Skip to Content
Vaccines aren’t just for kids. Is your teen protected?

Penicillin G (Parenteral/Aqueous)

Pronunciation

(pen i SIL in jee, pa REN ter al, AYE kwee us)

Index Terms

  • Aqueous Crystalline Penicillin G
  • Benzylpenicillin Potassium
  • Benzylpenicillin Sodium
  • Crystalline Penicillin
  • Penicillin G Potassium
  • Penicillin G Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as potassium:

Generic: 20,000 units/mL (50 mL); 40,000 units/mL (50 mL); 60,000 units/mL (50 mL)

Solution Reconstituted, Injection, as potassium:

Pfizerpen-G: 5,000,000 units (1 ea); 20,000,000 units (1 ea)

Pfizerpen-G: 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 potassium [preservative free]:

Generic: 20,000,000 units (1 ea)

Solution Reconstituted, Injection, as sodium:

Generic: 5,000,000 units (1 ea)

Brand Names: U.S.

  • Pfizerpen-G

Pharmacologic Category

  • Antibiotic, Penicillin

Pharmacology

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: Normal meninges: <1%; Inflamed meninges: 2% to 6%

Metabolism

Hepatic (10% to 30%) to penicilloic acid

Excretion

Urine (58% to 85% as unchanged drug)

Time to Peak

Serum: IM: ~30 minutes; IV: ~1 hour

Half-Life Elimination

Neonates: <6 days old: 3.2 to 3.4 hours; 7 to 13 days old: 1.2 to 2.2 hours; >14 days old: 0.9 to 1.9 hours

Infants and Children: 0.5 to 1.2 hours

Adults: Normal renal function: 30 to 50 minutes

End-stage renal disease: 3.3 to 5.1 hours

Protein Binding

65%

Special Populations: Renal Function Impairment

Excretion is delayed.

Special Populations: Hepatic Function Impairment

When combined with impaired renal function, elimination is further delayed.

Special Populations: Elderly

Renal Cl is delayed and caused by decreased renal function.

Use: Labeled Indications

Treatment of infections (including sepsis, 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

Contraindications

Hypersensitivity to penicillin or any component of the formulation

Dosing: Adult

Actinomyces species: IV: 10 to 20 million units/day divided every 4 to 6 hours for 4 to 6 weeks

Clostridium species: IV:

Manufacturer’s labeling: 20 million units/day in divided doses every 4 to 6 hours

Skin and soft tissue necrotizing infections (off-label use): 2 to 4 million units every 4 to 6 hours; 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 (IDSA [Stevens 2014])

Corynebacterium diphtheriae: IV: 2 to 3 million units/day in divided doses every 4 to 6 hours for 10 to 12 days

Endocarditis, treatment (off-label dose; AHA [Baddour 2015): IV:

Enterococcus, native or prosthetic valve (penicillin-susceptible/gentamicin-susceptible strains): 18 to 30 million units/day as continuous infusion or in divided doses every 6 hours with concomitant gentamicin. Duration of therapy: 4 weeks (native valve and symptoms present <3 months); 6 weeks (native valve and symptoms present ≥3 months or prosthetic valve).

Enterococcus, native or prosthetic valve (penicillin-susceptible/streptomycin-susceptible/gentamicin-resistant strains): 18 to 30 million units/day as continuous infusion or in divided doses every 6 hours with concomitant streptomycin. Duration of therapy: 4 weeks (native valve and symptoms present <3 months); ≥6 weeks (native valve and symptoms present ≥3 months or prosthetic valve).

Viridans group streptococcus (VGS) and S. bovis:

Native valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 12 to 18 million units/day as continuous infusion or in divided doses every 4 or 6 hours for 4 weeks or 12 to 18 million units/day as continuous infusion or in divided doses every 6 hours for 2 weeks with concomitant gentamicin

Native valve: Relatively penicillin-resistant (MIC >0.12 to <0.5 mcg/mL): 24 million units/day as continuous infusion or in divided doses every 4 or 6 hours for 4 weeks with concomitant gentamicin for the first 2 weeks

Prosthetic valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 24 million units/day as continuous infusion or in divided doses every 4 or 6 hours for 6 weeks (with or without concomitant gentamicin for the first 2 weeks)

Prosthetic valve: Relatively or fully penicillin-resistant (MIC >0.12 mcg/mL): 24 million units/day as continuous infusion or in divided doses every 4 or 6 hours with concomitant gentamicin for 6 weeks

Erysipelas: IV: 1 to 2 million units every 4 to 6 hours

Erysipelothrix: IV: 2 to 4 million units every 4 hours

Fascial space infections: IV: 2 to 4 million units every 4 to 6 hours with metronidazole

Leptospirosis: IV: 1.5 million units every 6 hours for 7 days

Listeria: IV: 15 to 20 million units/day in divided doses every 4 to 6 hours for 2 weeks (meningitis) or 4 weeks (endocarditis)

Lyme disease (meningitis): IV: 20 million units/day in divided doses

Neurosyphilis (including ocular syphilis) (off-label dose): IV: 18 to 24 million units/day in divided doses every 4 hours (or by continuous infusion) for 10 to 14 days (CDC [Workowski 2015])

Prosthetic joint infection: IV:

Enterococcus spp (penicillin-susceptible), streptococci (beta-hemolytic): 20 to 24 million units daily continuous infusion every 24 hours or in divided doses every 4 hours for 4 to 6 weeks (Osmon 2013); Note: For penicillin-susceptible Enterococcus spp, consider addition of aminoglycoside.

Propionibacterium acnes: 20 million units daily continuous infusion every 24 hours or in divided doses every 4 hours for 4 to 6 weeks (Osmon 2013)

Streptococcus:

Brain abscess: IV: 18 to 24 million units/day in divided doses every 4 hours with metronidazole

Endocarditis or osteomyelitis: IV: 3 to 4 million units every 4 hours for at least 4 weeks

Group B streptococcus (neonatal prophylaxis): IV: 5 million units x 1 dose, then 2.5 to 3.0 million units every 4 hours until delivery (CDC 2010)

Skin infections, including skin and soft tissue necrotizing infections (off-label use): IV: 2 to 4 million units every 4 to 6 hours; use in combination with clindamycin for necrotizing infections and continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014])

Toxic shock: IV: 24 million units/day in divided doses with clindamycin

Streptococcal pneumonia: IV: 2 to 3 million units every 4 hours

Whipple's disease: IV: 2 million units every 4 hours for 2 weeks, followed by oral trimethoprim/sulfamethoxazole or doxycycline for 1 year

Relapse or CNS involvement: 4 million units every 4 hours for 4 weeks

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Susceptible infections: IM, IV:

Infants ≥1 month and Children: 100,000 to 400,000 units/kg/day in divided doses every 4 to 6 hours (maximum dose: 24 million units/day)

Community-acquired pneumonia (CAP) (IDSA/PIDS 2011): IV: Infants and Children >3 months: Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected. In children ≥5 years, a macrolide antibiotic should be added if atypical pneumonia cannot be ruled out.

Empiric treatment or S. pneumoniae (moderate-to-severe; MICs to penicillin ≤2.0 mcg/mL) (preferred): 200,000 to 250,000 units/kg/day divided every 4 to 6 hours

Group A Streptococcus (moderate-to-severe) (preferred): 100,000 to 250,000 units/kg/day divided every 4 to 6 hours

Meningitis (gonococcal): IV: 250,000 units/kg/day in 4 divided doses

Moderate infections: IM, IV: 100,000 to 250,000 units/kg/day in 4 divided doses

Neurosyphilis: IV: 200,000 to 300,000 units/kg/day divided every 4 to 6 hours for 10 to 14 days (maximum dose: 24 million units/day)

Severe infections: IM, IV: 250,000 to 400,000 units/kg/day in divided doses every 4 to 6 hours (maximum dose: 24 million units/day)

Skin and soft tissue necrotizing infections due to Clostridium species (off-label use): IV: 60,000 to 100,000 units/kg every 6 hours; 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 (IDSA [Stevens 2014])

Streptococcal skin infections, including skin and soft tissue necrotizing infections (off-label use): IV: 60,000 to 100,000 units/kg every 6 hours; use in combination with clindamycin for necrotizing infections and continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014])

Syphilis (congenital) (off-label dose; CDC [Workowski 2015]): IV:

Infants <30 days: 50,000 units/kg/dose every 12 hours for first 7 days of life, then every 8 hours for a total of 10 days. If more than one day of therapy is missed, the entire course needs to be restarted.

Infants ≥1 month and Children: 50,000 units/kg/dose every 4 to 6 hours for 10 days

Dosing: Renal Impairment

Manufacturer's labeling:

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

Alternate recommendation:

GFR >50 mL/minute: No dosage adjustments are necessary (Aronoff 2007).

GFR 10-50 mL/minute: Administer 75% of the normal dose (Aronoff 2007).

GFR <10 mL/minute: Administer 20% to 50% of the normal dose (Aronoff 2007).

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days) (Heintz 2009): Administer a normal dose followed by either 25% to 50% of normal dose every 4 to 6 hours or 50% to 100% of normal dose every 8 to 12 hours. For mild-to-moderate infections, administer 0.5 to 1 million units every 4 to 6 hours or 1 to 2 million units every 8 to 12 hours. For neurosyphilis, endocarditis, or serious infections, administer up to 2 million units every 4 to 6 hours; administer after dialysis on dialysis days or supplement with 500,000 units after dialysis. Note: Dosing dependent on the assumption of 3 times weekly, complete IHD sessions.

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: Loading dose of 4 million units, followed by 2 million units every 4 to 6 hours

CVVHD: Loading dose of 4 million units, followed by 2 to 3 million units every 4 to 6 hours

CVVHDF: Loading dose of 4 million units, followed by 2 to 4 million units every 4 to 6 hours

Dosing: Hepatic Impairment

No dosage adjustment provided in 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.

Reconstitution

Intermittent IV: 5 million unit vial: Add 8.2 mL for a final concentration of 500,000 units/mL; add 3.2 mL for a final concentration of 1,000,000 units/mL. Dilute further to 50,000-145,000 units/mL prior to infusion.

Continuous IV infusion: 20 million unit vial: Add 11.5 mL for a final concentration of 1,000,000 units/mL. Dilute further in 1-2 L of infusion solution and administer over a 24-hour period.

Administration

IM; Administer IM by deep injection in the upper outer quadrant of the buttock

IV: Note: The 20 million unit dosage form may be administered by continuous IV infusion only.

Intermittent IV: May be dissolved in small amounts of SWFI, NS, D5W and administered peripherally as a 50,000-100,000 unit/mL solution. In fluid-restricted patients, 146,000 units/mL in SW results in a maximum recommended osmolality for peripheral infusion. Infuse over 15-30 minutes.

Continuous IV infusion: Determine the volume of fluid and rate of its administration required by the patient in a 24-hour period. Add the appropriate daily dosage of penicillin to this fluid. For example, if the daily dose is 10 million units and 2 L of fluid/day is required, add 5 million units to 1 L and adjust the rate of flow so the liter will be infused over 12 hours (83 mL/hour). Repeat steps (5 million units/L at 83 mL/hour) for the remaining 12 hours.

Dietary Considerations

Some products may contain potassium and/or sodium.

Compatibility

Inactivated in acidic or alkaline solutions.

Penicillin G potassium: Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, 1/2NS, NS, hetastarch 6%; incompatible with dextran 70 6% in dextrose, dextran 40 10% in dextrose.

Compatibility in syringe: Incompatible with metoclopramide.

Penicillin G sodium: Stable in dextran 40 10%; incompatible with fat emulsion 10%.

Storage

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 in the freezer (-20°C or -4°F); frozen bags may be thawed at room temperature or in refrigerator. Once thawed, solution is stable for 14 days if stored in refrigerator or for 24 hours when stored at room temperature. Do not refreeze once thawed.

Penicillin G sodium powder for injection should be stored at controlled room temperature. Reconstituted solution may be stored under refrigeration for up to 3 days.

Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. 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. Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification

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. Consider therapy modification

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

False-positive or negative urinary glucose determination using Clinitest®; positive Coombs' [direct]; false-positive urinary and/or serum proteins

Adverse Reactions

Frequency not defined.

Cardiovascular: Localized phlebitis, local thrombophlebitis

Central nervous system: Coma (high doses), hyperreflexia (high doses), myoclonus (high doses), seizure (high doses)

Dermatologic: Contact dermatitis, skin rash

Endocrine & metabolic: Electrolyte disturbance (high doses)

Gastrointestinal: Pseudomembranous colitis

Hematologic & oncologic: Neutropenia, positive direct Coombs test (rare, high doses)

Hypersensitivity: Anaphylaxis, hypersensitivity reaction (immediate and delayed), serum sickness

Immunologic: Jarisch-Herxheimer reaction

Local: Injection site reaction

Renal: Acute interstitial nephritis (high doses), renal tubular disease (high doses)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients.

• 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.

• 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.

• Prolonged use: Extended duration of therapy or use associated with high serum concentrations (eg, in renal insufficiency) may be associated with an increased risk for some adverse reactions (neutropenia, hemolytic anemia, serum sickness).

Monitoring Parameters

Periodic electrolyte, hepatic, renal, cardiac and hematologic function tests during prolonged/high-dose therapy; observe for signs and symptoms of anaphylaxis during first dose

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Penicillin crosses the placenta and distributes into amniotic fluid. Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects. Penicillin G is the drug of choice for treatment of syphilis during pregnancy and penicillin G (parenteral/aqueous) is the drug of choice for the prevention of early-onset Group B Streptococcal (GBS) disease in newborns (consult current guidelines).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, mouth sores, tongue discoloration, or injection site irritation. Have patient report immediately to prescriber signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), severe dizziness, passing out, severe loss of strength and energy, jaundice, muscle pain, joint pain, abdominal pain, bruising; bleeding; twitching, seizures, urinary retention, change in amount of urine passed, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Hide