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    Penicillinase-Sensitive Penicillin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Aminopenicillin similar to amoxicillin; not stable to beta-lactamases of either gram-positive or gram-negative bacteria; used commonly for obstetric infections, otitis media, sinusitis and other infections due to susceptible organisms; oral ampicillin exhibits lower bioavailability and higher incidence of GI effects than amoxicillin.

    COMMON BRAND NAMES

    Principen

    HOW SUPPLIED

    Ampicillin/Ampicillin Sodium Intramuscular Inj Pwd F/Sol: 1g, 2g, 250mg, 500mg
    Ampicillin/Ampicillin Sodium Intravenous Inj Pwd F/Sol: 1g, 2g, 10g, 125mg, 250mg, 500mg
    Ampicillin/Ampicillin trihydrate/Principen Oral Cap: 250mg, 500mg
    Ampicillin/Ampicillin trihydrate/Principen Oral Pwd F/Recon: 5mL, 125mg, 250mg

    DOSAGE & INDICATIONS

    For the treatment of severe infections, including bacteremia.
    Intravenous or Intramuscular dosage
    Adults

    150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours. While the product labeling does not recommend a maximum dose, guidelines note 12 g/day IV for serious infections.

    Infants, Children, and Adolescents

    50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

    Neonates older than 34 weeks gestation

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates 34 weeks gestation and younger and older than 7 days

    75 mg/kg/dose IV or IM every 12 hours.

    Neonates 34 weeks gestation and younger and 0 to 7 days

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of meningitis.
    NOTE: The Infectious Diseases Society of America (IDSA) recommends ampicillin as an option for the definitive treatment of Streptococcus pneumoniae with penicillin MICs less than 0.1 mcg/mL, Neisseria meningitides with MICs less than 0.1 mcg/mL, Beta-lactamase negative Haemophilus influenzae, ampicillin susceptible Enterococcus sp. (plus gentamicin), Listeria monocytogenes, and Streptococcus agalactiae. They also recommend ampicillin as empiric therapy in patients younger than 1 month of age (with cefotaxime or an aminoglycoside) or older than 50 years old (with vancomycin and a third generation cephalosporin).
    Intravenous or Intramuscular dosage
    Adults

    2 g IV every 4 hours is recommended by guidelines. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

    Infants, Children, and Adolescents

    300 to 400 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 12 g/day) is recommended by guidelines. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

    Neonates older than 34 weeks gestation and older than 7 days

    50 mg/kg/dose IV every 6 hours is recommended by guidelines in general; however, higher doses of 75 mg/kg/dose IV or IM every 6 hours are recommended for group B streptococcal (GBS) meningitis. The FDA-approved dosage is 50 mg/kg/dose IV or IM every 8 hours. A treatment duration of 14 to 21 days is recommended for GBS meningitis or meningitis due to L. monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative enteric bacilli.

    Neonates older than 34 weeks gestation and 0 to 7 days

    50 mg/kg/dose IV every 8 hours is recommended by guidelines in general; however, higher doses up to 100 mg/kg/dose IV or IM every 8 hours are recommended for group B streptococcal (GBS) meningitis. The FDA-approved dosage is 50 mg/kg/dose IV or IM every 8 hours. A treatment duration of 14 to 21 days is recommended for GBS meningitis or meningitis due to L. monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative enteric bacilli.

    Neonates 34 weeks gestation and younger and older than 7 days

    50 mg/kg/dose IV every 6 hours is recommended by guidelines in general; however, higher doses of 75 mg/kg/dose IV or IM every 6 hours are recommended for group B streptococcal (GBS) meningitis. The FDA-approved dosage is 75 mg/kg/dose IV or IM every 12 hours. A treatment duration of 14 to 21 days is recommended for GBS meningitis or meningitis due to L. monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative enteric bacilli.

    Neonates 34 weeks gestation and younger and 0 to 7 days

    50 mg/kg/dose IV every 8 hours is recommended by guidelines in general; however, higher doses up to 100 mg/kg/dose IV or IM every 8 hours are recommended for group B streptococcal (GBS) meningitis. The FDA-approved dosage is 50 mg/kg/dose IV or IM every 12 hours. A treatment duration of 14 to 21 days is recommended for GBS meningitis or meningitis due to L. monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative enteric bacilli.

    For the treatment of infective endocarditis.
    Intravenous or Intramuscular dosage
    Adults

    2 g IV every 4 hours is recommended by guidelines. Ampicillin in combination with gentamicin is recommended as an alternative to penicillin in the setting of shortage for endocarditis due to highly penicillin-susceptible or resistant Viridans group streptococci and S. gallolyticus (bovis) infections; treat for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis (PVE). Ampicillin in combination with gentamicin (or streptomycin) or ceftriaxone is preferred for penicillin-susceptible enterococcal endocarditis; treat for 4 to 6 weeks for NVE and for 6 weeks for PVE or if used with ceftriaxone. Combination therapy with daptomycin may be considered in patients with persistent penicillin-resistant enterococcal bacteremia or strains with high daptomycin MICs; treat for at least 6 weeks. Pending susceptibility data, ampicillin may be an option for endocarditis due to HACEK microorganisms; treat for 4 weeks for NVE and for 6 weeks for PVE. The FDA-approved labeling recommends 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

    Children and Adolescents

    200 to 400 mg/kg/day IV divided every 4 to 6 hours (Max: 12 g/day) is recommended by guidelines. Ampicillin is recommended as an alternative to penicillin in the setting of penicillin unavailability for streptococcal endocarditis; treat for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis (PVE). Use in combination with gentamicin for streptococcal PVE; duration of concurrent gentamicin (2 or 6 weeks) depends on susceptibility and/or organism. Ampicillin in combination with gentamicin is recommended as preferred therapy for enterococcal infections; treat for 4 to 6 weeks, with a longer course for PVE. Alternately, may use in combination with ceftriaxone in aminoglycoside-resistant enterococcal infection or aminoglycoside-intolerant patient. Ampicillin plus an aminoglycoside for 4 weeks is recommended as an alternate therapy for endocarditis due to HACEK microorganisms. The FDA-approved labeling recommends 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

    Infants

    300 to 400 mg/kg/day IV or IM divided every 4 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

    Neonates older than 34 weeks gestation

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates 34 weeks gestation and younger and older than 7 days

    75 mg/kg/dose IV or IM every 12 hours.

    Neonates 34 weeks gestation and younger and 0 to 7 days

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP).
    For the treatment of nonspecific respiratory tract infections (RTIs).
    Oral dosage
    Adults

    250 mg PO 4 times daily.

    Infants, Children, and Adolescents

    50 to 100 mg/kg/day PO in 4 divided doses (Max: 2 g/day) is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dose is 50 mg/kg/day PO in 3 to 4 divided doses (Max: 1 g/day).[51868] Compared to amoxicillin, oral ampicillin has a lower bioavailability and is more likely to cause adverse GI effects.[51854]

    Intravenous or Intramuscular dosage
    Adults weighing 40 kg or more

    250 to 500 mg IV or IM every 6 hours.

    Adults weighing less than 40 kg

    25 to 50 mg/kg/day IV or IM divided every 6 to 8 hours.

    Infants, Children, and Adolescents

    50 to 200 mg/kg/day IV or IM divided every 6 hours (Max: 8 g/day) is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dose is 25 to 50 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/day).[43344]

    Neonates older than 34 weeks gestation†

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates 34 weeks gestation and younger and older than 7 days†

    75 mg/kg/dose IV or IM every 12 hours.

    Neonates 34 weeks gestation and younger and 0 to 7 days†

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of community-acquired pneumonia (CAP).
    Intravenous or Intramuscular dosage
    Infants 4 to 11 months, Children, and Adolescents

    150 to 200 mg/kg/day IV or IM in divided doses every 6 hours (Max: 12 g/day) for 10 days as empiric treatment and 300 to 400 mg/kg/day IV or IM divided every 6 hours for 10 days as an alternative to ceftriaxone for resistant strains of S. pneumoniae.

    For the treatment of skin and skin structure infections (e.g., cellulitis).
    Intravenous or Intramuscular dosage
    Adults weighing 40 kg or more

    250 to 500 mg IV or IM every 6 hours.

    Adults weighing less than 40 kg

    25 to 50 mg/kg/day IV or IM divided every 6 to 8 hours.

    Infants, Children, and Adolescents

    50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours. The FDA-approved dosage is 25 to 50 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/day).

    Neonates older than 34 weeks gestation†

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates 34 weeks gestation and younger and older than 7 days†

    75 mg/kg/dose IV or IM every 12 hours.

    Neonates 34 weeks gestation and younger and 0 to 7 days†

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of genitourinary tract infections, including urinary tract infection (UTI) (e.g., cystitis and pyelonephritis).
    Intravenous or Intramuscular dosage
    Adults

    500 mg IV or IM every 6 hours for patients weighing 40 kg or more and 50 mg/kg/day IV or IM divided every 6 to 8 hours for those weighing less than 40 kg is the FDA-approved dosage. Higher doses may be needed for severe infections. The Infectious Diseases Society of America (IDSA) does not recommend ampicillin for empiric cystitis treatment due to the antimicrobial resistance; however, ampicillin plus gentamicin may be used initially for the treatment of pyelonephritis.

    Infants, Children, and Adolescents

    50 to 200 mg/kg/day IV or IM divided every 6 hours (Max: 8 g/day) is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 50 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/day).

    Neonates older than 34 weeks gestation†

    50 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP).

    Neonates 34 weeks gestation and younger and older than 7 days†

    75 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP).

    Neonates 34 weeks gestation and younger and 0 to 7 days†

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP).

    Oral dosage
    Adults

    500 mg PO 4 times per day. The Infectious Diseases Society of America (IDSA) does not recommend ampicillin for empiric cystitis treatment due to the antimicrobial resistance.

    Infants, Children, and Adolescents

    100 mg/kg/day PO in 4 divided doses (Max: 2 g/day).

    For the treatment of gastrointestinal infections (e.g. enterocolitis, gastroenteritis), including dysentery/shigellosis, salmonellosis, and typhoid fever.
    For the treatment of general gastrointestinal infections, including dysentery/shigellosis and salmonellosis.
    Oral dosage
    Adults

    500 mg PO every 6 hours.

    Infants, Children, and Adolescents

    100 mg/kg/day (Max: 2 g/day) PO divided every 6 hours.

    Intravenous or Intramuscular dosage
    Adults weighing 40 kg or more

    500 mg IV or IM every 6 hours. Higher doses may be needed for severe infections.

    Adults weighing less than 40 kg

    50 mg/kg/day IV or IM divided every 6 to 8 hours. Higher doses may be needed for severe infections.

    Infants, Children, and Adolescents

    50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 50 mg/kg/day (Max: 2 g/day) IV or IM divided every 6 to 8 hours.

    Neonates older than 34 weeks gestation†

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates 34 weeks gestation and younger and older than 7 days†

    75 mg/kg/dose IV or IM every 12 hours.

    Neonates 34 weeks gestation and younger and 0 to 7 days†

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of fully sensitive uncomplicated typhoid fever.
    Oral dosage
    Adults

    50 to 100 mg/kg/day PO divided every 6 to 8 hours for 14 days as an alternative.

    Infants, Children, and Adolescents

    50 to 100 mg/kg/day PO divided every 6 to 8 hours for 14 days as an alternative.

    For the treatment of fully sensitive severe typhoid fever.
    Intravenous or Intramuscular dosage
    Adults

    100 mg/kg/day IV or IM divided every 6 to 8 hours for 14 days as an alternative. Usual dose: 2 g IV every 6 hours.

    Infants, Children, and Adolescents

    100 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 to 8 hours for 14 days as an alternative.

    For the treatment of leptospirosis†.
    Intravenous dosage
    Adults, Adolescents, and Children

    As alternative therapy, 0.5—1 g IV every 6 hours has been used.

    For bacterial endocarditis prophylaxis†.
    Intramuscular or Intravenous dosage
    Adults

    2 g IV or IM as a single dose given 30 to 60 minutes before procedure as an alternative for patients unable to take oral medication. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.

    Children and Adolescents

    50 mg/kg/dose (Max: 2 g/dose) IV or IM as a single dose given 30 to 60 minutes before procedure as an alternative for patients unable to take oral medication. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.

    For perinatal Group B streptococcal infection prophylaxis†.
    Intravenous dosage
    Pregnant females

    2 g IV load initiated at the time of labor or rupture of membranes, followed by 1g IV every 4 hours until delivery. Penicillin is the agent of choice for preventing Group B streptococcal disease, with ampicillin as an acceptable alternative. Antibiotics administered for at least 4 hours before delivery have been found to be highly effective at preventing the transmission of Group B Streptococcus.[64407] Antibiotics given to prolong latency for preterm PROM with adequate Group B Streptococcus coverage (specifically 2 g ampicillin IV every 6 hours for 48 hours) are sufficient for prophylaxis if delivery occurs while the patient is receiving that antibiotic regimen.[64407] [64408]

    For the treatment of intraabdominal infections†, including peritonitis†, appendicitis†, intraabdominal abscess†, neonatal necrotizing enterocolitis†, and peritoneal dialysis-related peritonitis†.
    For the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections† with adequate source control.
    Intravenous dosage
    Adults

    1 to 2 g IV every 4 to 6 hours as part of combination therapy 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 (Max: 8 g/day) IV divided every 6 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Neonates older than 34 weeks gestation

    50 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. Ampicillin is an option for necrotizing enterocolitis.

    Neonates 34 weeks gestation and younger and older than 7 days

    75 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. Ampicillin is an option for necrotizing enterocolitis.

    Neonates 34 weeks gestation and younger and 0 to 7 days

    50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. Ampicillin is an option for necrotizing enterocolitis.

    For the treatment of uncomplicated intraabdominal infections†.
    Intravenous dosage
    Adults

    1 to 2 g IV every 4 to 6 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Infants, Children, and Adolescents

    100 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 hours part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

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

    125 mg/L in each dialysate exchange. Treat for 14 to 21 days.

    Infants, Children, and Adolescents

    125 mg/L in each dialysate exchange. Treat for 14 to 21 days.

    For surgical infection prophylaxis† in patients undergoing liver transplantation.
    Intravenous or Intramuscular dosage
    Adults

    2 g IV or IM as a single dose within 60 minutes prior to the surgical incision, in combination with cefotaxime. Intraoperative redosing 2 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours are recommended by clinical practice guidelines.

    Infants, Children, and Adolescents

    50 mg/kg IV or IM as a single dose (Max: 2 g/dose) within 60 minutes prior to the surgical incision, in combination with cefotaxime. Intraoperative redosing 2 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours are recommended by clinical practice guidelines.

    For the treatment of systemic anthrax† infection.
    Intravenous dosage
    Adults

    3 g IV every 6 hours. Ampicillin, in combination with a fluoroquinolone and protein synthesis inhibitor (i.e., linezolid, clindamycin), is an alternative therapy for the treatment of systemic anthrax due to penicillin-susceptible strains in which meningitis cannot be excluded. Ampicillin, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy in systemic anthrax infection due to penicillin-susceptible strains without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Infants, Children, and Adolescents

    50 mg/kg/dose IV every 6 hours (Max: 3 g/dose) for systemic infection without CNS involvement and 100 mg/kg/dose IV every 6 hours (Max: 3 g/dose) for systemic infection with documented/suspected CNS involvement. For systemic infection in which meningitis can be excluded, IV treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, IV treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ampicillin, in combination with appropriate antimicrobial therapy, is an alternative therapy for the treatment of systemic anthrax due to penicillin-susceptible strains. For systemic infection without CNS involvement, dual combination IV therapy with ampicillin and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended. For documented or suspected CNS infection, triple IV therapy with ampicillin, a fluoroquinolone, and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended.

    Premature Neonates 34 to 37 weeks gestation and Term Neonates older than 7 days

    50 mg/kg/dose IV every 6 hours. For systemic infection in which meningitis can be excluded, IV treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, IV treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ampicillin, in combination with appropriate antimicrobial therapy, is an alternative therapy for the treatment of systemic anthrax due to penicillin-susceptible strains. For systemic infection without CNS involvement, dual combination IV therapy with ampicillin and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended. For documented or suspected CNS infection, triple IV therapy with ampicillin, a fluoroquinolone, and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended.

    Premature Neonates 34 to 37 weeks gestation and Term Neonates 0 to 7 days

    50 mg/kg/dose IV every 8 hours. For systemic infection in which meningitis can be excluded, IV treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, IV treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ampicillin, in combination with appropriate antimicrobial therapy, is an alternative therapy for the treatment of systemic anthrax due to penicillin-susceptible strains. For systemic infection without CNS involvement, dual combination IV therapy with ampicillin and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended. For documented or suspected CNS infection, triple IV therapy with ampicillin, a fluoroquinolone, and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended.

    Premature Neonates 32 to 34 weeks gestation and older than 7 days

    50 mg/kg/dose IV every 8 hours. For systemic infection in which meningitis can be excluded, IV treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, IV treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ampicillin, in combination with appropriate antimicrobial therapy, is an alternative therapy for the treatment of systemic anthrax due to penicillin-susceptible strains. For systemic infection without CNS involvement, dual combination IV therapy with ampicillin and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended. For documented or suspected CNS infection, triple IV therapy with ampicillin, a fluoroquinolone, and a protein synthesis inhibitor (i.e., linezolid, clindamycin) is recommended.

    Premature Neonates 32 to 34 weeks gestation and 0 to 7 days

    50 mg/kg/dose IV every 12 hours. For systemic infection in which meningitis can be excluded, IV treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, IV treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ampicillin, in combination with appropriate antimicrobial therapy, is an alternative therapy for the treatment of systemic anthrax due to penicillin-susceptible strains. For systemic infection without CNS involvement, dual combination IV therapy with ampicillin and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended. For documented or suspected CNS infection, triple IV therapy with ampicillin, a fluoroquinolone, and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended.

    For the prolongation of latency and reduction of maternal and neonatal infections and neonatal morbidity in patients with preterm premature rupture of membranes† (PROM).
    Intravenous dosage
    Pregnant females

    2 g IV every 6 hours in combination with IV erythromycin for 48 hours, followed by oral amoxicillin and erythromycin for 5 days. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant women with preterm PROM who are less than 34 0/7 weeks gestation. Administration of broad-spectrum antibiotics has been shown to prolong pregnancy, reduce maternal and neonatal infections, and reduce gestational age-dependent morbidity. Women with preterm PROM who are candidates for Group B streptococcal (GBS) intrapartum prophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.[64408]

    For chronic typhoid carriage eradication†.
    Oral dosage
    Adults

    100 mg/kg/day PO divided every 6 to 8 hours plus probenecid for 4 to 6 weeks.

    Infants, Children, and Adolescents

    100 mg/kg/day PO divided every 6 to 8 hours plus probenecid for 4 to 6 weeks.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2 g/day PO. 200 mg/kg/day IV/IM per FDA-approved product labeling (Max: 12 g/day).

    Geriatric

    2 g/day PO. 200 mg/kg/day IV/IM per FDA-approved product labeling (Max: 12 g/day).

    Adolescents

    100 mg/kg/day PO (Max: 2 g/day); 200 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 400 mg/kg/day IV (Max: 12 g/day) have been used off-label for serious infections.

    Children

    100 mg/kg/day PO (Max: 2 g/day); 200 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 400 mg/kg/day IV (Max: 12 g/day) have been used off-label for serious infections.

    Infants

    100 mg/kg/day PO; 200 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 400 mg/kg/day IV have been used off-label for serious infections.

    Neonates

    older than 7 days: 150 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 300 mg/kg/day IV have been used off-label for serious infections.
    0 to 7 days and older than 34 weeks gestation: 150 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 300 mg/kg/day IV have been used off-label for serious infections.
    0 to 7 days and 34 weeks gestation or younger: 100 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 300 mg/kg/day IV have been used off-label for serious infections.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed.

    Renal Impairment

    Adults:
    CrCl more than 50 mL/minute: No dosage adjustment needed.
    CrCl 10 to 50 mL/minute: Extend dosing interval to every 6 to 12 hours.
    CrCl less than 10 mL/minute: Extend dosing interval to every 12 to 24 hours.
     
    Pediatrics:
    GFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
    GFR 10 to 29 mL/minute/1.73 m2: Extend dosing interval to every 8 to 12 hours.
    GFR less than 10 mL/minute/1.73 m2: Extend dosing interval to every 12 hours.
     
    Intermittent hemodialysis
    Ampicillin is significantly removed during a standard hemodialysis session; give recommended dose after dialysis. For pediatric patients, give the recommended dose every 12 hours after dialysis.
     
    Peritoneal dialysis
    Adults: 250 mg every 12 hours.
    Pediatrics: Extend dosing interval to every 12 hours.
     
    Continuous renal replacement therapy (CRRT)
    Adults: Give recommended dose every 6 to 12 hours.
    Pediatrics: Give recommended dose every 6 hours.

    ADMINISTRATION

    Oral Administration

    All dosage forms: Take on an empty stomach (i.e., at least 30 minutes prior to or 2 hours after a meal).

    Oral Liquid Formulations

    Shake well prior to each use.
     
    Reconstitution
    Review the manufacturer reconstitution instructions for the particular product and package size.
    Add water in 2 portions and shake well after each addition.
    Storage: Store reconstituted suspension in refrigerator; discard after 14 days.

    Injectable Administration

    Ampicillin sodium may be administered intramuscularly (IM), by slow intravenous (IV) push, or by IV infusion.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Do not administer ampicillin at the same time or mix in the same container as aminoglycosides. Beta-lactam antibiotics such as ampicillin may inactivate aminoglycoside antibiotics when combined.

    Intravenous Administration

    IV Push
    Reconstitution
    Bacteriostatic Water for Injection should not be used for preparation of neonatal doses.
    125 mg, 250 mg, and 500 mg vials: Reconstitute the 125 mg, 250 mg, and 500 mg vials with 5 mL of Sterile Water for Injection or Bacteriostatic Water for Injection for a resultant concentration of 25 mg/mL, 50 mg/mL, and 100 mg/mL, respectively.
    1 and 2 g vials: Reconstitute the 1 g and 2 g vials with 7.4 or 14.8 mL of Sterile Water for Injection or Bacteriostatic Water for Injection, respectively, for a resultant concentration of 125 mg/mL.
    Swirl vial and ensure that all drug is completely dissolved into solution.
    Withdraw the appropriate dose from the vial and administer within 1 hour of reconstitution.
    IV Push Administration
    125 mg, 250 mg, and 500 mg doses: Administer as slow IV push over at least 3 to 5 minutes.
    1 and 2 g doses: Administer as slow IV push over at least 10 to 15 minutes.
    Do not administer faster than recommended as more rapid administration may result in seizures.
     
    Intermittent IV Infusion
    Reconstitution/Dilution
    125 mg, 250 mg, and 500 mg vials: Reconstitute the 125 mg, 250 mg, and 500 mg vials with 5 mL of Sterile Water for Injection or Bacteriostatic Water for Injection for a resultant concentration of 25 mg/mL, 50 mg/mL, and 100 mg/mL, respectively.
    1 and 2 g vials: Reconstitute the 1 g and 2 g vials with 7.4 or 14.8 mL of Sterile Water for Injection or Bacteriostatic Water for Injection, respectively, for a resultant concentration of 125 mg/mL.
    Pharmacy Bulk Vial: The 10 g vial is designed for use in preparing multiple IV admixtures. Add 94 mL Sterile Water for Injection. The resulting solution will contain 100 mg/mL ampicillin and is stable up to 1 hour at room temperature.
    Once vials are prepared, withdraw the appropriate dose and further dilute with a compatible fluid (e.g., 0.9% NaCl Injection) to a usual concentration of 10 to 30 mg/mL.
    Stability is dependent on the diluent chosen, the final concentration, and the storage conditions and may range from 1 hour to 72 hours. Consult ampicillin full prescribing information (i.e., package insert) for detailed stability information.
     
    Intermittent IV Infusion Administration
    Infuse appropriate dose IV over 15 to 30 minutes.

    Intramuscular Administration

    Reconstitution
    Reconstitute the 125 mg vial with 1.2 mL of Sterile Water for Injection or Bacteriostatic Water for Injection for a resultant concentration of 125 mg/mL. Reconstitute 250 mg, 500 mg, 1 g, and 2 g vials with 1 mL, 1.8 mL, 3.5 mL, and 6.8 mL of Sterile Water for Injection or Bacteriostatic Water for Injection, respectively, for a resultant concentration of 250 mg/mL.
    Administer within 1 hour of preparation.
     
    Intramuscular (IM) Injection
    Withdraw appropriate dose and inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]).
    In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    STORAGE

    Generic:
    - Do not freeze reconstituted product
    - Store reconstituted product in accordance with package insert instructions
    - Store unreconstituted product at 68 to 77 degrees F
    Principen:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    A false-positive reaction for glucose in the urine has been observed in patients receiving penicillins, such as ampicillin, and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix). Patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on ampicillin treatment.

    Dialysis, renal disease, renal failure, renal impairment

    Ampicillin should be used with caution in patients with renal disease or renal impairment since the drug is eliminated by the kidneys. Ampicillin dosage interval should be adjusted in those patients with CrCl <= 50 mL/min and in those patients with renal failure. Supplemental doses are recommended for patients receiving dialysis. During prolonged therapy in patients without preexisting renal impairment, renal function should be periodically evaluated.

    Asthma, carbapenem hypersensitivity, cephalosporin hypersensitivity, eczema, penicillin hypersensitivity, serious rash, urticaria

    Ampicillin is a penicillin and should not be used in patients with a penicillin hypersensitivity. Ampicillin should also be used cautiously in patients with cephalosporin hypersensitivity and carbapenem hypersensitivity. These patients are more susceptible to hypersensitivity reactions during therapy with ampicillin. Patients with allergies or allergic conditions including asthma, eczema, hives (urticaria), or hay fever may have a greater risk for hypersensitivity reactions to penicillins. Serious rash events, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, and acute generalized exanthematous pustulosis (AGEP), have been reported in patients receiving treatment with ampicillin. If a severe skin reaction occurs, discontinue ampicillin and institute appropriate therapy.

    Mononucleosis

    Ampicillin should be used with caution in patients with mononucleosis as a high incidence (43—100%) of skin rashes has been reported in these patients. The rash (maculopapular, pruritic, and generalized) typically appears 7—10 days after therapy initiation and resolves a few days to a week after treatment is discontinued.

    Antimicrobial resistance

    Oral ampicillin is contraindicated for the treatment of infections caused by penicillinase-producing organisms due to antimicrobial resistance. In general, any ampicillin product will not treat organisms that are penicillinase-producing. Antibiotic therapy can result in superinfection or suprainfection with non susceptible organisms. Overgrowth of Candida can occur during antibiotic therapy. Patients should be monitored closely during therapy.

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including ampicillin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Pregnancy

    Ampicillin is classified in FDA pregnancy category B. Animal data reveal no teratogenic effects. While ampicillin should be used with caution in pregnancy, penicillins are usually considered safe during pregnancy when clearly needed.

    Breast-feeding

    Penicillins, including ampicillin, are excreted in breast milk in small amounts. The manufacturer recommends caution with the use of ampicillin during nursing. However, unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal ampicillin therapy. Breast milk concentrations range from 0.015—1.67 mcg/mL with a milk:plasma ratio of 0.02—0.525. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in the breast-feeding infant. The infant should be observed for potential effects. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Infants, neonates

    Neonates and young infants with incompletely developed renal function will experience delayed excretion of ampicillin; dosage schedules should be modified in these patients (see Indications/Dosage).

    Geriatric

    Geriatric patients respond similarly to younger adults receiving ampicillin therapy; proper dosage adjustments should occur according to renal function. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    ADVERSE REACTIONS

    Severe

    serum sickness / Delayed / 0-5.0
    erythema multiforme / Delayed / 0-5.0
    exfoliative dermatitis / Delayed / 0-5.0
    enterocolitis / Delayed / 2.0-5.0
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    odynophagia / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known

    Moderate

    stomatitis / Delayed / 2.0-5.0
    glossitis / Early / 2.0-5.0
    dysphagia / Delayed / 2.0-5.0
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    platelet dysfunction / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    prolonged bleeding time / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known

    Mild

    rash / Early / 0-5.0
    maculopapular rash / Early / 0-5.0
    urticaria / Rapid / 0-5.0
    pruritus / Rapid / 0-5.0
    nausea / Early / 2.0-5.0
    tongue discoloration / Delayed / 2.0-5.0
    vomiting / Early / 2.0-5.0
    diarrhea / Early / 2.0-5.0
    fever / Early / Incidence not known
    Jarisch-Herxheimer reaction / Early / Incidence not known

    DRUG INTERACTIONS

    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; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (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.
    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; Butalbital; 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.
    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; Dihydrocodeine: (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.
    Aspirin, ASA; Pravastatin: (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.
    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.
    Chloroquine: (Moderate) Administer oral ampicillin 2 hours before or 2 hours after chloroquine. In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin. The reduction of ampicillin bioavailability could be attributed to slower gastric emptying and enhancement of gut motility produced by chloroquine.
    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.
    Erythromycin; Sulfisoxazole: (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.
    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: (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; Levonorgestrel; Folic Acid; 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.
    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.
    Hydroxychloroquine: (Moderate) Administer oral ampicillin 2 hours before or 2 hours after hydroxychloroquine. Ampicillin bioavailability may be decreased with coadministration of hydroxychloroquine as a significant reduction in ampicillin bioavailability was observed with the structurally similar chloroquine in a study of healthy volunteers. The reduction of ampicillin bioavailability could be attributed to slower gastric emptying and enhancement of gut motility produced by chloroquine.
    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.
    Lansoprazole; Naproxen: (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.
    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.
    Mestranol; 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.
    Methotrexate: (Major) Penicillins may reduce the renal clearance of methotrexate. Increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with concurrent administration of high or low doses of methotrexate and penicillins. Patients should be carefully monitored while receiving this combination.
    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 pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    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: (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: (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.
    Pyrimethamine; Sulfadoxine: (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.
    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 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.
    Sulfisoxazole: (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: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    Ampicillin is classified in FDA pregnancy category B. Animal data reveal no teratogenic effects. While ampicillin should be used with caution in pregnancy, penicillins are usually considered safe during pregnancy when clearly needed.

    Penicillins, including ampicillin, are excreted in breast milk in small amounts. The manufacturer recommends caution with the use of ampicillin during nursing. However, unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal ampicillin therapy. Breast milk concentrations range from 0.015—1.67 mcg/mL with a milk:plasma ratio of 0.02—0.525. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in the breast-feeding infant. The infant should be observed for potential effects. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    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. Penicillin-binding proteins 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. Penicillin-binding proteins 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.

    PHARMACOKINETICS

    Ampicillin is administered orally and parenterally by intravenous or intramuscular routes. Ampicillin is the least serum-bound of all the penicillins, averaging roughly 20% compared to approximately 60% to 90% for other penicillins. The drug is 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 concentrations are attained within the cerebral spinal fluid (CSF) in the presence of inflammation. The drug does cross the placenta. Approximately 10% of an ampicillin dose is metabolized to inactive derivatives. Parent drug and metabolites are excreted into the urine primarily via tubular secretion and glomerular filtration. A small percentage is excreted in breast milk. In patients with normal renal function, the elimination half-life of ampicillin is 1 to 1.5 hours.
     
    Affected cytochrome P450 isoenzymes: none

    Oral Route

    Approximately 30% to 55% of an oral dose of ampicillin is absorbed, significantly less than for amoxicillin. Peak serum levels of ampicillin occur within 1 to 2 hours after an oral dose. Food in the stomach inhibits the rate and extent of absorption. Oral administration should be either 1 hour prior to or 2 hours after a meal for maximal absorption.

    Intravenous Route

    Peak serum concentrations of ampicillin occur almost immediately after a 15-minute intravenous (IV) infusion. After a 2,000-mg ampicillin dose in adults, peak ampicillin serum concentrations range roughly 80 to 150 mcg/mL. Peak ampicillin concentrations are roughly 40 to 70 mcg/mL after administration of 1,000 mg ampicillin.

    Intramuscular Route

    Peak serum concentrations of ampicillin occur within 1 hour after an intramuscular (IM) dose. After an IM injection of 1,000 mg ampicillin to adults, peak ampicillin serum concentrations ranging from 8 to 37 mcg/mL are attained.