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  • CLASSES

    Penicillinase-Sensitive Penicillin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Naturally derived antibiotic for parenteral use. Commercially available as salts of potassium or sodium; these aqueous and crystalline forms administered IV or IM. Primary agent for Streptococcus pyogenes, S. pneumoniae, and enterococcal infections. Drug of choice for the treatment of treponemal infection.

    COMMON BRAND NAMES

    Pfizerpen

    HOW SUPPLIED

    Penicillin/Penicillin G Potassium Intravenous Inj Sol: 50mL, 1000000U, 2000000U, 3000000U
    Penicillin/Penicillin G Potassium/Penicillin G Sodium/Pfizerpen Intravenous Inj Pwd F/Sol: 5000000U, 20000000U
    Penicillin/Penicillin G Potassium/Pfizerpen Intramuscular Inj Pwd F/Sol: 5000000U, 20000000U
    Penicillin/Penicillin G Potassium/Pfizerpen Intrapleural Inj Pwd F/Sol: 5000000U, 20000000U
    Penicillin/Penicillin G Potassium/Pfizerpen Intrathecal Inj Pwd F/Sol: 5000000U, 20000000U

    DOSAGE & INDICATIONS

    For the treatment of bacteremia or empyema.
    For the treatment of meningococcal bacteremia.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV or IM divided every 2 hours.

    Infants, Children, and Adolescents

    100,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).

    Neonates older than 7 days

    50,000 units/kg/dose IV or IM every 8 hours.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV or IM every 12 hours.

    For the treatment of bacteremia due to Pasteurella multocida.
    Intravenous or Intramuscular dosage
    Adults

    4 to 6 million units/day IV or IM divided every 4 to 6 hours for 2 weeks.

    For the treatment of streptococcal bacteremia or pleural empyema.
    Intravenous or Intramuscular dosage
    Adults

    12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    100,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).

    Neonates older than 7 days

    50,000 units/kg/dose IV or IM every 8 hours.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV or IM every 12 hours.

    For the treatment of staphylococcal bacteremia or pleural empyema.
    Intravenous or Intramuscular dosage
    Adults

    5 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    100,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).

    Neonates older than 7 days

    50,000 units/kg/dose IV or IM every 8 hours.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV or IM every 12 hours.

    For the treatment of clostridial diseases, including botulism, gas gangrene, and tetanus.
    For the treatment of tetanus as adjunctive therapy to tetanus immune globulin .
    Intravenous or Intramuscular dosage
    Adults

    20 million units/day IV or IM in divided doses every 4 to 6 hours for 7 to 10 days.[30078] [43696] [64480] [64481]

    Infants†, Children†, and Adolescents†

    100,000 units/kg/day (Max: 12 million units/day) IV or IM in divided doses every 4 to 6 hours for 7 to 10 days.[63245]

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours.[63245]

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours.[63245]

    For the treatment of botulism as adjunctive therapy to antitoxin.
    Intravenous or Intramuscular dosage
    Adults

    20 million units/day IV or IM in divided doses every 4 to 6 hours.[30078] [43696]

    Infants†, Children†, and Adolescents†

    100,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM in divided doses every 4 to 6 hours.[63245]

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours.[63245]

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours.[63245]

    For the treatment of gas gangrene.
    Intravenous or Intramuscular dosage
    Adults

    2 to 4 million units IV every 4 to 6 hours.[57437] Alternatively, 20 million units/day IV or IM in divided doses every 4 to 6 hours.[30078] [43696] Penicillin plus clindamycin is recommended for necrotizing clostridial infections.[57437]

    Infants†, Children†, and Adolescents†

    60,000 to 100,000 units/kg/dose IV every 6 hours. Penicillin plus clindamycin is recommended for necrotizing clostridial infections.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours.[63245] Penicillin plus clindamycin is recommended for necrotizing clostridial infections.[57437]

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours.[63245] Penicillin plus clindamycin is recommended for necrotizing clostridial infections.[57437]

    For the treatment of inhalation anthrax infection caused by susceptible strains of Bacillus anthracis.
    NOTE: In the setting where high concentrations of B. anthracis organisms are present, the treatment of infections with a penicillin-type drug alone is a concern due to the risk of a beta-lactamase induction event, which would significantly increase the MIC.
    Intravenous dosage
    Adults

    4 million units IV every 4 hours. Total treatment is for 60 days; switch to oral antibiotics as soon as clinically possible. Postexposure vaccination might permit the treatment duration to be shortened to 30—45 days, with concomitant administration of the anthrax vaccine at weeks 0, 2, and 4. The manufacturer recommends a minimum of 5—8 million units/day IV divided every 6 hours.

    Children >= 12 years† and Adolescents†

    4 million units IV every 4 hours. Total treatment is for 60 days; switch to oral antibiotics as soon as clinically possible. Postexposure vaccination might permit the treatment duration to be shortened to 30—45 days, with concomitant administration of the anthrax vaccine at weeks 0, 2, and 4.

    Children < 12 years†

    50,000 units/kg IV every 6 hours. Total treatment is for 60 days; switch to oral antibiotics as soon as clinically possible. Postexposure vaccination might permit the treatment duration to be shortened to 30—45 days, with concomitant administration of the anthrax vaccine at weeks 0, 2, and 4.

    For the treatment of infective endocarditis.
    NOTE: For gonococcal endocarditis, see gonococcal infections.
    For the treatment of native valve endocarditis due to highly susceptible viridans group streptococci and nonenterococcal group D streptococci.
    Intravenous or Intramuscular dosage
    Adults

    12 to 18 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks as monotherapy or for 2 weeks plus gentamicin. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 weeks. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours for 4 weeks.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours for 4 weeks.

    For the treatment of native valve endocarditis due to relatively resistant viridans group streptococci and nonenterococcal group D streptococci.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks plus gentamicin for 2 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 weeks plus gentamicin for 2 weeks. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours for 4 weeks plus gentamicin for 2 weeks.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours for 4 weeks plus gentamicin for 2 weeks.

    For the treatment of native valve endocarditis due to group B, C, F, and G streptococci.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 to 6 weeks plus gentamicin for at least 2 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 weeks plus gentamicin for 2 weeks for relatively resistant strains. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours for 4 weeks plus gentamicin for 2 weeks for relatively resistant strains.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours for 4 weeks plus gentamicin for 2 weeks for relatively resistant strains.

    For the treatment of native valve endocarditis due to highly susceptible S. pneumoniae.
    Intravenous or Intramuscular dosage
    Adults

    12 to 18 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    Optimal therapy is not established. 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.

    For the treatment of native valve endocarditis due to intermediate or highly penicillin-resistant S. pneumoniae.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    Not recommended by guidelines. 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.

    For the treatment of native valve endocarditis due to S. pyogenes.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 to 6 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    For the treatment of prosthetic valve endocarditis due to penicillin-susceptible Streptococcus sp..
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 6 weeks with or without gentamicin for 2 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 6 weeks plus gentamicin for 2 weeks. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours for 6 weeks plus gentamicin for 2 weeks.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours for 6 weeks plus gentamicin for 2 weeks.

    For the treatment of native valve endocarditis due to Enterococcus sp.† with symptoms of illness less than 3 months.
    Intravenous or Intramuscular dosage
    Adults

    18 to 30 million units/day IV divided every 4 hours or as a continuous IV infusion for 4 weeks plus gentamicin or streptomycin.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 to 6 weeks plus gentamicin.

    Neonates older than 7 days

    50,000 units/kg/dose IV or IM every 8 hours for 4 to 6 weeks plus gentamicin.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV or IM every 12 hours for 4 to 6 weeks plus gentamicin.

    For the treatment of native valve endocarditis due to Enterococcus sp.† with symptoms of illness more than 3 months or prosthetic valve endocarditis due to Enterococcus sp.†.
    Intravenous or Intramuscular dosage
    Adults

    18 to 30 million units/day IV divided every 4 hours or as a continuous IV infusion for 6 weeks plus gentamicin or streptomycin.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 to 6 weeks plus gentamicin.

    Neonates older than 7 days

    50,000 units/kg/dose IV or IM every 8 hours for 4 to 6 weeks plus gentamicin.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV or IM every 12 hours for 4 to 6 weeks plus gentamicin.

    For the treatment of native valve endocarditis due to susceptible Staphylococcus sp..
    Intravenous or Intramuscular dosage
    Adults

    Not recommended by guidelines. 5 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants†, Children†, and Adolescents†

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 to 6 weeks; consider the addition of gentamicin for 3 to 5 days.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours for 4 to 6 weeks; consider the addition of gentamicin for 3 to 5 days.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours for 4 to 6 weeks; consider the addition of gentamicin for 3 to 5 days.

    For the treatment of prosthetic valve endocarditis due to susceptible Staphylococcus sp..
    Intravenous or Intramuscular dosage
    Adults

    Not recommended by guidelines. 5 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants†, Children†, and Adolescents†

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks.

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

    12 to 20 million units/day IV or IM divided every 4 to 6 hours for 4 to 6 weeks.

    For the treatment of endocarditis due to Listeria sp..
    Intravenous or Intramuscular dosage
    Adults

    15 to 20 million units/day IV or IM divided every 4 to 6 hours for 4 weeks.

    For the treatment of prosthetic valve endocarditis due to relatively or fully penicillin-resistant Streptococcus sp..
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 6 weeks plus gentamicin. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 6 weeks plus gentamicin. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.

    Neonates older than 7 days†

    50,000 units/kg/dose IV or IM every 8 hours for 6 weeks plus gentamicin.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV or IM every 12 hours for 6 weeks plus gentamicin.

    For the treatment of disseminated gonorrhea.
    For the treatment of gonococcal arthritis.
    Intravenous or Intramuscular dosage
    Adults

    Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 7 to 10 days.

    Children and Adolescents weighing 45 kg or more

    Not recommended by guidelines. 10 million units/day IV or IM doses every 6 hours for 7 to 10 days.

    Infants, Children, and Adolescents weighing less than 45 kg

    Not recommended by guidelines. 100,000 units/kg/day IV or IM divided every 6 hours for 7 to 10 days.

    For the treatment of gonococcal meningitis.
    Intravenous or Intramuscular dosage
    Adults

    Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 10 to 14 days.

    Children and Adolescents weighing 45 kg or more

    Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 10 to 14 days.

    Infants, Children, and Adolescents weighing less than 45 kg

    Not recommended by guidelines. 250,000 units/kg/day IV or IM divided every 4 hours for 10 to 14 days.

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

    Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 4 weeks.

    Children and Adolescents weighing 45 kg or more

    Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 4 weeks.

    Infants, Children, and Adolescents weighing less than 45 kg

    Not recommended by guidelines. 250,000 units/kg/day IV or IM divided every 4 hours for 4 weeks.

    For the treatment of listeriosis.
    Intravenous or Intramuscular dosage
    Adults

    15 to 20 million units/day IV or IM given in divided doses every 4 to 6 hours. Give for 2 weeks for meningitis and 4 weeks for endocarditis.

    For the adjunctive treatment of diphtheria and to prevent establishment of carrier state.
    Intravenous or Intramuscular dosage
    Adults

    2 to 4 million units/day IV or IM divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.

    Infants, Children, and Adolescents

    100,000 to 250,000 units/kg/day (Max: 4 million units/day) IV or IM divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.

    For the treatment of rat-bite fever or Haverhill fever.
    Intravenous or Intramuscular dosage
    Adults

    12 to 20 million units/day IV or IM divided every 4 to 6 hours for at least 3 to 4 weeks.

    Infants, Children, and Adolescents

    20,000 to 50,000 units/kg/day IV or IM divided every 6 hours for 5 to 7 days, followed by oral penicillin V for 7 days. For endocarditis, 150,000 to 250,000 units/kg/day (Max: 20 million units/day) IV or IM divided every 4 hours for at least 4 weeks.

    For the treatment of actinomycosis.
    Intravenous or Intramuscular dosage
    Adults

    18 to 24 million units/day IV divided every 4 hours for 2 to 6 weeks, followed by oral therapy for 6 to 12 months. Shorter courses may be appropriate for less extensive infections. The FDA-approved dose is 10 to 20 million units/day IV or IM divided every 4 to 6 hours for thoracic/abdominal disease and 1 to 6 million units/day IV or IM divided every 4 to 6 hours for cervicofacial disease.

    For the treatment of fusospirochetosis or Vincent's infection, including necrotizing ulcerative gingivitis, oropharynx infections, lower respiratory tract infections, and genital infections caused by Fusobacterium sp..
    Intravenous dosage
    Adults

    5—10 million units/day IV divided every 4—6 hours.

    For the treatment of pneumonia, including community-acquired pneumonia (CAP).
    For the treatment of community-acquired pneumonia (CAP).
    Intravenous or Intramuscular dosage
    Infants, Children, and Adolescents 4 months to 17 years

    200,000 to 250,000 units/kg/day IV or IM divided every 4 to 6 hours for 10 days for susceptible strains of S. pneumoniae and 100,000 to 250,000 units/kg/day IV or IM divided every 4 to 6 hours for 10 days for Group A Streptococcus. Guidelines also recommend penicillin G as empiric therapy in hospitalized patients who are fully immunized and in regions with low concentrations of penicillin-resistant pneumococcal strains. Atypical and/or community-acquired MRSA therapy may be added empirically.

    Intravenous or Intramuscular dosage
    Adults

    5 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).

    Neonates older than 7 days

    50,000 units/kg/dose IV or IM every 8 hours.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV or IM every 12 hours.

    For the treatment of pericarditis.
    For the treatment of streptococcal pericarditis.
    Intravenous or Intramuscular dosage
    Adults

    12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    For the treatment of staphylococcal pericarditis.
    Intravenous or Intramuscular dosage
    Adults

    5 to 24 million units/day IV or IM divided every 4 to 6 hours.

    For the treatment of meningitis and ventriculitis†.
    NOTE: For gonococcal meningitis, see gonococcal infections. For neurologic Lyme infections, see Lyme borreliosis.
    For the treatment of beta-hemolytic streptococcal meningitis.
    Intravenous or Intramuscular dosage
    Adults

    12 to 24 million units/day IV or IM divided every 4 to 6 hours. Treat S. agalactiae with 24 million units/day IV divided every 4 hours for 14 to 21 days; consider the addition of an aminoglycoside.

    Infants†, Children†, and Adolescents†

    300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours. Treat S. agalactiae for 14 to 21 days; consider the addition of an aminoglycoside.

    Neonates older than 7 days†

    125,000 units/kg/dose IV every 6 hours. Treat S. agalactiae for 14 to 21 days; consider the addition of an aminoglycoside.

    Neonates 0 to 7 days†

    150,000 units/kg/dose IV every 8 hours. Treat S. agalactiae for 14 to 21 days; consider the addition of an aminoglycoside.

    For the treatment of meningococcal meningitis.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 hours for 7 days. The FDA-approved dose is 24 million units/day IV or IM divided every 2 hours.

    Infants, Children, and Adolescents

    300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for 7 days. The FDA-approved dose is 250,000 units/kg/day (Max: 20 million units/day) IV or IM divided every 4 hours for 7 to 14 days.

    Neonates older than 7 days†

    125,000 units/kg/dose IV every 6 hours for 7 days.

    Neonates 0 to 7 days†

    150,000 units/kg/dose IV every 8 hours for 7 days.

    For the treatment of staphylococcal meningitis.
    Intravenous or Intramuscular dosage
    Adults

    5 to 24 million units/day IV or IM divided every 4 to 6 hours.

    For the treatment of Listeria meningitis.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 hours for at least 21 days; consider the addition of an aminoglycoside. The FDA-approved dose is 15 to 20 million units/day IV or IM divided every 4 to 6 hours for 14 days.

    Infants†, Children†, and Adolescents†

    300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for at least 21 days; consider the addition of an aminoglycoside.

    Neonates older than 7 days†

    125,000 units/kg/dose IV every 6 hours for at least 21 days; consider the addition of an aminoglycoside.

    Neonates 0 to 7 days†

    150,000 units/kg/dose IV every 8 hours for at least 21 days; consider the addition of an aminoglycoside.

    For the treatment of meningitis due to P. multocida.
    Intravenous or Intramuscular dosage
    Adults

    4 to 6 million units/day IV or IM divided every 4 to 6 hours for 14 days.

    For the treatment of pneumococcal meningitis or ventriculitis†.
    Intravenous or Intramuscular dosage
    Adults

    24 million units/day IV divided every 4 hours for 10 to 14 days. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.

    Infants, Children, and Adolescents

    300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for 10 to 14 days. The FDA-approved dose is 250,000 units/kg/day (Max: 20 million units/day) IV or IM divided every 4 hours for 7 to 14 days.

    Neonates older than 7 days†

    125,000 units/kg/dose IV every 6 hours for 10 to 14 days.

    Neonates 0 to 7 days†

    150,000 units/kg/dose IV every 8 hours for 10 to 14 days.

    For the treatment of meningitis or ventriculitis due to C. acnes†.
    Intravenous dosage
    Adults

    24 million units/day IV divided every 4 hours for 10 to 14 days.

    Infants, Children, and Adolescents

    300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for 10 to 14 days.

    For the treatment of neurologic Lyme disease†, including Lyme meningitis†, cranial neuropathy†, and radiculoneuropathy/radiculoneuritis†.
    Intravenous dosage
    Adults

    18 to 24 million units/day IV in divided doses every 4 hours until clinical improvement, then switch to oral stepdown therapy for a total of 14 to 21 days treatment as an alternative. For acutely ill patients, patients with parenchymal involvement, or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.

    Infants, Children, and Adolescents

    200,000 to 400,000 units/kg/day (Max: 18 to 24 million units/day) IV in divided doses every 4 hours until clinical improvement, then switch to oral stepdown therapy for a total of 14 to 21 days treatment as an alternative. For acutely ill patients, patients with parenchymal involvement, or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.

    For the treatment of leptospirosis†.
    Intravenous dosage
    Adults

    1.5 million units IV every 6 hours for 7 days as first-line therapy for severe disease.

    Infants, Children, and Adolescents

    50,000 to 100,000 units/kg/day (Max: 6 million units/day) IV divided every 4 to 6 hours for 7 to 10 days as first-line therapy for severe disease.

    For the treatment of syphilis, including congenital syphilis and neurosyphilis or syphilitic eye disease† (e.g., uveitis†, neuroretinitis†, or optic neuritis†).
    NOTE: Pregnant women with syphilis in any stage who report with penicillin allergy should be desensitized and treated with penicillin.
    For the treatment of neurosyphilis or syphilitic eye disease† (e.g., uveitis†, neuroretinitis†, or optic neuritis†).
    Intravenous or Intramuscular dosage
    Adults

    18 to 24 million units/day IV given as 3 to 4 million units IV every 4 hours or as a continuous infusion for 10 to 14 days; may consider penicillin G benzathine for 1 to 3 doses after IV therapy to provide a comparable duration of treatment for late syphilis. The FDA-approved dosage is 12 to 24 million units/day IV given as 2 to 4 million units IV every 4 hours for 10 to 14 days, then 3 doses of penicillin G benzathine weekly.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 to 6 hours for 10 to 14 days. 

    For the treatment of congenital syphilis.
    NOTE: Current guidelines should be consulted to determine the appropriate course of treatment in neonates born to mothers with syphilis. Therapy is based on physical examination, serum quantitative nontreponemal serologic titer, and whether or not the mother was treated properly before delivery.
    Intravenous or Intramuscular dosage
    Infants and Children

    200,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours for 10 days. FDA- labeling suggests a 10 to 14 day duration. A single follow-up dose of penicillin G benzathine can be considered after IV therapy. If more than 1 day of therapy is missed, the entire course should be restarted.

    Neonates 8 days and older†

    50,000 units/kg/dose IV every 8 hours for 10 days. If more than 1 day of therapy is missed, the entire course should be restarted.

    Neonates 0 to 7 days†

    50,000 units/kg/dose IV every 12 hours for 10 days. If more than 1 day of therapy is missed, the entire course should be restarted.

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

    5 million units IV load initiated at the time of labor or rupture of membranes, followed by 3 million units IV every 4 hours until delivery. Penicillin is the agent of choice for preventing Group B streptococcal disease. 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]

    For the treatment of skin and skin structure infections†, including cellulitis†, erysipelas†, and necrotizing infections†.
    For the treatment of nonpurulent skin infections, such as cellulitis and erysipelas†.
    Intravenous dosage
    Adults

    2 to 4 million units IV every 4 to 6 hours for 5 to 14 days.

    Infants, Children, and Adolescents

    60,000 to 100,000 units/kg/dose (Max: 4 million units/dose) IV every 6 hours for 5 to 14 days.

    Neonates older than 7 days

    50,000 units/kg/dose IV every 8 hours for 5 to 14 days.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV every 12 hours for 5 to 14 days.

    For the treatment of necrotizing infections of the skin, fascia, and muscle†.
    Intravenous dosage
    Adults

    2 to 4 million units IV every 4 to 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.

    Infants, Children, and Adolescents

    60,000 to 100,000 units/kg/dose (Max: 4 million units/dose) IV every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.

    Neonates older than 7 days

    50,000 units/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.

    Neonates 0 to 7 days

    50,000 units/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.

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

    50,000 units/L intraperitoneal loading dose, followed by 25,000 units/L in each dialysate exchange. Treat for 14 days.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    24 million units/day IV/IM is FDA-approved maximum; up to 30 million units/day IV/IM has been used off-label.

    Geriatric

    24 million units/day IV/IM is FDA-approved maximum; up to 30 million units/day IV/IM has been used off-label.

    Adolescents

    300,000 units/kg/day IV/IM (Max: 24 million units/day) is FDA-approved maximum; up to 400,000 units/kg/day IV/IM (Max: 24 million units/day) has been used off-label.

    Children

    300,000 units/kg/day IV/IM (Max: 24 million units/day) is FDA-approved maximum; up to 400,000 units/kg/day IV/IM (Max: 24 million units/day) has been used off-label.

    Infants

    300,000 units/kg/day IV/IM is FDA-approved maximum; up to 400,000 units/kg/day IV/IM has been used off-label.

    Neonates

    8 days and older: 200,000 units/kg/day IV/IM.
    0 to 7 days: 150,000 units/kg/day IV/IM.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment required. Dosage modifications may be necessary in patients with hepatic disease and renal impairment.

    Renal Impairment

    The manufacturer recommends: 
    CrCl >= 10 ml/min/1.73m2 in patients with uremia: A full loading dose then 50% of the usual dose given every 4—5 hours.
    CrCl < 10 ml/min/1.73m2: A full loading dose then 50% of the usual dose given every 8—12 hours.
     
    Other guidelines recommend:
    CrCl > 50 ml/min: No dosage adjustment necessary.
    CrCl 10—50 ml/min: Adjust the dose to 75% of the usual dose.
    CrCl < 10 ml/min: Adjust the dose to 20—50% of the usual dose.
     
    Intermittent hemodialysis
    Hemodialysis has been shown to reduce penicillin G serum concentrations. Recommendations suggest giving a normal loading dose and then give 25—50% of the normal dose at regular intervals or 50—100% of the normal dose every 8—12 hours. These guidelines recommend 0.5—1 million units IV every 4—6 hours or 1—2 million units IV every 8—12 hours for mild/moderate infections or doses up to 2 million units IV every 4—6 hours for serious infections. Administer the dose after dialysis on hemodialysis days or give a 500,000 unit supplement after dialysis.
     
    Peritoneal dialysis
    Recommendations suggest dosing for a CrCl < 10 ml/min by adjusting the dose to 20—50% of the usual dose.
     
    Continuous renal replacement therapy (CRRT)
    Recommendations suggest dosing for a CrCl of 10—50 ml/min by adjusting the dose to 75% of the usual dose. Specific recommendations by type of CRRT suggest a 4 million unit loading dose IM/IV and then 2 million units IM/IV every 4—6 hours during continuous venovenous hemofiltration (CVVH), or 2—3 million units IM/IV  every 4—6 hours during continuous venovenous hemodialysis (CVVHD), or 2—4 million units IM/IV  every 4—6 hours during continuous venovenous hemodiafiltration (CVVHDF). These recommendations assume an ultrafiltration and dialysis flow rate of 1—2 L/hr and minimal residual renal function.

    ADMINISTRATION

    Injectable Administration

    Penicillin G potassium or sodium salts may be administered intravenously or intramuscularly. Outside of electrolyte content, there is no difference therapeutically between the sodium and potassium salts.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Vials and pharmacy bulk package reconstitution:
    Reconstitute according to manufacturer's directions with a compatible IV infusion fluid, such as D5W or NS.
    Storage: After injection solution is mixed, the constituted solution may be stored in a refrigerator between 2 and 8 degrees C (36 and 46 degrees F) for a duration as specified by the manufacturer; do not freeze.
     
    Frozen bag preparation: 
    Thaw at room temperature. Do not force thaw. No reconstitution necessary.
    Storage: Prepared infusion solutions may be kept at room temperature for 24 hours or under refrigeration for 14 days.
    Do not refreeze thawed antibiotics.
     
    Infusion:
    Intermittent IV infusions have been administered over 15—30 minutes for infants and children and over 1—2 hours for adults.
    For continuous infusion, determine the patient's daily fluid volume requirement and add the reconstituted solution to a compatible IV solution with half the daily dose administered over 12 hours.

    Intramuscular Administration

    Vials containing more than 5 million units are not intended for IM use. Dilute with a minimum amount of compatible diluent. Concentrations of 100,000 units/ml may be used IM with a minimum of discomfort. Higher concentrations may be administered when clinically necessary; however, when large doses are necessary, consider IV administration.[30078]
    In adults: injection into the midlateral thigh or upper outer quadrant of the gluteus maximus is preferred.
    In children and infants: injection into the midlateral muscles of the thigh is preferred. In infants and small children, the periphery of the upper outer quadrant of the gluteus maximus should be used only if necessary (e.g., in burn patients) in order to avoid injury to the sciatic nerve.

    Other Injectable Administration

    Intrapleural or other local infusion
    If fluid is aspirated, give infusion volume equal to 1/4 or 1/2 the amount of fluid aspirated, otherwise, solution containing up to 100,000 units/ml may be used.

    STORAGE

    Generic:
    - Store frozen product at or below -4 degrees F
    Pfizerpen:
    - Discard reconstituted product if not used within 7 days
    - Store reconstituted product in refrigerator (36 to 46 degrees F)
    - Store unreconstituted product at 68 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Asthma, carbapenem hypersensitivity, cephalosporin hypersensitivity, penicillin hypersensitivity

    Penicillin is contraindicated for use in patients with penicillin hypersensitivity. It should be used cautiously in patients with cephalosporin hypersensitivity or carbapenem hypersensitivity. These patients are more susceptible to cross-hypersensitivity reactions. Penicillin can cause a variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis. Patients with allergies or allergic conditions including asthma may have a greater risk for hypersensitivity reactions to penicillins.

    Infants, neonates, renal failure, renal impairment

    Penicillin G is eliminated primarily unchanged via renal tubular secretion. With normal renal function the drug is rapidly eliminated. In individuals with renal impairment or renal failure, excretion is considerably delayed. Incomplete development of renal function in neonates and infants may delay elimination of penicillin. Dosages of penicillin G may need to be reduced in these patients. Large doses of penicillin administered to patients with renal impairment have been associated with seizures.

    Electrolyte imbalance

    Use large doses of parenteral penicillin G potassium or penicillin G sodium with caution in patients with electrolyte imbalance and those who are particularly sensitive to sodium intake (e.g., newborns, patients with heart failure or hypertension). Large doses of sodium or potassium may be administered daily as a result of the administration of these penicillin G salts and the amount of sodium and/or potassium can vary among products.

    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, such as penicillin G, 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

    Human experience with penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. Animal reproduction studies have also not revealed any evidence of impaired fertility or harmful fetal effects. However, there are no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of penicillins on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, use penicillin G in pregnant women only if clearly needed. The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache, myalgia, and other symptoms that usually occurs within the first 24 hours after any therapy for syphilis, most often among patients who have early syphilis. Antipyretics may be used, but they have not been proven to prevent this reaction. The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress in pregnant women; this concern should not prevent or delay therapy.

    Breast-feeding

    Penicillins are excreted in breast milk. Use caution when penicillin G is administered to a breast-feeding woman. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin G therapy. Breast milk concentrations range from 0.015 to 0.37 mcg/mL with a milk:plasma ratio of 0.02 to 0.13. Penicillins may cause diarrhea, candidiasis, and skin rash in the breast-feeding infant. The infant should be observed for potential effects.

    Geriatric

    Reported clinical experience with penicillin G has not identified differences in responses between geriatric and younger adult patients. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Caution is also advisable since the elderly may respond to sodium loading from penicillin G sodium with a blunted natriuresis which may be clinically important in regard to such diseases as congestive heart failure. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents 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 / 2.0-5.0
    azotemia / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    laryngeal edema / Rapid / 0-1.0
    renal tubular necrosis / Delayed / 0-1.0
    bronchospasm / Rapid / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    exfoliative dermatitis / Delayed / 0-1.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    anaphylactic shock / Rapid / 0-1.0
    angioedema / Rapid / 0-1.0
    laryngospasm / Rapid / 0-1.0
    interstitial nephritis / Delayed / 0-1.0
    acute generalized exanthematous pustulosis (AGEP) / Delayed / 0-1.0
    coma / Early / 0-1.0
    seizures / Delayed / 0-1.0
    hemolytic anemia / Delayed / 0-1.0
    C. difficile-associated diarrhea / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    hyperkalemia / Delayed / Incidence not known

    Moderate

    proteinuria / Delayed / 0-1.0
    hypotension / Rapid / 0-1.0
    eosinophilia / Delayed / 0-1.0
    hematuria / Delayed / 0-1.0
    hyperreflexia / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    bleeding / Early / 0-1.0
    phlebitis / Rapid / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    fluid retention / Delayed / Incidence not known
    hypernatremia / Delayed / Incidence not known
    myoclonia / Delayed / Incidence not known

    Mild

    fever / Early / 2.0-5.0
    maculopapular rash / Early / 2.0-5.0
    rash / Early / 2.0-5.0
    arthralgia / Delayed / 2.0-5.0
    urticaria / Rapid / 2.0-5.0
    myalgia / Early / 2.0-5.0
    malaise / Early / 2.0-5.0
    nausea / Early / 2.0-5.0
    vomiting / Early / 2.0-5.0
    tongue discoloration / Delayed / 2.0-5.0
    diarrhea / Early / 2.0-5.0
    pruritus / Rapid / Incidence not known
    injection site reaction / Rapid / 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; Aspirin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Amiloride: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    Amiloride; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    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; 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: (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.
    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.
    Cholestyramine: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    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.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Colestipol: (Moderate) Colestipol can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of colestipol.
    Desogestrel; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Dichlorphenamide: (Moderate) Use of dichlorphenamide and with OAT1 substrates like penicillin G is not recommended because of increased penicillin G exposure. If use cannot be avoided, monitor for increased adverse effects due to increased penicillin G exposure. Dichlorphenamide inhibits OAT1. Dichlorphenamide also increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including penicillin G. 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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.
    Eplerenone: (Minor) Potassium-containing medications, such as penicillin G potassium, may potentially increase the risk of hyperkalemia in patients receiving eplerenone. Monitor serum potassium if eplerenone is used concurrently with drugs with potential to induce hyperkalemia.
    Estradiol; Levonorgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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.
    Finerenone: (Moderate) Monitor serum potassium concentrations closely if finerenone and penicillin G potassium are used together. Concomitant use may increase the risk of hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    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.
    Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Ibritumomab Tiuxetan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity. (Moderate) Use potassium phosphates cautiously with high-doses of IV potassium penicillin G, as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
    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.
    Iodine; Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Leflunomide: (Moderate) Closely monitor for penicillin G-induced side effects such as nausea, vomiting, diarrhea, or seizures when these drugs are used together. In some patients, a dosage reduction of penicillin G may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with penicillin G, a substrate of OAT3, may increase penicillin G plasma concentrations.
    Leuprolide; Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Mafenide: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
    Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
    Mestranol; Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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) Avoid concomitant use of methotrexate with penicillins due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions.
    Nitisinone: (Moderate) Monitor for increased penicillin-related adverse effects if coadministered with nitisinone. Increased penicillin exposure is possible. Nitisinone inhibits OAT3. Penicillin is an OAT3 substrate.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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.
    Oral Contraceptives: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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.
    Potassium Acetate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium Bicarbonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium Citrate; Citric Acid: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium Gluconate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium Phosphate: (Moderate) Use potassium phosphates cautiously with high-doses of IV potassium penicillin G, as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
    Potassium Phosphate; Sodium Phosphate: (Moderate) Use potassium phosphates cautiously with high-doses of IV potassium penicillin G, as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
    Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Potassium-sparing diuretics: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    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.
    Pyrimethamine; Sulfadoxine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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 was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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 penicillins and their 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 (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) 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.
    Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
    Spironolactone: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    Sulfadiazine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
    Sulfasalazine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
    Sulfonamides: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
    Teriflunomide: (Moderate) Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with penicillin G, a substrate of OAT3, may increase penicillin G plasma concentrations. Monitor for increased adverse effects from penicillin G, such as nausea, vomiting, diarrhea, or seizures. Adjust the dose of penicillin G as necessary and clinically appropriate.
    Tetracyclines: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Triamterene: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    Triamterene; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    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

    Human experience with penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. Animal reproduction studies have also not revealed any evidence of impaired fertility or harmful fetal effects. However, there are no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of penicillins on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, use penicillin G in pregnant women only if clearly needed. The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache, myalgia, and other symptoms that usually occurs within the first 24 hours after any therapy for syphilis, most often among patients who have early syphilis. Antipyretics may be used, but they have not been proven to prevent this reaction. The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress in pregnant women; this concern should not prevent or delay therapy.

    Penicillins are excreted in breast milk. Use caution when penicillin G is administered to a breast-feeding woman. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin G therapy. Breast milk concentrations range from 0.015 to 0.37 mcg/mL with a milk:plasma ratio of 0.02 to 0.13. Penicillins may cause diarrhea, candidiasis, and skin rash in the breast-feeding infant. The infant should be observed for potential effects.

    MECHANISM OF ACTION

    Penicillin G is a beta-lactam antibiotic. It is mainly bactericidal in action. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several different 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 penicillin G, as well as the other penicillins, against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, penicillin G'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.[31209] [43696] [49841]
     
    Beta-lactams exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism. This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval.
     
    The susceptibility interpretive criteria for penicillin are delineated by pathogen. The MICs are defined for Streptococcus pneumoniae in cases with meningitis as susceptible at 0.06 mcg/mL or less and resistant at 0.12 mcg/mL or more. The MICs are defined for Streptococcus pneumoniae in cases without meningitis as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for beta-hemolytic Streptococcus sp. as susceptible at 0.12 mcg/mL or less. The MICs are defined for Enterococcus sp. as susceptible at 8 mcg/mL or less and resistant at 16 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 0.12 mcg/mL or less and resistant at 0.25 mcg/mL or more. The MICs are defined for Streptococcus sp. viridans group as susceptible at 0.12 mcg/mL or less, intermediate at 0.25 to 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Neisseria gonorrhoeae as susceptible at 0.06 mcg/mL or less, intermediate at 0.12 to 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for Neisseria meningitidis as susceptible at 0.6 mcg/mL or less, intermediate at 0.12 to 0.25 mcg/mL, and resistant at 0.5 mcg/mL or more.[63320] [63321]

    PHARMACOKINETICS

    Penicillin G sodium or potassium are administered by continuous or intermittent IV infusion or by IM injection. The procaine and benzathine salts of penicillin G are administered by intramuscular (IM) injection only (see separate Penicillin G Procaine and Penicillin G Benzathine monographs). Penicillin G potassium is susceptible to destruction by gastric acid and oral dosage forms of penicillin G are no longer commercially available in the US. Therefore, when oral penicillin therapy is required, penicillin V or amoxicillin, which have higher oral bioavailability, are used. The parenteral pharmacokinetic parameters of penicillin G sodium and penicillin G potassium are the same.
     
    Approximately 45—68% of the circulating penicillin is protein-bound, mainly to albumin. It is distributed into most body tissues and fluids including lung; liver; kidney; bone; muscle; sputum; bile; urine; and peritoneal, pleural, and synovial fluids. It penetrates inflamed meninges and reaches therapeutic levels within the CSF. Penicillin G potassium or sodium penetrates the peritoneal cavity following local instillation. Penicillin crosses the placenta and is distributed in breast milk.
     
    Between 15—30% of an IM penicillin G dose is metabolized to inactive derivatives. The drug is excreted into the urine primarily via tubular secretion. A small percentage is excreted in feces, bile, and breast milk. In patients with normal renal function, the elimination half-life of penicillin G is 20—30 minutes. 

    Intravenous Route

    Following intermittent IV infusion of 2 million units every 2 hours or 3 million units every 3 hours, serum concentrations of penicillin G average 20 mcg/ml.

    Intramuscular Route

    Peak penicillin concentrations occur within 15—30 minutes following an IM dose. Administration of a single IM dose of 600,000 or 1 million units produces a peak serum concentration of 6—8 mcg/ml or 20 mcg/ml, respectively.