily cross the placenta. Use ampicillin; sulbactam during pregnancy only if clearly needed. Penicillins are generally considered safe during pregnancy. Ampicillin and ampicillin; sulbactam have been used in pregnant women for a variety of clinical situations, including premature rupture of membranes (PROM) and prevention of premature birth. Animal data reveal no teratogenic effects; however, animal data are not always indicative of human response.

Penicillins, including ampicillin, are excreted in breast milk in small amounts. Sulbactam is also excreted in low amounts. Use caution when administering ampicillin; sulbactam during breast-feeding. However, unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal ampicillin; sulbactam therapy. Ampicillin breast milk concentrations range from 0.015 to 1.67 mcg/mL with a milk:plasma ratio of 0.02 to 0.525. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in the breast-feeding infant. Previous American Academy of Pediatrics recommendations considered sulbactam as usually compatible with breast-feeding.