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Penicillin G (Parenteral/Aqueous)

Medically reviewed by Drugs.com. Last updated on May 9, 2020.

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 [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)

Brand Names: U.S.

  • Pfizerpen

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: Inflamed meninges: 2% to 6%

Excretion

Urine (58% to 85% as unchanged drug)

Time to Peak

Serum: IV: Immediately after infusion

Half-Life Elimination

Neonates: <6 days of age: 3.2 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)

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 clearance may be delayed (caused by decreased renal function).

Use: Labeled Indications

Anthrax: Treatment of anthrax caused by Bacillus anthracis.

Actinomycosis, severe or extensive: Treatment of actinomycosis (cervicofacial disease and thoracic and abdominal disease) caused by Actinomyces israelii.

Bloodstream infection: Treatment of bloodstream infection caused by Streptococcus spp., Listeria monocytogenes, Neisseria meningitidis, and Pasteurella multocida.

Botulism, wound: Treatment of botulism caused by Clostridium spp. as an adjunctive agent following antitoxin administration.

Diphtheria: Treatment of diphtheria caused by Corynebacterium diphtheriae as an adjunctive agent following antitoxin administration.

Endocarditis, treatment: Treatment of endocarditis caused by Streptococcus spp. and Erysipelothrix rhusiopathiae.

Meningitis, bacterial: Treatment of meningitis caused by L. monocytogenes, N. meningitidis, P. multocida, and Streptococcus spp.

Neurosyphilis (including ocular and otosyphilis): Treatment of syphilis (congenital and neurosyphilis) caused by Treponema pallidum.

Odontogenic infection: Treatment of pyogenic odontogenic infection, including severe infections of the oropharynx, caused by Fusobacterium spp. and spirochetes.

Rat bite fever: Treatment of rat bite fever (including Haverhill fever) caused by Spirillum minus or Streptobacillus moniliformis.

Tetanus: Treatment of tetanus caused by Clostridium tetani as an adjunctive agent following tetanus immune globulin and vaccine administration.

Toxic shock syndrome: Treatment of toxic shock syndrome caused by Streptococcus spp.

Off Label Uses

Bloodstream infection

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection, penicillin G (parenteral/aqueous) is an effective and recommended agent for bloodstream infections caused by Enterococcus spp. [IDSA [Mermel 2009]].

Endocarditis, treatment

Based on the American Heart Association scientific statement on infective endocarditis in adults, penicillin G (parenteral/aqueous) may be considered for treatment of native or prosthetic valve infective endocarditis due to penicillin-susceptible/gentamicin-susceptible Enterococcus spp. [AHA [Baddour 2015]].

Leptospirosis, severe

In randomized controlled trials, penicillin G (parenteral/aqueous) demonstrated efficacy equal to third-generation cephalosporins or doxycycline for the treatment of severe leptospirosis [Panaphut 2003], [Suputtamongkol 2004].

Based on the World Health Organization/International Leptospirosis Society guidance for diagnosis, surveillance, and control of human leptospirosis, penicillin G (parenteral/aqueous) is an effective and recommended option for treatment of severe leptospirosis [WHO 2003].

Lyme disease (Borrelia spp. infection)

Based on the IDSA guidelines for the clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis, penicillin G (parenteral/aqueous) is effective and recommended for the treatment of Lyme disease with early disseminated neurologic disease (eg, meningitis, radiculopathy), Lyme carditis (severe disease), Lyme arthritis with evidence of neurologic disease, and late Lyme disease with central or peripheral nervous system disease [IDSA [Wormser 2006]].

Based on the American Academy of Neurology guidelines for the treatment of nervous system Lyme disease, penicillin G (parenteral/aqueous) is an effective option for treatment of Lyme neuroborreliosis and has rates of efficacy comparable to ceftriaxone [Halperin 2007].

Osteomyelitis and/or discitis

Based on the IDSA guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, penicillin G (parenteral/aqueous) is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to Enterococcus spp. (penicillin-susceptible), beta-hemolytic streptococci, or Cutibacterium acnes [IDSA [Berbari 2015]].

Prosthetic joint infection

Based on the IDSA guidelines for the diagnosis and management of prosthetic joint infection, penicillin G (parenteral/aqueous) is an effective and recommended agent for the treatment of prosthetic joint infection with Enterococcus spp. (penicillin-susceptible) (with or without an aminoglycoside), beta-hemolytic streptococci, and C. acnes [IDSA [Osmon 2013]].

Skin and soft tissue infection, streptococcal

Based on the IDSA guidelines for the diagnosis and management of skin and soft tissue infections, penicillin G (parenteral/aqueous) is an effective and recommended option for treatment of streptococcal skin infections and is recommended in combination with clindamycin for necrotizing infections of the skin, fascia, and muscle due to group A Streptococcus and/or Clostridium species [IDSA [Stevens 2014]].

Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease

Based on the American College of Obstetricians and Gynecologists guideline on prevention of group B streptococcal early-onset disease in newborns, IV penicillin is the preferred antibiotic for intrapartum prophylaxis to prevent early-onset group B streptococcal disease in the newborn [ACOG 2020].

Contraindications

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.

Dosing: Adult

Note: For ease of outpatient administration, the total daily dose may be administered as a 24-hour continuous infusion (AHA [Baddour 2015]; IDSA [Berbari 2015]; IDSA [Osmon 2013]; Walton 2007).

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 (Brook 2008; Brook 2020).

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 (IDSA [Mermel 2009]; Murray 2020). 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) (IDSA [Mermel 2009]). Some experts recommend a duration of 5 to 7 days for uncomplicated infection if blood cultures clear within 24 hours (Murray 2020).

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) (Gelfand 2020; Hof 1997).

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 (Barshak 2020; Wessels 2020).

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 (Hoen 2020).

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 (Pegram 2020; manufacturer's labeling).

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 (manufacturer's labeling).

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 (AHA [Baddour 2015]). For native-valve endocarditis due to ampicillin-susceptible Enterococcus faecalis, some experts prefer a different beta-lactam combination regimen (Sexton 2020a).

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 (AHA [Baddour 2015]).

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 (AHA [Baddour 2015]).

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 (AHA [Baddour 2015]).

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) (AHA [Baddour 2015]). Some experts prefer giving in combination with gentamicin for all patients without contraindications (Karchmer 2020).

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 (AHA [Baddour 2015]). For relatively resistant strains, some experts prefer a shorter duration of the gentamicin component (≥2 weeks) (Karchmer 2020).

Leptospirosis, severe (off-label use): IV: 1.5 million units every 6 hours for 7 days (Panaphut 2003; Suputtamongkol 2004; Watt 1988).

Lyme disease (Borrelia spp. infection) (alternative agent) (off-label use):

Early disseminated, 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 28 days. Some experts prefer 28 days for patients with more serious cardiac disease (Hu 2020; IDSA [Wormser 2006]).

Early disseminated, neurologic disease (eg, meningitis, radiculopathy): IV: 18 to 24 million units/day in divided doses every 4 hours for 14 days for patients with mild to moderate infections; some experts prefer 21 to 28 days for patients with severe infection (AAN [Halperin 2007]; Halperin 2013; Hu 2020; IDSA [Wormser 2006]; Sanchez 2016). Note: For patients who are not hospitalized and do not have parenchymal involvement, some experts recommend oral doxycycline instead of parenteral regimens (Hu 2020).

Late disease, neurologic disease: IV: 18 to 24 million units/day in divided doses every 4 hours for 28 days (Hu 2020; IDSA [Wormser 2006]).

Late disease, recurrent arthritis after adequate oral regimen: IV: 18 to 24 million units/day in divided doses every 4 hours for 14 to 28 days (IDSA [Wormser 2006]).

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 (Hof 1997; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). For treatment of L. monocytogenes, use as part of an appropriate combination regimen (Drevets 1994; Hof 1997; IDSA [Tunkel 2004]). Treatment duration is 7 to 21 days, depending on causative pathogen(s) and clinical response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Neurosyphilis (including ocular and otosyphilis): Note: Penicillin desensitization and treatment is recommended in patients with a history of severe penicillin allergy.

IV: 18 to 24 million units/day as a continuous infusion or in divided doses every 4 hours for 10 to 14 days (CDC [Workowski 2015]; Hicks 2020). For late neurosyphilis, some experts give a dose of benzathine penicillin G upon completion of the IV course (Hicks 2020).

Odontogenic infection, pyogenic (alternative agent): IV: 2 to 4 million units every 4 to 6 hours in combination with metronidazole; total duration (including oral step-down therapy) is 7 to 14 days (Chow 2020).

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) (IDSA [Berbari 2015]; Osmon 2020).

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 (IDSA [Osmon 2013]). Duration varies but is generally 4 to 6 weeks depending on patient-specific factors, infection site, and intervention (Berbari 2020; IDSA [Osmon 2013]). Note: For enterococcal infections, the addition of an aminoglycoside is optional (IDSA [Osmon 2013]), 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 (Berbari 2020).

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 (CDC 2005; King 2020).

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). Treatment duration is 4 weeks (King 2020).

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 (IDSA [Stevens 2014]; Spelman 2020). Note: Some experts favor other regimens unless a streptococcal- or penicillin-susceptible infection has been microbiologically confirmed (Spelman 2020).

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 (IDSA [Stevens 2014]; Stevens 2020).

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 (ACOG 2020).

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 (Sexton 2020b; manufacturer's labeling).

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 (Stevens 2020; Walker 2014).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

General dosing, susceptible infection (non-CNS) (Red Book [AAP 2018]): 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.

Anthrax, systemic; treatment:

Non-CNS infection; preferred agent for penicillin-susceptible strains: Infants, Children, and Adolescents: IV: 400,000 units/kg/day in divided doses every 4 hours; maximum dose: 4 million units/dose; use in combination with clindamycin, linezolid, doxycycline, or rifampin for ≥14 days until clinical stability is achieved (ie, appear well with no signs or symptoms of active infection and can tolerate oral therapy); treatment must be followed by prophylaxis for a total antibiotic course of 60 days (AAP [Bradley 2014]).

Meningitis; preferred agent for penicillin-susceptible strains: Infants, Children, and Adolescents: IV: 400,000 units/kg/day in divided doses every 4 hours; maximum dose: 4 million units/dose; use in combination with a fluoroquinolone plus linezolid, clindamycin, rifampin, or chloramphenicol for ≥2 to 3 weeks until clinical stability is achieved (ie, appear well with no signs or symptoms of active infection and can tolerate oral therapy); treatment must be followed by prophylaxis for a total antibiotic course of 60 days (AAP [Bradley 2014]).

Clostridial myonecrosis (gas gangrene): Infants, Children, and Adolescents: IV: 250,000 to 400,000 units/kg/day in divided doses every 4 to 6 hours with or without clindamycin (Red Book [AAP 2018]).

Diphtheria: Infants, Children, and Adolescents: IM, IV: 150,000 to 250,000 units/kg/day in divided doses every 6 hours for 7 to 10 days. AAP suggests a duration of 14 days (Red Book [AAP 2018]).

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 at least 4 weeks; longer durations may be necessary; may use in combination with gentamicin for some resistant organisms (AHA [Baltimore 2015]). 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: 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 (AAN [Halperin 2007]; IDSA [Wormser 2006]).

Meningitis: Note: Dosing varies based on organism being treated.

Group B streptococcus: Infants: IV: 450,000 to 500,000 units/kg/day divided every 6 hours (Red Book [AAP 2018]).

S. pneumoniae: Infants, Children, and Adolescents: IV: 250,000 to 400,000 units/kg/day divided every 4 to 6 hours (Red Book [AAP 2018]).

Other susceptible organisms (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 daily dose: 24 million units/day (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Red Book [AAP 2018]).

Meningococcal disease: Infants, Children, and Adolescents: IV: 300,000 units/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 12 million units/day (Red Book [AAP 2018]).

Pneumonia, community-acquired (CAP): Infants >3 months and Children:

Empiric treatment or S. pneumoniae (moderate to severe; MICs to penicillin ≤2.0 mcg/mL): IV: 200,000 to 250,000 units/kg/day divided every 4 to 6 hours (IDSA/PIDS [Bradley 2011]).

Alternate dosing (AAP recommendation): IV: 250,000 to 400,000 units/kg/day divided every 4 to 6 hours; maximum daily dose: 24 million units/day (Red Book [AAP 2018]).

Group A Streptococcus (moderate to severe): IV: 100,000 to 250,000 units/kg/day divided every 4 to 6 hours (IDSA/PIDS [Bradley 2011]).

Skin and soft tissue necrotizing infections due to Clostridium species: Infants, Children, and Adolescents: IV: 60,000 to 100,000 units/kg/dose 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: Infants, Children, and Adolescents: IV: 60,000 to 100,000 units/kg/dose every 6 hours; maximum dose: 4 million units/dose; 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: Infants and Children: IV: 50,000 units/kg/dose every 4 to 6 hours for 10 days (CDC [Workowski 2015]).

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.

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 (CDC [Workowski 2015]).

Tetanus; treatment: Infants, Children, and Adolescents: IV: 100,000 units/kg/day in divided doses every 4 to 6 hours for 7 to 10 days; maximum daily dose: 12 million units/day (Red Book [AAP 2018]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Intermittent IV infusion: 5 million unit vial: Add 8.2 mL SWFI or NS 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 to 145,000 units/mL prior to infusion.

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

Intramuscular: 5 million unit vial: Add 8.2 mL SWFI or NS 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, up to 100,000 units/mL, for less discomfort. If larger doses are needed, consider IV infusion.

Intrapleural: If fluid is aspirated, administer local infusion in a volume equal to 25 to 50% of the amount of fluid aspirated. If fluid is not aspirated, prepare as directed for IM injection and infuse locally.

Administration

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.

Dietary Considerations

Some products may contain potassium and/or sodium.

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 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).

Drug Interactions

Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy

Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Monitor therapy

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. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy

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

Nitisinone: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Pretomanid: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. 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. Consider therapy modification

Teriflunomide: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Tetracyclines: May diminish the therapeutic effect of Penicillins. 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. 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 by certain test methods

Adverse Reactions

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)

Warnings/Precautions

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).

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. In older adults, especially those with decreased renal function, monitor for seizure activity.

Pregnancy Considerations

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 2015]). 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 women 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 women. This reaction may induce early labor or fetal distress; however, it is not a reason to prevent or delay maternal therapy (CDC [Workowski 2015]).

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 women, penicillin G may be used as an alternative agent. The dose and duration of antibiotic therapy in pregnant and postpartum women is the same as in nonpregnant adults. Adjustments in dose for pregnancy are not recommended until additional pharmacokinetic data becomes available (Meaney-Delman 2014).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Nausea

• Vomiting

• Mouth irritation

• Mouth sores

• Tongue discoloration

• Injection site irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Severe dizziness

• Passing out

• Chills

• Sore throat

• Headache

• Fast heartbeat

• Fast breathing

• Flushing

• Severe loss of strength and energy

• Yellow skin or eyes

• Muscle pain

• Joint pain

• Abdominal pain

• Bruising

• Bleeding

• Twitching

• Seizures

• Unable to pass urine

• Change in amount of urine passed

• Numbness

• Tingling

• Weakness

Clostridioides (formerly Clostridium) difficile-associated diarrhea like stomach pain or cramps, very loose or watery stools, or bloody stools.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.