Note: International considerations: Dosages are expressed in international units; 1 million units is equal to approximately 600 mg (Ref). International product labeling may express strength and dosing in mg instead of units.
General dosing, susceptible infection (non-CNS) (Ref): IV, IM:
Gestational Age |
Postnatal Age |
Dose |
---|---|---|
≤34 weeks |
≤7 days |
50,000 units/kg/dose every 12 hours |
8 to 28 days |
50,000 units/kg/dose every 8 hours | |
>34 weeks |
≤7 days |
50,000 units/kg/dose every 12 hours |
8 to 28 days |
50,000 units/kg/dose every 8 hours |
Anthrax, systemic (including meningitis); treatment:
Note: Consult public health officials for event-specific recommendations. Use as part of an appropriate combination regimen for ≥14 days if meningitis is excluded or ≥14 to 21 days if meningitis cannot be excluded, and until patient clinically stable. May transition to oral step-down therapy when clinically appropriate to complete course if meningitis has been excluded. Treatment should be followed by prophylaxis for a total antibiotic course of 60 days (Ref).
IV:
Gestational Age |
Postnatal Age |
Dose |
---|---|---|
32 to 34 weeks |
≤7 days |
100,000 units/kg/dose every 12 hours |
8 to 28 days |
100,000 units/kg/dose every 8 hours | |
>34 weeks |
≤7 days |
100,000 units/kg/dose every 8 hours |
8 to 28 days |
100,000 units/kg/dose every 6 hours |
Meningitis, including Group B streptococcal (GBS): Note: Duration of therapy dependent upon pathogen and clinical response; in general, durations are as follows: GBS (uncomplicated courses): 14 days, GBS ventriculitis: ≥4 weeks, Listeria: ≥21 days; longer durations may be necessary for prolonged or complicated courses (Ref).
AAP dosing (Ref): Preterm and term neonates:
PNA ≤7 days: IV, IM: 150,000 units/kg/dose every 8 hours.
PNA 8 to 60 days: IV, IM: 125,000 units/kg/dose every 6 hours.
IDSA dosing (Ref): Neonates ≥2 kg:
PNA ≤7 days: IV: 150,000 units/kg/day in divided doses every 8 to 12 hours.
PNA 8 to 28 days: IV: 200,000 units/kg/day in divided doses every 6 to 8 hours.
Syphilis, congenital (with or without CNS involvement): Note: If >1 day of therapy is missed, the entire course needs to be restarted (Ref).
Preterm and term neonates:
PNA ≤7 days: IV: 50,000 units/kg/dose every 12 hours; at PNA 8 days, increase to 50,000 units/kg/dose every 8 hours for a total of 10 days (Ref).
PNA 8 to 28 days: IV: 50,000 units/kg/dose every 8 hours for a total of 10 days (Ref).
PNA 29 to 60 days:
Preterm neonates: IV: 50,000 units/kg/dose every 6 hours for a total of 10 days (Ref).
Term neonates: IV: 50,000 units/kg/dose every 4 to 6 hours for a total of 10 days (Ref).
Note: International considerations: Dosages are expressed in international units; 1 million units is equal to approximately 600 mg (Ref). International product labeling may express strength and dosing in mg instead of units.
General dosing, susceptible infection (non-CNS): Infants, Children, and Adolescents: IM, IV: 100,000 to 300,000 units/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 24 million units/day (Ref).
Anthrax, systemic (including meningitis); treatment: Note: Consult public health officials for event-specific recommendations.
Infants, Children, and Adolescents: IV: 400,000 units/kg/day in divided doses every 4 hours; maximum dose: 4 million units/dose. Use as part of an appropriate combination regimen for ≥14 days if meningitis is excluded or ≥14 to 21 days if meningitis cannot be excluded, and until patient clinically stable. Note: May transition to oral step-down therapy when clinically appropriate to complete course if meningitis has been excluded. Treatment must be followed by prophylaxis for a total antibiotic course of 60 days (Ref).
Endocarditis, bacterial; treatment: Children and Adolescents: IV: 200,000 to 300,000 units/kg/day in divided doses every 4 hours; maximum daily dose: 24 million units/day; treat for ≥4 weeks; longer durations may be necessary; may use in combination with gentamicin for some resistant organisms (Ref). Note: For endocarditis from rat-bite fever/haverhill fever, the manufacturer recommends a lower dose of 150,000 to 250,000 units/kg/day in divided doses every 4 hours; maximum daily dose: 20 million units/day.
Lyme disease (Borrelia spp. infection) (alternative agent): Infants, Children, and Adolescents: IV: 200,000 to 400,000 units/kg/day in divided doses every 4 hours; maximum daily dose: 24 million units/day. Duration of therapy depends on clinical syndrome; treat meningitis or radiculopathy for 14 to 21 days (Ref).
Meningitis, including health care-associated ventriculitis/meningitis: Infants, Children, and Adolescents: IV: 300,000 to 400,000 units/kg/day divided every 4 to 6 hours; maximum dose: 4 million units/dose; maximum daily dose: 24 million units/day (Ref).
Pneumonia, community-acquired (CAP):
Infants >3 months and Children:
Empiric treatment or S. pneumoniae (moderate to severe; MICs to penicillin ≤2 mcg/mL): IV: 200,000 to 250,000 units/kg/day divided every 4 to 6 hours (Ref).
Group A Streptococcus (moderate to severe): IV: 100,000 to 250,000 units/kg/day divided every 4 to 6 hours (Ref).
Skin and soft tissue infection (Streptococcal infection or necrotizing infections due to Clostridium or Streptococcus species):
Infants, Children, and Adolescents: IV: 60,000 to 100,000 units/kg/dose every 6 hours; maximum dose: 4 million units/dose; adult dose: 2 to 4 million units every 4 to 6 hours. For necrotizing infections, use in combination with clindamycin and continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (Ref).
Syphilis:
Congenital: Infants and Children: IV: 50,000 units/kg/dose every 4 to 6 hours for 10 days (Ref).
Neurosyphilis (including ocular syphilis):
Infants and Children: IV: 50,000 units/kg/dose every 4 to 6 hours for 10 to 14 days; maximum daily dose: 24 million units/day (Ref).
Adolescents: IV: 3 to 4 million units every 4 hours or as a continuous infusion for 10 to 14 days; maximum daily dose: 24 million units/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: IM, IV:
Uremic patients with CrCl >10 mL/minute/1.73 m2: Administer a normal dose followed by 50% of the normal dose every 4 to 5 hours.
CrCl <10 mL/minute/1.73 m2: Administer a normal dose followed by 50% of the normal dose every 8 to 10 hours.
Hemodialysis: Dialyzable.
There are no dosage adjustments provided in the manufacturer's labeling; however, the manufacturer's labeling recommends further adjustment of doses adjusted for renal impairment in patients with both renal and hepatic impairment.
(For additional information see "Penicillin G (intravenous and short-acting intramuscular): Drug information")
Note: For ease of outpatient administration, the total daily dose may be administered as a 24-hour continuous infusion (Ref).
International considerations : Dosages below are expressed as international units; 1 million units is equal to approximately 600 mg (Ref). International product labeling may express strength and dosing in mg instead of units.
Actinomycosis, severe or extensive: IV: 10 to 20 million units/day as a continuous infusion or in divided doses every 4 to 6 hours for 4 to 6 weeks followed by appropriate long-term oral therapy (Ref).
Bloodstream infection:
Pathogen-directed therapy for Enterococcus spp. (off-label use): IV: 18 to 30 million units/day as a continuous infusion or in divided doses every 4 hours; use as part of an appropriate combination regimen in the setting of suspected endocarditis or critical illness (Ref). Duration of therapy is 7 to 14 days for uncomplicated infection (ie, fever resolution within 72 hours and absence of metastatic focus of infection or endovascular hardware) (Ref). Some experts recommend a duration of 5 to 7 days for uncomplicated infection if blood cultures clear within 24 hours (Ref).
Pathogen-directed therapy for Listeria monocytogenes: IV: 24 million units/day in divided doses every 4 hours; use in combination with gentamicin for nonpregnant patients. Duration should be individualized based on patient factors, source and extent of infection, and clinical response. Penicillin is usually continued for at least 2 weeks; patients who are immunocompromised warrant a longer course (eg, at least 3 to 6 weeks) (Ref).
Pathogen directed therapy for beta-hemolytic streptococci: IV: 18 to 24 million units/day in divided doses every 4 hours. Duration of therapy is generally 14 days; some experts suggest a shorter course (eg, 10 days) for patients with rapid clearance of bacteremia and clinical improvement (Ref).
Pathogen-directed therapy for group D streptococci (Streptococcus bovis/Streptococcus equinus complex) (alternative agent): IV: 12 to 24 million units/day in divided doses every 4 hours. Duration of therapy is 14 days in the absence of other clinical manifestations (Ref).
Note: The role of systemic antimicrobials is uncertain in the absence of local signs of infection (Ref).
Botulism, wound (adjunctive agent following antitoxin administration): IV: 18 to 20 million units/day in divided doses every 4 to 6 hours in combination with wound debridement; duration depends on extent of the wound (Ref).
Diphtheria (adjunctive agent following antitoxin administration) (alternative agent): IV: 2 to 3 million units/day in divided doses every 4 to 6 hours for 10 to 12 days (Ref).
Endocarditis, treatment:
Enterococcus, native or prosthetic valve (penicillin-susceptible/gentamicin-susceptible) (off-label use): IV: 18 to 30 million units/day as a continuous infusion or in divided doses every 4 hours in combination with an aminoglycoside (eg, gentamicin). Duration is usually 6 weeks; for patients with native valve endocarditis and symptoms <3 months, antibiotic therapy may be given for 4 weeks. Note: Reserve this regimen for patients with CrCl >50 mL/minute (Ref). For native-valve endocarditis due to ampicillin-susceptible Enterococcus faecalis, some experts prefer a different beta-lactam combination regimen (Ref).
Viridans group streptococci and Streptococcus gallolyticus (S. bovis):
Native valve: Highly penicillin-susceptible (minimum inhibitory concentration [MIC] ≤0.12 mcg/mL): IV: 12 to 18 million units/day as a continuous infusion or in divided doses every 4 or 6 hours for 4 weeks; for patients with uncomplicated infection, rapid response to therapy, and no underlying disease, an alternative is 12 to 18 million units/day as a continuous infusion or in divided doses every 4 hours in combination with gentamicin for 2 weeks (Ref).
Native valve: Relatively penicillin-resistant (MIC >0.12 to <0.5 mcg/mL): IV: 24 million units/day as a continuous infusion or in divided doses every 4 or 6 hours for 4 weeks in combination with gentamicin for the first 2 weeks (Ref).
Native valve: Penicillin-resistant (MIC ≥0.5 mcg/mL): IV: 18 to 30 million units/day as a continuous infusion or in divided doses every 4 or 6 hours in combination with gentamicin. The duration of this regimen is not well established; infectious diseases consultation recommended (Ref).
Prosthetic valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): IV: 24 million units/day as a continuous infusion or in divided doses every 4 or 6 hours for 6 weeks (with or without concomitant gentamicin for the first 2 weeks) (Ref). Some experts prefer giving in combination with gentamicin for all patients without contraindications (Ref).
Prosthetic valve: Relatively or fully penicillin-resistant (MIC >0.12 mcg/mL): IV: 24 million units/day as a continuous infusion or in divided doses every 4 or 6 hours in combination with gentamicin for 6 weeks (Ref). For relatively resistant strains, some experts prefer a shorter duration of the gentamicin component (≥2 weeks) (Ref).
Leptospirosis, severe (off-label use): IV: 1.5 million units every 6 hours for 7 days (Ref).
Lyme disease (Borrelia spp. infection) (alternative agent) (off-label use):
Carditis, severe disease (patients who are symptomatic, have second- or third-degree atrioventricular block, or have first-degree atrioventricular block with PR interval ≥300 msec): IV: 18 to 24 million units/day in divided doses every 4 hours until high-grade atrioventricular block resolved and PR interval <300 msec; may switch to oral therapy to complete a total of 14 to 21 days (Ref).
Acute neurologic disease (eg, meningitis, radiculopathy), patients requiring hospitalization: IV: 18 to 24 million units/day in divided doses every 4 hours for 14 to 21 days (Ref).
Late neurologic disease: IV: 18 to 24 million units/day in divided doses every 4 hours for 14 to 28 days (Ref); some experts favor a duration of 28 days (Ref).
Recurrent arthritis after adequate oral regimen: IV: 18 to 24 million units/day in divided doses every 4 hours for 14 days; may extend to 28 days if inflammation is not resolving (Ref).
Meningitis, bacterial:
Pathogen-directed therapy for Cutibacterium acnes, L. monocytogenes, Neisseria meningitidis (with MIC <0.1 mcg/mL), Streptococcus agalactiae, or Streptococcus pneumoniae (with MIC ≤0.06 mcg/mL): IV: 4 million units every 4 hours (Ref). For treatment of L. monocytogenes, use as part of an appropriate combination regimen (Ref). Treatment duration is 7 to 21 days, depending on causative pathogen(s) and clinical response (Ref).
Neurosyphilis (including ocular and otosyphilis ): Note: Penicillin desensitization and treatment is recommended in patients with a history of severe penicillin allergy (Ref).
IV: 18 to 24 million units/day as a continuous infusion or in divided doses every 4 hours for 10 to 14 days. For late neurosyphilis (syphilis exposure >1 year ago), may consider administration of penicillin G benzathine following initial IV penicillin G aqueous therapy to provide a comparable total duration of therapy for late syphilis (Ref).
Odontogenic soft tissue infection, pyogenic (alternative agent): IV: 2 to 4 million units every 4 to 6 hours in combination with metronidazole; following clinical improvement, transition to oral step-down therapy and continue antibiotics until resolution, typically for a total of 7 to 14 days (Ref).
Osteomyelitis and/or discitis (off-label use):
Pathogen-directed therapy for C. acnes, Enterococcus spp. (penicillin-susceptible), or beta-hemolytic streptococci: IV: 20 to 24 million units/day as a continuous infusion or in divided doses every 4 hours, generally for ≥6 weeks depending on patient-specific factors such as organism, extent of infection, debridement, and clinical response. Shorter courses are appropriate if the affected bone is completely resected (eg, by amputation) (Ref).
Prosthetic joint infection (off-label use):
Pathogen-directed therapy for C. acnes, Enterococcus spp. (penicillin-susceptible), or Streptococcus spp.: IV: 20 to 24 million units/day as a continuous infusion or in divided doses every 4 hours (Ref). Duration varies but is generally 4 to 6 weeks depending on patient-specific factors, infection site, and intervention (Ref). Note: For enterococcal infections, the addition of an aminoglycoside is optional (Ref), but some experts prefer other regimens in the setting of retained hardware unless an aminoglycoside-impregnated implant is present, in which case beta-lactam monotherapy is likely sufficient (Ref).
Rat bite fever:
Uncomplicated infection: IV: 200,000 units every 4 hours; if patient clinically improves, may switch to an oral antibiotic after 5 to 7 days to complete a 14-day course (Ref).
Serious invasive infection (including bacteremia, meningitis, endocarditis, and other focal organ involvement): IV: 12 to 18 million units/day as a continuous infusion or in divided doses every 4 to 6 hours; may increase dose to 24 million units/day in patients with an isolate that is not highly penicillin-susceptible (eg, MIC >0.1 mcg/mL) or in patients with prosthetic valve endocarditis. Duration depends on site of infection and extent of disease (eg, 4 weeks for endocarditis) (Ref).
Skin and soft tissue infection, streptococcal (group A Streptococcus, beta-hemolytic streptococci) (off-label use):
Erysipelas: IV: 2 to 4 million units every 4 to 6 hours. Total duration of therapy is ≥5 days (including oral step-down therapy); may extend to 14 days depending on severity and clinical response (Ref). Note: Some experts favor other regimens unless a streptococcal- or penicillin-susceptible infection has been microbiologically confirmed (Ref).
Necrotizing soft tissue infection: Note: Use in conjunction with early and aggressive surgical exploration and debridement of necrotic tissue.
IV: 4 million units every 4 hours in combination with clindamycin. Once the patient is clinically and hemodynamically stable for 48 to 72 hours, can give penicillin monotherapy. Total duration is individualized and depends on need for further debridement and patient clinical status (Ref).
Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease (off-label use): IV: 5 million units as a single dose at onset of labor or prelabor rupture of membranes, then 2.5 to 3 million units every 4 hours until delivery (Ref).
Tetanus (Clostridium tetani infection) (adjunctive agent following tetanus immune globulin and vaccine administration) (alternative agent): IV: 2 to 4 million units every 4 to 6 hours for 7 to 10 days (Ref).
Toxic shock syndrome, streptococcal: IV: 4 million units every 4 hours in combination with clindamycin. Duration of therapy depends on extent and severity of infection and response to treatment; treat patients who are bacteremic for ≥14 days (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Reduced kidney function may increase the risk of penicillin G accumulation, and monitoring for evidence of toxicity (eg, neurotoxicity) is recommended (manufacturer's labeling).
Altered kidney function:
Note: Recommendations are expert opinion derived from Bryan 1975 and Komatsu 2016.
CrCl >50 mL/minute: IV: No dosage adjustment necessary.
CrCl >30 to 50 mL/minute: IV: Administer 50% to 75% of the usual indication-specific dose as a continuous infusion or in divided doses every 4 to 6 hours.
CrCl 10 to 30 mL/minute: IV: Administer 25% to 50% of the usual indication-specific dose as a continuous infusion or in divided doses every 4 to 6 hours.
CrCl <10 mL/minute: IV: Administer 20% to 25% of the usual indication-specific dose as a continuous infusion or in divided doses every 4 to 6 hours.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: Use of the indication-specific maximum dose is recommended; administer via continuous infusion, if feasible (Ref).
Hemodialysis, intermittent (thrice weekly): Likely to be significantly dialyzable (Ref).
IV: Administer 100% of the usual indication-specific dose for the first dose, then administer 25% to 50% of the usual indication-specific dose as a continuous infusion or in divided doses every 4 to 6 hours thereafter (Ref).
Peritoneal dialysis: Likely to be dialyzed:
IV: Dose as for CrCl <10 mL/minute (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: Administer 100% of the usual indication-specific dose for the first dose, then administer 50% to 75% of the usual indication-specific dose as a continuous infusion or in divided doses every 4 to 6 hours (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
PIRRT days: IV: Administer 100% of the usual indication-specific dose for the first dose, then administer 50% to 75% of the usual indication-specific dose as a continuous infusion or in divided doses every 4 to 6 hours (Ref).
Non-PIRRT days: IV: Dose as for CrCl <10 mL/minute (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. However, the manufacturer's labeling recommends further adjustment of doses adjusted for renal impairment in patients with both renal and hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Local thrombophlebitis, localized phlebitis
Central nervous system: Coma (high doses), hyperreflexia (high doses), myoclonus (high doses), seizure (high doses)
Dermatologic: Exfoliative dermatitis, maculopapular rash, skin rash
Endocrine & metabolic: Electrolyte disorder (high doses)
Gastrointestinal: Clostridioides difficile associated diarrhea, Clostridioides difficile colitis
Hematologic & oncologic: Neutropenia, positive direct Coombs test (rare, high doses)
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction (immediate and delayed), serum sickness-like reaction
Immunologic: Jarisch-Herxheimer reaction
Local: Pain at injection site
Renal: Acute interstitial nephritis (high doses), renal tubular disease (high doses)
Hypersensitivity to any penicillin or any component of the formulation
Documentation of allergenic cross-reactivity for beta-lactams (eg, penicillins and cephalosporins) is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Anaphylactic/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity (including cephalosporins) or history of sensitivity to multiple allergens. Use with caution in asthmatic patients. If a serious reaction occurs, discontinue treatment and institute supportive measures.
• Neurovascular damage: Avoid intra-arterial administration or injection into or near major peripheral nerves or blood vessels since such injections may cause severe and/or permanent neurovascular damage.
• Severe cutaneous adverse reactions: Severe cutaneous adverse reactions (SCAR) (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis) have been reported; discontinue immediately if SCAR is suspected.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended. In the presence of concomitant hepatic impairment, further dosage adjustment may be needed.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
Special populations:
• Neonates: Neonates may have decreased renal clearance of penicillin and require frequent dosage adjustments depending on age.
Other warnings/precautions:
• Electrolyte imbalance: Product contains sodium and potassium; high doses of IV therapy may alter serum levels. If high doses (eg, >10 million units) are used, administer at a slower rate (eg, >30 minutes for intermittent IV infusion).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as potassium [preservative free]:
Generic: 20,000 units/mL (50 mL); 40,000 units/mL (50 mL); 60,000 units/mL (50 mL)
Solution Reconstituted, Injection, as potassium [preservative free]:
Pfizerpen: 5,000,000 units (1 ea); 20,000,000 units (1 ea)
Pfizerpen: 5,000,000 units (1 ea); 20,000,000 units (1 ea) [pyrogen free]
Generic: 5,000,000 units (1 ea); 20,000,000 units (1 ea)
Solution Reconstituted, Injection, as sodium [preservative free]:
Generic: 5,000,000 units (1 ea)
Yes
Solution (reconstituted) (Penicillin G Potassium Injection)
5000000 unit (per each): $5.23 - $42.18
20000000 unit (per each): $59.99 - $160.26
Solution (reconstituted) (Penicillin G Sodium Injection)
5000000 unit (per each): $57.60
Solution (reconstituted) (Pfizerpen Injection)
5000000 unit (per each): $15.26
20000000 unit (per each): $61.06
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Generic: 1,000,000 units (1 ea); 10,000,000 units (1 ea)
Solution Reconstituted, Injection, as sodium:
Generic: 5,000,000 units (1 ea)
Penicillin G potassium: 1.7 mEq of potassium and 0.3 mEq of sodium per 1 million units of penicillin G
Penicillin G sodium: 2 mEq of sodium per 1 million units of penicillin G
Parenteral:
IM: Administer IM by deep injection in the upper outer quadrant of the buttock. Administer injection around-the-clock to promote less variation in peak and trough levels.
IV: Usually administered by intermittent infusion. In some centers, large doses may be administered by continuous IV infusion. The potassium or sodium content of the dose should be considered when determining the infusion rate.
Intermittent IV: Infuse over 15 to 30 minutes
Continuous IV infusion: Daily dose may be administered as a continuous infusion over 24 hours, or smaller increments (eg, 24 hour dose divided into two 12-hour infusions)
IM: Administer IM by deep injection in the upper outer quadrant of the buttock. Administer injection around-the-clock to promote less variation in peak and trough levels.
IV: Usually administered by intermittent infusion. In some centers, large doses may be administered by continuous IV infusion. Note: The 20 million unit dosage form may be administered by IV infusion only.
Intermittent IV: Infuse over 15 to 30 minutes.
Penicillin G potassium powder for injection should be stored below 86°F (30°C). Following reconstitution, solution may be stored for up to 7 days under refrigeration. Premixed bags for infusion should be stored at -20°C or -4°F; frozen bags may be thawed at 25°C (77°F) or in a refrigerator (5°C [41°F]). Once thawed, solution is stable for 14 days at 5°C (41°F) or for 24 hours at 25°C (77°F). Do not refreeze once thawed.
Penicillin G sodium powder for injection should be stored at 20°C to 25°C (68°F to 87°F). Once reconstituted, the manufacturer recommends refrigeration (2°C to 8°C [36°F to 46°F]) and use within 3 days of reconstitution. After further dilution to 2,500 to 50,000 units/mL in either D5W or NS (in PVC bags or elastomeric pump containers), one study demonstrated stability when stored under refrigeration for up to 21 days (Hossain 2014).
Treatment of infections (including sepsis, empyema, pneumonia, pericarditis, endocarditis, meningitis, anthrax, botulism, gas gangrene, and tetanus) caused by susceptible organisms; active against some gram-positive organisms, generally not Staphylococcus aureus; some gram-negative organisms such as Neisseria gonorrhoeae and some anaerobes and spirochetes (FDA approved in all ages).
Penicillin may be confused with penicillamine
Penicillin G (parenteral/aqueous) may be confused with penicillin G benzathine, penicillin G procaine, penicillin V potassium
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Benzoate: Penicillins may diminish the therapeutic effect of Sodium Benzoate. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain potassium and/or sodium.
Penicillin G crosses the placenta.
In a study of women administered IV penicillin G (parenteral/aqueous) for group B streptococcal (GBS) disease, peak fetal concentrations occurred within 1 hour (Barber 2008).
Penicillin is widely used in pregnant women. Based on available data, penicillin is generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Erić 2012; Heinonen 1977; Lamont 2014; Muanda 2017a; Muanda 2017b).
Maternal penicillin G serum concentrations are not decreased in obese patients following IV administration for GBS prophylaxis; however, cord blood concentrations may be less. Based on available data, minimum inhibitory concentrations for GBS are still achieved (McCoy 2020). Penicillin G (parenteral/aqueous) is the drug of choice for intrapartum prophylaxis to prevent neonatal GBS early onset disease. Untreated asymptomatic GBS disease can result in maternal urinary tract infection, intraamniotic infection, endometritis, preterm labor, and/or stillbirth. Vertical transmission from the mother can cause sepsis, pneumonia, or meningitis in the newborn. Treatment is intended to prevent early-onset disease in newborns. Prophylaxis is reserved for pregnant patients with a positive GBS vaginal or rectal screening in late gestation, GBS bacteriuria during the current pregnancy, history of birth of an infant with early-onset GBS disease, and unknown GBS culture status with any of the following: birth <37 0/7 weeks gestation, intrapartum fever, prolonged rupture of membranes, known GBS positive in a previous pregnancy, or intrapartum nucleic acid amplification testing positive for GBS (ACOG 2020).
Penicillin G is the drug of choice for treatment of syphilis during pregnancy (CDC [Workowski 2021]). Untreated maternal syphilis can cause congenital syphilis which is associated with bone deformities, neurologic impairment, stillbirth, or neonatal death (USPSTF 2018). Symptoms of congenital syphilis may include hepatosplenomegaly, jaundice, nonimmune hydrops, pseudoparalysis of an extremity, rhinitis, or skin rash. The CDC Sexually Transmitted Diseases Treatment Guidelines provide recommendations for the treatment of syphilis in pregnant patients. The penicillin regimen (dose, duration, and preparation) for the treatment of pregnant patients is the same as for a nonpregnant patient and depends on the stage of syphilis. Parenteral penicillin G is the only agent with documented efficacy in pregnancy. Patients who are allergic to penicillin should be desensitized and treated with penicillin. Pregnant patients being treated for latent syphilis must repeat the full course of therapy if any doses are missed. A Jarisch-Herxheimer reaction may occur in any patient within the first 24 hours of therapy, including pregnant patients. This reaction may induce early labor, fetal distress, or stillbirth (rare); however, it is not a reason to prevent or delay maternal therapy (CDC [Workowski 2021]).
Maternal infection with Bacillus anthracis may cause preterm labor, fetal infection, fetal distress, or fetal loss. Maternal death may also occur. When IV therapy is required for anthrax infection in pregnant and postpartum patients, penicillin G may be used as an alternative agent. The dose and duration of antibiotic therapy in pregnant and postpartum patients is the same as in nonpregnant adults. Adjustments in dose for pregnancy are not recommended until additional pharmacokinetic data becomes available (Meaney-Delman 2014).
Periodic serum electrolytes, renal and hematologic function tests, cardiac and hematologic function tests during prolonged/high-dose therapy; observe for signs and symptoms of anaphylaxis during first dose and changes in bowel frequency.
Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria
Distribution: Poor penetration across blood-brain barrier, despite inflamed meninges
Relative diffusion from blood into CSF: Poor unless meninges inflamed (exceeds usual MICs)
CSF:blood level ratio: Inflamed meninges: 2% to 6%
Half-life elimination:
Neonates: <6 days of age: 3.1 hours; ≥14 days of age: 1.4 hours
Adults: Normal renal function: 31 to 50 minutes
End-stage renal disease (ESRD): 6 to 20 hours (Aronoff 2007)
Time to peak, serum: IV: Immediately after infusion
Excretion: Urine (58% to 85% as unchanged drug)
Altered kidney function: Excretion is delayed.
Hepatic function impairment: When combined with impaired renal function, elimination is further delayed.
Older adult: Renal clearance may be delayed (caused by decreased renal function).
Anti-infective considerations:
Parameters associated with efficacy:
Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC), goal: ≥50% fT > MIC (bactericidal) (Craig 1996; Craig 1998).
Expected drug exposure in adults with normal renal function:
5 million units over 3 to 5 minutes (single dose): 400 mg/L (5 to 6 minutes postinfusion); 273 mg/L (10 minutes postinfusion); 3 mg/L (4 hours postinfusion).
Postantibiotic effect: Minimal bacterial killing continues after penicillin concentration falls below the MIC of targeted pathogen and varies based on the organism:
Gram-positive cocci: 1.5 to 3.5 hours (Craig 1991; Garcia 1995; Zhanel 1991).
Gram-negative bacilli: 0 to 1.5 hours (Craig 1991; Zhanel 1991).
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