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Penicillin G Benzathine/Procaine/Potassium/Sodium

Class: Natural Penicillins
VA Class: AM110
Chemical Name: [2S-(2α,5α,6β)]-3,3-Dimethyl-7-oxo-6-[(phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid compd. withN,N′-bis(phenylmethyl)-1,2-ethanediamine (2:1) tetrahydrate
Molecular Formula: (C16H18N2O4S)2•C16H20N2•4H2OC16H18N2O4S•C13H2O•N2O2•H2OC16H18N2O4S•KC16H18N2O4S•Na
CAS Number: 41372-02-5
Brands: Permapen, Pfizerpen

Medically reviewed on Oct 1, 2018

Warning

  • Penicillin G benzathine (Bicillin L-A, Permapen)2 3 penicillin G procaine,7 and fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300),4 5 are administered by deep IM injection only2 4 5 7 and should not be injected IV or admixed with other IV solutions.2 4 5

  • Inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.2 4 5

  • Prior to administration of penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine, carefully read the warnings, adverse reactions, and dosage and administration sections of the prescribing information.2 4 5 7

Introduction

Antibacterial; β-lactam antibiotic; natural penicillin.10 61 Available as penicillin G benzathine,2 3 penicillin G procaine,7 penicillin G potassium,9 11 12 and penicillin G sodium.8

Uses for Penicillin G Benzathine/Procaine/Potassium/Sodium

Bone and Joint Infections

Treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible β-hemolytic streptococci (penicillin G potassium or sodium).590 591

Treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible Enterococcus (penicillin G potassium or sodium);590 591 used with or without an aminoglycoside.591 590

Treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible Cutibacterium acnes (formerly Propionibacterium acnes) (penicillin G potassium or sodium).590 591

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of bone and joint infections.590 591

Endocarditis

Treatment of native valve endocarditis or endocarditis involving prosthetic valve or other prosthetic material caused by certain susceptible gram-positive bacteria (penicillin G potassium or sodium).8 9 11 12 450 452

Treatment of endocarditis caused by susceptible Streptococcus pyogenes (group A β-hemolytic streptococci; GAS), other β-hemolytic streptococci (including groups C, H, G, L, and M), or S. pneumoniae.8 9 11 12 AHA states IV penicillin G is a reasonable regimen for treatment of endocarditis caused by susceptible S. pyogenes, S. agalactiae (group B streptococci; GBS), groups C and G streptococci, and highly penicillin-susceptible S. pneumoniae (penicillin MIC ≤0.1 mcg/mL);450 consider concomitant use of gentamicin for endocarditis caused by streptococci groups B, C, or G.450

Treatment of endocarditis caused by viridans group streptococci or nonenterococcal group D streptococci, including S. gallolyticus (formerly S. bovis).450 452 AHA states IV penicillin G (with or without gentamicin) is a regimen of choice for such infections caused by highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL);450 452 use IV penicillin G in conjunction with gentamicin if strains are relatively resistant to penicillin G (penicillin MIC >0.12 mcg/mL but <0.5 mcg/mL).450 452

Treatment of endocarditis caused by viridans group streptococci, Abiotrophia defectiva, or Granulicatella with penicillin MIC ≥0.5 mcg/mL.450 452 AHA states IV penicillin G in conjunction with gentamicin is a reasonable regimen for such infections.450 452

Treatment of endocarditis caused by Enterococcus faecalis, E. faecium, or other enterococci susceptible to penicillin G and gentamicin.450 452 AHA states IV penicillin G in conjunction with gentamicin is a regimen of choice for such infections;450 452 streptomycin can be substituted for gentamicin if enterococci are susceptible to penicillin and streptomycin, but resistant to gentamicin.450

Has been used for treatment of endocarditis caused by nonpenicillinase-producing staphylococci.9 11 12 452 AHA states that IV penicillin G may be considered for treatment of endocarditis caused by penicillin-susceptible S. aureus or coagulase-negative staphylococci in pediatric patients;452 penicillin G not included in current AHA recommendations for treatment of staphylococcal endocarditis in adults.450

AHA recommends that treatment of endocarditis be managed in consultation with an infectious disease expert, especially when endocarditis is caused by S. pneumoniae, β-hemolytic streptococci, staphylococci, or enterococci.450 452

Consult current guidelines from AHA for additional information on management of endocarditis.450 452

Meningitis and Other CNS Infections

Treatment of meningitis caused by certain susceptible gram-positive or gram-negative bacteria (penicillin G potassium or sodium).8 9 11 12

Treatment of meningitis caused by susceptible Listeria monocytogenes; used alone or in conjunction with an aminoglycoside.8 9 11 12 61 418 475 476

Treatment of meningitis caused by susceptible Neisseria meningitidis.8 9 11 12 61 166 197 292 418 475 A drug of choice for penicillin-susceptible strains.166 197 292 418

Treatment of meningitis caused by susceptible S. agalactiae (group B streptococci; GBS).61 292 418 475 Consider concomitant use of an aminoglycoside.61 418

Treatment of meningitis caused by susceptible S. pyogenes or other β-hemolytic streptococci, including groups C, H, G, L and M.8 9 11 12 61

Treatment of meningitis or ventriculitis caused by susceptible S. pneumoniae (penicillin MIC <0.1 mcg/mL).8 9 11 12 61 292 416 418 475 Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G reported with increasing frequency.61

Treatment of healthcare-associated ventriculitis and meningitis caused by susceptible Cutibacterium acnes (formerly Propionibacterium acnes) (penicillin G potassium or sodium).416

Has been used for treatment of meningitis caused by susceptible nonpenicillinase-producing Staphylococcus (penicillin G potassium or sodium).9 11 12

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci; GAS) and prevention of initial attacks (primary prevention) of rheumatic fever (penicillin G benzathine).292 375 580

AAP, IDSA, and AHA recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as treatment of choice for S. pyogenes pharyngitis and tonsillitis;292 375 580 other anti-infectives (narrow-spectrum oral cephalosporins, oral macrolides, oral clindamycin) recommended as alternatives in penicillin-allergic patients.292 375 580

If signs and symptoms of pharyngitis recur shortly after initial treatment and presence of S. pyogenes documented, retreatment with original or alternative anti-infective recommended.292 375 580 Alternative regimens recommended for retreatment include a narrow-spectrum oral cephalosporin, oral clindamycin, oral fixed combination of amoxicillin and clavulanate, oral macrolide, or IM penicillin G benzathine.292 375 580

Consider that multiple, recurrent episodes of symptomatic pharyngitis within several months to years may indicate the patient is a long-term pharyngeal carrier of S. pyogenes experiencing repeated episodes of nonstreptococcal (e.g., viral) pharyngitis.292 375 580

Treatment not usually recommended for asymptomatic chronic pharyngeal carriers of S. pyogenes.292 375 580 Eradication of the carrier state may be desirable in certain situations (e.g., community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis, or invasive S. pyogenes infections; outbreak of S. pyogenes pharyngitis in a closed or partially closed community; multiple episodes of documented symptomatic S. pyogenes pharyngitis occurring within a family for many weeks despite appropriate treatment; personal or family history of acute rheumatic fever).292 580 In such situations, recommended regimens include oral clindamycin, oral fixed combination of amoxicillin and clavulanate, or oral rifampin used in conjunction with either IM penicillin G benzathine or oral penicillin V.292 580

Respiratory Tract Infections

Treatment of mild to moderate upper respiratory tract infections caused by susceptible S. pyogenes (group A β-hemolytic streptococci; GAS) (penicillin G benzathine).2 3

Treatment of moderately severe to severe upper respiratory tract infections caused by susceptible S. pyogenes (penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine).4 5 7

Treatment of serious respiratory tract infections (e.g., pneumonia, empyema) caused by susceptible S. pyogenes or other β-hemolytic streptococci (including groups C, H, G, L, and M) (penicillin G potassium or sodium).8 9 11 12 513

Treatment of moderately severe respiratory tract infections (pneumonia) caused by susceptible S. pneumoniae (penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine).4 5 7

Treatment of respiratory tract infections, including community-acquired pneumonia (CAP), caused by susceptible streptococci, including S. pneumoniae (penicillin G potassium or sodium).9 10 11 12 197 292 512 513 Consider that S. pneumoniae with resistance to penicillin G reported with increasing frequency.61 A drug of choice if CAP caused by penicillin-susceptible S. pneumoniae (MIC ≤2 mcg/mL).512 513 IDSA states parenteral penicillin G may be used for empiric treatment of CAP in infants or school-aged children fully immunized against invasive pneumococcal and Haemophilus influenzae type b (Hib) disease if local epidemiologic data for S. pneumoniae do not show substantial high-level penicillin resistance;513 other anti-infectives recommended for empiric treatment of CAP in adults and other infants and children.512 513

Treatment of serious respiratory tract infections (e.g., pneumonia, empyema) caused by susceptible nonpenicillinase-producing staphylococci (penicillin G potassium or sodium).8 9 11 12 513

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of respiratory tract infections, including CAP.512 513 514

Septicemia

Treatment of septicemia caused by susceptible S. pyogenes, other β-hemolytic streptococci (including groups C, H, G, L, and M), S. pneumoniae, or nonpenicillinase-producing staphylococci (penicillin G potassium or sodium).8 9 11 12

Skin and Skin Structure Infections

Treatment of moderately severe to severe skin and skin structure infections caused by susceptible S. pyogenes (penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine).4 5 7

Treatment of necrotizing infections of the skin, fascia, and muscle caused by susceptible S. pyogenes (penicillin G potassium or sodium).10 543 612 613 614 IDSA recommends IV penicillin G in conjunction with IV clindamycin for treatment of documented S. pyogenes necrotizing fasciitis.543

Treatment of moderately severe to severe skin and skin structure infections caused by susceptible staphylococci (penicillin G procaine).7 Because of high incidence of resistant strains, perform in vitro culture and susceptibility testing when treating suspected staphylococcal infections.7

Treatment of myonecrosis and gas gangrene caused by Clostridium perfringens or other clostridium (penicillin G potassium or sodium).8 9 11 12 543 (See Clostridium Infections under Uses.)

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of skin and skin structure infections.514 543

Actinomycosis

Treatment of actinomycosis (penicillin G potassium or sodium).8 9 10 11 12 27 28 29 32 61 197 292 898 901

IV penicillin G is a drug of choice for all forms of actinomycosis, including respiratory (pulmonary, bronchial, laryngeal), abdominal, genitourinary, CNS, and cervicofacial infections.10 27 28 29 32 61 197 292 898 901

Anthrax

Inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores (penicillin G procaine).7 Ciprofloxacin or doxycycline are initial drugs of choice for prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores, including exposures that occur in the context of biologic warfare or bioterrorism.663 668 671 672 673 681 682 683 686 703 If penicillin susceptibility confirmed, consideration can be given to changing prophylaxis to a penicillin (oral amoxicillin or penicillin V) in infants and children, pregnant or lactating women, or when drugs of choice not tolerated or not available;663 668 671 672 673 681 683 703 oral amoxicillin may be preferred, especially in infants and children.663 668 671 672 673 681 683 703

Treatment of mild, uncomplicated cutaneous anthrax caused by susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax (penicillin G procaine).7 680 If cutaneous anthrax occurs in the context of biologic warfare or bioterrorism, initial drugs of choice are ciprofloxacin and doxycycline.668 671 672 673 683 686 If penicillin susceptibility confirmed, consideration can be given to changing to a penicillin (oral amoxicillin or penicillin V) in infants and children, pregnant or lactating women, or when drugs of choice not tolerated or not available;668 671 672 673 683 686 oral amoxicillin may be preferred, especially in infants and children.668 671 672 673 683 686

Treatment of anthrax (inhalational, GI, or meningitis) caused by penicillin-susceptible B. anthracis that occurs as the result of natural or endemic exposures to anthrax (penicillin G potassium or sodium).670 680

Alternative for use in multiple-drug parenteral regimens for initial treatment of systemic anthrax (inhalational, GI, meningitis, cutaneous anthrax with systemic involvement, lesions on the head or neck, or extensive edema) caused by penicillin-susceptible B. anthracis that occurs in the context of biologic warfare or bioterrorism (penicillin G potassium or sodium).668 683 671 672 673 673 686

Clostridium Infections

Treatment of myonecrosis and gas gangrene caused by Clostridium perfringens or other clostridium (penicillin G potassium or sodium).8 9 10 11 12 61 197 292 543 IV penicillin G is a drug of choice;197 543 some experts recommend concomitant use of IV clindamycin.543 Anti-infectives are an adjunct to debridement and excision of the infected area.197 292 543

Adjunct to tetanus immune globulin (TIG) in management of tetanus caused by C. tetani (penicillin G potassium or sodium).8 9 11 12 10 61 197 292 886 Anti-infectives cannot neutralize toxin already formed and cannot eradicate C. tetani spores, which may revert to toxin-producing vegetative forms.10 Role of anti-infectives in treatment of tetanus unclear;10 if anti-infective used for adjunctive treatment, metronidazole usually preferred.10 292

Adjunct in management of botulism (penicillin G potassium or sodium).8 9 10 11 12 61 744 745 747 749 750 Botulism immune globulin IV (BIG-IV) is standard of care for infant botulism and anti-infectives not indicated unless clearly necessary for a concurrent infection.292 746 747 748 Botulism antitoxin (not commercially available in US, but may be available from CDC) is recommended treatment for other forms of botulism (e.g., foodborne and wound botulism) and for botulism that occurs in the context of biologic warfare or bioterrorism.10 292 683 746 747 751 753 Although role of anti-infectives in management of wound botulism unclear,10 61 penicillin G potassium or sodium has been used as adjunct to antitoxin and surgical debridement in wound botulism, including when antitoxin could not be administered.747 749 750

Diphtheria

Adjunct to diphtheria antitoxin (not commercially available in US, but may be available from CDC) for treatment of diphtheria caused by Corynebacterium diphtheriae (penicillin G procaine, penicillin G potassium or sodium).7 8 9 10 11 12 61 166 197 292 Anti-infectives are not a substitute for diphtheria antitoxin.292 If a penicillin used for adjunctive treatment of diphtheria, CDC recommends IM penicillin G procaine.166 Patients usually no longer contagious 48 hours after initiation of anti-infective treatment.166 Confirm eradication of C. diphtheriae 24 hours after completion of treatment by 2 consecutive negative cultures taken 24 hours apart.166 292 Because diphtheria infection may not confer immunity, initiate or complete immunization with a preparation containing diphtheria toxoid adsorbed during convalescence.292

Prevention of diphtheria in asymptomatic, household or close contacts of patients with respiratory or cutaneous diphtheria (penicillin G benzathine).166 292 If a penicillin used for prevention of diphtheria in contacts, CDC and AAP recommend IM penicillin G benzathine.166 292 Prompt initiation of prophylaxis indicated in all household or other close contacts of individuals with suspected or proven diphtheria, regardless of vaccination status of exposed individual.166 292 An immediate dose of age-appropriate preparation containing diphtheria toxoid adsorbed also indicated in contacts if inadequately immunized against diphtheria, immunization status unknown, or last booster dose received ≥5 years previously.166 292

Elimination of diphtheria carrier state in identified carriers of toxigenic C. diphtheriae (penicillin G benzathine, penicillin G procaine).7 10 64 166 292 900 If a penicillin used to eliminate diphtheria carrier state, CDC and AAP recommend IM penicillin G benzathine.166 292 Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers;166 if cultures positive, give a 10-day course of oral erythromycin and obtain additional follow-up cultures.166 292

Erysipelothrix rhusiopathiae Infections

Treatment of erysipeloid caused by Erysipelothrix rhusiopathiae (penicillin G procaine).7 10 64 197

Treatment of Erysipelothrix endocarditis (penicillin G potassium or sodium).8 9 11 12

Fusobacterium Infections

Treatment of moderately severe infections of the oropharynx caused by Fusobacterium, including Vincent’s gingivitis and pharyngitis (penicillin G procaine).7

Treatment of severe Fusobacterium infections of the oropharynx (including acute necrotizing ulcerative gingivitis [Vincent’s infection], trench mouth, Fusobacterium gingivitis or pharyngitis), lower respiratory tract, or genital area (penicillin G potassium or sodium).8 9 11 12 Not recommended for empiric treatment of such infections; although penicillin G may be effective against Fusobacterium, other organisms may also be involved (e.g., Bacteroides fragilis, Prevotella, Porphyromonas) that usually are resistant to the drug.10

Leptospirosis

Treatment of severe leptospirosis (penicillin G potassium or sodium).10 98 99 197 292 547

Leptospiral infections often result in asymptomatic or subclinical illness that is self-limited; however, severe, life-threatening infections can occur.10 292 Initiate anti-infective therapy as soon as possible after symptom onset;10 292 benefits of anti-infectives uncertain, especially if initiated in patients with late and/or severe disease.10 544 545 546

Listeria Infections

Treatment of serious infections caused by susceptible L. monocytogenes (e.g., infections during pregnancy, granulomatosis infantiseptica, septicemia, meningitis, endocarditis, pneumonia) (penicillin G potassium or sodium).8 9 10 61 64 11 12 476 Ampicillin used alone or in conjunction with gentamicin or streptomycin generally considered treatment of choice for invasive infections caused by L. monocytogenes.292 298 476

For information on treatment of meningitis caused by L. monocytogenes, see Meningitis and Other CNS Infections under Uses.

Lyme Disease

Treatment of early Lyme disease in patients with acute neurologic disease manifested as meningitis or radiculopathy (penicillin G potassium or sodium).292 329 Alternative to IV ceftriaxone.329

Treatment of late Lyme disease in patients with recurrent Lyme arthritis and objective evidence of neurologic disease (penicillin G potassium or sodium).329 Alternative to IV ceftriaxone.329

Treatment of late neurologic Lyme disease affecting central or peripheral nervous system (penicillin G potassium or sodium).329 342 Alternative to IV ceftriaxone.329

Neisseria Infections

Treatment of serious infections caused by susceptible N. meningitidis (e.g., meningococcal sepsis, meningitis, pneumonia, arthritis) (penicillin G potassium or sodium).8 9 11 12 61 166 197 292 (See Meningitis and Other CNS Infections under Uses.) A drug of choice for most invasive meningococcal infections.61 197 166 292

May not eliminate nasopharyngeal carriage of N. meningitidis.166 292 Chemoprophylaxis with ceftriaxone, ciprofloxacin, or rifampin usually recommended to eradicate nasopharyngeal carriage of N. meningitidis after treatment of invasive disease and prior to hospital discharge.166 292

Do not use for treatment of gonorrhea.344 345 Was used in the past for infections caused by penicillin-susceptible N. gonorrhoeae (penicillin G potassium or sodium).8 9 11 12 849 858 Penicillins no longer recommended by CDC or others for gonococcal infections (high incidence of penicillinase-producing strains of N. gonorrhoeae).7 344 345

Pasteurella Infections

Treatment of serious infections caused by Pasteurella multocida, including bacteremia and meningitis (penicillin G potassium or sodium).8 9 11 12 A drug of choice for local infections, septicemia, osteomyelitis, endocarditis, or other serious infections.10 61 197 292

Rat-bite Fever

Treatment of rat-bite fever caused by susceptible Streptobacillus moniliformis (erythema arthriticum epidemicum, Haverhill fever) or Spirillum minus (sodoku) (penicillin G procaine, penicillin G potassium or sodium).7 8 9 10 11 12 30 31 64 197 292 887

IV penicillin G usually drug of choice.10 30 64 197 292 887 Concomitant aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment of S. moniliformis endocarditis.10 30 292

Syphilis

Treatment of syphilis (penicillin G benzathine, penicillin G procaine, penicillin G potassium or sodium).2 3 7 292 344 345 440 441

CDC and other experts state IM penicillin G benzathine is drug of choice for treatment of primary syphilis (i.e., ulcer or chancre at infection site), secondary syphilis (i.e., manifestations that include, but are not limited to, rash, mucocutaneous lesions, and lymphadenopathy), and tertiary syphilis (i.e., cardiac syphilis, gummatous lesions, tabes dorsalis, and general paresis) in adults, adolescents, and children.344 345 350 440 441

IM penicillin G benzathine also drug of choice for treatment of latent syphilis (i.e., detected by serologic testing but lacking clinical manifestations), including both early latent syphilis (latent syphilis acquired within the preceding year) and late latent syphilis (i.e., all other cases of latent syphilis or syphilis of unknown duration) in all age groups.344 345 350 440 441

For treatment of neurosyphilis and otic or ocular syphilis, CDC and other experts state IV penicillin G potassium or sodium is drug of choice; IM penicillin G procaine (with oral probenecid) is an alternative if compliance can be ensured.344 345 440 441

For treatment of congenital syphilis, CDC recommends IV penicillin G potassium or sodium or IM penicillin G procaine in neonates with proven or highly probable congenital syphilis (i.e., abnormal physical examination consistent with congenital syphilis, serum quantitative nontreponemal serologic titer fourfold higher than the mother's titer, or positive darkfield test or polymerase chain reaction [PCR] of lesions or body fluids).344 IV penicillin G potassium or sodium, IM penicillin G procaine, or IM penicillin G benzathine recommended in neonates with possible congenital syphilis (i.e., normal physical examination and serum quantitative nontreponemal serologic titer no more than fourfold higher than the mother's titer and the mother received a recommended treatment regimen less than 4 weeks before delivery; the mother was not treated or was inadequately treated, including treatment with erythromycin or any regimen not included in CDC recommendations; or there is no documentation that the mother received treatment).344

CDC states that syphilis diagnosed in infants and children ≥1 month of age should be managed by a pediatric infectious disease specialist.344

HIV-infected neonates with congenital syphilis and HIV-infected children, adolescents, and adults with neurosyphilis or any stage of syphilis: Use same treatment regimens recommended for those without HIV infection.344 440 441 Because serologic nonresponse and neurologic complications may be more frequent in HIV-infected individuals, close follow-up is essential in those coinfected with syphilis and HIV.344 440 In addition, careful neurologic examinations indicated in all coinfected patients.440

Infant or child with congenital syphilis and known or suspected penicillin hypersensitivity: No proven alternatives to penicillin G; CDC recommends desensitization and treatment with appropriate penicillin G preparation.344

Nonpregnant patient with primary, secondary, or latent syphilis and penicillin hypersensitivity: Can consider certain alternatives to penicillin G (e.g., doxycycline, tetracycline); if compliance with alternatives or follow-up cannot be ensured, CDC recommends desensitization and treatment with IM penicillin G benzathine.344

Nonpregnant patient with neurosyphilis and penicillin hypersensitivity: No proven alternatives to penicillin G, but can consider ceftriaxone in certain circumstances; if compliance with alternatives or follow-up cannot be ensured, CDC recommends desensitization and treatment with appropriate penicillin G preparation.344

Pregnant woman with any stage of syphilis and penicillin hypersensitivity: No proven alternatives to penicillin G; CDC recommends desensitization and treatment with appropriate penicillin G preparation.344

Do not use a fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) for treatment of any form of syphilis;4 5 17 18 344 inadvertent use of a fixed combination may not provide the sustained serum concentrations of penicillin G required for syphilis treatment and could increase risk of treatment failure and neurosyphilis, especially in HIV-infected patients.18

Consult current CDC sexually transmitted diseases treatment guidelines available at [Web] for additional information regarding management of syphilis.344

Whipple's Disease

Treatment of Whipple’s disease caused by Tropheryma whipplei.10 197 716 717 719 720 724

Optimal regimens for treatment of Whipple’s disease not identified;717 718 719 720 relapses may occur, even after adequate and long-term anti-infective treatment.10 717 718 719 720 Some clinicians recommend an initial parenteral regimen (e.g., ceftriaxone, penicillin G with or without streptomycin) followed by a long-term regimen of oral co-trimoxazole.10 716

Yaws, Pinta, and Bejel

Treatment of yaws (T. pertenue), pinta (T. carateum), and bejel (T. pallidum var. endemic syphilis) (penicillin G benzathine, penicillin G procaine).2 3 7 10 197 674 675 Drugs of choice.10 197

Do not use fixed combinations of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) for treatment of yaws, pinta, and bejel.4 5

Prevention of Perinatal Group B Streptococcal Disease

Prevention of early-onset neonatal group B streptococcal (GBS) disease (penicillin G potassium or sodium).292 359 362

Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is indicated in women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks of gestation during the current pregnancy, in women with GBS bacteriuria identified at any time during current pregnancy, and in those with a previous infant diagnosed with invasive GBS disease.292 359 In those with unknown GBS status at onset of labor, intrapartum anti-infective prophylaxis indicated in those with delivery at <37 weeks of gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.292 359

When intrapartum anti-infective prophylaxis indicated in the mother for prevention of GBS in the neonate, initiate at onset of labor or rupture of membranes.359 If cesarean delivery performed before onset of labor in a woman with intact amniotic membranes, anti-infective prophylaxis not usually indicated, regardless of GBS colonization status of the woman or gestational age.292 359

IV penicillin G is drug of choice and IV ampicillin is preferred alternative.292 359 362 Penicillin G has a narrower spectrum of activity and is less likely to select for antibiotic-resistant organisms.292 359

Regardless of whether the mother received anti-infective prophylaxis, initiate appropriate diagnostic evaluations and anti-infective therapy in the neonate if signs or symptoms of active infection develop.292 359 362

Consult most recent CDC and AAP guidelines for additional information on prevention of perinatal GBS disease.359 362

Prevention of Rheumatic Fever Recurrence

Prevention of recurrent attacks of rheumatic fever (secondary prophylaxis) in individuals who have had a previous attack of rheumatic fever (penicillin G benzathine).2 3 61 375

IM penicillin G benzathine generally considered drug of choice for secondary prophylaxis of rheumatic fever because it ensures compliance;292 375 alternatives include oral penicillin V or oral sulfadiazine.292 375

AHA and AAP recommend long-term (continuous) prophylaxis following treatment of documented acute rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease (even after prosthetic valve replacement).292 375

Initiate prophylaxis as soon as rheumatic fever or rheumatic heart disease diagnosed,292 375 although patients with acute rheumatic fever should first receive usually recommended anti-infective treatment for S. pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis (see Pharyngitis and Tonsillitis under Uses).375

Penicillin G Benzathine/Procaine/Potassium/Sodium Dosage and Administration

Administration

Penicillin G benzathine,2 3 penicillin G procaine,7 fixed combinations containing penicillin G benzathine and penicillin G procaine:4 5 Administer only by deep IM injection. Do not give IV or admix with IV solutions.2 4 5 Take special precaution to avoid inadvertent intravascular or intra-arterial administration or injection into or near major peripheral nerves or blood vessels since such injections may result in severe and/or permanent neurovascular damage.2 4 5 7 (See Precautions Related to IM Administration under Cautions.)

Penicillin G potassium,9 11 12 penicillin G sodium:8 Administer by IM injection or by intermittent IV injection or infusion or continuous IV infusion.8 9 11 12 61 Has been administered by intrapleural,9 12 intraperitoneal,61 intra-articular,9 12 or other local instillations.9 12 Has been administered intrathecally;9 12 61 this route not recommended because of possible neurotoxicity (e.g., seizures).61 416

IM Injection

For IM injection, use penicillin G benzathine, penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine, penicillin G potassium, or penicillin G sodium based on indication.2 3 4 5 7 8 9 12

Penicillin G Benzathine, Penicillin G Procaine, Fixed Combinations of Penicillin G Benzathine and Penicillin G Procaine

Provided in prefilled syringes; administer undiluted according to manufacturer's directions.2 3 4 5 7

In adults, generally give IM injections deeply into gluteus maximus (upper outer quadrant of the buttock) or midlateral thigh.2 3 4 5 In neonates, infants, and small children, preferably give IM injections into midlateral muscles of the thigh.2 3 4 5

To minimize possibility of damage to sciatic nerve, one manufacturer recommends that the periphery of the upper outer quadrant of gluteal region be used in infants and small children only when necessary (e.g., in burn patients) and recommends that the deltoid area be used only if well developed, such as in certain adults and older children, and only with caution to avoid radial nerve injury.3

Inject IM at a slow, steady rate to avoid blockage of the needle.2 4 5 7

Rotate IM injection sites when repeated doses are given.2 3 4 5 7

Avoid repeated IM injections into anterolateral thigh, especially in neonates and infants, since quadriceps femoris fibrosis and atrophy reported.2 4 5 (See Precautions Related to IM Administration under Cautions.)

Penicillin G benzathine: IM injections may be less painful if warmed to room temperature before administration.292 375 One manufacturer suggests dose can be divided and given at 2 separate sites if necessary in children <2 years of age.3

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R): Manufacturer states dose usually given at a single session using multiple IM sites; alternatively, total dose can be divided and half given on day 1 and half on day 3 if compliance regarding the return visit is ensured.5

Penicillin G Potassium or Sodium

For IM injection, reconstitute vials containing 1 or 5 million penicillin G units (as penicillin G potassium)9 12 or vials containing 5 million penicillin G units (as penicillin G sodium)8 to desired concentration using amount of diluent specified by the manufacturer.8 9 12

Loosen powder in the vial; hold horizontally and rotate while slowly directing diluent against vial wall.8 9 12 Shake vigorously after diluent added.8 9 12

Refrigerate reconstituted vials if not used immediately;8 9 12 unstable in solution at room temperature.61

Vials containing 20 million penicillin G units (as penicillin G potassium) are intended only for IV administration; do not use to prepare IM injections.9 12

For IM injection, solutions containing up to 100,000 units/mL may be given with a minimum of discomfort; higher concentrations are physically possible and may be used when needed.9 12

If large doses of penicillin G potassium or sodium required, give the drug IV (not IM).9 12

IV Administration

For IV administration, use penicillin G potassium or sodium.8 9 11 12

Reconstitute vials containing 1, 5, or 20 million penicillin G units (as penicillin G potassium)9 12 or vials containing 5 million penicillin G units (as penicillin G sodium)8 to desired concentration using amount of diluent specified by manufacturer.8 9 12

Loosen powder in the vial; hold horizontally and rotate while slowly directing diluent against vial wall.8 9 12 Shake vigorously after diluent added.8 9 12

Refrigerate reconstituted vials if not used immediately;8 9 12 unstable in solution at room temperature.61

Alternatively, thaw commercially available frozen premixed penicillin G potassium injection in dextrose at room temperature (25°C) or in a refrigerator (5°C); do not force thaw by immersion in a water bath or by exposure to microwave radiation.11 Precipitates that may have formed in the frozen injection usually will dissolve with little or no agitation when the injection reaches room temperature.11 After thawing, agitate the injection.11 Discard thawed injection if the solution is cloudy or contains a precipitate or if container seals or outlet ports are not intact.11 Do not introduce additives into the injection container.11 Do not use in series connections with other plastic containers since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.11

Intermittent IV administration: Daily dosage usually given in equally divided doses every 4–6 hours; may be given in equally divided doses every 2–3 hours for treatment of severe infections (e.g., meningitis).8 9 12 61

Continuous IV infusion: Determine volume of IV fluid and rate of administration required by the patient in a 24-hour period and add the appropriate daily dosage of penicillin G to the fluid.9 12 For example, if an adult requires 2 L of fluid in 24 hours and a dosage of 10 million penicillin G units daily, add 5 million units to 1 L of IV solution and adjust administration rate so that the liter of fluid will be infused over 12 hours.9 12

Rate of Administration

Administer large IV doses of penicillin G potassium or sodium (>10 million penicillin G units) slowly because of potential for serious electrolyte disturbances from the potassium and/or sodium content of these preparations.8 9 11 12 (See Electrolyte Imbalance under Cautions.)

Intermittent IV administration: Has been given by IV infusion over 1–2 hours8 9 11 12 61 1563 or by IV infusion over 10–30 minutes.61 1414 Although doses have been injected IV over 3–5 minutes,8 9 11 12 61 large doses should be administered slowly.8 9 11 12

Dosage

Dosage of penicillin G benzathine, penicillin G procaine, penicillin G potassium, and penicillin G sodium usually expressed in terms of penicillin G units.2 3 7 8 9 11 12 Also has been expressed in terms of mg of penicillin G.61

Dosage of fixed combinations containing penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) usually expressed in terms of the total (sum) of penicillin G units of penicillin G benzathine and penicillin G units of penicillin G procaine.4 5

Pediatric Patients

General Dosage for Neonates
Penicillin G Procaine
IM

Neonates ≤28 days of age: AAP recommends 50,000 units/kg once every 24 hours.292

Penicillin G Potassium or Sodium
IV or IM

Neonates ≤7 days of age: AAP recommends 25,000–50,000 units/kg every 12 hours.292 AAP states higher dosage may be required for treatment of meningitis.292

Neonates 8–28 days of age: AAP recommends 25,000–50,000 units/kg every 8 hours.292 AAP states higher dosage may be required for treatment of meningitis.292

General Pediatric Dosage
Penicillin G Benzathine
IM

Pediatric patients beyond neonatal period: AAP recommends a single dose of 300,000–600,000 units in those weighing <27 kg and single dose of 900,000 units in those weighing ≥27 kg for treatment of mild to moderate infections.292 AAP states inappropriate for severe infections.292

Penicillin G Procaine
IM

Pediatric patients beyond neonatal period: AAP recommends 50,000 units/kg daily in 1 or 2 divided doses for treatment of mild to moderate infections.292 AAP states inappropriate for severe infections.292

Fixed Combinations of Penicillin G Benzathine and Penicillin G Procaine
IM

Pediatric patients beyond neonatal period (Bicillin C-R): AAP recommends a single dose of 600,000 units in those weighing <14 kg, single dose of 900,000 to 1.2 million units in those weighing 14–27 kg, and single dose of 2.4 million units in those weighing ≥27 kg.292

Penicillin G Potassium or Sodium
IV or IM

Children beyond neonatal period: AAP recommends 100,000–150,000 units/kg daily in 4 divided doses for treatment of mild to moderate infections or 200,000–300,000 units/kg daily in 4–6 divided doses for treatment of severe infections.292 AAP states use highest recommended dosage for treatment of meningitis.292

Endocarditis
Native Valve Endocarditis Caused by S. pyogenes, S. agalactiae, Streptococci Groups C or G, Viridans Streptococci, or Nonenterococcal Group D (S. gallolyticus, S. equinus)
IV

Penicillin G potassium or sodium for highly penicillin-susceptible strains (penicillin MIC ≤0.1 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 4 weeks.452

Penicillin G potassium or sodium for relatively resistant strains (penicillin MIC >0.1 but <0.5 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 4 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).452

Penicillin G potassium or sodium for viridans streptococci with penicillin MIC ≥0.5 mcg/mL: AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 4–6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).452

Native Valve Endocarditis Caused by Abiotrophia or Granulicatella
IV

Penicillin G potassium or sodium for strains with penicillin MIC ≥0.5 mcg/mL: AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 4–6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).452

Endocarditis Involving Prosthetic Valves or Other Prosthetic Material Caused by Viridans Streptococci, Other Streptococci, Abiotrophia, or Granulicatella
IV

Penicillin G potassium or sodium for penicillin-susceptible strains (penicillin MIC ≤0.1 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).452

Penicillin G potassium or sodium for strains with penicillin MIC ≥0.1 mcg/mL: AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) given in divided doses every 4 hours for 6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during entire 6 weeks of penicillin G treatment).452

Enterococcal Endocarditis
IV

Penicillin G potassium or sodium for enterococcal endocarditis involving native valves or prosthetic valves or other prosthetic material: AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours).452

Recommended treatment duration of the 2-drug regimen is 4–6 weeks for native valve enterococcal endocarditis; longer duration recommended if prosthetic valve or other prosthetic material involved.452

Endocarditis Caused by Staphylococci
IV

Penicillin G potassium or sodium for susceptible S. aureus or coagulase-negative staphylococci (penicillin MIC ≤0.1 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours.452

Endocarditis Caused by Streptococci
IV or IM

Penicillin G potassium or sodium for susceptible streptococci, including S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 150,000–300,000 units/kg daily in divided doses every 4–6 hours.8 9 11 12

Meningitis
Meningitis Caused by L. monocytogenes
IV

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age.418 Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.418

Penicillin G potassium or sodium in infants and children: IDSA recommends 300,000 units/kg daily in divided doses every 4–6 hours for ≥21 days.418 Consider using an aminoglycoside concomitantly.418

Meningitis Caused by N. meningitidis
IV

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age.418 Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.418

Penicillin G potassium or sodium in infants and children: IDSA and AAP recommend 300,000 units/kg daily (up to 12 million units daily) in divided doses every 4–6 hours for 7 days.292 418

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 250,000 units/kg daily (up to 12–20 million units daily) in divided doses every 4 hours for 7–14 days.8 9 11 12

Meningitis Caused by S. agalactiae (Group B Streptococci; GBS)
IV

Penicillin G potassium or sodium in neonates: AAP recommends 250,000–450,000 units/kg daily in 3 divided doses in those ≤7 days of age and 450,000–500,000 units/kg daily in 4 divided doses in those >7 days of age.292 Continue treatment for ≥14 days.292

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age.418 Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.418

Penicillin G potassium or sodium in infants and children: IDSA recommends 300,000 units/kg daily in divided doses every 4–6 hours for 14–21 days.418 Consider using an aminoglycoside concomitantly.418

Meningitis Caused by S. pneumoniae
IV

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age.418 Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.418

Penicillin G potassium or sodium in infants and children ≥1 month of age: AAP recommends 250,000–400,000 units/kg daily in divided doses every 4–6 hours.292 IDSA recommends that infants and children receive 300,000 units/kg daily in divided doses every 4–6 hours for 10–14 days.418

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 250,000 units/kg daily (up to 12–20 million units daily) in divided doses every 4 hours for 7–14 days.8 9 11 12

Healthcare-associated Ventriculitis and Meningitis Caused by C. acnes
IV

Penicillin G potassium or sodium: IDSA recommends 300,000 units/kg daily in divided doses every 4–6 hours.416 Treatment duration is 10 days in those with no or minimal CSF pleocytosis, normal CSF glucose, and few clinical symptoms or systemic features or 10–14 days in those with significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features.416

Pharyngitis and Tonsillitis
Treatment of S. pyogenes Pharyngitis and Tonsillitis
IM

Penicillin G benzathine: AAP, IDSA, and AHA recommend a single dose of 600,000 units in those weighing <27 kg and single dose of 1.2 million units in those weighing ≥27 kg.292 375 580 Manufacturers recommend a single dose of 300,000–600,000 units in those weighing <27 kg and single dose of 900,000 units in older children.2 3

Penicillin G procaine: Manufacturer recommends 300,000 units daily for at least 10 days in children weighing <27 kg and 600,000 to 1 million units daily for at least 10 days in others.7 AHA, IDSA, and AAP recommend penicillin G benzathine.292 375 580

Eradication of Pharyngeal Carriage of S. pyogenes
IM

Penicillin G benzathine in certain circumstances when eradication of carrier state is desirable (see Pharyngitis and Tonsillitis under Uses): IDSA states a single of 600,000 units in those weighing <27 kg or single dose of 1.2 million units in those weighing ≥27 kg given in conjunction with oral rifampin (20 mg/kg daily [up to 600 mg daily] given in 2 doses for 4 days) is an option.580

Respiratory Tract Infections
IM

Penicillin G benzathine for mild to moderate upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 300,000–600,000 units in children weighing <27 kg and single dose of 900,000 units in older pediatric patients.2

Penicillin G procaine for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends 300,000 units daily for ≥10 days in children weighing <27 kg and 600,000 to 1 million units daily for ≥10 days in others.7

Penicillin G procaine for moderately severe, uncomplicated respiratory infections (pneumonia) caused by susceptible S. pneumoniae: Manufacturer recommends 300,000 units daily in children weighing <27 kg and 600,000 to 1 million units daily in others.7

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 600,000 units in children weighing <13.6 kg, single dose of 900,000 to 1.2 million units in those weighing 13.6–27.2 kg, and single dose of 2.4 million units in those weighing >27.2 kg.5

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe respiratory infections (pneumonia, otitis media) caused by susceptible S. pneumoniae: Manufacturer recommends 600,000 units once every 2 or 3 days until patient is afebrile for 48 hours.5

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R 900/300) for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer states a single dose of 1.2 million units usually sufficient in pediatric patients.4

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R 900/300) for moderately severe respiratory infections (pneumonia, otitis media) caused by susceptible S. pneumoniae: Manufacturer recommends 1.2 million units once every 2 or 3 days until patient has been afebrile for 48 hours.4

IV or IM

Penicillin G potassium or sodium for CAP caused by susceptible S pyogenes in infants and children ≥3 months of age: IDSA recommends 100,000–200,000 units/kg daily in 4–6 divided doses; 200,000–250,000 units/kg daily may be used for severe infections.513

Penicillin G potassium or sodium for CAP caused by susceptible S. pneumoniae (penicillin MIC ≤2 mcg/mL) in infants and children ≥3 months of age: IDSA recommends 200,000–250,000 units/kg daily in divided doses every 4–6 hours.513 For nonmeningeal infections caused by susceptible S. pneumoniae in infants and children ≥1 month of age, AAP recommends 250,000–400,000 units/kg daily in divided doses every 4–6 hours.292

Penicillin G potassium or sodium for serious infections (e.g., pneumonia) caused by susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae in pediatric patients: Manufacturers recommend 150,000–300,000 units/kg daily in divided doses every 4–6 hours.8 9 11 12

Skin and Skin Structure Infections
IM

Penicillin G procaine for moderately severe infections (including erysipelas) caused by susceptible staphylococci: Manufacturer recommends 300,000 units daily in children weighing <27 kg and 600,000 to 1 million units daily in others.7

Penicillin G procaine for moderately severe to severe infections caused by susceptible S. pyogenes: Manufacturer recommends 300,000 units daily for at least 10 days in children weighing <27 kg and 600,000 to 1 million units daily for at least 10 days in others.7

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections (including erysipelas) caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 600,000 units in children weighing <13.6 kg, single dose of 900,000 to 1.2 million units in those weighing 13.6–27.2 kg, and single dose of 2.4 million units in those weighing >27.2 kg.5

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R 900/300) for moderately severe infections (including erysipelas) caused by susceptible S. pyogenes: Manufacturer states a single dose of 1.2 million units usually sufficient in pediatric patients.4

IV

Penicillin G potassium or sodium for necrotizing infections of skin, fascia, and muscle caused by susceptible S. pyogenes in pediatric patients: IDSA recommends 60,000–100,000 units/kg every 6 hours in conjunction with clindamycin (10–13 mg/kg IV every 8 hours).543

Anthrax
Postexposure Prophylaxis (Inhalational Anthrax)
IM

Penicillin G procaine: 25,000 units/kg (up to 1.2 million units) every 12 hours recommended by manufacturer.7 AAP and CDC recommend other penicillins (oral amoxicillin or penicillin V) for prophylaxis following exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism when penicillin-susceptible strains involved.671 672 673

Total duration of anti-infective prophylaxis following aerosol exposure to B. anthracis spores in the context of biologic warfare or bioterrorism should be ≥60 days.7 663 668 671 672 681 682 683 686 Manufacturer states safety data for penicillin G procaine administered at dosage recommended for inhalational anthrax (postexposure) supports a duration ≤2 weeks; consider risks versus benefits of continuing the drug for >2 weeks or switching to an appropriate alternative anti-infective.7

Treatment of Mild, Uncomplicated Cutaneous Anthrax (Naturally Occurring or Endemic Exposure)
IM

Penicillin G procaine in children weighing <20 kg: 25,000–50,000 units/kg daily (single or 2 divided doses daily) recommended by some experts.680

Although 3–10 days of anti-infective therapy may be adequate if mild, uncomplicated cutaneous anthrax occurred as the result of natural or endemic exposures,668 680 681 683 686 some experts recommend duration of 7–14 days.680 CDC and others recommend 60 days of anti-infective treatment if cutaneous anthrax occurred as the result of exposure to aerosolized B. anthracis spores (e.g., in the context of biologic warfare or bioterrorism).668 671 680 681 683 686

Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)
IV

Penicillin G potassium or sodium in children with inhalational, GI, or meningeal anthrax: Some clinicians recommend 100,000–150,000 units/kg daily given in divided doses every 4–6 hours.670

Penicillin G potassium or sodium in children with severe or life-threatening systemic anthrax (inhalational, GI, meningoencephalitis, sepsis) or cutaneous anthrax with signs of systemic involvement, lesions on head or neck, or extensive edema: Some experts recommend 300,000–400,000 units/kg daily given in divided doses every 4–6 hours.680

Concomitant use of other anti-infectives (e.g., streptomycin or other aminoglycoside, clindamycin, clarithromycin, rifampin, vancomycin) may also be indicated.670 680 Continue treatment of naturally occurring or endemic anthrax for ≥14 days after symptoms abate.670

Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism Exposure)
IV

Penicillin G potassium or sodium in full-term neonates: AAP recommends 300,000 units/kg daily given in divided doses every 8 hours in those ≤7 days of age and 400,000 units/kg daily given in divided doses every 6 hours in those 1–4 weeks of age.671

Penicillin G potassium or sodium in premature neonates (gestational age 32–34 weeks): AAP recommends 200,000 units/kg daily given in divided doses every 12 hours in those ≤7 days of age and 300,000 units/kg daily given in divided doses every 8 hours in those 1–4 weeks of age.671

Penicillin G potassium or sodium in premature neonates (gestational age 34–37 weeks): AAP recommends 300,000 units/kg given in divided doses every 8 hours in those ≤7 days of age and 400,000 units/kg daily given in divided doses every 6 hours in those 1–4 weeks of age.671

Penicillin G potassium or sodium in infants and children ≥1 month of age: 400,000 units/kg daily in divided doses every 4 hours (up to 4 million units per dose).671

Use in multiple-drug parenteral regimen for initial treatment of systemic anthrax (inhalational, GI, meningitis, cutaneous anthrax with systemic involvement, lesions on the head or neck, or extensive edema).671 Continue parenteral regimen for ≥2–3 weeks until patient is clinically stable; treatment can then be switched to an oral regimen.671 CDC and other experts state that total duration of anti-infective treatment for anthrax in the context of biologic warfare or bioterrorism should be 60 days.668 671 683 686

Clostridium Infections
Myonecrosis and Gas Gangrene
IV

Penicillin G potassium or sodium: IDSA recommends 60,000–100,000 units/kg every 6 hours in conjunction with clindamycin (10–13 mg/kg IV every 8 hours).543 AAP recommends 250,000–400,000 units/kg daily and states that concomitant use of clindamycin may be more effective than penicillin G alone.292

Perform surgical debridement and/or surgery as indicated.8 9 11 12

Tetanus
IV

Potassium G potassium or sodium: AAP recommends 100,000 units/kg daily (up to 12 million units daily) given in divided doses every 4–6 hours for 7–10 days.292

Adjunct to TIG.292 (See Clostridium Infections under Uses.)

Diphtheria
Treatment of Diphtheria
IM

Penicillin G procaine: Manufacturer recommends 300,000–600,000 units daily for 14 days.7 CDC recommends 300,000 units daily in those weighing ≤10 kg or 600,000 units daily in those weighing >10 kg.166

Adjunct to diphtheria antitoxin.7 166 (See Diphtheria under Uses.)

IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 150,000–250,000 units/kg daily given in divided doses every 6 hours for 7–10 days.8 9 11 12 CDC recommends penicillin G procaine if a penicillin used.166

Adjunct to diphtheria antitoxin.8 9 11 12 (See Diphtheria under Uses.)

Prevention of Diphtheria in Close Contacts
IM

Penicillin G benzathine: CDC and AAP recommend a single dose of 600,000 units in children <6 years of age or weighing <30 kg or single dose of 1.2 million units in those ≥6 years of age or weighing ≥30 kg.166 292

Provide anti-infective prophylaxis regardless of immunization status and closely monitor for symptoms of diphtheria for 7 days.166 292

Contacts inadequately immunized against diphtheria or with unknown immunization status: Give immediate dose of age-appropriate preparation containing diphtheria toxoid adsorbed and complete primary series according to recommended schedules.292

Contacts fully immunized against diphtheria but received last booster dose ≥5 years previously: Give immediate booster dose of age-appropriate preparation containing diphtheria toxoid adsorbed.166 292

Elimination of Diphtheria Carrier State
IM

Penicillin G benzathine: CDC and AAP recommend a single dose of 600,000 units in children <6 years of age or weighing <30 kg or single dose of 1.2 million units in those ≥6 years of age or weighing ≥30 kg.166 292

Penicillin G procaine: Manufacturer recommends 300,000 units daily for 10 days.7 CDC and AAP recommend penicillin G benzathine if a penicillin used.166 292

Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures are positive, give a 10-day course of oral erythromycin and obtain additional follow-up cultures.166 292

Lyme Disease
Early Lyme Disease with Acute Neurologic Disease
IV

Penicillin G potassium or sodium: 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in 6 divided doses (every 4 hours) for 10–28 days.292 329

Late Lyme Disease with Recurrent Lyme Arthritis and Evidence of Neurologic Disease
IV

Penicillin G potassium or sodium: 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in 6 divided doses (every 4 hours) for 14–28 days.292 329

Late Neurologic Lyme Disease
IV

Penicillin G potassium or sodium: 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in 6 divided doses (every 4 hours) for 14–28 days.292 329

Neisseria meningitidis Infections
Serious Infections
IV or IM

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 150,000–300,000 units/kg daily in divided doses every 4–6 hours.8 9 11 12

Also see Pediatric Patients: Meningitis Caused by L. monocytogenes, under Dosage and Administration.

Rat-bite Fever
IV or IM

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 150,000–250,000 units/kg daily in divided doses every 4 hours for 4 weeks.8 9 11 12

Penicillin G potassium or sodium in pediatric patients: Some clinicians recommend 20,000–50,000 units/kg IV daily for 5–7 days followed by oral penicillin V (25–50 mg/kg daily [up to 3 g daily] in 4 divided doses for 7 days).30 For S. moniliformis endocarditis caused by a strain less susceptible to penicillin G (MIC >0.1 mcg/mL), some clinicians recommend 160,000–240,000 units/kg IV daily (up to 20 million units daily) for 6 weeks;30 concomitant use of an aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment.10 30 292

Syphilis
Neonates with Proven or Highly Probable Congenital Syphilis
IM

Penicillin G procaine: CDC and AAP recommend 50,000 units/kg once daily for 10 days.292 344 If >1 day of treatment missed, restart entire course of treatment.292 344

IV

Penicillin G potassium or sodium: CDC recommends 50,000 units/kg every 12 hours during first 7 days of life and 50,000 units/kg every 8 hours thereafter for total duration of 10 days.344 If >1 day of treatment missed, restart entire course of treatment.344

Neonates with Possible Congenital Syphilis or When Congenital Syphilis Less Likely
IM

Penicillin G benzathine: CDC and manufacturers recommend a single dose of 50,000 units/kg.2 3 344

Penicillin G procaine: CDC recommends 50,000 units/kg once daily for 10 days.344

IV

Penicillin G potassium or sodium: CDC recommends 50,000 units/kg every 12 hours during first 7 days of life and 50,000 units/kg every 8 hours thereafter for total duration of 10 days.344

Infants and Children ≥1 Month of Age with Reactive Serologic Test for Syphilis and Normal CSF Evaluation
IM

Penicillin G benzathine: CDC states 50,000 units/kg (up to 2.4 million units) once weekly for up to 3 weeks can be considered.344 Alternatively, may consider a single dose of 50,000 units/kg (up to 2.4 million units) after completion of 10-day regimen of IV penicillin G potassium or sodium.344

IV

Penicillin G potassium or sodium: CDC recommends 50,000 units/kg every 4–6 hours for 10 days.344 Some clinicians recommend that this regimen be followed by a single dose of IM penicillin G benzathine (50,000 units/kg).292 344

Congenital Syphilis or Neurosyphilis in Infants and Children >1 Month of Age
IV

Penicillin G potassium or sodium: CDC, AAP, and manufacturers recommend 200,000–300,000 units/kg daily (50,000 units every 4–6 hours) for 10–14 days.8 9 11 12 292 344 Some clinicians recommend that this regimen be followed by a single dose of IM penicillin G benzathine (50,000 units/kg [up to 2.4 million units]).292 344

Primary, Secondary, or Early Latent Syphilis in Infants and Children ≥1 Month of Age
IM

Penicillin G benzathine: CDC, AAP, and others recommend a single dose of 50,000 units/kg (up to 2.4 million units).292 344 441

When syphilis diagnosed in infants and children ≥1 month of age, CDC states treatment should be managed by a pediatric infectious disease specialist.344

Late Latent Syphilis in Infants and Children ≥1 Month of Age
IM

Penicillin G benzathine: CDC, AAP, and others recommend 50,000 units/kg (up to 2.4 million units) once weekly for 3 consecutive weeks (up to a maximum total dosage of 7.2 million units).292 344 441

When syphilis diagnosed in infants and children ≥1 month of age, CDC states treatment should be managed by a pediatric infectious disease specialist.344 Examination of CSF indicated in those with latent syphilis.344

Primary, Secondary, or Early Latent Syphilis in Adolescents
IM

Penicillin G benzathine in adolescents 10–19 years of age: Some experts recommend a single dose of 2.4 million units.350 440

Penicillin G procaine in adolescents 10–19 years of age: Some experts recommend 1.2 million units once daily for 10–14 days as an alternative to penicillin G benzathine.350

Penicillin G procaine in children >12 years of age: Manufacturer recommends 600,000 units daily for 8 days (total dosage 4.8 million units).7 CDC and others recommend penicillin G benzathine.344 350 440

Tertiary or Late Latent Syphilis in Adolescents
IM

Penicillin G benzathine in adolescents 10–19 years of age: Some experts recommend 2.4 million units once weekly for 3 consecutive weeks for late latent syphilis or syphilis of unknown duration.350 440 Interval between doses should not be >14 days.350

Penicillin G procaine in adolescents 10–19 years of age: Some experts recommend 1.2 million units once daily for 20 days as an alternative to penicillin G benzathine for late latent syphilis or syphilis of unknown duration.350

Penicillin G procaine in children >12 years of age: Manufacturer recommends 600,000 units daily for 10–15 days (total dosage 6–9 million units).7 CDC and others recommend penicillin G benzathine.344 350 440

Neurosyphilis and Otic or Ocular Syphilis in Adolescents
IV

Penicillin G potassium or sodium: 18–24 million units daily (by continuous IV infusion or given as 3–4 million units every 4 hours) for 10–14 days.440 Some clinicians recommend this regimen be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).440

Yaws, Pinta, and Bejel
IM

Penicillin G benzathine in children: A single dose of 600,000 units in children <10 years of age or single dose of 1.2 million units in those ≥10 years of age has been used.35 36 676 678 For treatment of yaws, a single dose of 50,000 units/kg (up to 2.4 million units) has been used.679

Penicillin G procaine: Manufacturer states dosage is the same as that recommended for corresponding stage of syphilis.7

Prevention of Rheumatic Fever Recurrence
IM

Penicillin G benzathine: AAP and AHA recommend 600,000 units once every 4 weeks in children weighing ≤27 kg and 1.2 million units once every 4 weeks in those weighing >27 kg.292 375 Manufacturers recommend 1.2 million units once monthly or 600,000 units once every 2 weeks.2 3

AAP and AHA state that 4-week dosing interval seems adequate and is recommended for most US patients, but 3-week dosing interval may be warranted and is recommended when risk of rheumatic fever is particularly high (e.g., recurrent acute rheumatic fever despite adherence to 4-week regimen).292 375 There is some evidence that serum penicillin concentrations may decline to subtherapeutic concentrations before fourth week in some patients.37 38 323 375

Initiate prophylaxis as soon as active rheumatic fever or rheumatic heart disease diagnosed;292 375 however, patients with acute rheumatic fever should first receive usually recommended anti-infective regimen for treatment of S. pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis (see Pharyngitis and Tonsillitis under Uses).375

Long-term, continuous prophylaxis required.292 375 (See Table 1.) Some clinicians use IM penicillin G benzathine initially and change to oral prophylaxis (usually penicillin V) when patient reaches late adolescence or young adulthood and has remained free of rheumatic attacks for ≥5 years.375

Table 1. Recommended Duration of Prophylaxis for Prevention of Rheumatic Fever Recurrence292375

Patient Category

Duration

Rheumatic fever without carditis

5 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis but no residual heart disease (no valvular disease)

10 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis and residual heart disease (persistent valvular disease)

10 years since last episode or until 40 years of age, whichever is longer; sometimes for life

Adults

Bone and Joint Infections
Native Vertebral Osteomyelitis or Prosthetic Joint Infections
IV

Penicillin G potassium or sodium for infections caused by susceptible β-hemolytic streptococci: IDSA recommends 20–24 million units daily (by continuous IV infusion or in 6 divided doses).590 591 Recommended treatment duration is 6 weeks in those with native vertebral osteomyelitis590 or 4–6 weeks in those with prosthetic joint infections.591

Penicillin G potassium or sodium for infections caused by susceptible Enterococcus: IDSA recommends 20–24 million units daily (by continuous IV infusion or in 6 divided doses) for 4–6 weeks.590 591 Consider concomitant treatment with an aminoglycoside given for 4–6 weeks;591 concomitant treatment recommended if infective endocarditis also present.590

Penicillin G potassium or sodium for infections caused by susceptible C. acnes (formerly P. acnes): IDSA recommends 20 million units daily (by continuous IV infusion or in 6 divided doses).590 591 Recommended treatment duration is 6 weeks in those with native vertebral osteomyelitis590 or 4–6 weeks in those with prosthetic joint infections.591

Endocarditis
Native Valve Endocarditis Caused by Viridans Streptococci or S. gallolyticus
IV

Penicillin G potassium or sodium for highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): AHA recommends 12–18 million units daily (by continuous IV infusion or in 4 or 6 divided doses) given for 4 weeks.450 Alternatively, 12–18 million units daily (by continuous IV infusion or in 6 divided doses) given for 2 weeks in conjunction with gentamicin (3 mg/kg IM or IV as a single daily dose or as 1 mg/kg every 8 hours given for 2 weeks) can be used in those at low risk for aminoglycoside-associated adverse effects.450 Do not use 2-week regimen in those with known cardiac or extracardiac abscesses, Clcr <20 mL/minute, impaired eighth cranial nerve function, or infection with Abiotrophia, Granulicatella, or Gemella.450

Penicillin G potassium or sodium for strains relatively resistant to penicillin G (penicillin MIC >0.12 mcg/mL but <0.5 mcg/mL): AHA recommends 24 million units daily (by continuous IV infusion or in 4–6 divided doses) given for 4 weeks in conjunction with gentamicin (3 mg/kg IV or IM daily given as a single daily dose or as 1 mg/kg every 8 hours during first 2 weeks of penicillin G treatment).450

Penicillin G potassium or sodium for viridans streptococci with penicillin MIC ≥0.5 mcg/mL: AHA states 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg IV or IM daily in 2 or 3 divided doses) is a reasonable regimen.450 AHA states consult with an infectious disease expert to determine treatment duration for such infections.450

Native Valve Endocarditis Caused by Abiotrophia or Granulicatella
IV

Penicillin G potassium or sodium for strains with penicillin MIC ≥0.5 mcg/mL: AHA states 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg IV or IM daily in 2 or 3 divided doses) is a reasonable regimen.450 AHA states consult with an infectious disease expert to determine treatment duration for such infections.450

Endocarditis Involving Prosthetic Valves or Other Prosthetic Material Caused by Viridans Streptococci, Abiotrophia, or Granulicatella
IV

Penicillin G potassium or sodium for highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): AHA recommends 24 million units daily (by continuous IV infusion or in 4–6 divided doses) given for 6 weeks with or without gentamicin (3 mg/kg IV or IM as a single daily dose or as 1 mg/kg every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).450

Penicillin G potassium or sodium for strains relatively or highly resistant to penicillin (penicillin MIC >0.12 mcg/mL): Use same regimen recommended for highly penicillin-susceptible strains, but AHA states it is reasonable to extend the duration of concomitant gentamicin to 6 weeks.450

Enterococcal Endocarditis
IV

Penicillin G potassium or sodium for endocarditis involving native valve or prosthetic valve or other prosthetic material caused by enterococci susceptible to penicillin and gentamicin: AHA recommends 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg IV or IM daily in 2 or 3 divided doses; adjust dose to achieve gentamicin peak serum concentrations of 3–4 mcg/mL and trough concentrations <1 mcg/mL).450

Enterococcal endocarditis involving native valves: Continue both drugs for 4 weeks if symptoms were present for <3 months prior to treatment or for 6 weeks if symptoms were present for ≥3 months prior to treatment.450

Enterococcal endocarditis involving prosthetic heart valves or other prosthetic material: Continuation of both drugs for 6 weeks is reasonable.450

Enterococci resistant to gentamicin, but susceptible to penicillin and streptomycin: In above regimen, may substitute streptomycin (15 mg/kg IV or IM daily in 2 divided doses; dose adjusted to achieve streptomycin peak serum concentrations of 20–35 mcg/mL and trough concentrations <10 mcg/mL) instead of gentamicin.450 Consider alternative regimens (e.g., double β-lactam regimens) in patients with Clcr <50 mL/minute.450

Endocarditis Caused by Staphylococci
IV or IM

Penicillin G potassium or sodium for susceptible staphylococci: Manufacturers recommend 5–24 million units daily in divided doses every 4–6 hours.8 9 11 12 Penicillin G not included in current AHA recommendations for treatment of staphylococcal endocarditis.450

Endocarditis Caused by Streptococci
IM

Penicillin G procaine for susceptible S. pyogenes: Manufacturer recommends 600,000 to 1 million units daily.7 If a penicillin used, AHA recommends IV penicillin G potassium or sodium.450

IV or IM

Penicillin G potassium or sodium for susceptible streptococci, including S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 12–24 million units daily in divided doses every 4–6 hours.8 9 11 12

Meningitis
Meningitis Caused by L. monocytogenes
IV

Penicillin G potassium or sodium: IDSA and others recommend 24 million units daily (4 million units every 4 hours)418 475 for ≥21 days.418 Consider using an aminoglycoside concomitantly.418

Penicillin G potassium or sodium: Manufacturers recommend 15–20 million units daily given in divided doses every 4–6 hours for 2 weeks.8 9 11

Meningitis Caused by N. meningitidis
IV

Penicillin G potassium or sodium: IDSA recommends 24 million units daily (4 million units every 4 hours) for 7 days.418

Penicillin G potassium or sodium: Manufacturers recommend 24 million units daily (2 million units every 2 hours).8 9 11 12

Meningitis Caused by S. agalactiae (Group B Streptococci; GBS)
IV

Penicillin G potassium or sodium: IDSA recommends 24 million units daily (4 million units every 4 hours) for 14–21 days.418 Consider using an aminoglycoside concomitantly.418

Meningitis Caused by S. pneumoniae
IV

Penicillin G potassium or sodium: IDSA and others recommend 24 million units daily (4 million units every 4 hours) for 10–14 days.418 475

Penicillin G potassium or sodium: Manufacturers recommend 12–24 million units daily given in divided doses every 4–6 hours.9 11 12 One manufacturer recommends 5–24 million units daily given in divided doses every 4–6 hours.8

Healthcare-associated Ventriculitis and Meningitis Caused by C. acnes
IV

Penicillin G potassium or sodium: IDSA recommends 24 million units daily given in divided doses every 4 hours.416 Treatment duration is 10 days in those with no or minimal CSF pleocytosis, normal CSF glucose, and few clinical symptoms or systemic features or 10–14 days in those with significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features.416

Pharyngitis and Tonsillitis
Treatment of S. pyogenes Pharyngitis and Tonsillitis
IM

Penicillin G benzathine: A single dose of 1.2 million units.2 3 375 580

Eradication of Pharyngeal Carriage of S. pyogenes
IM

Penicillin G benzathine in certain circumstances when eradication of carrier state is desirable (see Pharyngitis and Tonsillitis under Uses): IDSA states a single dose of 600,000 units in those weighing <27 kg or single dose of 1.2 million units in those weighing ≥27 kg given in conjunction with oral rifampin (20 mg/kg daily [up to 600 mg daily] given in 2 doses for 4 days) is an option.580

Respiratory Tract Infections
IM

Penicillin G benzathine for mild to moderate upper respiratory infections caused by susceptible S. pyogenes: Manufacturers recommend a single dose of 1.2 million units.2 3

Penicillin G procaine for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends 600,000 to 1 million units daily for ≥10 days.7

Penicillin G procaine for moderately severe, uncomplicated respiratory infections (pneumonia) caused by susceptible S. pneumoniae: Manufacturer recommends 600,000 to 1 million units daily for ≥10 days.7

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 2.4 million units.5

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections (pneumonia, otitis media) caused by susceptible S. pneumoniae: Manufacturer recommends 1.2 million units once every 2 or 3 days until patients has been afebrile for 48 hours.5

IV or IM

Penicillin G potassium or sodium for serious infections (e.g., pneumonia, empyema) caused by susceptible nonpenicillinase-producing staphylococci: Manufacturers recommend 5–24 million units daily in divided doses every 4–6 hours depending on severity.9 11 12

Penicillin G potassium for serious infections (e.g., pneumonia, empyema) caused by susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 12–24 million units daily in divided doses every 4–6 hours depending on severity.9 11 12

Penicillin G sodium for serious infections (e.g., pneumonia, empyema) caused by susceptible streptococci: Manufacturer recommends 5–24 million units daily in divided doses every 4–6 hours depending on severity.8

Septicemia
IV or IM

Penicillin G potassium or sodium for susceptible nonpenicillinase-producing staphylococci: Manufacturers recommend 5–24 million units daily in divided doses every 4–6 hours depending on severity.8 9 11 12

Penicillin G potassium or sodium for susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 12–24 million units daily in divided doses every 4–6 hours depending on severity.8 9 11 12

Skin and Skin Structure Infections
IM

Penicillin G procaine for moderately severe to severe infections caused by susceptible staphylococci: Manufacturer recommends 600,000 to 1 million units daily.7

Penicillin G procaine for moderately severe to severe infections (including erysipelas) caused by susceptible streptococci: Manufacturer recommends 600,000 to 1 million units daily for ≥10 days.7

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections (including erysipelas) caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 2.4 million units.5

IV

Penicillin G potassium or sodium for necrotizing infections of skin, fascia, and muscle caused by susceptible S. pyogenes: IDSA recommends 2–4 million units every 4–6 hours in conjunction with clindamycin (600–900 mg IV every 8 hours).543

Actinomycosis
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 1–6 million units daily in divided doses every 4–6 hours for cervicofacial infections or 10–20 million units daily in divided doses every 4–6 hours for thoracic or abdominal infections.8 9 11 12

Penicillin G potassium or sodium: Some clinicians recommend 18–24 million units daily IV (3–4 million units every 4 hours) for ≥2–6 weeks followed by 6–12 additional months of an oral regimen (penicillin V or amoxicillin) for pulmonary or other severe infections.10 27 28 898 901 Shorter treatment duration may be sufficient for less extensive disease (e.g., cervicofacial region).10 27 28 29

Individualize dosage and treatment duration based on severity and response;10 27 28 perform surgical procedures as indicated.8 9 10 11 12 27

Anthrax
Postexposure Prophylaxis (Inhalational Anthrax)
IM

Penicillin G procaine: Manufacturer recommends 1.2 million units every 12 hours.7 CDC recommends other penicillins (oral amoxicillin or penicillin V) for prophylaxis following exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism when penicillin-susceptible strains involved.672 673

Total duration of anti-infective prophylaxis following aerosol exposure to B. anthracis spores in the context of biologic warfare or bioterrorism should be ≥60 days.7 663 668 672 673 681 682 683 686 Manufacturer states safety data for penicillin G procaine administered at dosage recommended for inhalational anthrax (postexposure) supports a duration ≤2 weeks; consider risks versus benefits of continuing the drug for >2 weeks or switching to an appropriate alternative anti-infective.7

Treatment of Mild, Uncomplicated Cutaneous Anthrax (Naturally Occurring or Endemic Exposure)
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily.7 Some experts recommend 600,000 to 1.2 million units every 12–24 hours.680

Although 3–10 days of anti-infective therapy may be adequate for treatment if mild, uncomplicated cutaneous anthrax occurred as the result of natural or endemic exposures,668 680 681 683 686 some experts recommend duration of 7–14 days.680 CDC and others recommend 60 days of anti-infective treatment if cutaneous anthrax occurred as the result of exposure to aerosolized B. anthracis spores (e.g., in the context of biologic warfare or bioterrorism).668 672 673 680 681 683 686

Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend minimum dosage of 8 million units daily given in divided doses every 6 hours; higher dosage may be required depending on susceptibility.8 9 11 12

Penicillin G potassium or sodium in adults with inhalational, GI, or meningeal anthrax: Some clinicians recommend 8–12 million units IV daily given in divided doses every 4–6 hours.670

Penicillin G potassium or sodium in adults with severe or life-threatening systemic anthrax (inhalational, GI, meningoencephalitis, sepsis) or cutaneous anthrax with signs of systemic involvement or extensive edema: Some clinicians recommend 16–24 million units IV daily (4 million units every 4–6 hours).680

Concomitant use of other anti-infectives (e.g., streptomycin or other aminoglycoside, clindamycin, clarithromycin, rifampin, vancomycin) may also be indicated.670 680 Continue treatment of naturally occurring or endemic anthrax for ≥14 days after symptoms abate.670

Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism Exposure)
IV

Penicillin G potassium or sodium in adults (including pregnant and postpartum women): 4 million units every 4 hours if penicillin-susceptible B. anthracis involved.672 673

Use in multiple-drug parenteral regimen for initial treatment of systemic anthrax (inhalational, GI, meningitis, cutaneous anthrax with systemic involvement or extensive edema).672 673 Continue parenteral regimen for ≥2–3 weeks until patient is clinically stable; treatment can then be switched to an oral regimen.672 673 CDC and other experts state that total duration of anti-infective treatment in the context of biologic warfare or bioterrorism should be 60 days.668 672 673 683 686

Clostridium Infections
Botulism
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 20 million units daily given in divided doses every 4–6 hours.8 9 11 12 Some clinicians recommend 10–20 million units daily for wound botulism.10

Adjunct to botulinum antitoxin.8 9 11 12 (See Clostridium Infections under Uses.)

Myonecrosis and Gas Gangrene
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 20 million units daily given in divided doses every 4–6 hours.8 9 11 12 IDSA recommends 2–4 million units every 4–6 hours in conjunction with clindamycin (600–900 mg IV every 8 hours).543

Perform surgical debridement and/or surgery as indicated.8 9 11 12

Tetanus
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 20 million units daily given in divided doses every 4–6 hours.8 9 11 12

Adjunct to TIG.8 9 11 12 (See Clostridium Infections under Uses.)

Diphtheria
Treatment of Diphtheria
IM

Penicillin G procaine: Manufacturer recommends 300,000–600,000 units daily for 14 days.7 CDC recommends 600,000 units daily in those weighing >10 kg.166

Adjunct to diphtheria antitoxin.7 166 (See Diphtheria under Uses.)

IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 2–3 million units daily given in divided doses every 4–6 hours for 10–12 days.8 9 11 12 CDC recommends penicillin G procaine if a penicillin used.166

Adjunct to diphtheria antitoxin.8 9 11 12 (See Diphtheria under Uses.)

Prevention of Diphtheria in Close Contacts
IM

Penicillin G benzathine: CDC recommends a single dose of 1.2 million units.166

Provide anti-infective prophylaxis regardless of immunization status and closely monitor for symptoms of diphtheria for 7 days.166 292

Contacts inadequately immunized against diphtheria or with unknown immunization status: Give immediate dose of age-appropriate preparation containing diphtheria toxoid adsorbed and complete primary series according to recommended schedules.166 292

Contacts fully immunized against diphtheria but received last booster dose ≥5 years previously: Give immediate booster dose of age-appropriate preparation containing diphtheria toxoid adsorbed.166 292

Elimination of Diphtheria Carrier State
IM

Penicillin G benzathine: CDC recommends a single dose of 1.2 million units.166

Penicillin G procaine: Manufacturer recommends 300,000 units daily for 10 days.7 CDC recommends penicillin G benzathine if a penicillin used.166

Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures are positive, give a 10-day course of oral erythromycin and obtain additional follow-up cultures.166

Erysipelothrix rhusiopathiae Infections
Uncomplicated Infections (e.g., Erysipeloid)
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily.7

Severe Infections (e.g., Endocarditis)
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 12–20 million units daily given in divided doses every 4–6 hours for 4–6 weeks.8 9 11 12

Fusobacterium Infections
Oropharyngeal, Lower Respiratory Tract, or Genital Infections
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 5–10 million units daily in divided doses every 4–6 hours.8 9 11 12

Necrotizing Ulcerative Gingivitis
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily.7

Leptospirosis
IV

Penicillin G potassium or sodium: Has been given in a dosage of 6 million units daily (1.5 million units every 6 hours) for 7 days.10 98 99 Initiate anti-infective treatment as soon as possible after symptom onset.10 292

Listeria Infections
Serious Infections
IV

Penicillin G potassium or sodium: Manufacturers recommend 15–20 million units daily in divided doses every 4–6 hours.8 9 11 12

Also see Adults: Meningitis Caused by L. monocytogenes, under Dosage and Administration.

Lyme Disease
Early Lyme Disease with Acute Neurologic Symptoms
IV

Penicillin G potassium or sodium: 18–24 million units daily given in 6 divided doses (every 4 hours) for 10–28 days.329

Late Lyme Disease with Recurrent Lyme Arthritis Symptoms
IV

Penicillin G potassium or sodium: 18–24 million units daily given in 6 divided doses (every 4 hours) for 14–28 days.329

Late Neurologic Lyme Disease
IV

Penicillin G potassium or sodium: 18–24 million units daily given in 6 divided doses (every 4 hours) for 14–28 days.329

Neisseria meningitidis Infections
Serious Infections
IV

Penicillin G potassium or sodium: Manufacturers recommend 24 million units daily (2 million units every 2 hours).8 9 11 12

Also see Adults: Meningitis Caused by N. meningitidis, under Dosage and Administration.

Pasteurella multocida Infections
Serious Infections
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 4–6 million units daily given in divided doses every 4–6 hours for 2 weeks for serious infections, including bacteremia and meningitis.8 9 11 12

Rat-bite Fever
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily.7 Has been given in a dosage of 600,000 units every 12 hours for 10–14 days.10 30 Some clinicians state that IV penicillin G potassium or sodium preferred.10 30

IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 12–20 million units daily given in divided doses every 4–6 hours for 3–4 weeks.8 9 11 12

Penicillin G potassium or sodium: CDC recommends 1.2 million units IV daily for 5–7 days; if improvement occurs, treatment can be switched to oral penicillin V or oral ampicillin.31 Some clinicians suggest 400,000–600,000 units IV daily for at least 7 days; if no response occurs within 2 days, increase dosage to 1.2 million units IV daily.30

Penicillin G potassium or sodium: Some clinicians suggest 20 million units IV daily given for 4 weeks may be necessary for S. moniliformis endocarditis caused by strain less susceptible to penicillin G (MIC >0.1 mcg/mL);30 concomitant use of an aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment.10 30

Syphilis
Primary, Secondary, or Early Latent Syphilis
IM

Penicillin G benzathine: CDC, manufacturers, and others recommend a single dose of 2.4 million units.2 3 344 345 350 440 For pregnant women, some clinicians recommend that a second penicillin G benzathine dose of 2.4 million units be given 1 week after the initial dose.344 440

Penicillin G benzathine for retreatment (no evidence of neurosyphilis): CDC and others recommend 2.4 million units once weekly for 3 successive weeks.344 440

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 8 days (total dosage 4.8 million units).7 CDC and others recommend penicillin G benzathine for primary, secondary, or early latent syphilis.344 350 440

Tertiary or Late Latent Syphilis
IM

Penicillin G benzathine: CDC and others recommend 2.4 million units once weekly for 3 successive weeks (total dosage 7.2 million units).2 344 345 350 440 Interval between doses should not be >14 days.350

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 10–15 days (total dosage 6–9 million units).7 CDC and others recommend penicillin G benzathine for late latent or tertiary syphilis.344 350 440

Neurosyphilis and Otic or Ocular Syphilis
IM

Penicillin G benzathine: Manufacturers recommend 2.4 or 3 million units once weekly for 3 weeks;2 3 treatment failures reported.702 874 CDC and others recommend IV penicillin G potassium or sodium or, alternatively, IM penicillin G procaine (with oral probenecid) for neurosyphilis.344 345 440

Penicillin G procaine: CDC recommends 2.4 million units once daily for 10–14 days in conjunction with oral probenecid (500 mg every 6 hours for 10–14 days);344 440 use only if compliance can be ensured.344 Some clinicians recommend that this regimen be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).344 440

IV

Penicillin G potassium or sodium: CDC and others recommend 18–24 million units daily (given as 3–4 million units every 4 hours or by continuous IV infusion) for 10–14 days.344 440 Some clinicians recommend that this regimen be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).344 440

Penicillin G potassium or sodium: Manufacturers recommend 12–24 million units daily (2–4 million units every 4 hours) for 10–14 days;8 9 11 12 this may be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).8 9 11 12

Whipple's Disease
IV

Penicillin G potassium or sodium: Some clinicians recommend 10 million units daily for initial treatment.10 Others recommend 12–24 million units daily (2–4 million units every 4 hours).724 Regimen of 1.2 million units daily in conjunction with parenteral streptomycin (1 g daily) also recommended.716 Continue initial parenteral treatment for 2–4 weeks followed by 1–2 years of treatment with an oral regimen (e.g., co-trimoxazole).10 716

Yaws, Pinta, and Bejel
IM

Penicillin G benzathine: Single dose of 1.2 million units recommended by manufacturers and others.2 3 35 36 676 678 For treatment of yaws, a single dose of 2.4 million units has been used.61 674 675

Penicillin G procaine: Manufacturer states dosage is the same as that recommended for corresponding stage of syphilis.7

Prevention of Perinatal Group B Streptococcal (GBS) Disease
IV

Penicillin G potassium or sodium: Initial dose of 5 million units given at onset of labor or membrane rupture followed by 2.5–3 million units every 4 hours until delivery.292 359 362

Regardless of whether anti-infective prophylaxis was administered to the mother, initiate appropriate diagnostic evaluations and empiric anti-infective therapy in the neonate if signs or symptoms of active infection develop.292 359 362

Prevention of Rheumatic Fever Recurrence
IM

Penicillin G benzathine: AHA recommends 1.2 million units once every 4 weeks.375 Manufacturers recommend 1.2 million units once monthly or 600,000 units once every 2 weeks.2 3

AHA states that 4-week dosing interval seems adequate and is recommended for most US patients, but 3-week dosing interval may be warranted and is recommended when risk of rheumatic fever is particularly high (e.g., recurrent acute rheumatic fever despite adherence to a 4-week regimen).375 There is some evidence that serum penicillin concentrations may decline to subtherapeutic concentrations before fourth week in some patients37 38 323 375

Initiate prophylaxis as soon as rheumatic fever or rheumatic heart disease diagnosed;292 375 however, patients with acute rheumatic fever should first receive usually recommended anti-infective regimen for treatment of S. pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis (see Pharyngitis and Tonsillitis under Uses).375

Long-term, continuous prophylaxis required.292 375 (See Table 2.)

Table 2. Recommended Duration of Prophylaxis for Prevention of Rheumatic Fever Recurrence292375

Patient Category

Duration

Rheumatic fever without carditis

5 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis but no residual heart disease (no valvular disease)

10 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis and residual heart disease (persistent valvular disease)

10 years since last episode or until 40 years of age, whichever is longer; sometimes for life

Special Populations

Renal Impairment

Doses and/or frequency of administration of penicillin G may need modification in response to degree of impairment.8 9 11 12 61 348 369 384 385

IM or IV penicillin G potassium or sodium: Manufacturers state adjust dosage in patients with severe renal impairment.8 9 11 12 In patients with Clcr <10 mL/minute per 1.73 m2, manufacturers and others recommend a loading dose using usually recommended dose followed by 50% of usually recommended dose given every 8–10 hours.8 9 11 12 348 In uremic patients with Clcr >10 mL/minute per 1.73 m2, manufacturers and others recommend a loading dose using usually recommended dose followed by 50% of usually recommended dose given every 4–5 hours.8 9 11 12 348

Alternatively, some clinicians suggest that if the usual dosing interval for penicillin G potassium or sodium in patients with normal renal function (Clcr >50 mL/minute) is every 6 or 8 hours, then give usual dose every 8–12 hours in those with Clcr 10–50 mL/minute or every 12–18 hours in those with Clcr <10 mL/minute.61 385

Some clinicians suggest a maximum daily dosage of 4–10 million penicillin G units in adults with severe renal failure.369 384

In patients with impaired hepatic function in addition to impaired renal function, further dosage reductions may be advisable.8 9 11 12 61 348

Cautions for Penicillin G Benzathine/Procaine/Potassium/Sodium

Contraindications

  • Penicillin G benzathine, penicillin G procaine, fixed combinations of penicillin G benzathine and penicillin G procaine, penicillin G potassium or sodium: Hypersensitivity to any penicillin.2 3 4 5 7 8 9 11 12

  • Penicillin G procaine and fixed combinations of penicillin G benzathine and penicillin G procaine: Hypersensitivity to procaine.4 5 7

  • Commercially available frozen premixed penicillin G potassium injection in dextrose: May be contraindicated in patients with known allergy to corn or corn products.11

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.2 3 4 5 7 8 9 11 12 Monitor carefully;3 discontinue and institute appropriate therapy if superinfection occurs.2 3 4 5 7 8 9 11 12

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.2 4 5 7 8 9 11 12 302 303 304 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including penicillin G, and may range in severity from mild diarrhea to fatal colitis.2 4 5 7 8 9 11 12 302 303 304 C. difficile produces toxins A and B which contribute to development of CDAD;2 4 5 8 9 11 12 302 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.2 4 5 8 9 11 12

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.2 4 5 7 8 9 11 12 302 303 304 Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.2 4 5 8 9 11 12

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile as soon as possible.2 4 5 8 9 11 12 302 Initiate appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.2 4 5 7 8 9 11 12 302 303 304

Procaine Toxicity

Immediate toxic reactions to procaine reported rarely with IM penicillin G procaine, especially with large single doses (4.8 million penicillin G units).7 These reactions may be manifested by mental disturbances (anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, fear of impending death) and usually are transient (lasting about 15–30 minutes).7

A small percentage of the population is hypersensitive to procaine; sensitivity reactions to IM penicillin G procaine reported.4 5 7 (See Procaine Sensitivity under Cautions.)

Precautions Related to IM Administration

IM penicillin G benzathine, penicillin G procaine, fixed combinations of penicillin G benzathine and penicillin G procaine, penicillin G potassium or sodium: Take special precaution to avoid IV, intravascular, or intra-arterial administration or injection into or near major peripheral nerves or blood vessels.2 4 5 7 9

Inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.2 4 5

Inadvertent intravascular or intra-arterial injection of penicillin G benzathine and/or penicillin G procaine may produce severe and/or permanent neurovascular damage.2 4 5 7 Transverse myelitis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, and necrosis and sloughing at and surrounding injection site reported following inadvertent intravascular administration, including buttock, thigh, and deltoid areas.2 4 5 7

Other serious complications of suspected intravascular administration (especially in infants and small children) include immediate pallor, mottling, or cyanosis of the extremity (both distal and proximal to injection site), followed by bleb formation.2 4 5 7 Severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity also reported.2 4 5 7

Repeated IM injection of penicillin preparations into the anterolateral thigh has resulted in quadriceps femoris fibrosis and atrophy.2 4 5 7

If evidence of compromise of the blood supply occurs at or proximal or distal to administration site, consult appropriate specialist immediately.2 4 5 7

Precautions Related to IV Administration

IV penicillin G potassium or sodium: Use caution;9 possibility of phlebitis and thrombophlebitis.8 9 11 12

Administer large IV doses slowly because of potential for serious electrolyte disturbances.8 9 11 12 (See Electrolyte Imbalance under Cautions.)

Neurotoxic reactions (e.g., hyperreflexia, myoclonic twitches, seizures, coma) reported with massive IV doses of penicillin G.8 9 11 12 Renal tubular damage and interstitial nephritis (e.g., fever, rash, eosinophilia, proteinuria, esophinophiluria, hematuria, increased BUN concentrations) reported with large IV doses of penicillin G.8 9 11 12 These reactions most likely to occur in patients with impaired renal function.8 9 11 12

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.2 3 4 5 7 8 9 10 11 12 61 611 615 713 769 Hypersensitivity reactions are the most frequent adverse effects of penicillins.64 611 715

Hypersensitivity reactions to penicillins may be immediate (usually occurring within 20 minutes of administration) and range in severity from urticaria and pruritus to angioedema, laryngospasm, bronchospasm, hypotension, vascular collapse, and death.8 9 11 12 Accelerated reactions (usually occurring between 20 minutes to 48 hours after administration) may include urticaria, pruritus, fever and, occasionally, laryngeal edema.8 9 11 12 Delayed reactions (usually occurring within 1–2 weeks after initiation of penicillin therapy) may include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and rash ranging from maculopapular eruptions to exfoliative dermatitis.8 9 11 12

Prior to administration, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.2 3 4 5 7 8 9 11 12 There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.2 3 4 5 7 8 9 11 12 611 615 769 770 779

Hypersensitivity reactions to penicillins more likely to occur in individuals with a history of penicillin hypersensitivity and/or history of sensitivity to multiple allergens.2 3 4 5 7 8 9 11 12 Use with caution in patients with history of clinically important allergies and/or asthma.2 3 4 5 7 8 9 11 12

If hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).2 3 4 5 7 8 9 11 12

Desensitization to penicillins has been used to enable a penicillin to be administered to penicillin-hypersensitive patients who have life-threatening infections for which other effective anti-infective agents are not available (e.g., endocarditis, neurosyphilis or congenital syphilis, syphilis during pregnancy).61 64 344 345 350 450 611 615 761 762 763 779 Usually performed in a hospital setting; expert consultation may be indicated.344 Consult specialized references for specific information on sensitivity testing and desensitization protocols.344 761 763

Procaine Sensitivity

A small percentage of patients are sensitive to procaine.7 If considering use of penicillin G procaine or fixed combinations of penicillin G benzathine and penicillin G procaine in patient with history of procaine sensitivity, give a test dose of procaine (0.1 mL of a 1–2% procaine solution) intradermally prior to IM administration of full doses of penicillin G procaine or fixed combination containing penicillin G procaine.4 5 7 Development of erythema, wheal, flare, or eruption at intradermal test site indicates procaine sensitivity and patient should not receive any preparation containing penicillin G procaine.4 5 7

If a hypersensitivity reaction to procaine occurs, treat with usual methods; antihistamines may be beneficial and barbiturates should be used if seizures occur.4 5 7

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of penicillin G and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.2 4 5 8 9 11 12

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.2 4 5 8 9 11 12 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.2 4 5 8 9 11 12

Because penicillin susceptibility can no longer be assumed, routinely test staphylococci or S. pneumoniae isolates for in vitro susceptibility.7 8 9 10 11 12 61 64

IM or IV penicillin potassium or sodium: Use for treatment of severe infections caused by susceptible organisms when rapid and high concentrations of penicillin G required.8 9 10 11 12 61 64

IM penicillin G benzathine2 3 64 or IM penicillin G procaine:7 Use only for treatment of mild to moderately severe infections caused by organisms susceptible to low concentrations of penicillin G. IM penicillin G benzathine also can be used for prophylaxis of infections caused by organisms susceptible to low concentrations of penicillin G or as follow-up therapy to IM or IV penicillin G potassium or sodium.2 64

Fixed combinations of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300): Use only for labeled indications, including treatment of moderately severe to severe infections caused by susceptible organisms.4 5 Do not use for treatment of any venereal diseases, including syphilis, yaws, bejel, or pinta.4 5

Jarisch-Herxheimer Reactions

Jarisch-Herxheimer reactions may occur in patients receiving penicillin G for treatment of syphilis or other spirochetal infections (e.g., leptospirosis, Lyme disease, relapsing fever).7 8 9 11 12 61

These reactions usually begin 1–2 hours after initiation of the drug, resolve within 12–24 hours, and are characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension.8 9 11 12

Laboratory Monitoring

Periodically assess renal, hepatic, and hematologic systems during prolonged therapy, especially if high dosage is used.3 4 5 7 8 9 11 12

Electrolyte Imbalance

Penicillin G potassium or sodium: Serious and potentially fatal electrolyte disturbances may occur, particularly if high IV dosage used.8 9 11 12 61

Massive IV dosages of penicillin G sodium has resulted in a syndrome of hypokalemia, metabolic alkalosis, and hypernatremia.61 Although it has been suggested that hypokalemia during penicillin G potassium therapy may result from redistribution of potassium within the body,790 the effect appears to be related to the fact that penicillins act as nonabsorbable anions in the distal renal tubules and therefore promote urinary loss of potassium.61

Assess electrolyte balance and cardiac and vascular status in patients receiving penicillin G potassium or sodium, especially if high doses are given IV.8 9 11 12

Administer large IV doses of penicillin G potassium (>10 million penicillin G units) slowly because of potential effects on electrolyte balance.9 11 12

Potassium and Sodium Content

Penicillin G potassium powder for injection: Each 1 million penicillin G units contains approximately 66 mg (1.7 mEq) of potassium and approximately 7 mg (0.3 mEq) of sodium.9 12

Frozen premixed penicillin G potassium injection in dextrose: Each 1 million penicillin G units contains approximately 1.7 mEq of potassium and approximately 1 mEq of sodium.11

Penicillin G sodium powder for injection: Each 1 million penicillin G units contains approximately 1.7 mEq of sodium.8

Specific Populations

Pregnancy

Reproduction studies evaluating penicillin G in mice, rats, and rabbits have not revealed evidence of impaired fertility or harm to the fetus.2 3 4 5 7 8 9 11 12 25

Although experience using penicillins during pregnancy has not shown any evidence of adverse effects on the fetus, there are no adequate or controlled studies using penicillin G in pregnant women.2 3 4 5 7 8 9 11 12

Some clinicians state penicillin G is considered low risk25 and safe for use during pregnancy.61 Penicillin G is included in CDC recommendations for treatment of syphilis during pregnancy.344

Manufacturers state use penicillin G during pregnancy only when clearly needed.2 3 4 5 7 8 9 11 12

Lactation

Distributed into milk.2 3 4 5 7 8 9 11 12 61 64 355 364 374 Some clinicians state penicillin G usually considered compatible with breast-feeding.25 The manufacturers and others state use with caution in nursing women.2 3 4 5 7 8 9 11 12 24

Pediatric Use

Renal clearance of penicillin G may be delayed in neonates and premature or young infants because of incompletely developed renal function.2 3 4 5 7 8 9 10 11 12 61

Penicillin G potassium or sodium: Make appropriate reductions in dosage and frequency of administration.8 9 11 12 When used in neonates, monitor closely for clinical and laboratory evidence of toxic or adverse effects.8 9 11 12

Geriatric Use

Clinical studies of penicillin G benzathine, penicillin G procaine, and penicillin G potassium did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.2 4 5 7 9 11 12 Other clinical experience has not identified differences in responses between geriatric and younger patients.2 4 5 7 9 11 12

Penicillin G is substantially eliminated by the kidneys and risk of adverse effects may be greater in those with impaired renal function.2 4 5 7 9 11 12 Because geriatric patients more likely to have reduced renal function, select dosage with caution, usually starting at low end of dosage range, and consider monitoring renal function.2 4 5 7 9 11 12

Penicillin G potassium or sodium: Consider potassium and/or sodium content and potential for electrolyte imbalance;8 9 11 12 geriatric patients may respond with a blunted natriuresis to salt loading that may be clinically important in those with certain conditions (e.g., CHF).9 11 12

Renal Impairment

Dosage adjustments may be needed based on degree of renal impairment.8 9 11 12 61 348 369 384 385 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Hypersensitivity reactions (rash, urticaria, serum sickness); local effects.2 3 4 5 7 8 9 10 11 12 61

Interactions for Penicillin G Benzathine/Procaine/Potassium/Sodium

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Aminoglycosides

In vitro evidence of synergistic antibacterial effects against enterococci or viridans streptococci80 282 288 297 used to therapeutic advantage in treatment of certain infections (e.g., enterococcal endocarditis)64 80 282 288 450 947

Physical and/or chemical incompatibility between penicillins and aminoglycosides; potential in vitro or in vivo inactivation of aminoglycoside255 260 262 263 264 267 270 341 HID

If concomitant use indicated, administer separately341 HID

Chloramphenicol

Possible in vitro antagonism;8 9 11 12 clinical importance unclear8 9 11 12

Avoid concomitant use8 9 11 12

Erythromycins

Possible in vitro antagonism;3 8 9 11 12 clinical importance unclear3 8 9 11 12

Avoid concomitant use8 9 11 12

Ethacrynic acid

Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin8 9 11 12

Furosemide

Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin8 9 11 12

Methotrexate

Penicillins may decrease renal clearance of methotrexate; possible increased methotrexate concentrations and hematologic and GI toxicity778

Monitor closely if used concomitantly778

NSAIAs

Aspirin, indomethacin: Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin8 9 11 12

Probenecid

Decreased renal tubular secretion of penicillin G; increased and prolonged penicillin G serum concentrations may occur;2 3 4 5 7 8 9 11 12 61 64 70 81 320 347 348 351 354 CSF concentrations also may be increased61 64 70 81 320 324 345 351 354

Sulfonamides

Possible in vitro antagonism;8 9 11 12 clinical importance unclear8 9 11 12

Avoid concomitant use8 9 11 12

Thiazide diuretics

Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin8 9 11 12

Tests for glucose

Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution8 9 11 12 759 798

Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)8 9 11 12 759

Tests for uric acid

Possible falsely increased serum uric acid concentrations when copper-chelate method is used;800 phosphotungstate and uricase methods appear to be unaffected800

Tetracyclines

Possible in vitro antagonism;2 3 4 5 7 8 9 11 12 clinical importance unclear3 8 9 11 12

Avoid concomitant use2 4 5 7 8 9 11 12

Penicillin G Benzathine/Procaine/Potassium/Sodium Pharmacokinetics

Absorption

Bioavailability

Penicillin G benzathine, penicillin G procaine: Relatively insoluble; IM administration provides a tissue depot from which the drugs are slowly absorbed and hydrolyzed to penicillin G.2 4 5 7 61 63 64 70 81 IM administration results in serum concentrations of penicillin G that are more prolonged, but lower, than those attained with an equivalent IM dose of penicillin G potassium or sodium.2 3 10 61 64 70 81

Penicillin G benzathine: IM administration of a single dose in adults,67 70 81 children,234 or neonates353 365 371 results in peak serum concentrations of penicillin G that are attained in 13–24 hours81 234 353 365 371 and usually detectable for 1–4 weeks (depending on the dose).70 81 234 353 365 371

Penicillin G procaine: IM administration of a single dose in adults61 64 67 or neonates352 368 results in peak serum concentrations of penicillin G that are attained in 1–4 hours61 64 67 352 and usually detectable for 1–2 days; may be detectable in serum for up to 5 days (depending on the dose).61 64 67 70 352 368 In general, increasing the dose to >600,000 units tends to prolong duration of penicillin G serum concentrations rather than increase peak serum concentrations.63 70

Fixed combination of penicillin G benzathine and penicillin G procaine containing 1.2 million penicillin G units (i.e., 600,000 units as penicillin G benzathine with 600,000 units as penicillin G procaine; Bicillin C-R): Single IM dose of 1.2 million penicillin G units in adults usually produces peak blood penicillin G concentrations of 2.1–2.6 units/mL within 3 hours and concentrations average 0.75 units/mL at 12 hours, 0.28 units/mL at 24 hours, and 0.04 units/mL at 7 days.5

Fixed combination of penicillin G benzathine and penicillin G procaine containing 1.2 million penicillin G units (i.e., 900,000 units as penicillin G benzathine with 300,000 units as penicillin G procaine; Bicillin C-R 900/300): Single IM dose of 1.2 million penicillin G units in patients weighing 45–64 kg resulted in average blood penicillin G concentrations of 0.24 units/mL at 24 hours, 0.039 units/mL at 7 days, and 0.024 units/mL at 10 days after the dose.4

Penicillin G potassium or sodium: Rapidly absorbed followed IM administration;9 61 64 70 72 peak serum concentrations of penicillin G generally similar with equivalent IM doses of either salt and attained within 15–30 minutes.61 64 70 72

Penicillin G potassium or sodium: Following IV infusion, peak serum concentrations attained immediately after infusion completed.8 9 11 12 In 10 patients who received 5 million penicillin G units given IV over 3–5 minutes, mean serum concentrations were 400, 273, and 3 mcg/mL at 5–6 minutes, 10 minutes, and 4 hours after administration, respectively.8 9 11 12 In 5 healthy adults who received 1 million penicillin G units given IV over 4 minutes or IV over 60 minutes, mean serum concentrations 8 minutes after administration were 45 or 14.4 mcg/mL, respectively.8 9 11 12

Penicillin G potassium or sodium: Following intermittent IV infusion of 2 million penicillin G units every 2 hours or 3 million penicillin G units every 3 hours (as either salt), serum penicillin G concentrations reportedly average 20 mcg/mL.61

Penicillin G potassium or sodium: Absorbed from peritoneal cavity following local instillation;61 64 also absorbed from pleural surfaces, pericardium, and joint cavities.64

Distribution

Extent

Penicillin G widely distributed following absorption from IM or IV administration sites.2 3 4 5 7 8 9 11 12 61 64 70 81 320 Highest concentrations generally attained in the kidneys,2 3 4 5 7 with lower amounts in the liver,2 3 4 5 7 64 lungs,320 skin,2 3 4 5 7 intestines,2 3 4 5 7 64 and muscle.320 Also distributed into ascitic,9 11 61 339 synovial,8 9 11 12 61 64 320 326 pleural,8 9 11 12 61 pericardial,9 61 peritoneal,8 9 11 12 and interstitial fluids9 and tonsils,330 maxillary sinus secretions,61 599 and saliva.64

Minimal concentrations of penicillin G generally attained in CSF following IM or IV administration of penicillin G potassium or sodium or IM administration of penicillin G benzathine or penicillin G procaine in patients with uninflamed meninges;7 8 9 11 12 61 70 320 324 325 349 352 353 354 360 688 higher CSF concentrations attained when meninges are inflamed8 9 11 12 61 320 325 349 or when oral probenecid administered concomitantly.61 64 70 81 320 325 354

Crosses the placenta8 9 11 12 40 61 70 320 362 and is distributed into milk.2 3 4 5 7 8 9 11 12 61 64 355 364 374

Plasma Protein Binding

45–68%.2 3 4 5 7 61 63 64 67 70 81 320 336 337 340 361

Elimination

Metabolism

Penicillin G benzathine, penicillin G procaine: Slowly absorbed following IM administration and hydrolyzed to penicillin G.2 3 10 61 63 64

Penicillin G sodium: Approximately 16–30% of an IM dose is metabolized to penicilloic acid which is microbiologically inactive.366 Small amounts of 6-aminopenicillanic acid (6-APA) have also been found in the urine of patients receiving penicillin G.64 70 366 In addition, the drug appears to be hydroxylated to a small extent to one or more microbiologically active metabolites which are also excreted in urine.61

Elimination Route

Penicillin G and its metabolites excreted in urine mainly by tubular secretion.2 3 4 5 7 64 320 348 369 Small amounts of the drug also are excreted in bile.61 64

Penicillin G benzathine, penicillin G procaine: Following IM administration, slowly absorbed and excretion of penicillin G in urine continues over a prolonged period of time.64 234 Penicillin G has been detected in urine for up to 12 weeks after a single IM dose of 1.2 million units given as penicillin G benzathine.64

Penicillin G sodium or potassium: Following single IM or IV dose in adults with normal renal function, 58–85% of the dose excreted in urine as unchanged drug and active metabolites within 6 hours.8 9 11 12 61

Removed by hemodialysis8 9 10 11 12 61 63 320 369 and, to a lesser extent, by peritoneal dialysis.10

Half-life

Adults with normal renal function: 0.4–0.9 hours.8 9 11 12 61 64 67 81 320 338 340 348 361

Neonates: Serum half-life varies inversely with age8 9 11 12 61 and appears to be independent of birthweight.368 Serum half-life reported to be 3.2–3.4 hours in neonates ≤6 days of age, 1.2–2.2 hours in neonates 7–13 days of age, and 0.9–1.9 hours in neonates ≥14 days of age.8 9 11 12 61 368

Special Populations

Renal impairment: Serum concentrations of penicillin G may be higher and the serum half-life prolonged.8 9 11 12 64 70 320 348 369 Serum half-life is 1–2 hours in azotemic patients with serum creatinine concentrations <3 mg/dL8 9 11 12 348 and ranges from 6–20 hours in anuric patients.8 9 12 64 81 320 348 369

Anuric patients with hepatic impairment: Serum half-life of penicillin G may be 2–3 times more prolonged compared with anuric patients with normal hepatic function.70 320 348

Neonates and premature or young infants: Renal clearance of penicillin G may be delayed.2 3 4 5 7 8 9 10 11 12 61 64

Geriatric patients: Renal clearance of penicillin G may be delayed because of diminished tubular secretion ability.61

Pregnant women: Renal clearance of penicillin G may be increased40 61 during second and third trimesters.40

Stability

Storage

Parenteral

Powder for IM or IV Use

Penicillin G potassium: <30°C.9 12 Following reconstitution, store at 2–8°C for up to 7 days.9 12

Penicillin G sodium: 20–25°C.8 Following reconstitution, store at 2–8°C for up to 3 days.8

Suspension for IM Injection

Penicillin G benzathine: 2–8°C; do not freeze.2 3

Penicillin G procaine: 2–8°C; do not freeze.7

Fixed combinations of penicillin G benzathine and penicillin G procaine: 2–8°C; do not freeze.4 5

Injection (Frozen)

Penicillin G potassium: −20°C or lower.11 Thawed solutions are stable for 24 hours at room temperature (25°C) or 14 days when refrigerated at 5°C.11

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility (Penicillin G Potassium)HID

Compatible

Amino acids 4.25%, dextrose 25%

Dextrose 2.5 or 5% in half-strength Ringer’s injection

Dextrose 5% in Ringer’s injection

Dextrose 2.5, 5, or 10% in Ringer’s injection, lactated

Dextrose 2.5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in sodium chloride 0.225, 0.45, or 0.9%

Dextrose 2.5, 5, or 10% in water

Ionosol B or MB in dextrose 5%

Isolyte M or P in dextrose 5%

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Drug Compatibility
Admixture Compatibility (Penicillin G Potassium)HID

Compatible

Amikacin sulfate

Ascorbic acid

Calcium chloride

Calcium gluconate

Chloramphenicol sodium succinate

Colistimethate sodium

Dimenhydrinate

Diphenhydramine HCl

Ephedrine sulfate

Erythromycin lactobionate

Furosemide

Hydrocortisone sodium succinate

Kanamycin sulfate

Lidocaine HCl

Lincomycin HCl

Magnesium sulfate

Methylprednisolone sodium succinate

Metronidazole

Polymyxin B sulfate

Potassium chloride

Ranitidine HCl

Verapamil HCl

Incompatible

Aminophylline

Amphotericin B

Chlorpromazine HCl

Dopamine HCl

Hydroxyzine HCl

Pentobarbital sodium

Prochlorperazine mesylate

Tranexamic acid

Variable

Heparin sodium

Promethazine HCl

Sodium bicarbonate

Y-site Compatibility (Penicillin G Potassium)HID

Compatible

Acyclovir sodium

Amiodarone HCl

Ceftolozane sulfate-tazobactam sodium

Cyclophosphamide

Diltiazem HCl

Enalaprilat

Esmolol HCl

Fluconazole

Foscarnet sodium

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Labetalol HCl

Magnesium sulfate

Meperidine HCl

Morphine sulfate

Nicardipine HCl

Potassium chloride

Tacrolimus

Theophylline

Verapamil HCl

Incompatible

Tedizolid

Variable

Isavuconazonium sulfate

Solution Compatibility (Penicillin G Sodium)HID

Variable

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility (Penicillin G Sodium)
Admixture CompatibilityHID

Compatible

Calcium chloride

Calcium gluconate

Chloramphenicol sodium succinate

Colistimethate sodium

Dextran 40

Diphenhydramine HCl

Erythromycin lactobionate

Gentamicin sulfate

Hydrocortisone sodium succinate

Lincomycin HCl

Polymyxin B sulfate

Ranitidine HCl

Verapamil HCl

Incompatible

Amphotericin B

Bleomycin sulfate

Chlorpromazine HCl

Cytarabine

Hydroxyzine HCl

Methylprednisolone sodium succinate

Prochlorperazine mesylate

Promethazine HCl

Variable

Heparin sodium

Potassium chloride

Y-Site Compatibility (Penicillin G Sodium)HID

Compatible

Clarithromycin

Levofloxacin

Actions and Spectrum

  • Penicillin G is a β-lactam antibacterial classified as a natural penicillin.61 64

  • Available as penicillin G benzathine,2 3 penicillin G procaine,7 and fixed combinations of penicillin G benzathine and penicillin G procaine;4 5 these preparations are referred to as long-acting, depot, or repository forms of penicillin G.2 3 4 5 7 61

  • Available as penicillin G potassium9 11 12 and penicillin G sodium;8 these preparations are referred to as aqueous, crystalline forms of penicillin G.10 61 64 63 72

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.8 9 10 11 12 61 64 88 Usually bactericidal against susceptible organisms.8 9 10 11 12 61 64 Induces a postantibiotic effect (PAE) in some susceptible bacteria.61

  • Spectrum of activity of penicillin G includes some non-β-lactamase-producing gram-positive and -negative aerobes, some gram-positive anaerobes, and most spirochetes.8 9 11 12 10 61 64 72 88 Generally inactive against mycobacteria, Chlamydia, Mycoplasma, Rickettsia, and fungi.61

  • Gram-positive aerobes: Active in vitro against streptococci, including S. pyogenes (group A β-hemolytic streptococci; GAS),61 other β-hemolytic streptococci (e.g., groups C, G, H, L, M, R),61 S. agalactiae (group B streptococci; GBS),61 and some strains of S. pneumoniae,61 α-hemolytic streptococci (including viridans streptococci),61 and nonenterococcal group D streptococci.61 Active against some non-penicillinase-producing Staphylococcus.61 Also active against some strains of Bacillus anthracis,61 Corynebacterium diphtheriae,61 Erysipelothrix rhusiopathiae,61 and Listeria monocytogenes.61 Some strains of enterococci are susceptible to penicillin G, but many strains are resistant and penicillin tolerance reported.61

  • Gram-negative aerobes: Active in vitro against Neisseria meningitidis,61 non-β-lactamase-producing H. influenzae,61 Bordetella pertussis,61 Eikenella corrodens,61 Kingella kingae,61 Legionella,61 and Pasteurella multocida.61 Generally inactive against Enterobacteriaceae and Pseudomonas.61

  • Anaerobes: Active in vitro against Actinomyces,61 Clostridium (including C. botulinum, C. perfringens, and C. tetani),61 Cutibacterium acnes (formerly Propionibacterium acnes),61 Eubacterium,61 Lactobacillus,61 Peptococcus,61 Peptostreptococcus,61 and Veillonella.61 C. botulinum resistant to penicillin reported.61 Although Fusobacterium and some strains of Bacteroides melaninogenicus or B. oralis may be susceptible, B. fragilis usually resistant.61

  • Spirochetes: Active against Treponema pallidum,61 Leptospira,61 Streptobacillus moniliformis,61 Spirillum minus, and Borrelia hemsii.61 Also active against B. burgdorferi.61 711 712

  • Penicillinase-producing bacteria, including penicillinase-producing S. aureus, S. epidermidis, and Neisseria, are resistant.61 64 S. pneumoniae resistant to penicillin G, including strains that are relatively or highly resistant, reported with increasing frequency.61

Advice to Patients

  • Advise patients that antibacterials (including penicillin G) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).2 4 5 8 9 11 12

  • Importance of completing full course of therapy, even if feeling better after a few days.2 4 5 8 9 11 12

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with penicillin G or other antibacterials in the future.2 4 5 8 9 11 12

  • Importance of discontinuing therapy if an allergic reaction occurs.2 4 5 8 9 11 12

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.2 4 5 8 9 11 12 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.2 4 5 8 9 11 12

  • Importance of informing clinician of existing or contemplated therapy, including prescription and OTC drugs, and any concomitant illnesses.2 3 4 5 7 8 9 11 12

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.2 3 4 5 7 8 9 11 12

  • Importance of advising patients of other important precautionary information.2 3 4 5 7 8 9 11 12 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Penicillin G Benzathine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, for IM Injection

600,000 units (of penicillin G) per mL

Bicillin L-A

Pfizer

Permapen

Casper

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Penicillin G Potassium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

1 million units (of penicillin G)*

Penicillin G Potassium for Injection

5 million units (of penicillin G)*

Penicillin G Potassium for Injection

Pfizerpen

Pfizer

20 million units (of penicillin G)*

Penicillin G Potassium for Injection

Pfizerpen

Pfizer

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Penicillin G Potassium in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (frozen), for IV infusion

20,000 units (of penicillin G) per mL (1 million units) in 4% Dextrose*

Penicillin G Potassium in Iso-osmotic Dextrose Injection Galaxy

40,000 units (of penicillin G) per mL (2 million units) in 2.4% Dextrose*

Penicillin G Potassium in Iso-osmotic Dextrose Injection Galaxy

60,000 units (of penicillin G) per mL (3 million units) in 0.7% Dextrose*

Penicillin G Potassium in Iso-osmotic Dextrose Injection Galaxy

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Penicillin G Procaine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, for IM Injection

600,000 units (of penicillin G) per mL*

Penicillin G Procaine Suspension

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Penicillin G Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

5 million units (of penicillin G)*

Penicillin G Sodium for Injection

Penicillin G Benzathine and Penicillin G Procaine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, for IM Injection

1.2 million units of penicillin G per 2 mL (600,000 units as penicillin G benzathine and 600,000 units as penicillin G procaine)

Bicillin C-R

Pfizer

1.2 million units of penicillin G per 2 mL (900,000 units as penicillin G benzathine and 300,000 units as penicillin G procaine)

Bicillin C-R 900/300

Pfizer

AHFS DI Essentials™. © Copyright 2018, Selected Revisions October 1, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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