BICILLIN C-R
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BICILLIN C-R (BICILLIN C-R).
Benzathine penicillin G and procaine penicillin G are beta-lactam antibiotics that inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and activating autolytic enzymes, leading to cell lysis.
| Metabolism | Penicillin G is primarily eliminated unchanged by renal tubular secretion (90%) and glomerular filtration. Hepatic metabolism is minimal; less than 10% is metabolized to penicilloic acid. |
| Excretion | Renal excretion primarily via glomerular filtration and tubular secretion; approximately 60-70% of penicillin G is excreted unchanged in urine within 6 hours; benzathine and procaine components are metabolized and excreted renally as well; small amounts in bile and feces. |
| Half-life | Penicillin G: 0.5-1 hour in normal renal function; prolonged to 7-10 hours in anuria. Benzathine component sustains low levels for days; effective half-life of benzathine penicillin G is 3-5 days due to slow release. |
| Protein binding | Penicillin G: approximately 60% bound to serum albumin; procaine and benzathine salts exhibit similar binding profiles. |
| Volume of Distribution | Penicillin G: Vd approximately 0.3-0.4 L/kg; distributes into extracellular fluid; poor penetration into CSF except with inflamed meninges. |
| Bioavailability | Intramuscular: nearly complete for the combined components; oral not available due to acid lability; intravenous not used because formulation is for IM only. |
| Onset of Action | Intramuscular injection: benzathine component provides slow release with therapeutic serum levels within 24 hours; procaine component provides earlier peak at 1-4 hours; clinical effect within 24-48 hours for susceptible organisms. |
| Duration of Action | Benzathine component provides sustained serum levels for 2-4 weeks; procaine component duration 12-24 hours. Clinical efficacy for prophylaxis of rheumatic fever: single dose every 3-4 weeks. |
| Molecular Weight | 909.1 Da (penicillin G benzathine); 588.7 Da (penicillin G procaine) |
1.2 million units intramuscularly as a single dose (600,000 units procaine penicillin G and 600,000 units benzathine penicillin G) for moderate to severe infections; for mild infections, 600,000 units intramuscularly as a single dose.
| Dosage form | INJECTABLE |
| Renal impairment | For GFR <10 mL/min: increase dosing interval to every 24-48 hours or use alternative therapy; for GFR 10-50 mL/min: administer every 12 hours; no adjustment for GFR >50 mL/min. |
| Liver impairment | No specific dosing adjustments recommended for hepatic impairment; however, monitor for adverse effects in severe hepatic dysfunction (Child-Pugh class C). |
| Pediatric use | Children weighing <27 kg: 600,000 units intramuscularly as a single dose; children weighing ≥27 kg: 1.2 million units intramuscularly as a single dose. |
| Geriatric use | No specific dose adjustment required, but monitor renal function and adjust according to creatinine clearance due to age-related decline in GFR; use with caution in patients with impaired renal function. |
| 1st trimester | Penicillin G benzathine and procaine are FDA pregnancy category B. No evidence of teratogenicity. |
| 2nd trimester | Safe; used for syphilis treatment. |
| 3rd trimester | Safe; consider risk of kernicterus with sulfonamides, but Bicillin C-R contains penicillin, not sulfa. |
Clinical note
Comprehensive clinical and safety monograph for BICILLIN C-R (BICILLIN C-R).
| Placental transfer | Penicillins cross the placenta; therapeutic levels achieved in fetal circulation. |
| Breastfeeding | Penicillins excreted in breast milk in low levels; generally considered compatible with breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: NOT FOR INTRAVENOUS USE. Inadvertent intravenous administration may result in serious anaphylactic reactions, including cardiac arrest and death. Accidental intravascular injection can cause severe neurovascular damage, including transverse myelitis, permanent paralysis, gangrene, and necrosis. Avoid injection near major nerves or blood vessels.
| Serious Effects |
Hypersensitivity to penicillinsHypersensitivity to procaineHypersensitivity to benzathine
| Precautions | Severe hypersensitivity reactions including anaphylaxis; obtain careful history of previous hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactams., Clostridium difficile-associated diarrhea (CDAD) may occur., Neurotoxicity (e.g., seizures, encephalopathy) with high doses, especially in renal impairment or with IV administration; avoid intravascular injection., Procaine component may cause central nervous system disturbances including anxiety, confusion, agitation, psychosis, and seizures (Hoigne syndrome)., Monitor renal function; dose adjustment in severe renal impairment., Benzathine component may cause injection site reactions (pain, induration, sterile abscess)., Prolonged use may result in superinfection with resistant organisms. |
Loading safety data…
| L1 (Safe) |
| Teratogenic Risk | No evidence of teratogenicity in animal studies; human data limited. Penicillins are considered low risk in pregnancy; avoid in penicillin-allergic patients. First trimester: no increased risk of major malformations. Second/third trimesters: safe; use only if clearly needed. |
| Fetal Monitoring | Monitor maternal vital signs and for allergic reactions. In prolonged use, monitor renal function and CBC with differential. Fetal heart rate monitoring not required but may be considered in severe infections. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. |
| Food/Dietary |
| No specific food interactions with BICILLIN C-R. However, alcohol consumption may cause a disulfiram-like reaction (nausea, vomiting, flushing, headache) due to the procaine component; advise patients to avoid alcohol during treatment and for at least 48 hours after the last dose. |
| Clinical Pearls | BICILLIN C-R is a combination of benzathine penicillin G and procaine penicillin G, providing both sustained and rapid action. Used primarily for moderate-to-severe streptococcal infections (e.g., Group A strep pharyngitis, scarlet fever). Administer deep IM only; do not give IV or intravascularly. Inadvertent intravascular injection can cause immediate neurovascular damage. Aspiration before injection is critical. Do not administer in patients with a history of penicillin allergy; cross-reactivity with cephalosporins may occur. Use with caution in renal impairment, as accumulation may increase seizure risk. Monitor for Jarisch-Herxheimer reaction in syphilis treatment. Not indicated for syphilis in pregnancy (use benzathine penicillin G alone). |
| Patient Advice | This medication is given as an injection into a muscle, usually in the buttock or thigh. · Complete the full course of therapy even if you feel better. · Report any signs of allergic reaction (hives, itching, difficulty breathing, swelling of face or throat) immediately. · Possible side effects include pain at injection site, nausea, diarrhea, and dizziness. · Avoid alcohol consumption during treatment due to potential disulfiram-like reaction with procaine component. · Take all doses on schedule; do not miss any appointments for injections. · Inform your healthcare provider if you have kidney disease, asthma, bleeding disorders, or a history of penicillin allergy before receiving this medication. · Injectable penicillin should not be administered if you have had a severe allergic reaction to any penicillin or cephalosporin antibiotic. · If you develop severe diarrhea, especially if it contains blood or mucus, contact your doctor right away. |