Penicillin G Benzathine / Potassium / Sodium

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 procaine14 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 ≤7 days of age: AAP recommends 25,000–50,000 units/kg every 12 hours.41 AAP states higher dosage may be required for treatment of meningitis.41

Neonates 8–28 days of age: AAP recommends 25,000–50,000 units/kg every 8 hours.41 AAP states higher dosage may be required for treatment of meningitis.41

Penicillin G Procaine IM

Neonates ≤28 days of age: AAP recommends 50,000 units/kg once every 24 hours.41

General Pediatric Dosage Penicillin G Benzathine IM

Children beyond neonatal period: AAP recommends single dose of 300,000–600,000 units in those weighing <27 kg or single dose of 900,000 units in those weighing ≥27 kg for treatment of mild to moderate infections.41 Inappropriate for severe infections according to AAP.41

Penicillin G Potassium or Penicillin G 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 6 divided doses for treatment of severe infections.41

Penicillin G Procaine IM

Children beyond neonatal period: AAP recommends 50,000 units/kg daily in 1 or 2 divided doses for treatment of mild to moderate infections.41 Inappropriate for severe infections according to AAP.41

Fixed Combination of Penicillin G Benzathine and Penicillin G Procaine IM

Children beyond neonatal period: AAP recommends a single dose of 600,000 units (penicillin G benzathine 300,000 units with penicillin G procaine 300,000 units [Bicillin C-R]) in those weighing <14 kg or a single dose of 900,000–1.2 million units in those weighing 14–27 kg.41

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 Treatment of 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 450,000–500,000 units/kg daily IV in 4 divided doses in neonates >7 days of age.41

Usual treatment duration for uncomplicated meningitis is 14 days; longer duration may be necessary.41 If infection involves septic arthritis or osteomyelitis, 3–4 weeks of treatment required; ≥4 weeks of treatment required for endocarditis or ventriculitis.41

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 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.

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 50,000 units/kg every 12 hours in those ≤7 days of age or every 8 hours in those >7 days of age for a total duration of 10 days.41 CDC and AAP state that if >1 day of therapy is missed, the entire course of therapy should be readministered.41

IM

Penicillin G benzathine: Manufacturers recommend a single dose of 50,000 units/kg in those <27 kg.6 CDC and AAP recommend 10-day regimen of IV penicillin G potassium or sodium or, alternatively, IM penicillin G procaine for neonates ≤1 month of age with proven or highly probable congenital syphilis.41

Penicillin G procaine: CDC and AAP recommend 50,000 units/kg once daily for 10 days.41 If >1 day of therapy is missed, the entire course should be readministered.41

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.41 Some clinicians recommend that this regimen be followed by a single dose of IM penicillin G benzathine (50,000 units/kg).41

IM

Penicillin G benzathine: 50,000 units/kg once weekly for 3 weeks.41 IV penicillin G potassium or sodium preferred; consider penicillin G benzathine if there are no clinical manifestations of syphilis, normal CSF, and negative CSF VDRL.41

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). 41

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 penicillin G benzathine for treatment of 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 late latent syphilis or latent syphilis of unknown duration be treated with 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).41

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 penicillin G benzathine for treatment of latent or tertiary syphilis.

Neurosyphilis in Children >1 Month of Age IV

Penicillin G potassium or penicillin G sodium: AAP recommends 200,000–300,000 units/kg daily (given in divided doses every 4–6 hours) for 10–14 days;41 some clinicians recommend that this regimen be followed by a regimen of IM penicillin G benzathine (50,000 units/kg [up to 2.4 million units] once weekly for up to 3 weeks).41

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 and AAP recommend penicillin G potassium or sodium for treatment of neurosyphilis.41

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) as an alternative to penicillin G potassium or penicillin G sodium 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 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 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 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 given at onset of labor or after membrane rupture followed by 2.5–3 million units IV every 4 hours until delivery.41

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 Clcr >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 Clcr <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 (Clcr >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 Clcr <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.

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

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

Penicillin G benzathine: 2–8°C; do not freeze.6 16

Penicillin 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

• 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, Rickettsia, 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, Corynebacterium diphtheriae, Erysipelothrix rhusiopathiae, and Listeria monocytogenes.1 3 6 7

• Gram-positive 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

• 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.)