Last reviewed 2026-04-20 · How we verify

Bicillin C-R (Penicillin G Benzathine)

Penicillin G inhibits bacterial cell-wall peptidoglycan biosynthesis, rendering the cell wall osmotically unstable.

Penicillin G benzathine is a beta-lactam antibiotic indicated for treatment of penicillin-susceptible infections including upper-respiratory tract infections and venereal infections, as well as prophylaxis for rheumatic fever. Its extremely low solubility results in slow intramuscular absorption with prolonged serum levels lasting 4-14 days depending on dose. Contraindications include prior hypersensitivity to penicillins, and concurrent use with tetracyclines should be avoided due to antagonistic effects. The drug's efficacy depends on bacteriological confirmation of susceptibility and appropriate dosing based on infection severity and renal function.

At a glance

Mechanism of action

Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall peptidoglycan, rendering the cell wall osmotically unstable. The drug is not active against penicillinase-producing bacteria or organisms resistant to beta-lactams due to alterations in penicillin-binding proteins.

Approved indications

• Moderately severe to severe infections of the upper-respiratory tract
• Scarlet fever
• Erysipelas
• Skin and soft-tissue infections due to susceptible streptococci
• Moderately severe pneumonia
• Otitis media due to susceptible Streptococcus pneumoniae

Boxed warnings

• WARNING: NOT FOR INTRAVENOUS USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS 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 DOSAGE AND ADMINISTRATION sections of the labeling.

Common side effects

• Injection site pain
• Skin eruptions (maculopapular to exfoliative dermatitis)
• Urticaria
• Fever
• Chills
• Edema
• Arthralgia
• Nausea
• Vomiting
• Headache
• Dizziness
• Injection site inflammation

Serious adverse events

• Anaphylaxis including shock and death
• Stevens-Johnson syndrome (SJS)
• Toxic epidermal necrolysis (TEN)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Acute myocardial ischemia with or without myocardial infarction (Kounis syndrome)
• Pseudomembranous colitis
• Cardiac arrest
• Pulmonary embolism
• Transverse myelitis
• Seizures

Drug interactions

• Tetracycline
• Probenecid

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Bicillin C-R CI brief — competitive landscape report
• Bicillin C-R updates RSS · CI watch RSS
• Pfizer Inc. portfolio CI