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: Bicillin C-R, Bicillin C-R 900/300, Bicillin L-A, Permapen, Pfizerpen

Introduction

Antibacterial; β-lactam antibiotic; natural penicillin. Available as penicillin G benzathine, penicillin G potassium, penicillin G procaine, and penicillin G sodium.^{1 6 7}

Uses for Penicillin G Benzathine/Potassium/Sodium

Endocarditis

Treatment of native valve endocarditis caused by penicillin-susceptible staphylococci. Consider that the majority of staphylococci are resistant to penicillin G and must be treated with a penicillinase-resistant penicillin (e.g., nafcillin, oxacillin).⁵

Treatment of endocarditis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).⁷

Treatment of native valve or prosthetic valve endocarditis caused by viridans streptococci (e.g., S. milleri, S. mitis, S. mutans) or S. bovis (nonenterococcal group D streptococcus).⁵ Used alone or in conjunction with gentamicin.⁵

Treatment of enterococcal endocarditis;^{5 9} used in conjunction with an aminoglycoside.⁵

Meningitis and Other CNS Infections

Treatment of meningitis caused by nonpenicillinase-producing S. aureus or S. epidermidis.¹ Consider that the majority of staphylococci are resistant to penicillin G.

Treatment of meningitis caused by susceptible S. pneumoniae.¹ Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G have been reported with increasing frequency; treatment failures have occurred when penicillin G was used alone in treatment of CNS infections caused by these strains.

Treatment of meningitis caused by susceptible S. agalactiae (group B streptococci). Ampicillin usually the preferred penicillin for empiric treatment of neonatal S. agalactiae meningitis; treatment can be changed to penicillin G after in vitro susceptibility testing is completed.

Treatment of meningitis caused by L. monocytogenes; used alone or in conjunction with an aminoglycoside (e.g., gentamicin).¹ Ampicillin in conjunction with an aminoglycoside usually is the regimen of choice for L. monocytogenes meningitis.

Treatment of meningitis caused by Neisseria meningitidis.^{1 9} Drug of choice.

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).^{6 8 11 12 13}

AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;^{8 9 11 12 13} oral cephalosporins and oral macrolides are considered alternatives.^{8 11 12 13} Amoxicillin sometimes used instead of penicillin V, especially for young children.^{8 13}

A second episode can be retreated with the same or other treatment of choice;^{8 13} other regimens (amoxicillin and clavulanate, clindamycin, penicillin G benzathine with or without rifampin) recommended for symptomatic patients with multiple, recurrent episodes.^{8 11 13}

Consider that multiple, recurrent episodes of symptomatic pharyngitis within several months to years may indicate that a streptococcal carrier experiencing repeated episodes of nonstreptococcal (e.g., viral) pharyngitis;^{11 13} treatment not usually recommended for streptococcal pharyngeal carriers.^{8 11 13}

Respiratory Tract Infections

Treatment of respiratory tract infections caused by susceptible streptococci, including S. pneumoniae.^{1 6 7} Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G have been reported with increasing frequency.

Septicemia

Treatment of bacteremia caused by susceptible streptococci.¹

Has been used for treatment of bacteremia caused by susceptible Acinetobacter faecalis, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Salmonella, and Shigella,¹ but other more effective anti-infectives (e.g., third generation cephalosporins, aminoglycosides, aminopenicillins, extended-spectrum penicillins) are preferred for these infections.

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by susceptible staphylococci or streptococci.⁷

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Drug of choice for treatment of severe S. pyogenes infections, including cellulitis, erysipelas, and necrotizing fasciitis; if presence of staphylococci is suspected, a penicillinase-resistant penicillin (with or without vancomycin) usually is used.

Actinomycosis

Treatment of actinomycosis;^{1 9} drug of choice for all forms of actinomycosis, including thoracic, abdominal, CNS, and cervicofacial infections.⁹

Anthrax

Treatment of clinically apparent inhalational, GI, or meningeal anthrax or anthrax septicemia caused by susceptible Bacillus anthracis that occurs as the result of natural or endemic exposures to the organism.^{1 7 9 1} Considered a drug of choice, but B. anthracis with naturally-occurring penicillin resistance have been reported rarely and there are published reports of strains engineered to have penicillin and tetracycline resistance as well as resistance to other anti-infectives (e.g., macrolides, chloramphenicol, rifampin).

Alternative for use in multiple-drug regimens for treatment of anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism. Initiate treatment with IV ciprofloxacin or doxycycline and 1 or 2 anti-infectives predicted to be effective (e.g., chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, ampicillin); if meningitis is established or suspected, use IV ciprofloxacin (rather than doxycycline) and chloramphenicol, rifampin, or penicillin. Because of concerns regarding possible penicillin resistance or induction of penicillin resistance during treatment, use of a penicillin alone is not recommended for treatment of inhalational anthrax that occurs as the result of biologic warfare or bioterrorism when high concentrations of the organism are likely to be present, although penicillin can be included in appropriate combination regimens.

Treatment of mild, uncomplicated cutaneous anthrax caused by susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax. If cutaneous anthrax occurs in the context of biologic warfare or bioterrorism, initial drugs of choice are ciprofloxacin or doxycycline. If penicillin susceptibility is confirmed, consideration can be given to changing to a penicillin in infants and children or in pregnant or lactating women; amoxicillin usually is recommended.

Alternative for postexposure prophylaxis of anthrax following exposure to B. anthracis spores (inhalational anthrax). Ciprofloxacin and doxycycline are initial drugs of choice following suspected or confirmed bioterrorism-related anthrax exposure. If penicillin susceptibility is confirmed, consideration can be given to changing prophylaxis to a penicillin (e.g., amoxicillin, penicillin V, penicillin G procaine) in infants and children and in pregnant or lactating women; amoxicillin usually is recommended.

Clostridium Infections

Treatment of infections caused by Clostridium perfringens, including empyema and gas gangrene.^{1 9} The drug of choice.⁹ In treatment of gas gangrene, used as an adjunct to debridement and excision of the infected area; hyperbaric oxygen therapy also may be useful in the management of spreading, necrotic types of infections.⁹

Adjunct to tetanus immune globulin (TIG), tetanus toxoid adsorbed, sedatives, and muscle relaxants in the treatment of active tetanus infection.^{1 9} Although C. tetani is susceptible to penicillin G, the nature of the infected wound generally makes the organism inaccessible to anti-infectives. Anti-infective agents cannot neutralize toxin already formed and cannot eradicate C. tetani spores which may revert to toxin-producing vegetative forms. Treatment of a tetanus wound consists of surgical debridement and prevention of associated infections that could create an anaerobic environment and help proliferation of C. tetani.

Adjunct to active immunization with tetanus toxoid or, preferably, tetanus toxoid adsorbed and passive immunization with TIG in the prophylactic treatment of individuals with tetanus-prone wounds (e.g., a severe deep puncture wound). ACIP states that chemoprophylaxis against tetanus is neither practical nor useful in managing wounds and proper immunization is the most important measure.

Adjunct in the treatment of wound botulism caused by germination of C. botulinum spores in a contaminated wound with in vivo toxin production. Anti-infective agents have no known direct effects on botulinum toxin and therefore are not usually indicated in the management of most forms of botulism (foodborne botulism, infant botulism, adult or child infectious botulism), except for the treatment of secondary infection (e.g., respiratory or urinary tract infections). If anti-infective therapy is needed for the treatment of secondary infection in a patient with botulism, aminoglycosides, tetracyclines, and clindamycin should not be used since these anti-infective agents may exacerbate neuromuscular blockade.

Treatment strategies for most forms of botulism include intensive supportive care (including aggressive use of respiratory care) and prompt administration of botulinum antitoxin when appropriate. Botulinum antitoxin also may be indicated for botulism that occurs in the context of biologic warfare or bioterrorism. Timely administration of botulinum antitoxin is important since it can minimize subsequent nerve damage but will not reverse existent paralysis. Botulinum antitoxin is not commercially available in the US but is available from the CDC.

The mainstay of treatment of foodborne botulism, infant botulism, and adult and child infectious botulism is use of botulinum antitoxin and supportive care. Anti-infectives are not indicated for the treatment of these forms of botulism since lysis of intraluminal C. botulinum may increase the amount of toxin in the body, but anti-infectives may be used for the treatment of secondary infections if necessary.

Diphtheria

Adjunct to diphtheria antitoxin for treatment of diphtheria caused by Corynebacterium diphtheriae.^{1 7 9} Diphtheria antitoxin is the most important aspect of treatment of respiratory diphtheria. Anti-infectives may eliminate C. diphtheriae from infected sites, prevent spread of the organism and further toxin production, and prevent or terminate the diphtheria carrier state, but appear to be of no value in neutralizing diphtheria toxin and should not be considered a substitute for antitoxin therapy.

Because diphtheria infection often does not confer immunity, active immunization with a diphtheria toxoid preparation should be initiated or completed during convalescence.

Prevention of diphtheria in close contacts of patients with respiratory or cutaneous diphtheria. Prophylaxis is indicated in all household or other close contacts of individuals with suspected or proven diphtheria, regardless of vaccination status; prophylaxis should be initiated promptly and should not be delayed pending culture results. An age-appropriate diphtheria toxoid preparation also may be indicated.

Elimination of diphtheria carrier state in individuals known to carry toxigenic strains of C. diphtheriae.¹

Erysipelothrix rhusiopathiae Infections

Treatment of infections caused by Erysipelothrix rhusiopathiae, including erysipeloid or endocarditis.^{1 7 9} A drug of choice.⁹

Leptospirosis

Treatment of leptospirosis†.⁹ A drug of choice.⁹ Many leptospiral infections are self-limited, and the effectiveness of anti-infective therapy in the treatment of the disease has been questioned. Anti-infective therapy initiated after the fifth day of illness probably will not alter the course of the disease.

Listeria Infections

Treatment of infections caused by L. monocytogenes (e.g., infections during pregnancy, granulomatosis infantiseptica, sepsis, meningitis, endocarditis, foodborne infections).¹ Ampicillin used alone or in conjunction with gentamicin or streptomycin generally is considered the treatment of choice for these infections.

For treatment of foodborne Listeria infections, the CDC recommends use of ampicillin, penicillin G, or co-trimoxazole when there is invasive disease.

Lyme Disease

Treatment of early or late Lyme disease† when a parenteral regimen is indicated.⁹

Treatment of late Lyme disease when neurologic manifestations affecting the CNS or peripheral nervous system are present.

Alternative to IV ceftriaxone or IV cefotaxime for patients with late neurologic disease affecting the CNS or peripheral nervous system (e.g., encephalopathy, neuropathy). Treatment of neurologic (e.g., radicular pain, motor deficits) abnormalities in patients with Lyme meningitis† or arthritis associated with Lyme disease†. Ceftriaxone may be preferable to penicillin G for serious manifestations of early disseminated or late Lyme disease (i.e., those involving major organs) based on ceftriaxone’s greater in vitro and in vivo activity against B. burgdorferi, excellent CSF penetration, and prolonged serum concentrations achievable with once-daily administration.

Necrotizing Ulcerative Gingivitis

Treatment of acute necrotizing ulcerative gingivitis (Vincent’s infection, trench mouth, Fusobacterium gingivitis or pharyngitis, Leptotrichia buccalis infection).^{1 7 9}

Neisseria Infections

Treatment of upper respiratory tract infections, bacteremia, and meningitis caused by N. meningitidis.¹ (See Meningitis and Other CNS Infections under Uses.) The drug of choice for most meningococcal infections.

Does not eliminate the meningococcus carrier state and should not be used for chemoprophylaxis in asymptomatic N. meningitidis carriers. Ceftriaxone, ciprofloxacin, or rifampin usually used to eliminate nasopharyngeal carriage of N. meningitidis.

Should not be used for treatment of gonorrhea.^{7 14 15} Previously used for treatment of uncomplicated gonorrhea and disseminated gonococcal infections caused by susceptible nonpenicillinase-producing N. gonorrhoeae.¹ No longer recommended by CDC or other experts (high incidence of penicillinase-producing strains).

Pasteurella Infections

Treatment of infections caused by Pasteurella multocida; a drug of choice for local infections, septicemia, osteomyelitis, endocarditis, or other serious infections.^{1 9}

Rat-bite Fever

Treatment of rat-bite fever caused by Streptobacillus moniliformis (erythema arthriticum epidemicum, Haverhill fever) or Spirillum minus (sodoku).^{1 7 9} Drug of choice.⁹

Relapsing Fever

Alternative to tetracyclines for treatment of tick-borne (endemic) or louse-borne (epidemic) relapsing fever† caused by Borrelia.

Syphilis

Treatment of syphilis.^{1 6 7} Penicillin G is drug of choice for all stages and forms of syphilis, including primary infection (i.e., ulcer or chancre at the infection site), secondary infection (i.e., manifestations that include rash, mucocutaneous lesions, and adenopathy), tertiary infection (i.e., cardiac, ophthalmic, auditory, or gummatous lesions), early latent syphilis (latent syphilis acquired within the preceding year), late latent syphilis or latent syphilis of unknown duration, neurosyphilis, and congenital syphilis.

Penicillin G benzathine is drug of choice for treatment of primary syphilis, secondary syphilis, latent syphilis, and tertiary syphilis in adults, adolescents, and children.

Penicillin G potassium or penicillin G sodium is drug of choice for treatment of neurosyphilis in adults and adolescents; alternatively, penicillin G procaine (with oral probenecid) may be used if compliance can be ensured.

Penicillin G potassium or sodium or penicillin G procaine recommended for congenital syphilis (proven or highly probable). Penicillin G benzathine is not recommended for the treatment of known congenital syphilis, but may be used in infants at lower risk of congenital syphilis.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) should not be used for treatment of any form of syphilis^{17 18} since it may not result in the sustained serum concentrations required for syphilis treatment and could increase the risk for treatment failure and neurosyphilis, especially among HIV-infected patients.¹⁸

Efficacy of currently recommended syphilis treatment regimens may be reduced in HIV-infected patients; higher doses and/or more prolonged duration of therapy may be necessary in these patients. Careful follow-up is recommended in all patients coinfected with syphilis and HIV to assure adequacy of treatment.

There are no proven alternatives to penicillin G for treatment of congenital syphilis or syphilis during pregnancy in patients with penicillin hypersensitivity. These patients should be desensitized, if necessary, and treated with penicillin G.

Whipple's Disease

Treatment of Whipple’s disease† caused by Tropheryma whippelii.⁹

Yaws, Pinta, and Bejel

Treatment of yaws (T. pertenue), pinta (T. carateum), and bejel (T. pallidum var. endemic syphilis).^{6 7 9} Drug of choice.⁹

Prevention of Perinatal Group B Streptococcal Disease

Prevention of early-onset neonatal group B streptococcal (GBS) disease†.

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

When intrapartum GBS prophylaxis is indicated, IV penicillin G is the drug of choice. Although IV ampicillin can be used, CDC and AAP state that penicillin G is preferred since it has a narrower spectrum of activity and is less likely to select for antibiotic-resistant organisms.

Prevention of Rheumatic Fever Recurrence

Prevention of recurrence of rheumatic fever (secondary prophylaxis).⁶ Continuous prophylaxis recommended following treatment of documented rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease.

AHA recommends IM penicillin G benzathine, oral penicillin V, or oral sulfadiazine for such prophylaxis.

Penicillin G Benzathine/Potassium/Sodium Dosage and Administration

Administration

Administer penicillin G potassium or sodium by IM injection or IV infusion;^{1 4} also has been administered intrathecally or by intrapleural, intra-articular, or other local instillations.^{1 4}

Administer penicillin G benzathine,^{6 16} penicillin G procaine,⁷ or fixed combination containing penicillin G benzathine and penicillin G procaine^{14 15} only by deep IM injection. Do not inject these drugs IV or admix with other IV solutions; inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.^{6 7 14 15 16} Also take special precaution to avoid intravascular or intra-arterial administration or injection of these drugs into or near major peripheral nerves or blood vessels since such injections may produce severe and/or permanent neurovascular damage.^{6 7 14 15 16} (See Administration Precautions under Cautions.)

Vials containing 20 million units of penicillin G potassium are intended for IV administration only and should not be used to prepare IM injections.¹ Penicillin G potassium or sodium should generally be given IV when large doses (10 million units or more) are required.

IV Infusion

For IV infusions, use penicillin G potassium or penicillin G sodium.¹ Do not administer penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine IV.^{6 7 14 15 16}

Reconstitution and Dilution (Penicillin G Potassium or Penicillin G Sodium)

Reconstitute penicillin G potassium or sodium powders with the amount of diluent specified by the manufacturer.¹

For continuous IV infusion, reconstituted solutions of penicillin G potassium or sodium generally should be added to 1–2 L of a compatible IV solution. The volume of IV fluid and rate of administration required by the patient in a 24-hour period should be determined and the appropriate daily dosage of penicillin G added to the fluid.⁴ For example, if an adult patient requires 2 L of fluid in 24 hours and a dosage of 10 million units of penicillin G daily, 5 million units can be added to 1 L of IV solution and the rate of administration adjusted so that the liter of fluid will be infused over 12 hours.⁴

Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; do not force thaw by immersion in a water bath or by exposure to microwave radiation. A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature. Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact. The injection should not be used 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.

Rate of Administration (Penicillin G Potassium or Penicillin G Sodium)

For intermittent IV infusion, penicillin G potassium or sodium generally should be infused over 1–2 hours. One suggested method for adults is to administer (1/6) or ¼ of the total daily dose as a 1- to 2-hour infusion every 4 or 6 hours, respectively. Divided doses of the drug have also been infused intermittently IV over 15–30 minutes in neonates and children.

IM Injection

For IM injection, use penicillin G potassium, penicillin G sodium, penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine based on the indication.^{1 6 7 14 15 16}

Penicillin G potassium or sodium solutions containing up to 100,000 units/mL may be administered IM with a minimum of discomfort; higher concentrations are physically possible and may be used when needed.¹

When penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine is given IM, inject deeply into the gluteus maximus or into the midlateral thigh (may be preferred for neonates and small children).^{6 7 14 15 16} Avoid injection or injection into the fat layer since such injections may cause pain and induration.⁶ In addition, avoid injection into or near a nerve since permanent neurologic damage may result.^{6 7 14 15 16} Repeated IM injections into the anterolateral thigh, especially in neonates and infants, also should be avoided since quadriceps femoris fibrosis and atrophy may occur.⁶ (See Administration Precautions under Cautions.)

IM injections should be made at a slow, steady rate to avoid blockage of the needle.^{6 7 14 15 16} Rotate IM injection sites when repeated doses are given.^{6 7 14 15 16}

Discontinue IM injection of the dose if patient complains of severe, immediate pain at the injection site or if (especially in neonates, infants, and young children) symptoms occur suggesting onset of severe pain.^{6 7 14 15 16}

Reconstitution and Dilution

Penicillin G benzathine and penicillin G procaine are provided in prefilled syringes or Tubex injectors and should be administered undiluted according to manufacturer's directions.^{6 7}

Prepare IM injections of penicillin G potassium or penicillin G sodium according to manufacturer's directions.

Dosage

Dosage of penicillin G potassium, penicillin G sodium, penicillin G benzathine, penicillin G procaine, and fixed combination of penicillin G benzathine and penicillin G procaine is expressed in terms of USP penicillin G units.^{1 6 7 14 15 16}

Pediatric Patients

General Dosage for Neonates

Penicillin G Potassium or Penicillin G Sodium

IV or IM

Neonates <1 week of age: AAP recommends 25,000–50,000 units/kg every 12 hours in those weighing ≤2 kg and 25,000–50,000 units/kg every 8 hours for those weighing >2 kg.

Neonates 1–4 weeks of age: AAP recommends 25,000–50,000 units/kg every 12 hours in those weighing <1.2 kg, 25,000–50,000 units every 8 hours for those weighing 1.2–2 kg, and 25,000–50,000 units every 6 hours for those weighing >2 kg.

Penicillin G Procaine

IM

Neonates <1 week of age: AAP recommends 50,000 units/kg every 24 hours in those weighing ≥1.2 kg.

Neonates 1–4 weeks of age: AAP recommends 50,000 units/kg every 24 hours in those weighing ≥1.2 kg.

General Pediatric Dosage

Penicillin G Benzathine

IM

Children ≥1 month of age: AAP recommends 600,000 units/kg daily in children weighing <27.3 kg or 1.2 million units/kg daily for those weighing ≥27.3 kg for treatment of mild to moderate infections. Inappropriate for severe infections according to AAP.

Penicillin G Potassium or Penicillin G Sodium

IV or IM

Children ≥1 month of age: AAP recommends 25,000–50,000 units/kg daily given in 4 divided doses for treatment of mild to moderate infections and 250,000–400,000 units/kg daily given in 4–6 divided doses for treatment of severe infections.

Penicillin G Procaine

IM

Children ≥1 month of age: AAP recommends 25,000–50,000 units/kg daily given in 1 or 2 divided doses for treatment of mild to moderate infections. Inappropriate for severe infections according to AAP.

Fixed Combination of Penicillin G Benzathine and Penicillin G Procaine

IM

Treatment of S. pyogenes infections (upper respiratory tract, skin and soft-tissue, scarlet fever, erysipelas): A single dose containing 1.2 million units (2 mL of Bicillin C-R 900/300) usually sufficient.¹⁴ Alternatively, if Bicillin C-R is used, children weighing <13.6 kg may receive 600,000 units, those weighing 13.6–27.2 kg may receive 0.9–1.2 million units, and those weighing >27.2 kg may receive 2.4 million units.¹⁵ When Bicillin C-R is used, the dose usually is given at a single session using multiple IM sites; alternatively, if compliance regarding the return visit is assured, the total dose can be divided and half given on day 1 and half on day 3.¹⁵

Treatment of S. pneumoniae infections (except meningitis): 1.2 units (2 mL of Bicillin C-R 900/300) as a single dose repeated every 2 or 3 days until temperature is normal for 48 hours.¹⁴ Alternatively, if Bicillin C-R is used, 600,000 units as a single dose repeated every 2 or 3 days until temperature is normal for 48 hours.¹⁵ Other penicillin formulations (penicillin G potassium or penicillin G sodium) may be necessary for severe infections.^{14 15}

Endocarditis

Treatment of Native Valve Endocarditis Caused by Viridans Streptococci or S. bovis

IV

Penicillin G potassium or penicillin G sodium (for penicillin-susceptible strains; MIC≤0.1 mcg/mL): 200,000 units daily given in 4–6 equally divided doses for 4 weeks.⁵ Alternatively, 200,000 units daily given in 4–6 divided doses for 2 weeks in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 2 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).⁵

Penicillin G potassium or penicillin G sodium (for relatively resistant strains; MIC >0.1–0.5 mcg/mL): 300,000 units daily given in 4–6 equally divided doses for 4 weeks; used in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 4 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).⁵

Penicillin G potassium or penicillin G sodium (for nutritionally variant or strains with high-level resistance; MIC >0.5 mcg/mL): 300,000 units daily given in 4–6 equally divided doses for 4–6 weeks; used in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 4–6 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).⁵

Treatment of Enterococcal Endocarditis

IV

Penicillin G potassium or penicillin G sodium: 300,000 units daily given in 4–6 equally divided doses for 4–6 weeks; used in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 4–6 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).⁵

Meningitis

Meningitis Caused by S. pneumoniae

IV

Penicillin G potassium or penicillin G sodium: AAP recommends 250,000–400,000 units/kg daily given in 4–6 divided doses in those ≥1 month of age. A dosage of 250,000 units/kg daily given in 6 divided doses generally results in mean CSF concentrations of 0.8 mcg/mL sustained throughout the 4 hours between infusions.

Meningitis Caused by S. agalactiae (Group B Streptococci)

IV

Penicillin G potassium or penicillin G sodium: AAP recommends 250,000–450,000 units/kg daily IV in 3 divided doses in neonates ≤7 days of age or 450,000 units/kg daily IV in 4 divided doses in neonates >7 days of age.

Penicillin G potassium or penicillin G sodium: AAP recommends 250,000–400,000 units/kg daily given IV in 4–6 divided doses in those ≥1 month of age. A dosage of 250,000 units/kg daily given in 6 divided doses generally results in mean CSF concentrations of 0.8 mcg/mL sustained throughout the 4 hours between infusions.

Pharyngitis and Tonsillitis

IM

Penicillin G benzathine: AAP, AHA, and IDSA recommend a single dose of 600,000 units for those weighing ≤27 kg and a single dose of 1.2 million units for those weighing >27 kg.^{8 11 13}

Penicillin G benzathine: Manufacturer recommends a single dose of 300,000–600,000 units in those weighing <27 kg and a single dose of 900,000 units in older children.⁶

Anthrax

Treatment of Naturally Occurring or Endemic Anthrax

IV

Penicillin G potassium or penicillin G sodium: 100,000–150,000 units/kg daily given in divided doses every 4–6 hours.

Continue for ≥14 days after symptoms abate.

Treatment of Inhalational, GI, or Oropharyngeal Anthrax

IV

Penicillin G potassium or penicillin G sodium: 50,000 units/kg IV every 6 hours in children <12 years of age.

Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism

IM

Penicillin G procaine: 25,000 units/kg (maximum 1.2 million units) every 12 hours; use only if penicillin susceptibility is confirmed.⁷

Total duration of postexposure prophylaxis usually is 60 days.⁷ Safety data for penicillin G procaine administered at the dosage recommended for prophylaxis of anthrax supports a duration of therapy of ≤2 weeks, and clinicians must consider the risks versus benefits of administering penicillin G procaine for >2 weeks or switching to an appropriate alternative anti-infective (e.g., oral amoxicillin or penicillin V).⁷

Diphtheria

Treatment of Diphtheria

IV

Penicillin G potassium or penicillin G sodium: 100,000–150,000 units/kg daily given IV in 4 divided doses daily for 14 days; used as an adjunct to diphtheria antitoxin.

IM

Penicillin G procaine: CDC recommends 300,000 units daily in those weighing ≤10 kg or 600,000 units daily in those weighing >10 kg as an adjunct to diphtheria antitoxin. AAP recommends 25,000–50,000 units/kg daily (maximum 1.2 million units daily) given in 2 divided doses for 14 days.

Prevention of Diphtheria in Close Contacts

IM

Penicillin G benzathine: A single dose of 600,000 units in children <6 years of age or weighing <30 kg or 1.2 million units in those ≥6 years of age or weighing ≥30 kg.

Provide prophylaxis regardless of immunization status and closely monitor for symptoms of diphtheria for 7 days.

In addition, contacts who are inadequately immunized against diphtheria (i.e., have previously received <3 doses of diphtheria toxoid) or whose immunization status is unknown should receive an immediate dose of an age-appropriate diphtheria toxoid preparation and the primary series should be completed according to the recommended schedule.

Contacts who are fully immunized should receive an immediate booster dose of an age-appropriate diphtheria toxoid preparation if it has been ≥5 years since their last booster dose.

Elimination of Diphtheria Carrier State

IM

Penicillin G potassium or penicillin G sodium: 300,000–400,000 units daily given in divided doses for 10–12 days.¹

Penicillin G benzathine: A single dose of 600,000 units in children <6 years of age or weighing <30 kg or 1.2 million units in those ≥6 years of age or weighing ≥30 kg.

Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures are positive, a 10-day course of oral erythromycin should be given and additional follow-up cultures obtained.

Listeria Infections

Serious Listeria Infections in Neonates

IV

Penicillin G potassium or penicillin G sodium: 500,000 to 1 million units daily.¹

Lyme Disease†

Early or Late Lyme Disease with Serious Neurologic, Cardiac, and/or Arthritic Manifestations†

IV

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

Severe Lyme Carditis†

IV

Penicillin G potassium or penicillin G sodium: 200,000–400,000 units/kg daily (maximum 18–24 million units daily) given in 4 or 6 divided doses (every 4–6 hours) for 14–21 days.

Syphilis

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) should not be used for treatment of any form of syphilis.^{17 18}

Neonates with Proven or Presumed Congenital Syphilis

IV

Penicillin G potassium or penicillin G sodium: CDC and AAP recommend 100,000–150,000 units/kg daily (administered as 50,000 units/kg IV every 12 hours during the first 7 days of life and every 8 hours thereafter) for a total duration of 10 days. CDC and AAP state that if >1 day of therapy is missed, the entire course of therapy should be readministered.

IM

Penicillin G benzathine: Manufacturer recommends a single dose of 50,000 units/kg.⁶ CDC and AAP state that penicillin G benzathine is not recommended for treatment of known congenital syphilis; these experts recommend IV penicillin G potassium or sodium or IM penicillin G procaine for neonates with proven or highly probable congenital syphilis.

Penicillin G procaine: CDC and AAP recommend 50,000 units/kg once daily for 10 days; if >1 day of therapy is missed, the entire course should be readministered.

Children ≥1 Month of Age with Suspected Congenital Syphilis or Late and Previously Untreated Congenital Syphilis

IV

Penicillin G potassium or penicillin G sodium: 200,000–300,000 units/kg daily (given as 50,000 units/kg every 4–6 hours) for 10 days. Some clinicians recommend that this regimen be followed by a regimen of IM penicillin G benzathine (50,000 units/kg once weekly for 1–3 weeks).

IM

Penicillin G benzathine: 50,000 units/kg once weekly for 3 weeks.

Primary or Secondary Syphilis in Children ≥1 Month of Age

IM

Penicillin G benzathine: A single dose of 50,000 units/kg (up to 2.4 million units).

Primary or Secondary Syphilis in Adolescents

IM

Penicillin G benzathine: A single dose of 2.4 million units.⁶ For HIV-infected adolescents, some clinicians suggest that additional doses of 2.4 million units be given once weekly for a total of 3 weeks of therapy.

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 8 days.⁷ CDC recommends use of penicillin G benzathine for primary or secondary syphilis.

Latent Syphilis or Tertiary Syphilis in Children ≥1 Month of Age

IM

Penicillin G benzathine: CDC and AAP recommend that early latent syphilis be treated with a single dose of 50,000 units/kg (up to 2.4 million units) and that those with late latent syphilis or latent syphilis of unknown duration receive 50,000 units/kg (up to 2.4 million units) once weekly for 3 successive weeks (up to a maximum total dosage of 7.2 million units).

Latent Syphilis or Tertiary Syphilis in Adolescents

IM

Penicillin G benzathine: For early latent syphilis (syphilis of <1-year duration), CDC recommends a single dose of 2.4 million units. For late latent syphilis, latent syphilis of unknown duration, and tertiary syphilis, CDC recommends 2.4 million units once weekly for 3 successive weeks (7.2 million units total). These regimens also can be used to treat early latent syphilis, late latent syphilis, or syphilis of unknown duration in HIV-infected adolescents, provided they have a normal CSF examination.

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 10–15 days.⁷ CDC recommends use of penicillin G benzathine for latent or tertiary syphilis.

Neurosyphilis in Children

IV

Penicillin G potassium or penicillin G sodium: AAP recommends 200,000–300,000 units/kg daily for 10–14 days; some clinicians recommend that this regimen be followed by a single IM dose of 50,000 units/kg of penicillin G benzathine (up to 2.4 million units).

IM

Penicillin G benzathine: Manufacturer recommends 2.4 million units once weekly for 3 weeks.⁶ CDC recommends use of penicillin G potassium or sodium or penicillin G procaine for treatment of neurosyphilis.

Neurosyphilis in Adolescents

IV

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

IM

Penicillin G benzathine: Manufacturer recommends 2.4 million units once weekly for 3 weeks.⁶ CDC recommends use of penicillin G potassium or sodium or penicillin G procaine for treatment of neurosyphilis.

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

Yaws, Pinta, and Bejel

IM

Penicillin G benzathine: A single dose of 300,000 units in children <6 years of age or a single dose of 1.2 million units in children 6–15 years of age.

Prevention of Rheumatic Fever Recurrence

IM

Penicillin G benzathine: 1.2 million units once every 3–4 weeks.^{6 11} The 4-week regimen recommended for most patients in the US.¹¹

Long-term, continuous prophylaxis for 5 years or into adulthood required.^{8 11} (See Prevention of Rheumatic Fever Recurrence under Dosage and Administration.)

Adults

General Adult Dosage

Penicillin G Potassium or Penicillin G Sodium

IV or IM

Treatment of severe streptococcal or staphylococcal infections: Minimum 5 million units daily.¹ Some clinicians suggest that adults with meningitis caused by susceptible organisms receive 15 million units daily given IV in divided doses every 4 hours.

Fixed Combination of Penicillin G Benzathine and Penicillin G Procaine

IM

Treatment of S. pyogenes infections (upper respiratory tract, skin and soft-tissue, scarlet fever, erysipelas): 2.4 million units.¹⁵ The dose usually is given at a single session using multiple IM sites; alternatively, if compliance regarding the return visit is assured, the total dose can be divided and 1.2 million units given on day 1 and 1.2 million units given on day 3.¹⁵

Treatment of S. pneumoniae infections (except meningitis): 1.2 units as a single dose repeated every 2 or 3 days until temperature is normal for 48 hours.¹⁵ Other penicillin formulations (penicillin G potassium or penicillin G sodium) may be necessary for severe infections.^{14 15}

Endocarditis

Treatment of Endocarditis Caused by S. pyogenes (Group A Streptococci)

IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily.⁷ AHA states that penicillin G potassium or sodium usually preferred.

Native Valve Endocarditis Caused by Penicillin-susceptible Staphylococci

IV

Penicillin G potassium or penicillin G sodium: 12–18 million units daily (by continuous IV infusion or in 6 equally divided doses) given for 4–6 weeks.

Treatment of Endocarditis Caused by Viridans Streptococci or S. bovis

IV

Penicillin G potassium or penicillin G sodium (penicillin susceptible strains; MIC ≤0.1 mcg/mL): 12–18 million units daily (by continuous IV infusion or in 6 equally divided doses) given for 4 weeks for native valve endocarditis. Alternatively, 12–18 million units daily (by continuous IV infusion or in 6 equally divided doses) given for 2 weeks in conjunction with IM or IV gentamicin (1 mg/kg every 8 hours given for 2 weeks). The 2-week regimen is not recommended for patients with complications such as extracardiac foci of infection or intracardiac abscesses.

Penicillin G potassium or penicillin G sodium (nutritionally variant or relatively resistant strains; MIC >0.1 and <0.5 mcg/mL): 18 million units daily (by continuous IV infusion or in 6 equally divided IV doses) for 4 weeks in conjunction with IM or IV gentamicin (1 mg/kg every 8 hours during the first 2 weeks).

Penicillin G potassium or penicillin G sodium (high level penicillin resistance; MIC >5 mcg/mL): 18–30 million units daily (by continuous IV infusion or in 6 equally divided IV doses) for 4–6 weeks in conjunction with IM or IV gentamicin (1 mg/kg every 8 hours for 4–6 weeks).

Treatment of Enterococcal Endocarditis

IV

Penicillin G potassium or penicillin G sodium: 18–30 million units daily (by continuous IV infusion or in 6 equally divided IV doses) given for 4–6 weeks in conjunction with IM or IV gentamicin (1 mg/kg every 8 hours given for 4–6 weeks). Treatment with both drugs generally should be continued for 4–6 weeks, but patients who had symptoms of infection for >3 months before treatment was initiated and patients with prosthetic heart valves require ≥6 weeks of therapy with both drugs.

Pharyngitis and Tonsillitis

IM

Penicillin G benzathine: A single dose of 1.2 million units.^{6 8 11 13}

Respiratory Tract Infections

IM

Penicillin G procaine: 600,000 to 1 million units daily for ≥10 days.⁷

Septicemia

IV

Penicillin G potassium or penicillin G sodium: 20–80 million units daily.¹

Skin and Skin Structure Infections

IM

Penicillin G procaine: 600,000 to 1 million units daily for ≥10 days.⁷

Actinomycosis

IV

Penicillin G potassium or penicillin G sodium: 1–6 million units daily for cervicofacial infections¹ or 10–20 million units daily for pulmonary or abdominal infections.¹

Prolonged therapy (1.5–18 months or longer) may be necessary. Many clinicians recommend that patients with pulmonary actinomycosis or other severe infections receive 4–6 weeks of IV therapy followed by 6–12 additional months of oral therapy (e.g., penicillin V, a tetracycline).

Anthrax

Treatment of Naturally Occurring or Endemic Anthrax

IV

Penicillin G potassium or penicillin G sodium: Minimum parenteral dosage is 5 million units daily given in divided doses;¹ IV dosages up to 20 million units daily have been used in the treatment of anthrax septicemia and intestinal, pulmonary, and meningeal anthrax. Some clinicians recommend that adults receive IV penicillin G in a dosage of 8–12 million units daily given in divided doses every 4–6 hours.

Treatment of Inhalational, GI, or Oropharyngeal Anthrax

IV

Penicillin G potassium or penicillin G sodium: 4 million units IV every 4 hours suggested if used for treatment of anthrax in the context of biologic warfare or bioterrorism when the organism has been shown to be susceptible to penicillin.

Oral anti-infective therapy may be substituted for IV therapy as soon as the patient’s clinical condition improves.

Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure in the context of biologic warfare or bioterrorism, the CDC and other experts recommend that anti-infective therapy should be continued for 60 days.

Treatment of Cutaneous Anthrax

IM

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

Although 5–10 days of treatment may be adequate for mild, uncomplicated cutaneous anthrax that occurs as the result of naturally occurring or endemic exposures to anthrax, 60 days of treatment necessary it occurs as the result of exposure to aerosolized B. anthracis spores (e.g., in context of biologic warfare or bioterrorism).

Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism

IM

Penicillin G procaine: 1.2 million units every 12 hours; use only if penicillin susceptibility is confirmed.⁷

Total duration of postexposure prophylaxis usually is 60 days.⁷ Safety data for penicillin G procaine administered at the dosage recommended for prophylaxis of anthrax supports a duration of therapy of ≤2 weeks, and clinicians must consider the risks versus benefits of administering penicillin G procaine for >2 weeks or switching to an appropriate alternative anti-infective (e.g., oral amoxicillin or penicillin V).⁷

Clostridium Infections

Tetanus

IV or IM

Penicillin G potassium or penicillin G sodium: 20 million units daily; used as an adjunct to antitoxin.¹

Botulism

IV

Penicillin G potassium or penicillin G sodium: When used in the management of wound botulism as an adjunct to botulinum antitoxin (available from the CDC), 2 million units every 4 hours in conjunction with IV metronidazole (250 mg every 6 hours). Anti-infectives have no known direct effects on botulinum toxin but may be indicated to eradicate C. botulinum at the wound site.

Diphtheria

Treatment of Diphtheria

IV

Penicillin G potassium or penicillin G sodium: 100,000–150,000 units/kg daily given IV in 4 divided doses daily for 14 days; used as an adjunct to diphtheria antitoxin.

Prevention of Diphtheria in Close Contacts

IM

Penicillin G benzathine: A single dose of 1.2 million units.

Penicillin G procaine: 300,000–600,000 units daily for 14 days as an adjunct to diphtheria antitoxin.⁷

Provide prophylaxis regardless of immunization status and closely monitor for symptoms of diphtheria for 7 days.

In addition, contacts who are inadequately immunized against diphtheria (i.e., have previously received <3 doses of diphtheria toxoid) or whose immunization status is unknown should receive an immediate dose of an age-appropriate diphtheria toxoid preparation and the primary series should be completed according to the recommended schedule.

Contacts who are fully immunized should receive an immediate booster dose of an age-appropriate diphtheria toxoid preparation if it has been ≥5 years since their last booster dose.

Elimination of Diphtheria Carrier State

IM

Penicillin G benzathine: A single dose of 1.2 million units.

Penicillin G procaine: 300,000 units daily for 10 days.⁷

Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures are positive, a 10-day course of oral erythromycin should be given and additional follow-up cultures obtained.

Erysipelothrix rhusiopathiae Infections

Endocarditis Caused by Erysipelothrix rhusiopathiae

IV

Penicillin G potassium or penicillin G sodium: 2–20 million units daily for 4–6 weeks.¹

Uncomplicated Infections (e.g., Erysipeloid) Caused by Erysipelothrix rhusiopathiae

IM

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

Fusobacterium Infections

Oropharyngeal, Lower Respiratory Tract, and Genital Infections

IV or IM

Penicillin G potassium or penicillin G sodium: 5–10 million units daily.¹

Necrotizing Ulcerative Gingivitis

IM

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

Listeria Infections

Endocarditis or Meningitis Caused by Listeria

IV

Penicillin G potassium or penicillin G sodium: 15–20 million units daily given for 4 weeks for endocarditis or for 2 weeks for meningitis.¹

Lyme Disease†

Early or Late Lyme Disease with Serious Neurologic, Cardiac, and/or Arthritic Manifestations†

IV

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

Severe Lyme Carditis

IV

Penicillin G potassium or penicillin G sodium: 18–24 million units daily given in 4 or 6 divided doses (every 4 or 6 hours) for 14–21 days.

Neisseria meningitidis Infections

Meningitis

IV

Penicillin G potassium or penicillin G sodium: 20–30 million units daily given by continuous IV infusion for ≥10–14 days.¹

Pasteurella multocida Infections

Bacteremia or Meningitis Caused by P. multocida

IV or IM

Penicillin G potassium or penicillin G sodium: 4–6 million units daily for 2 weeks.¹

Rat-bite Fever

IV

Penicillin G potassium or penicillin G sodium: 12–15 million units daily for ≥3–4 weeks.¹

IM

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

Syphilis

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) should not be used for treatment of any form of syphilis.^{17 18}

Primary or Secondary Syphilis

IM

Penicillin G benzathine: A single dose of 2.4 million units.⁶ For HIV-infected adults, some clinicians suggest that additional doses of 2.4 million units be given once weekly for a total of 3 weeks of therapy. For pregnant women, some clinicians recommend that a second penicillin G benzathine dose of 2.4 million units be administered 1 week after the initial dose.

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 8 days.⁷ CDC recommends use of penicillin G benzathine (not penicillin G procaine) for primary or secondary syphilis.

Latent Syphilis or Tertiary Syphilis

IM

Penicillin G benzathine: For early latent syphilis (syphilis of <1-year duration), CDC recommends a single dose of 2.4 million units. For late latent syphilis, latent syphilis of unknown duration, and tertiary syphilis, CDC recommends 2.4 million units once weekly for 3 successive weeks (7.2 million units total). These regimens also can be used to treat early latent syphilis, late latent syphilis, or syphilis of unknown duration in HIV-infected adults, provided they have a normal CSF examination.

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 10–15 days.⁷ CDC recommends use of penicillin G benzathine (not penicillin G procaine) for latent or tertiary syphilis.

Neurosyphilis

IV

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

IM

Penicillin G benzathine: Manufacturer recommends 2.4 million units once weekly for 3 weeks.⁶ CDC recommends use of penicillin G potassium or sodium or penicillin G procaine (with probenecid) for treatment of neurosyphilis.

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

Yaws, Pinta, and Bejel

IM

Penicillin G benzathine: A single dose of 1.2 million units.⁶

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

Prevention of Perinatal Group B Streptococcal (GBS) Disease†

IV

Penicillin G potassium or penicillin G sodium: A single dose of 5 million units of IV penicillin G be given at onset of labor or after membrane rupture followed by 2.5 million units IV every 4 hours until delivery.

Prevention of Rheumatic Fever Recurrence

IM

Penicillin G benzathine: 1.2 million units once every 3–4 weeks.^{6 11} The 4-week regimen recommended for most patients in the US.¹¹

Long-term, continuous prophylaxis required.^{8 11}

Recommended Duration of Prophylaxis for Prevention of Rheumatic Fever Recurrence

Patient Category	Duration
Rheumatic fever without carditis	5 years or until 21 years of age, whichever is longer11
Rheumatic fever with carditis but no residual heart disease (no valvular disease)	10 years or well into adulthood, whichever is longer11
Rheumatic fever with carditis and residual heart disease (persistent valvular disease)	At least 10 years since last episode and at least until 40 years of age; sometimes for life11

Special Populations

Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration of penicillin G must be modified in response to the degree of impairment, severity of the infection, and susceptibility of the causative organism.

Some clinicians suggest that patients who are uremic but have a Cl_cr >10 mL/minute receive a full loading dose of IM or IV penicillin G potassium or sodium followed by one-half the usual dose every 4–5 hours and that patients with Cl_cr <10 mL/minute receive a full loading dose followed by one-half the usual dose every 8–10 hours.

Alternatively, some clinicians suggest that if the usual dosing interval for penicillin G potassium or sodium in patients with normal renal function (Cl_cr >50 mL/minute) is every 6 or 8 hours, then the usual dose should be given at 8- to 12-hour intervals or 12- to 18-hour intervals in patients with Cl_cr <10–50 or less than 10 mL/minute, respectively.

Some clinicians suggest that a maximum dosage of 4–10 million units of penicillin G potassium or sodium daily be used in adults with severe renal failure.

In patients with impaired hepatic function in addition to impaired renal function, further dosage reductions may be advisable.

Cautions for Penicillin G Benzathine/Potassium/Sodium

Contraindications

• Hypersensitivity to any penicillin.^{1 6 7}

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.^{1 6 7} Close observation of the patient is essential.¹ Discontinue and institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives may permit overgrowth of clostridia.^{1 6 7} Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.^{1 6 7}

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.^{1 6 7} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.^{1 6 7}

Procaine Toxicity

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

Administration Precautions

Take special precaution to avoid IV, intravascular, or intra-arterial administration of penicillin G benzathine or penicillin G procaine or injection of the drugs into or near major peripheral nerves or blood vessels since such injections may produce severe and/or permanent neurovascular damage.^{6 7} Transverse myelitis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, and necrosis and sloughing at and surrounding the injection site have been reported.^{6 7}

Inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.^{6 14 15 16}

Suspected intravascular administration (especially in infants and small children) has resulted in immediate pallor, mottling, or cyanosis of the extremity, both distal and proximal to the injection site, followed by bleb formation.^{6 7} Severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity also reported.^{6 7}

Repeated IM injection of penicillin preparations into the anterolateral thigh has resulted in quadriceps femoris fibrosis and atrophy.^{6 7}

Discontinue IM injection of the dose if patient complains of severe, immediate pain at the injection site or if (especially in neonates, infants, and young children) symptoms occur suggesting onset of severe pain.^{6 7 14 15 16}

If evidence of compromise of the blood supply occurs at or proximal or distal to the site of injection, an appropriate specialist should be consulted immediately.^{6 7}

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.^{1 6 7} Hypersensitivity reactions are the most frequent adverse effects of penicillins.

Hypersensitivity reactions may be immediate reactions (occurring within 1 hour after administration) and include anaphylaxis, allergic bronchial asthma, and angioedema or may be accelerated reactions (occurring 1–72 hours after administration) and include urticaria, fever, and laryngospasm and hypotension. Hematologic reactions such as hemolytic anemia, agranulocytosis, and leukopenia can occur. In addition, some patients may have serum sickness-like reactions, drug fever, acute interstitial nephritis, allergic vasculitis, and Arthus phenomenon. Delayed hypersensitivity reactions to penicillins generally include dermatologic reactions.

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.^{1 6} Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.^{1 6}

Use with caution in patients with a history of sensitivity to multiple allergens and/or asthma.^{1 6 7}

If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).^{1 6}

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, congenital syphilis). Specialized references should be consulted for specific information on desensitization procedures and dosages.

Procaine Sensitivity

A small percentage of patients are sensitive to procaine.⁷ If use of penicillin G procaine is being considered in patients with a history of procaine sensitivity, a test dose (0.1 mL of a 1–2% procaine solution) should be used.⁷ Development of erythema, wheal, flare, or eruption indicates procaine sensitivity and use of penicillin G procaine should be avoided.⁷

If a hypersensitivity reaction to procaine occurs, it should be treated by usual methods; antihistamines may be beneficial, and barbiturates should be used if seizures occur.⁷

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of penicillin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{1 6} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

IM penicillin G benzathine^{6 16} or IM penicillin G procaine⁷ should be used only for the treatment of mild to moderately severe infections caused by organisms susceptible to low concentrations of penicillin G. In addition, IM penicillin G benzathine 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.^{6 16} When high, sustained concentrations of penicillin G are required, parenteral penicillin G potassium or sodium should be used.^{1 7}

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) should be used only for labeled indications including the treatment of moderately severe to severe infections of the upper respiratory tract, scarlet fever, erysipelas, or skin and soft-tissue infections caused by susceptible streptococci or for moderately severe pneumonia and otitis media caused by susceptible S. pneumoniae.^{14 15} The fixed-combination preparation should not be used for the treatment of any venereal diseases, including syphilis, yaws, bejel, or pinta.^{14 15} When high, sustained concentrations of penicillin G are required, parenteral penicillin G potassium or sodium should be used.^{14 15}

Because penicillin susceptibility can no longer be assumed, S. pneumoniae or staphylococcal isolates should be routinely tested for in vitro susceptibility.⁷

Potassium and Sodium Content

Penicillin G potassium powder for injection contains 65.6 mg (1.7 mEq) of potassium and 6.8 mg (0.3 mEq) of sodium in each 1 million units of penicillin G.¹

Penicillin G sodium powder for injection contains 2 mEq of sodium in each 1 million units of penicillin G.

Laboratory Monitoring

Periodically assess renal, hepatic, and hematologic systems during prolonged therapy, especially if high dosage is used.^{1 6 7}

Electrolyte Imbalance

Because of their potassium and sodium content, penicillin G potassium and penicillin G sodium can cause serious and potentially fatal electrolyte disturbances, particularly if high IV dosage is used in patients with impaired renal function.

Administration of massive IV dosages of penicillin G sodium (100 million penicillin G units daily) has resulted in a syndrome of hypokalemia, metabolic alkalosis, and hypernatremia.

Although it has been suggested that hypokalemia during penicillin G potassium therapy may result from redistribution of potassium within the body, 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.

Severe and potentially fatal hyperkalemia, manifested as hyperreflexia, seizures, coma, and, rarely, cardiac arrhythmia and arrest, may occur if penicillin G potassium is administered by continuous IV infusion in high dosage (10–100 million penicillin G units daily), particularly in patients with renal impairment.

If high IV doses are used (>10 million units of penicillin G potassium), administer slowly and evaluate electrolyte balance and renal function frequently.¹

Specific Populations

Pregnancy

Category B.^{1 6 7}

Use of penicillin G potassium or sodium is included in CDC recommendations for the treatment of syphilis during pregnancy.

Lactation

Distributed into milk.^{1 6 7} Use with caution.^{1 6 7}

Pediatric Use

Renal clearance of penicillin G may be delayed in neonates and young infants because of incompletely developed renal function.^{1 6 7} Use caution and evaluate organ system function frequently.^{1 7}

Renal Impairment

Dosage adjustments necessary in renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Hypersensitivity reactions (rash, urticaria, serum sickness); local effects.¹

Interactions for Penicillin G Benzathine/Potassium/Sodium

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides	In vitro evidence of synergistic antibacterial effects against enterococci or viridans streptococci;1 used to therapeutic advantage in treatment of endocarditis and other severe enterococcal infections Potential in vitro and in vivo inactivation of aminoglycosidesHID
Chloramphenicol	In vitro evidence of antagonism	Clinical importance unclear
Erythromycins	Possible antagonism1	Concomitant use not recommended
Hormonal contraceptives	Possible decreased efficacy of estrogen-containing oral contraceptives and increased incidence of breakthrough bleeding reported with some penicillins (penicillin V, ampicillin)
Methotrexate	Possible decreased renal clearance of methotrexate with penicillins; possible increased methotrexate concentrations and hematologic and GI toxicity	Monitor closely if used concomitantly
Probenecid	Decreased renal tubular secretion of penicillin G; increased and prolonged penicillin G serum concentrations may occur; CSF concentrations also may be increased1 6 7
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)
Tests for uric acid	Possible falsely increased serum uric acid concentrations when copper-chelate method is used; phosphotungstate and uricase methods appear to be unaffected
Tetracyclines	Possible antagonism1 6 7	Concomitant use not recommended6 7

Penicillin G Benzathine/Potassium/Sodium Pharmacokinetics

Absorption

Bioavailability

Penicillin G potassium and penicillin G sodium are rapidly absorbed followed IM administration;¹ peak serum concentrations of penicillin G generally are similar and are attained within 15–30 minutes of IM administration of either salt.

Because penicillin G benzathine and penicillin G procaine are relatively insoluble, IM administration of these salts provides a tissue depot from which the drugs are slowly absorbed and hydrolyzed to penicillin G.^{6 7} IM administration of penicillin G benzathine results in serum concentrations of penicillin G that are more prolonged, but lower, than those attained with an equivalent IM dose of penicillin G procaine or penicillin G potassium or sodium.⁶

Following IM administration of a single dose of penicillin G benzathine in adults, children, or neonates, peak serum concentrations of penicillin G are attained in 13–24 hours and usually are detectable for 1–4 weeks depending on the dose.

Following IM administration of a single dose of penicillin G procaine in adults or neonates, peak serum concentrations of penicillin G are attained in 1–4 hours and the drug is detectable in serum for 1–2 days; the drug may be detectable in serum for up to 5 days depending on the dose.

Distribution

Extent

Widely distributed following absorption from injection sites.^{6 7 1} Highest concentrations generally attained in the kidneys, with lower amounts in the liver, lungs, skin, intestines, and muscle. Also distributed into ascitic,¹ synovial,¹ pleural,¹ and pericardial fluids¹ and tonsils, maxillary sinus secretions, and saliva.

Only negligible amounts attained in avascular areas, abscesses, aqueous humor, sweat, tears, or bone.

Minimal concentrations 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;¹ higher CSF concentrations attained when the meninges are inflamed or when oral probenecid is administered concomitantly.

Readily crosses the placenta and is distributed into milk.¹

Plasma Protein Binding

45–68%.^{6 7}

Elimination

Metabolism

Approximately 16–30% of an IM dose of penicillin G sodium is metabolized to penicilloic acid which is microbiologically inactive. Small amounts of 6-aminopenicillanic acid (6-APA) have also been found in the urine of patients receiving penicillin G. 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.

Elimination Route

Penicillin G and its metabolites are excreted in urine mainly by tubular secretion.^{7 1} Small amounts of the drug also are excreted in bile.

Following IM or IV administration of a single dose of penicillin G sodium in adults with normal renal function, ≥60% of the dose is excreted in urine as unchanged drug and active metabolites within 6 hours.¹

Because penicillin G is slowly absorbed following IM penicillin G benzathine or penicillin G procaine, excretion of penicillin G in urine continues over a prolonged period of time. Penicillin G has been detected in urine for up to 12 weeks after a single IM dose of 1.2 million units of penicillin G benzathine.

Removed by hemodialysis, but only minimally removed by peritoneal dialysis.

Half-life

0.4–0.9 hours in adults with normal renal function.

Serum half-life of penicillin G in neonates varies inversely with age and appears to be independent of birthweight. Serum half-life of the drug is 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.

Special Populations

Serum concentrations of penicillin G may be higher and the serum half-life prolonged in patients with impaired renal function.¹ The serum half-life of the drug is 1–2 hours in azotemic patients with serum creatinine concentrations <3 mg/dL and ranges from 6–20 hours in anuric patients.

In anuric patients with hepatic impairment, the serum half-life of penicillin G may be 2–3 times more prolonged than in anuric patients with normal hepatic function.

Renal clearance of penicillins is delayed may be delayed in geriatric patients because of diminished tubular secretion ability.

Stability

Storage

Parenteral

Powder for IM Injection or IV Infusion

Penicillin G potassium or penicillin G sodium: <30°C.¹ Following reconstitution, may be stored for up to 7 days at 2–8°C.^{1 4}

Suspension for IM Injection

Pencillin G benzathine: 2–8°C; do not freeze.^{6 16}

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

Fixed combination of penicillin G benzathine and penicillin G procaine: 2–8°C; do not freeze.^{14 15}

Injection (Frozen)

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

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%
Dextran 6% in dextrose 5%
Dextran 6% in sodium chloride 0.9%
Dextrose–Ringer’s injection combinations
Dextrose–Ringer’s injection, lactated, combinations
Dextrose 5% in Ringer’s injection, lactated
Dextrose–saline combinations
Dextrose 5% in sodium chloride 0.9%
Dextrose 2.5, 5, or 10% in water
Fructose 10% in sodium chloride 0.9%
Fructose 10% in water
Hetastarch 6%
Invert sugar 5 and 10% in sodium chloride 0.9%
Invert sugar 5 and 10% in water
Isolyte M or P with dextrose 5%
Ionosol products
Ringer’s injection
Ringer’s injection, lactated
Sodium chloride 0.45 or 0.9%
Incompatible
Alcohol 5%, dextrose 5%
Dextran 70 6% in dextrose 5%
Dextran 40 10% in dextrose 5%
Variable
Fat emulsion 10%, IV

Drug Compatibility

Admixture Compatibility (Penicillin G Potassium)HID

Compatible
Ascorbic acid injection
Calcium chloride
Calcium gluconate
Chloramphenicol sodium succinate
Cimetidine HCl
Clindamycin phosphate
Colistimethate sodium
Dimenhydrinate
Diphenhydramine HCl
Ephedrine sulfate
Erythromycin lactobionate
Furosemide
Hydrocortisone sodium succinate
Kanamycin sulfate
Lidocaine HCl
Magnesium sulfate
Methylprednisolone sodium succinate
Metronidazole HCl with sodium bicarbonate
Polymyxin B sulfate
Potassium chloride
Potassium chloride with vitamin B complex with C
Procaine HCl
Prochlorperazine edisylate
Ranitidine HCl
Verapamil HCl
Vitamin B complex with C with potassium chloride
Incompatible
Aminophylline
Amphotericin B
Chlorpromazine HCl
Dopamine HCl
Hydroxyzine HCl
Metaraminol bitartrate
Pentobarbital sodium
Prochlorperazine mesylate
Thiopental sodium
Variable
Amikacin sulfate
Heparin sodium
Metronidazole
Promethazine HCl
Sodium bicarbonate
Vitamin B complex with C

Y-site Compatibility (Penicillin G Potassium)HID

Compatible
Acyclovir sodium
Amiodarone HCl
Cyclophosphamide
Diltiazem HCl
Enalaprilat
Esmolol HCl
Fluconazole
Foscarnet sodium
Heparin sodium
Heparin sodium with hydrocortisone sodium succinate
Hydromorphone HCl
Labetalol HCl
Magnesium sulfate
Meperidine HCl
Morphine sulfate
Nicardipine HCl
Perphenazine
Potassium chloride
Tacrolimus
Theophylline
Verapamil HCl
Vitamin B complex with C

Solution Compatibility (Penicillin G Sodium)^HID

Compatible
Dextran 40 10%
Incompatible
Fat emulsion 10%
Invert sugar 10%
Variable
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility (Penicillin G Sodium)

Admixture CompatibilityHID

Compatible
Calcium chloride
Calcium gluconate
Chloramphenicol sodium succinate
Clindamycin phosphate
Colistimethate sodium
Diphenhydramine HCl
Erythromycin lactobionate
Furosemide
Gentamicin sulfate
Hydrocortisone sodium succinate
Kanamycin sulfate
Polymyxin B sulfate
Procaine HCl
Ranitidine HCl
Verapamil HCl
Vitamin B complex with C
Incompatible
Amphotericin B
Bleomycin sulfate
Chlorpromazine HCl
Cytarabine
Hydroxyzine HCl
Methylprednisolone sodium succinate
Prochlorperazine mesylate
Promethazine HCl
Variable
Heparin sodium
Lincomycin HCl
Potassium chloride

Y-Site Compatibility (Penicillin G Sodium)HID

Compatible
Clarithromycin
Levofloxacin

Actions and Spectrum

• A β-lactam antibacterial classified as a natural penicillin.

• Produced by fermentation of Penicillium chrysogenum in a medium containing phenylacetic acid. Available as penicillin G potassium and penicillin G sodium (referred to as aqueous, crystalline forms of penicillin G) and as penicillin G benzathine and penicillin G procaine (referred to as long-acting, depot, or repository forms of penicillin G).^{1 6 7}

• Usually bactericidal.^{1 3 6 7}

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.^{1 3 6 7}

• Spectrum of activity includes many gram-positive and -negative aerobes, some gram-positive anaerobes, and most spirochetes.^{1 3 6 7} Generally inactive against gram-negative anaerobes and inactive against mycobacteria, Mycoplasma, Rickettsie, fungi, and viruses.³

• Gram-positive aerobes: Active in vitro and in clinical infections against Staphylococcus (nonpenicillinase-producing strains only), S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), other streptococci (e.g., groups C, G, H, L, M), and some enterococci (e.g., Enterococcus faecalis).^{1 3 6 7} Also active against B. anthracis, Corynebacteriun diphtheriae, Erysipelothrix rhusiopathiae, and Listeria monocytogenes.^{1 3 6 7}

• Gram-positve aerobes: Active in vitro against N. meningitidis, H. influenzae, Bordetella pertussis, Eikenella corrodens, Legionella, and Pasteurella multocida.³ Generally inactive against Enterobacteriaceae and Pseudomonas.³

• Anaerobes: Active in vitro against Actinomyces, Clostridium (including C. botulinum, C. perfringens, and C. tetani), Eubacterium, Lactobacillus, Peptococcus, Peptostreptococcus, and Propionibacterium.³

• Penicillinase-producing S. aureus, S. epidermidis, and Neisseria are resistant.³ S. pneumoniae resistant to penicillin G are being reported with increasing frequency.³

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).¹

• Importance of completing full course of therapy, even if feeling better after a few days.¹

• 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.¹

• Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.¹

• Importance of informing clinician of existing or contemplated therapy, including prescription and OTC drugs, and any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

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

Penicillin G Benzathine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Suspension, sterile	300,000 units (of penicillin G) per mL	Bicillin L-A (with parabens and povidone; available as 10-mL vial)	King
		600,000 units (of penicillin G) per mL	Bicillin L-A (with parabens and povidone; available as 1-mL and 2-mL Tubex and as 4-mL disposable syringes)	King
			Permapen (with parabens and povidone; available as 2-mL Isoject disposable syringes)	Pfizer

Penicillin G Potassium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection	5 million units (of penicillin G)	Pfizerpen	Pfizer
		20 million units (of penicillin G)	Pfizerpen	Pfizer

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	Baxter
		40,000 units (of penicillin G) per mL (2 million units) in 2.3% Dextrose	Penicillin G Potassium in Iso-osmotic Dextrose Injection Galaxy	Baxter
		60,000 units (of penicillin G) per mL (3 million units) in 0.7% Dextrose	Penicillin G Potassium in 5% Dextrose Injection Galaxy	Baxter

Penicillin G Procaine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Suspension, sterile	600,000 units (of penicillin G) per mL	Penicillin G Procaine (with parabens and povidone; available as 1-mL and 2-mL Tubex)	King

Penicillin G Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection	5 million units (of penicillin G)	Penicillin G Sodium for Injection	Sandoz

Penicillin G Procaine and Penicillin G Benzathine Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Suspension, sterile	Penicillin G Procaine 150,000 units (of penicillin G) per mL with Penicillin G Benzathine 150,000 units (of penicillin G) per mL	Bicillin C-R (with parabens and povidone; available as 10-mL vial)	King
		Penicillin G Procaine 150,000 units (of penicillin G) per mL with Penicillin G Benzathine 450,000 units (of penicillin G) per mL	Bicillin C-R 900/300 (with parabens and povidone; available as 2-mL Tubex)	King
		Penicillin G Procaine 300,000 units (of penicillin G) per mL with Penicillin G Benzathine 300,000 units (of penicillin G) per mL	Bicillin C-R (with parabens and povidone; available as 1-mL and 2-mL Tubex and as 4-mL disposable syringe)	King

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Bicillin C-R (1200000) 300000-300000UNIT/ML Suspension (KING PHARMA): 20/$442.99 or 60/$1,322.97