BICILLIN C-R 900/300
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BICILLIN C-R 900/300 (BICILLIN C-R 900/300).
Penicillin G benzathine and penicillin G procaine are beta-lactam antibiotics that inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), disrupting peptidoglycan cross-linking, leading to cell lysis via autolytic enzymes. Synergistic action covers both susceptible Gram-positive cocci (e.g., Streptococcus pyogenes) and some Gram-negative cocci (e.g., Neisseria spp.).
| Metabolism | Primarily renal excretion (90% unchanged via tubular secretion). Minor hepatic hydrolysis. No significant cytochrome P450 metabolism. |
| Excretion | Renal: 60-90% as unchanged drug; biliary/fecal: minor (less than 10%) |
| Half-life | 0.5-1 hour for penicillin G; prolonged to 3-6 hours in renal impairment. Procaine component has no significant effect on elimination half-life |
| Protein binding | Penicillin G: 45-65% bound to serum albumin; procaine component: negligible binding |
| Volume of Distribution | 0.2-0.3 L/kg (penicillin G); penetrates well into tissues except brain, eye, and prostate |
| Bioavailability | IM: 100% bioavailable; oral: not applicable (penicillin G is acid-labile) |
| Onset of Action | IM: peak serum concentrations within 1-2 hours for penicillin G; procaine penicillin G reaches peak at 1-3 hours |
| Duration of Action | IM: penicillin G: 6-8 hours; procaine penicillin G: 12-24 hours. Clinical effect may last up to 3 days for susceptible organisms |
| Molecular Weight | 372.48 |
Intramuscular injection: 1.2 mL (900,000 units penicillin G benzathine and 300,000 units penicillin G procaine) every 48 hours for 3 doses; for severe infections, up to 2.4 mL (1,800,000/600,000 units) as a single dose.
| Dosage form | INJECTABLE |
| Renal impairment | No specific guidelines for BICILLIN C-R; penicillin elimination is prolonged in severe renal impairment (CrCl <10 mL/min). Caution advised, consider extended dosing intervals. |
| Liver impairment | No specific guidelines; primarily renally excreted, hepatic impairment unlikely to require dose adjustment. |
| Pediatric use | Weight-based: 1.2 mL (900,000/300,000 units) for patients ≥27 kg; 0.6 mL (450,000/150,000 units) for patients <27 kg. Administer intramuscularly every 48 hours for 3 doses. |
| Geriatric use | Increased risk of renal impairment; consider renal function and use lower end of dosing range. Standard adult dosing may be used if renal function normal. |
| 1st trimester | Penicillin G crosses the placenta. Use only if clearly needed; no known teratogenicity in human studies. |
| 2nd trimester | Safe with caution; therapeutic doses are considered low risk. |
| 3rd trimester | Safe; may be used for treatment of maternal infections (e.g., syphilis, group B streptococcus). |
Clinical note
Comprehensive clinical and safety monograph for BICILLIN C-R 900/300 (BICILLIN C-R 900/300).
| Placental transfer | Penicillin G crosses the placenta extensively; fetal serum levels may reach therapeutic concentrations. |
| Breastfeeding | Penicillin G is excreted into breast milk in low concentrations. Considered compatible with breastfeeding; monitor infant for possible GI effects (e.g., diarrhea) or allergic reactions. |
■ FDA Black Box Warning
WARNING: Accidental intravenous administration of penicillin G procaine has been associated with severe immediate reactions including cardiorespiratory arrest, malignant ventricular arrhythmias, and death. Do not administer intravenously. This product is for intramuscular injection only.
| Serious Effects |
Hypersensitivity to penicillins or any component of the formulationSevere hypersensitivity reaction (e.g., anaphylaxis) to beta-lactam antibiotics
| Precautions | Severe hypersensitivity reactions including anaphylaxis, angioedema, serum sickness, Stevens-Johnson syndrome., Do not inject into or near an artery or nerve (risk of neurovascular damage)., Prolonged use may lead to superinfection with Clostridioides difficile or resistant organisms., Use with caution in renal impairment (CrCl <30 mL/min): adjust dosing interval., Caution in patients with electrolyte disturbances (procaine component may cause CNS excitation)., Inadvertent intravascular injection can cause acute immediate cardiorespiratory collapse (see black box warning). |
| Food/Dietary |
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| Lactation Rating |
| L1 (Compatible) |
| Teratogenic Risk | Penicillin G benzathine and procaine combinations are generally considered low risk in pregnancy. No increased risk of major congenital malformations has been reported in first trimester exposure. Animal studies show no teratogenic effects. FDA Pregnancy Category B (outdated classification but still referenced). Risk of fetal harm secondary to maternal febrile reaction or severe infection should be considered. |
| Fetal Monitoring | Monitor for signs of hypersensitivity reactions (urticaria, anaphylaxis). Assess injection site for sterile abscess or neurovascular compromise. In pregnancy, monitor fetal heart rate if maternal febrile response occurs. No specific fetal monitoring required for drug alone. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies have not shown impaired fertility. |
| No clinically significant food interactions. Penicillin absorption is not affected by food. However, avoid excessive alcohol consumption as it may reduce immune response and increase side effects. |
| Clinical Pearls | BICILLIN C-R 900/300 is a combination of penicillin G benzathine and penicillin G procaine, providing both immediate and sustained therapeutic levels. It must be administered deep intramuscularly only, never intravenously or intravascularly, due to risk of severe anaphylaxis and embolic phenomena (e.g., Nicolau syndrome). Administer into the gluteal muscle in adults; deltoid in children. Do not massage injection site. Contraindicated in penicillin-allergic patients. Use with caution in renal impairment and during pregnancy (penicillins are generally safe but procaine component may cross placenta). Monitor for procaine toxicity (dizziness, seizures, respiratory depression) after large doses. |
| Patient Advice | This medication is an antibiotic combination used to treat bacterial infections, including strep throat and syphilis. · You will receive this as an injection into a large muscle; do not massage the injection site. · Report any signs of allergic reaction immediately: rash, hives, difficulty breathing, or swelling of the face/mouth. · Tell your healthcare provider if you have a history of penicillin allergy, kidney disease, or if you are pregnant or breastfeeding. · Contact your provider if you experience severe injection site pain, fever, or seizures. · Complete the full course of treatment even if you feel better. Do not skip doses. |