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penicillin
Classes
Penicillinase-Sensitive Penicillin Antibiotics
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.
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.
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.
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.
Adverse Reactions
serum sickness / Delayed / 2.0-5.0
azotemia / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
laryngeal edema / Rapid / 0-1.0
renal tubular necrosis / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
anaphylactic shock / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
laryngospasm / Rapid / 0-1.0
interstitial nephritis / Delayed / 0-1.0
acute generalized exanthematous pustulosis (AGEP) / Delayed / 0-1.0
coma / Early / 0-1.0
seizures / Delayed / 0-1.0
hemolytic anemia / Delayed / 0-1.0
C. difficile-associated diarrhea / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
hyperkalemia / Delayed / Incidence not known
proteinuria / Delayed / 0-1.0
hypotension / Rapid / 0-1.0
eosinophilia / Delayed / 0-1.0
hematuria / Delayed / 0-1.0
hyperreflexia / Delayed / 0-1.0
neutropenia / Delayed / 0-1.0
bleeding / Early / 0-1.0
phlebitis / Rapid / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
fluid retention / Delayed / Incidence not known
hypernatremia / Delayed / Incidence not known
myoclonia / Delayed / Incidence not known
fever / Early / 2.0-5.0
maculopapular rash / Early / 2.0-5.0
rash / Early / 2.0-5.0
arthralgia / Delayed / 2.0-5.0
urticaria / Rapid / 2.0-5.0
myalgia / Early / 2.0-5.0
malaise / Early / 2.0-5.0
nausea / Early / 2.0-5.0
vomiting / Early / 2.0-5.0
tongue discoloration / Delayed / 2.0-5.0
diarrhea / Early / 2.0-5.0
pruritus / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
Jarisch-Herxheimer reaction / Early / Incidence not known
Common Brand Names
Pfizerpen
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.
Dosage And Indications
24 million units/day IV or IM divided every 2 hours.
100,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).
50,000 units/kg/dose IV or IM every 8 hours.
50,000 units/kg/dose IV or IM every 12 hours.
4 to 6 million units/day IV or IM divided every 4 to 6 hours for 2 weeks.
12 to 24 million units/day IV or IM divided every 4 to 6 hours.
100,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).
50,000 units/kg/dose IV or IM every 8 hours.
50,000 units/kg/dose IV or IM every 12 hours.
5 to 24 million units/day IV or IM divided every 4 to 6 hours.
100,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).
50,000 units/kg/dose IV or IM every 8 hours.
50,000 units/kg/dose IV or IM every 12 hours.
20 million units/day IV or IM in divided doses every 4 to 6 hours for 7 to 10 days.[30078] [43696] [64480] [64481]
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]
50,000 units/kg/dose IV or IM every 8 hours.[63245]
50,000 units/kg/dose IV or IM every 12 hours.[63245]
20 million units/day IV or IM in divided doses every 4 to 6 hours.[30078] [43696]
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]
50,000 units/kg/dose IV or IM every 8 hours.[63245]
50,000 units/kg/dose IV or IM every 12 hours.[63245]
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]
60,000 to 100,000 units/kg/dose IV every 6 hours. Penicillin plus clindamycin is recommended for necrotizing clostridial infections.
50,000 units/kg/dose IV or IM every 8 hours.[63245] Penicillin plus clindamycin is recommended for necrotizing clostridial infections.[57437]
50,000 units/kg/dose IV or IM every 12 hours.[63245] Penicillin plus clindamycin is recommended for necrotizing clostridial infections.[57437]
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.
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.
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.
NOTE: For gonococcal endocarditis, see gonococcal infections.
For the treatment of native valve endocarditis due to highly susceptible viridans group streptococci and nonenterococcal group D streptococci. Intravenous or Intramuscular dosage Adults
12 to 18 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks as monotherapy or for 2 weeks plus gentamicin. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 weeks. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.
50,000 units/kg/dose IV or IM every 8 hours for 4 weeks.
50,000 units/kg/dose IV or IM every 12 hours for 4 weeks.
24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks plus gentamicin for 2 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 weeks plus gentamicin for 2 weeks. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.
50,000 units/kg/dose IV or IM every 8 hours for 4 weeks plus gentamicin for 2 weeks.
50,000 units/kg/dose IV or IM every 12 hours for 4 weeks plus gentamicin for 2 weeks.
24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 to 6 weeks plus gentamicin for at least 2 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 weeks plus gentamicin for 2 weeks for relatively resistant strains. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.
50,000 units/kg/dose IV or IM every 8 hours for 4 weeks plus gentamicin for 2 weeks for relatively resistant strains.
50,000 units/kg/dose IV or IM every 12 hours for 4 weeks plus gentamicin for 2 weeks for relatively resistant strains.
12 to 18 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
Optimal therapy is not established. 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.
24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
Not recommended by guidelines. 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.
24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 4 to 6 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 6 weeks with or without gentamicin for 2 weeks. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 6 weeks plus gentamicin for 2 weeks. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.
50,000 units/kg/dose IV or IM every 8 hours for 6 weeks plus gentamicin for 2 weeks.
50,000 units/kg/dose IV or IM every 12 hours for 6 weeks plus gentamicin for 2 weeks.
18 to 30 million units/day IV divided every 4 hours or as a continuous IV infusion for 4 weeks plus gentamicin or streptomycin.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 to 6 weeks plus gentamicin.
50,000 units/kg/dose IV or IM every 8 hours for 4 to 6 weeks plus gentamicin.
50,000 units/kg/dose IV or IM every 12 hours for 4 to 6 weeks plus gentamicin.
18 to 30 million units/day IV divided every 4 hours or as a continuous IV infusion for 6 weeks plus gentamicin or streptomycin.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 to 6 weeks plus gentamicin.
50,000 units/kg/dose IV or IM every 8 hours for 4 to 6 weeks plus gentamicin.
50,000 units/kg/dose IV or IM every 12 hours for 4 to 6 weeks plus gentamicin.
Not recommended by guidelines. 5 to 24 million units/day IV or IM divided every 4 to 6 hours.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 4 to 6 weeks; consider the addition of gentamicin for 3 to 5 days.
50,000 units/kg/dose IV or IM every 8 hours for 4 to 6 weeks; consider the addition of gentamicin for 3 to 5 days.
50,000 units/kg/dose IV or IM every 12 hours for 4 to 6 weeks; consider the addition of gentamicin for 3 to 5 days.
Not recommended by guidelines. 5 to 24 million units/day IV or IM divided every 4 to 6 hours.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks.
50,000 units/kg/dose IV or IM every 8 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks.
50,000 units/kg/dose IV or IM every 12 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks.
12 to 20 million units/day IV or IM divided every 4 to 6 hours for 4 to 6 weeks.
15 to 20 million units/day IV or IM divided every 4 to 6 hours for 4 weeks.
24 million units/day IV divided every 4 to 6 hours or as a continuous IV infusion for 6 weeks plus gentamicin. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 hours for 6 weeks plus gentamicin. The FDA-approved dose is 150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours.
50,000 units/kg/dose IV or IM every 8 hours for 6 weeks plus gentamicin.
50,000 units/kg/dose IV or IM every 12 hours for 6 weeks plus gentamicin.
Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 7 to 10 days.
Not recommended by guidelines. 10 million units/day IV or IM doses every 6 hours for 7 to 10 days.
Not recommended by guidelines. 100,000 units/kg/day IV or IM divided every 6 hours for 7 to 10 days.
Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 10 to 14 days.
Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 10 to 14 days.
Not recommended by guidelines. 250,000 units/kg/day IV or IM divided every 4 hours for 10 to 14 days.
Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 4 weeks.
Not recommended by guidelines. 10 million units/day IV or IM divided every 6 hours for 4 weeks.
Not recommended by guidelines. 250,000 units/kg/day IV or IM divided every 4 hours for 4 weeks.
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.
2 to 4 million units/day IV or IM divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.
100,000 to 250,000 units/kg/day (Max: 4 million units/day) IV or IM divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.
12 to 20 million units/day IV or IM divided every 4 to 6 hours for at least 3 to 4 weeks.
20,000 to 50,000 units/kg/day IV or IM divided every 6 hours for 5 to 7 days, followed by oral penicillin V for 7 days. For endocarditis, 150,000 to 250,000 units/kg/day (Max: 20 million units/day) IV or IM divided every 4 hours for at least 4 weeks.
18 to 24 million units/day IV divided every 4 hours for 2 to 6 weeks, followed by oral therapy for 6 to 12 months. Shorter courses may be appropriate for less extensive infections. The FDA-approved dose is 10 to 20 million units/day IV or IM divided every 4 to 6 hours for thoracic/abdominal disease and 1 to 6 million units/day IV or IM divided every 4 to 6 hours for cervicofacial disease.
5—10 million units/day IV divided every 4—6 hours.
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.
5 to 24 million units/day IV or IM divided every 4 to 6 hours.
150,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours (Max: 24 million units/day).
50,000 units/kg/dose IV or IM every 8 hours.
50,000 units/kg/dose IV or IM every 12 hours.
12 to 24 million units/day IV or IM divided every 4 to 6 hours.
5 to 24 million units/day IV or IM divided every 4 to 6 hours.
NOTE: For gonococcal meningitis, see gonococcal infections. For neurologic Lyme infections, see Lyme borreliosis.
For the treatment of beta-hemolytic streptococcal meningitis. Intravenous or Intramuscular dosage Adults
12 to 24 million units/day IV or IM divided every 4 to 6 hours. Treat S. agalactiae with 24 million units/day IV divided every 4 hours for 14 to 21 days; consider the addition of an aminoglycoside.
300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours. Treat S. agalactiae for 14 to 21 days; consider the addition of an aminoglycoside.
125,000 units/kg/dose IV every 6 hours. Treat S. agalactiae for 14 to 21 days; consider the addition of an aminoglycoside.
150,000 units/kg/dose IV every 8 hours. Treat S. agalactiae for 14 to 21 days; consider the addition of an aminoglycoside.
24 million units/day IV divided every 4 hours for 7 days. The FDA-approved dose is 24 million units/day IV or IM divided every 2 hours.
300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for 7 days. The FDA-approved dose is 250,000 units/kg/day (Max: 20 million units/day) IV or IM divided every 4 hours for 7 to 14 days.
125,000 units/kg/dose IV every 6 hours for 7 days.
150,000 units/kg/dose IV every 8 hours for 7 days.
5 to 24 million units/day IV or IM divided every 4 to 6 hours.
24 million units/day IV divided every 4 hours for at least 21 days; consider the addition of an aminoglycoside. The FDA-approved dose is 15 to 20 million units/day IV or IM divided every 4 to 6 hours for 14 days.
300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for at least 21 days; consider the addition of an aminoglycoside.
125,000 units/kg/dose IV every 6 hours for at least 21 days; consider the addition of an aminoglycoside.
150,000 units/kg/dose IV every 8 hours for at least 21 days; consider the addition of an aminoglycoside.
4 to 6 million units/day IV or IM divided every 4 to 6 hours for 14 days.
24 million units/day IV divided every 4 hours for 10 to 14 days. The FDA-approved dose is 12 to 24 million units/day IV or IM divided every 4 to 6 hours.
300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for 10 to 14 days. The FDA-approved dose is 250,000 units/kg/day (Max: 20 million units/day) IV or IM divided every 4 hours for 7 to 14 days.
125,000 units/kg/dose IV every 6 hours for 10 to 14 days.
150,000 units/kg/dose IV every 8 hours for 10 to 14 days.
24 million units/day IV divided every 4 hours for 10 to 14 days.
300,000 to 400,000 units/kg/day (Max: 24 million units/day) IV divided every 4 to 6 hours for 10 to 14 days.
18 to 24 million units/day IV in divided doses every 4 hours until clinical improvement, then switch to oral stepdown therapy for a total of 14 to 21 days as an alternative. For acutely ill patients or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.
200,000 to 400,000 units/kg/day (Max: 18 to 24 million units/day) IV in divided doses every 4 hours until clinical improvement, then switch to oral stepdown therapy for a total of 14 to 21 days as an alternative. For acutely ill patients or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.
18 to 24 million units/day IV in divided doses every 4 hours for 14 to 28 days. IV therapy is preferred.
200,000 to 400,000 units/kg/day (Max: 18 to 24 million units/day) IV in divided doses every 4 hours for 14 to 28 days. IV therapy is preferred.
1.5 million units IV every 6 hours for 7 days as first-line therapy for severe disease.
50,000 to 100,000 units/kg/day (Max: 6 million units/day) IV divided every 4 to 6 hours for 7 to 10 days as first-line therapy for severe disease.
NOTE: Pregnant women with syphilis in any stage who report with penicillin allergy should be desensitized and treated with penicillin.
For the treatment of neurosyphilis or syphilitic eye disease† (e.g., uveitis†, neuroretinitis†, or optic neuritis†). Intravenous or Intramuscular dosage Adults
18 to 24 million units/day IV given as 3 to 4 million units IV every 4 hours or as a continuous infusion for 10 to 14 days; may consider penicillin G benzathine for 1 to 3 doses after IV therapy to provide a comparable duration of treatment for late syphilis. The FDA-approved dosage is 12 to 24 million units/day IV given as 2 to 4 million units IV every 4 hours for 10 to 14 days, then 3 doses of penicillin G benzathine weekly.
200,000 to 300,000 units/kg/day (Max: 24 million units/day) IV or IM divided every 4 to 6 hours for 10 to 14 days.
NOTE: Current guidelines should be consulted to determine the appropriate course of treatment in neonates born to mothers with syphilis. Therapy is based on physical examination, serum quantitative nontreponemal serologic titer, and whether or not the mother was treated properly before delivery.
Intravenous or Intramuscular dosage Infants and Children
200,000 to 300,000 units/kg/day IV or IM divided every 4 to 6 hours for 10 days. FDA- labeling suggests a 10 to 14 day duration. Consider follow-up penicillin G benzathine after IV therapy. If more than 1 day of therapy is missed, the entire course should be restarted.
50,000 units/kg/dose IV every 8 hours for a total treatment duration of 10 days. If more than 1 day of therapy is missed, the entire course should be restarted.
50,000 units/kg/dose IV every 12 hours for a total treatment duration of 10 days. If more than 1 day of therapy is missed, the entire course should be restarted.
5 million units IV loading dose at the time of labor or rupture of membranes, followed by 2.5 to 3 million units IV every 4 hours until delivery as first-line therapy. Antibiotics administered for at least 4 hours before delivery have been found to be highly effective at preventing the transmission of Group B Streptococcus.
5 million units IV loading dose at the time of labor or rupture of membranes, followed by 2.5 to 3 million units IV every 4 hours until delivery as first-line therapy. Antibiotics administered for at least 4 hours before delivery have been found to be highly effective at preventing the transmission of Group B Streptococcus.
2 to 4 million units IV every 4 to 6 hours for 5 to 14 days.
60,000 to 100,000 units/kg/dose (Max: 4 million units/dose) IV every 6 hours for 5 to 14 days.
50,000 units/kg/dose IV every 8 hours for 5 to 14 days.
50,000 units/kg/dose IV every 12 hours for 5 to 14 days.
2 to 4 million units IV every 4 to 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.
60,000 to 100,000 units/kg/dose (Max: 4 million units/dose) IV every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.
50,000 units/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.
50,000 units/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin for group A streptococcal or clostridial infections.
50,000 units/L intraperitoneal loading dose, followed by 25,000 units/L in each dialysate exchange. Treat for 14 days.
†Indicates off-label use
Dosing Considerations
No dosage adjustment required. Dosage modifications may be necessary in patients with hepatic disease and renal impairment.
Renal ImpairmentThe 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.
Drug Interactions
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Amiloride: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Aspirin, ASA: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Dipyridamole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Omeprazole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Oxycodone: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Caffeine; Sodium Benzoate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Cholestyramine: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
Choline Salicylate; Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Colestipol: (Moderate) Colestipol can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of colestipol.
Desogestrel; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Dichlorphenamide: (Moderate) Use of dichlorphenamide and with OAT1 substrates like penicillin G is not recommended because of increased penicillin G exposure. If use cannot be avoided, monitor for increased adverse effects due to increased penicillin G exposure. Dichlorphenamide inhibits OAT1. Dichlorphenamide also increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including penicillin G. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Dienogest; Estradiol valerate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Digoxin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Drospirenone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Eplerenone: (Minor) Potassium-containing medications, such as penicillin G potassium, may potentially increase the risk of hyperkalemia in patients receiving eplerenone. Monitor serum potassium if eplerenone is used concurrently with drugs with potential to induce hyperkalemia.
Estradiol; Levonorgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethacrynic Acid: (Minor) Ethacrynic acid may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Ethinyl Estradiol; Norelgestromin: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Finerenone: (Moderate) Monitor serum potassium concentrations closely if finerenone and penicillin G potassium are used together. Concomitant use may increase the risk of hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Furosemide: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Ibritumomab Tiuxetan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity. (Moderate) Use potassium phosphates cautiously with high-doses of IV potassium penicillin G, as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
Indomethacin: (Minor) Indomethacin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Iodine; Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Leflunomide: (Moderate) Closely monitor for penicillin G-induced side effects such as nausea, vomiting, diarrhea, or seizures when these drugs are used together. In some patients, a dosage reduction of penicillin G may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with penicillin G, a substrate of OAT3, may increase penicillin G plasma concentrations.
Leuprolide; Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Mafenide: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Methotrexate: (Major) Avoid concomitant use of methotrexate with penicillins due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions.
Nitisinone: (Moderate) Monitor for increased penicillin-related adverse effects if coadministered with nitisinone. Increased penicillin exposure is possible. Nitisinone inhibits OAT3. Penicillin is an OAT3 substrate.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tet
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oral Contraceptives: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Potassium Acetate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium Bicarbonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium Citrate; Citric Acid: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium Gluconate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium Phosphate: (Moderate) Use potassium phosphates cautiously with high-doses of IV potassium penicillin G, as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
Potassium Phosphate; Sodium Phosphate: (Moderate) Use potassium phosphates cautiously with high-doses of IV potassium penicillin G, as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Potassium-sparing diuretics: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Probenecid; Colchicine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Salsalate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins. An enhanced effect of the displaced drug may occur.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Sparsentan: (Moderate) Monitor potassium during concomitant use of sparsentan and penicillin G potassium. Concomitant use increases the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Spironolactone: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Sulfadiazine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfasalazine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfonamides: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Teriflunomide: (Moderate) Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with penicillin G, a substrate of OAT3, may increase penicillin G plasma concentrations. Monitor for increased adverse effects from penicillin G, such as nausea, vomiting, diarrhea, or seizures. Adjust the dose of penicillin G as necessary and clinically appropriate.
Tetracyclines: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Triamterene: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Triamterene; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Typhoid Vaccine: (Major) Antibiotics which possess bacterial activity against salmonella typhi organisms may interfere with the immunological response to the live typhoid vaccine. Allow 24 hours or more to elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
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
Maximum Dosage
24 million units/day IV/IM is FDA-approved maximum; up to 30 million units/day IV/IM has been used off-label.
Geriatric24 million units/day IV/IM is FDA-approved maximum; up to 30 million units/day IV/IM has been used off-label.
Adolescents300,000 units/kg/day IV/IM (Max: 24 million units/day) is FDA-approved maximum; up to 400,000 units/kg/day IV/IM (Max: 24 million units/day) has been used off-label.
Children300,000 units/kg/day IV/IM (Max: 24 million units/day) is FDA-approved maximum; up to 400,000 units/kg/day IV/IM (Max: 24 million units/day) has been used off-label.
Infants300,000 units/kg/day IV/IM is FDA-approved maximum; up to 400,000 units/kg/day IV/IM has been used off-label.
Neonates8 days and older: 200,000 units/kg/day IV/IM.
0 to 7 days: 150,000 units/kg/day IV/IM.
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.
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 RoutePeak 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.
Pregnancy And Lactation
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.