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    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 serious infections caused by susceptible organisms, including pleural empyema and bacteremia.
    For the treatment of serious meningococcal infections.
    Intravenous or Intramuscular dosage
    Adults

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

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day) is recommended by the American Academy of Pediatrics (AAP) for severe infections. The manufacturer recommends 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day) for severe infections.

    Neonates older than 7 days

    75,000 to 150,000 units/kg/day IV or IM divided every 8 hours is recommended by the American Academy of Pediatrics (AAP). Longer dosing interval may be used in extremely low birth weight (less than 1000 g) neonates until 2 weeks of life.

    Neonates 7 days and younger

    50,000 to 100,000 units/kg/day IV or IM divided every 12 hours is recommended by the American Academy of Pediatrics (AAP).

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

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

    For the treatment of gram-negative bacilliary infections.
    Intravenous or Intramuscular dosage
    Adults

    Although some species of gram-negative bacilli may be sensitive to high doses of penicillin G, product labeling states that it is no longer the drug of choice for these organisms. 20 to 80 million units/day IM or IV given in divided doses every 4 to 6 hours.

    For the treatment of serious streptococcal infections.
    Intravenous or Intramuscular dosage
    Adults

    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 IV or IM divided every 4 to 6 hours (Max: 24 million units/day) is recommended by the American Academy of Pediatrics (AAP) for severe infections. The AAP suggests doses of 250,000 to 400,000 units/kg/day IV or IM in patients with invasive pneumococcal infections. The manufacturer recommends 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day) for severe infections.

    Neonates older than 7 days

    75,000 to 150,000 units/kg/day IV or IM divided every 8 hours is recommended by the American Academy of Pediatrics (AAP). Longer dosing interval may be used in extremely low birth weight (less than 1000 g) neonates until 2 weeks of life.

    Neonates 7 days and younger

    50,000 to 100,000 units/kg/day IV or IM divided every 12 hours is recommended by the American Academy of Pediatrics (AAP).

    For the treatment of serious staphylococcal infections.
    Intravenous or Intramuscular dosage
    Adults

    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 IV or IM divided every 4 to 6 hours (Max: 24 million units/day) is recommended by the American Academy of Pediatrics (AAP) for severe infections. The manufacturer recommends 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day) for severe infections.

    Neonates older than 7 days

    75,000 to 150,000 units/kg/day IV or IM divided every 8 hours is recommended by the American Academy of Pediatrics (AAP). Longer dosing interval may be used in extremely low birth weight (less than 1000 g) neonates until 2 weeks of life.

    Neonates 7 days and younger

    50,000 to 100,000 units/kg/day IV or IM divided every 12 hours is recommended by the American Academy of Pediatrics (AAP).

    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 endocarditis or pericarditis.
    For the treatment of endocarditis due to penicillin-susceptible viridans streptococci and Streptococcus bovis (MIC of 0.1 mcg/mL or less).
    Intravenous or Intramuscular dosage
    Adults

    The American Heart Association (AHA) recommends 12—18 million units/day IV, either as a continuous infusion or in 4—6 equally divided doses, for 4 weeks for native valve endocarditis or 24 million units/day for 6 weeks with or without 2 weeks of gentamicin IM or IV for prosthetic valve/material endocarditis. Alternatively for native valve endocarditis, a 2-week regimen can be given using the same dose of penicillin in combination with 2 weeks of streptomycin IM or gentamicin IM or IV. The manufacturer recommends 12—24 million units/day IV or IM given in divided doses every 4—6 hours for streptococcal endocarditis.

    Infants, Children, and Adolescents

    The AHA recommends 200,000 units/kg/day IV (not to exceed adult doses) in 4—6 equally divided doses for 4 weeks for native valve endocarditis or 300,000 units/kg/day IV for 6 weeks with or without 2 weeks of gentamicin IV or IM for prosthetic valve/material endocarditis. Alternatively for native valve endocarditis, a 2-week regimen can be given using the same dose of penicillin in combination with 2 weeks of streptomycin IM or gentamicin IM or IV. The manufacturer recommends 150,000—300,000 units/kg/day IM or IV given in divided doses every 4—6 hours.

    For the treatment of endocarditis due to strains of viridans streptococci and Streptococcus bovis relatively resistant to penicillin G (MIC greater than 0.12 mcg/mL and less than 0.5 mcg/mL).
    Intravenous or Intramuscular dosage
    Adults

    The American Heart Association (AHA) recommends 24 million units/day IV, either as a continuous infusion or in 4—6 equally divided doses, for 4 weeks in combination with streptomycin IM or gentamicin IM or IV for the first 2 weeks of therapy for native valve endocarditis or 6 weeks of penicillin plus gentamicin for prosthetic valve/material endocarditis. The manufacturer recommends 12—24 million units/day IV or IM given in divided doses every 4—6 hours for streptococcal endocarditis.

    Infants, Children, and Adolescents

    The AHA recommends 300,000 units/kg/day IV (not to exceed adult doses) in 4—6 equally divided doses for 4 weeks in combination with streptomycin IM or gentamicin IM or IV for the first 2 weeks of therapy for native valve endocarditis or 6 weeks of penicillin plus gentamicin for prosthetic valve/material endocarditis. The manufacturer recommends 150,000—300,000 units/kg/day IM or IV given in divided doses every 4—6 hours.

    For the treatment of endocarditis due to viridans streptococci with a MIC of 0.5 mcg/mL or greater or due to enterococci.
    Intravenous or Intramuscular dosage
    Adults

    The American Heart Association (AHA) recommends 18—30 million units/day IV, either as a continuous infusion or in 6 equally divided doses, for 4—6 weeks in combination with gentamicin IM or IV for 4—6 weeks; or 24 million units/day IV, either as a continuous infusion or in 6 equally divided doses, for 4—6 weeks in combination with streptomycin IM for 4—6 weeks, if the Enterococcus sp. is resistant to gentamicin. The manufacturer recommends 12—24 million units/day IV or IM given in divided doses every 4—6 hours for streptococcal endocarditis.

    Infants, Children, and Adolescents

    The AHA recommends 300,000 units/kg/day IV (not to exceed adult doses) in 6 equally divided doses for 4—6 weeks in combination with gentamicin IM or IV or streptomycin IM for 4—6 weeks. The manufacturer recommends 150,000—300,000 units/kg/day IM or IV given in divided doses every 4—6 hours.

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

    The American Heart Association (AHA) does not recommend penicillin G for the treatment of staphylococcal endocarditis. The manufacturer recommends 5—24 million units/day IM or IV given in divided doses every 4—6 hours.

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

    12—20 million units/day IM or IV in divided doses given every 4—6 hours for 4—6 weeks.

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

    Because of resistance, the CDC does not recommend penicillins for gonococcal infections. The manufacturer recommends 10 million units IM or IV given in divided doses every 4—6 hours.

    Children and Adolescents >= 45 kg

    Because of resistance, the CDC does not recommend penicillins for gonococcal infections. The manufacturer recommends 10 million units IM or IV given in divided doses every 4 hours for 4 weeks.

    Infants, Children, and Adolescents < 45 kg

    Because of resistance, the CDC does not recommend penicillins for gonococcal infections. The manufacturer recommends 250,000 units/kg/day IM or IV given in divided doses every 4 hours for 4 weeks.

    For the treatment of meningococcal endocarditis.
    Intravenous or Intramuscular dosage
    Infants, Children, and Adolescents

    150,000—300,000 units/kg/day IM or IV given in divided doses every 4—6 hours. Maximum dose is 24 million units/day.

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

    12—24 million units/day IM or IV given in divided doses every 4—6 hours.

    Infants, Children, and Adolescents

    250,000—400,000 units/kg/day IM or IV (max: 24 million units/day) given in divided doses every 4—6 hours. Suggested duration of therapy is 10—14 days for S. pneumoniae and 14—21 days for S. agalactiae.

    Neonates > 7 days

    450,000—500,000 units/kg/day IM or IV in 4 divided doses for 14 days for group B streptococcus is recommended by the American Academy of Pediatrics (AAP). Longer courses may be warranted for complicated cases. For other types of meningitis, 200,000 units/kg/day IM or IV given in divided doses every 6—8 hours. Smaller doses and longer intervals may be advisable for neonates weighing less than 2000 g. Suggested duration of therapy is 10—14 days for S. pneumoniae and 14—21 days for S. agalactiae.

    Neonates <= 7 days

    250,000—450,000 units/kg/day IM or IV in 3 divided doses for 14 days for group B streptococcus is recommended by the American Academy of Pediatrics (AAP). Longer courses may be warranted for complicated cases. For other types of meningitis, 150,000 units/kg/day IM or IV given in divided doses every 8—12 hours is recommended. Smaller doses and longer intervals may be advisable for neonates weighing less than 2000 g Suggested duration of therapy is 10—14 days for S. pneumoniae and 14—21 days for S. agalactiae.

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

    24 million units/day IM or IV given in divided doses every 2 hours or a continuous IV infusion of 20—30 million units/day.

    Infants, Children, and Adolescents

    250,000—400,000 units/kg/day IM or IV (max: 24 million units/day) given in divided doses every 4—6 hours for 7 days.

    Neonates > 7 days

    200,000 units/kg/day IM or IV given in divided doses every 6—8 hours for 7 days. Smaller doses and longer intervals may be advisable for neonates weighing less than 2000 g.

    Neonates <= 7 days

    150,000 units/kg/day IM or IV given in divided doses every 8—12 hours for 7 days is recommended. Smaller doses and longer intervals may be advisable for neonates weighing less than 2000 g .

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

    5—24 million units/day IM or IV given in divided doses every 4—6 hours.

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

    15—20 million units/day IV or IM given in divided doses every 4—6 hours for 2 weeks.

    Infants, Children, and Adolescents

    250,000—400,000 units/kg/day IM or IV (max: 24 million units/day) given in divided doses every 4—6 hours for at least 21 days.

    Neonates > 7 days

    200,000 units/kg/day IM or IV given in divided doses every 6—8 hours for at least 21 days. Smaller doses and longer intervals may be advisable for neonates weighing less than 2000 g.

    Neonates <= 7 days

    150,000 units/kg/day IM or IV given in divided doses every 8—12 hours is recommended for at least 21 days. Smaller doses and longer intervals may be advisable for neonates weighing less than 2000 g.

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

    Because of resistance, the CDC does not recommend penicillins for gonococcal infections. The manufacturer recommends 10 million units IM or IV given in divided doses every 4—6 hours.

    Children and Adolescents >= 45 kg

    Because of resistance, the CDC does not recommend penicillins for gonococcal infections. The manufacturer recommends 10 million units IM or IV given in divided doses every 6 hours for 10—14 days.

    Infants, Children, and Adolescents < 45 kg

    Because of resistance, the CDC does not recommend penicillins for gonococcal infections. The manufacturer recommends 250,000 units/kg/day IM or IV given in divided doses every 6 hours for 10—14 days.

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

    4—6 million units/day IM or IV given in divided doses every 4—6 hours for 2 weeks.

    For the treatment of disseminated gonorrhea, including infectious arthritis, due to Neisseria gonorrhoeae when the infecting strain has been tested and found to be susceptible to penicillin.
    NOTE: For meningitis infections, see meningitis dosing. For endocarditis infections, see endocarditis dosing.
    Intravenous or Intramuscular dosage
    Adults, Adolescents, and Children weighing 45 kg or more

    Because of resistance, the CDC does not recommend penicillins for gonorrhea. Product labeling recommends 10 million units per day IV or IM in divided doses every 6 hours for 7 to 10 days.

    Infants, Children, and Adolescents less than 45 kg

    Because of resistance, the CDC does not recommend penicillins for gonorrhea. Product labeling recommends 100,000 units/kg/day IV or IM in divided doses every 6 hours (Max: 10 million units/day) for 7 to 10 days.

    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 treatment of diphtheria and for the elimination of the diphtheria carrier state.
    Intravenous or Intramuscular dosage
    Adults

    2 to 3 million units/day IM or IV given in divided doses every 4 to 6 hours for 10 to 12 days. Penicillin G is used as an adjunct to diphtheria antitoxin.

    Infants, Children, and Adolescents

    150,000 to 250,000 units/kg/day IM or IV (Max: 3 million units/day) given in divided doses every 6 hours for 7 to 10 days. Penicillin G is used as an adjunct to diphtheria antitoxin.

    For the treatment of rat-bite fever or Haverhill fever due to Spirillum minus or Streptobacillus moniliformis.
    Intravenous or Intramuscular dosage
    Adults

    12—20 million units/day IV or IM in 4—6 divided doses for at least 3—4 weeks.

    Infants, Children, and Adolescents

    20,000—50,000 units/kg/day IM or IV divided every 6 hours for 7—10 days or for 5—7 days then oral penicillin V for 7 days. For endocarditis, 150,000—250,000 units/kg/day IM or IV given in divided doses every 4 hours for at least 4 weeks.  

    For the treatment of actinomycosis.
    Intravenous or Intramuscular dosage
    Adults

    For thoracic or abdominal disease, the dosage regimen recommended by the manufacturer is 10—20 million units/day IV in divided doses for 4—6 weeks. Some experts recommend 18—24 million units/day IV for 2—6 weeks, followed by 6—12 additional months of therapy with oral penicillin V or amoxicillin. For cases with less extensive involvement (e.g., oral-cervicofacial region), dosages of 1—6 million units/day IV in divided doses may be adequate.

    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 4 to 11 months, Children, and Adolescents

    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 is recommended by the American Academy of Pediatrics (AAP).

    Neonates 0 to 7 days

    50,000 units/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP).

    For the treatment of disseminated Lyme disease† (i.e., neuroborreliosis, carditis, recurrent/persistent arthritis).
    NOTE: Penicillin G is recommended as an alternative to ceftriaxone for the treatment of early Lyme disease with acute neurological disease, for the initial treatment of hospitalized patients with Lyme carditis, and for late manifestations of Lyme disease.
    Intravenous dosage
    Adults

    18 to 24 million units per day IV given in divided doses every 4 hours for 2 to 4 weeks as an alternative to ceftriaxone.

    Infants, Children, and Adolescents

    200,000 to 400,000 units/kg/day IV (Max: 18 to 24 million units/day) given in divided doses every 4 hours for 2 to 4 weeks as an alternative to ceftriaxone.

    For the treatment of leptospirosis† due to Leptospira sp..
    Intravenous or Intramuscular dosage
    Adults

    A dose of 1.5 million units IV or IM every 6 hours has been used.

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

    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 2.4 million units IM weekly per product labeling. The CDC recommends 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. The CDC also suggests penicillin G benzathine after IV therapy to provide a comparable duration of treatment for late syphilis. In HIV patients, 3 weekly doses of penicillin G benzathine are recommended after IV therapy.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day IV or IM given in divided doses every 4 to 6 hours for 10 to 14 days. The CDC suggests a single follow-up dose of penicillin G benzathine 50,000 units/kg IM (Max: 2.4 million units) may be considered. If more than 1 day of therapy is missed, the entire course should be restarted.

    For congenital syphilis.
    NOTE: Current CDC 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 given in divided doses every 4 to 6 hours for 10 to 14 days. Guidelines recommend a 10-day course and suggest that a single follow-up dose of penicillin G benzathine 50,000 units/kg IM (Max: 2.4 million units) can be considered. If more than 1 day of therapy is missed, the entire course should be restarted.

    Neonates†

    Guidelines recommend 50,000 units/kg/dose IV every 12 hours during the first 7 days of life, then 50,000 units/kg/dose IV every 8 hours thereafter, for a total of 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 serious streptococcal or staphylococcal infections, including necrotizing skin and skin structure infections† and erysipelas†.
    Intravenous or Intramuscular dosage
    Adults

    5 to 24 million units/day IM or IV given in divided doses every 4 to 6 hours. The Infectious Diseases Society of America (IDSA) recommends 2 to 4 million units every 4 to 6 hours in combination with clindamycin for necrotizing streptococcal skin and skin structure infections. The IDSA states that penicillin is the treatment of choice for erysipelas.

    Infants, Children, and Adolescents

    200,000 to 300,000 units/kg/day IV or IM in divided doses every 4 to 6 hours (Max: 24 million units/day) is recommended by the American Academy of Pediatrics (AAP) for severe infections. The AAP suggests doses of 250,000 to 400,000 units/kg/day IV or IM in patients with invasive pneumococcal infections. The manufacturer recommends 150,000 to 300,000 units/kg/day IV or IM in divided doses every 4 to 6 hours (Max: 24 million units/day) for severe infections. The IDSA states that penicillin is the treatment of choice for erysipelas.

    Neonates older than 7 days

    75,000 to 150,000 units/kg/day IV or IM given in divided doses every 8 hours is recommended by the American Academy of Pediatrics (AAP). Longer dosing interval may be used in extremely low birth weight (less than 1000 g) neonates until 2 weeks of life. The IDSA states that penicillin is the treatment of choice for erysipelas.

    Neonates 7 days or younger

    50,000 to 100,000 units/kg/day IV or IM given in divided doses every 12 hours is recommended by the American Academy of Pediatrics (AAP). The IDSA states that penicillin is the treatment of choice for erysipelas.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    80 million units/day IV/IM.

    Geriatric

    80 million units/day IV/IM.

    Adolescents

    300,000 units/kg/day IV/IM up to 24 million units/day; however, doses up to 400,000 units/kg/day IV/IM have been used.

    Children

    300,000 units/kg/day IV/IM up to 24 million units/day; however, doses up to 400,000 units/kg/day IV/IM have been used.

    Infants

    300,000 units/kg/day IV/IM; however, doses up to 400,000 units/kg/day IV/IM have been used.

    Neonates

    <= 7 days: Typically doses up to 100,000 units/kg/day IV/IM have been recommended; however doses up to 450,000 units/kg/day IM/IV have been used.
    > 7 days: Typically doses up to 150,000 units/kg/day IV/IM have been recommended; however doses up to 500,000 units/kg/day IM/IV have been used.

    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 below 86 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.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents, including penicillin G, have been associated with pseudomembranous colitis (antibiotic-associated colitis), which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may occur when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. Consider pseudomembranous colitis as a potential diagnosis in patients presenting with diarrhea after antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, discontinue the drug. After a diagnosis of pseudomembranous colitis, institute therapeutic measures. Practitioners should be aware that antibiotic-associated colitis can occur over 2 months or more after discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    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.

    Sexually transmitted disease

    Penicillin G may be used to treat certain sexually transmitted diseases (STD). All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, chlamydia, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

    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
    heart failure / Delayed / Incidence not known
    hyperkalemia / Delayed / Incidence not known

    Moderate

    superinfection / Delayed / 1.0-10.0
    pseudomembranous colitis / Delayed / 1.0-10.0
    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
    bleeding / Early / 0-1.0
    neutropenia / Delayed / 0-1.0
    phlebitis / Rapid / 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
    vomiting / Early / 2.0-5.0
    diarrhea / Early / 2.0-5.0
    nausea / Early / 2.0-5.0
    tongue discoloration / Delayed / 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; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
    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; Dihydrocodeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Aspirin, ASA; Carisoprodol: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Aspirin, ASA; Dipyridamole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
    Aspirin, ASA; Omeprazole: (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.
    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: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Colchicine; 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.
    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.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    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; 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.
    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.
    Erythromycin; Sulfisoxazole: (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.
    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; Desogestrel: (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; Ethynodiol Diacetate: (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; Etonogestrel: (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: (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; 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.
    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; Norethindrone Acetate; 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.
    Ethinyl 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.
    Ethinyl Estradiol; Norethindrone; 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.
    Ethinyl 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.
    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.
    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: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Hetastarch; Dextrose; Electrolytes: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    Hydrochlorothiazide, HCTZ; Triamterene: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    Hydrocodone; Potassium Guaiacolsulfonate: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Ibritumomab Tiuxetan: (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. (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    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: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    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.
    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) Penicillins may reduce the renal clearance of methotrexate. Increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with concurrent administration of high or low doses of methotrexate and penicillins. Patients should be carefully monitored while receiving this combination.
    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: (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: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Potassium Bicarbonate: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Potassium Chloride: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Potassium Citrate: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Potassium Gluconate: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    Potassium Iodide, KI: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    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: (Minor) Concomitant use of high doses of parenteral penicillin G potassium with potassium salts can cause hyperkalemia.
    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.
    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.
    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.
    Spironolactone: (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.
    Sulfisoxazole: (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: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Triamterene: (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.