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Penicillin G Benzathine and Penicillin G Procaine

Pronunciation

(pen i SIL in jee BENZ a theen & pen i SIL in jee PROE kane)

Index Terms

  • Pen G Benz/Pen G Procaine
  • Penicillin G Procaine and Benzathine Combined
  • Penicillin G Procaine/Benzath

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Injection, suspension [prefilled syringe]:

Bicillin C-R:

600,000 units: Penicillin G benzathine 300,000 units and penicillin G procaine 300,000 units per 1 mL (1 mL) [DSC]

1,200,000 units: Penicillin G benzathine 600,000 units and penicillin G procaine 600,000 units per 2 mL (2 mL)

2,400,000 units: Penicillin G benzathine 1,200,000 units and penicillin G procaine 1,200,000 units per 4 mL (4 mL) [DSC]

Bicillin C-R 900/300: 1,200,000 units: Penicillin G benzathine 900,000 units and penicillin G procaine 300,000 units per 2 mL (2 mL)

Brand Names: U.S.

  • Bicillin C-R
  • Bicillin C-R 900/300

Pharmacologic Category

  • Antibiotic, Penicillin

Pharmacology

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Absorption

IM: Released slowly

Distribution

Highest levels in the kidney; lesser amounts in liver, skin, intestines

Time to Peak

Serum: IM: Within 3 hours

Protein Binding

~60%

Special Populations: Renal Function Impairment

Excretion of the drug is considerably delayed in neonates, children, and individuals with renal function impairment.

Use: Labeled Indications

Pneumococcal infections: Treatment of moderately severe pneumonia and otitis media due to susceptible Pneumococcus spp. (eg, Streptococcus pneumoniae)

Streptococcal infections, group A: Treatment of moderately severe to severe infections, without associated bacteremia, of the upper respiratory tract, scarlet fever, erysipelas, and skin and soft tissue infections due to group A streptococci

Note: Bicillin C-R 900/300 is only indicated in pediatric patients.

Limitations of use: Do not use in the treatment of sexually transmitted diseases, including syphilis, gonorrhea, yaws, bejel, and pinta. When high, sustained serum levels are required, use penicillin G sodium or potassium, either IM or IV.

Contraindications

Hypersensitivity to penicillin(s), procaine, or any component of the formulation

Dosing: Adult

Note: Bicillin C-R 900/300 is only indicated in pediatric patients.

Pneumococcal infections (except meningitis): IM: 1.2 million units on day 1; may be repeated every 2 or 3 days until afebrile for 48 hours.

Streptococcal infections, group A: IM: 2.4 million units in a single dose. Note: Alternatively, 50% of the total dose can be administered on day 1 and 50% on day 3. For treatment of group A streptococcal pharyngitis in adults, penicillin G benzathine (Bicillin L-A) is preferred (IDSA [Shulman 2012]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Pneumococcal infections (except meningitis): Infants and Children: IM:

Bicillin C-R: 600,000 units on day 1; may repeat every 2 to 3 days until afebrile for 48 hours

Bicillin C-R 900/300: 1.2 million units on day 1; may repeat every 2 or 3 days until afebrile for 48 hours

Streptococcal infections, group A:

Infants, Children: IM:

Bicillin C-R:

<14 kg: 600,000 units in a single dose

14 to 27 kg: 900,000 units to 1.2 million units in a single dose

Bicillin C-R 900/300: 1.2 million units in a single dose

Children and Adolescents (>27 kg): IM:

Bicillin C-R: Refer to adult dosing.

Bicillin C-R 900/300: 1.2 million units in a single dose

Note (Bicillin C-R only): Alternatively, 50% of the total dose can be administered on day 1 and 50% on day 3.

Rheumatic fever, primary prevention (Bicillin C-R 900/300) (off-label use): Infants and Children 6 months to 12 years and Adolescents ≤14 years: IM: 1.2 million units as a single dose (Bass 1976; Gerber 2009). Note: The efficacy of this regimen for heavier adolescents is unknown.

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer's labeling.

Administration

IM: Administer by deep IM injection at a slow, steady rate in the upper outer quadrant of the buttock or anterolateral thigh; in neonates, infants, and small children, IM injections should be made into the midlateral muscle of the thigh. Dose is usually administered using multiple IM sites if indicated. When repeated doses are indicated, vary the injection site. Do not inject near an artery or a nerve; permanent neurological damage or gangrene may result. Do not administer IV, intravascularly, or intra-arterially.

Storage

Store at 2°C to 8°C (36°F to 46°F); do not freeze. The following stability information has also been reported: May be stored at 25°C (77°F) for 7 days (Cohen, 2007).

Drug Interactions

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

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

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

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

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

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Monitor therapy

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

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

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

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

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

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

Test Interactions

May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Clinitest®); may inactivate aminoglycosides in vitro; positive Coombs' [direct], increased protein

Adverse Reactions

See individual agents.

ALERT: U.S. Boxed Warning

Appropriate administration:

Not for intravenous (IV) use. Do not inject IV or admix with other IV solutions. There have been reports of inadvertent IV administration of penicillin G benzathine, which has been associated with cardiorespiratory arrest and death. Prior to administration of this drug, carefully read the Warnings, Adverse Reactions, and Administration and Dosage sections.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity (including cephalosporins), history of sensitivity to multiple allergens. Use with caution in asthmatic patients. If a serious reaction occurs, treatment with supportive care measures and airway protection should be instituted immediately.

• Fibrosis and atrophy: Quadriceps femoris fibrosis and atrophy have been reported following repeated IM injections of penicillins into the anterolateral thigh.

• Procaine sensitivity: If there is a history of hypersensitivity to procaine, test with 0.1 mL of procaine 1% or 2% solution. If erythema, wheal, flare, or eruption occurs, patient may be sensitive to procaine; do not use penicillin G procaine in these patients. Treat sensitivity with supportive measures, including antihistamines.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridium difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment. Monitor renal function periodically, especially with high-dose or prolonged therapy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate administration: [US Boxed Warning]: Not for IV use; cardiopulmonary arrest and death have occurred from inadvertent IV administration. Administer by deep IM injection only. Injection into or near an artery or nerve could result in severe neurovascular damage or permanent neurological damage or gangrene possibly requiring amputation, necrosis/sloughing at or surrounding the injection site, or other serious complications.

• Appropriate use: Do not use for the treatment of venereal diseases, including syphilis, gonorrhea, yaws, bejel, and pinta. When high, sustained serum levels are required, use penicillin G sodium or potassium, either IM or IV.

• Choice of preparation: Penicillin G benzathine-penicillin G procaine (eg, Bicillin C-R) is not the same preparation as penicillin G procaine. Dispensing errors have occurred (CDC 2005).

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

Monitoring Parameters

Hypersensitivity reactions with first dose, injection-site reactions, periodic renal and hematologic function tests with prolonged therapy

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects. See individual agents

Patient Education

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

• Patient may experience diarrhea. Have patient report immediately to prescriber bruising, bleeding, severe injection site irritation, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

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

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

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