PENICILLIN G PROCAINE
Clinical safety rating: safe
Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.
Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation, and activating autolytic enzymes.
| Metabolism | Hepatic hydrolysis to penicillin G (active) and p-aminobenzoic acid; penicillin G is primarily renally excreted unchanged (60-90%). |
| Excretion | Primarily renal excretion via tubular secretion and glomerular filtration. Approximately 60-90% of a dose is excreted unchanged in urine within 24 hours. Biliary/fecal elimination is minor (<10%). |
| Half-life | Terminal elimination half-life is approximately 0.5-1 hour in patients with normal renal function. Clinically, the prolonged absorption from the intramuscular depot results in sustained serum concentrations, with effective levels lasting 12-24 hours. |
| Protein binding | Approximately 60% bound to serum proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.3-0.4 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Intramuscular: Bioavailability is approximately 100% (complete absorption). No oral bioavailability due to acid lability. |
| Onset of Action | Intramuscular: Onset of clinical effect within 1-4 hours as peak serum concentrations are reached slowly due to the procaine salt formulation. |
| Duration of Action | Intramuscular: Duration of action is approximately 12-24 hours, due to slow release from the injection site. Serum concentrations decline slowly, with detectable levels for up to 24 hours. |
1.2 million to 2.4 million units intramuscularly once daily for most infections (e.g., uncomplicated pneumonia); for neurosyphilis, 2.4 million units intramuscularly once daily plus probenecid 500 mg orally four times daily for 10-14 days. Administer deep IM injection, not IV.
| Dosage form | INJECTABLE |
| Renal impairment | Creatinine clearance (CrCl) 10-50 mL/min: reduce dose to 50% of normal or extend interval to every 12-24 hours. CrCl <10 mL/min: 25% of normal dose or every 24-48 hours. For severe infections, monitor serum levels. |
| Liver impairment | No dosage adjustment is routinely recommended for Child-Pugh Class A, B, or C; penicillin G procaine is primarily renally eliminated. Use with caution in severe hepatic impairment due to potential for coagulopathy. |
| Pediatric use | Children: 25,000-50,000 units/kg intramuscularly once daily (maximum 2.4 million units/day). For congenital syphilis, 50,000 units/kg intramuscularly once daily for 10-14 days. Not recommended in neonates due to high risk of procaine toxicity. |
| Geriatric use | Start at the lower end of dosing range due to age-related renal function decline. Assess CrCl and adjust dose according to renal adjustment guidelines. Monitor for neurologic adverse effects (procaine toxicity) and ensure adequate hydration. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.
| FDA category | Human |
| Breastfeeding | Penicillin G is excreted into breast milk in low concentrations. The milk-to-plasma (M/P) ratio is approximately 0.2. Although unlikely to be harmful to the nursing infant, it may cause alteration of gut flora, diarrhea, or allergic sensitization. Use with caution in breastfeeding women. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Diarrhea |
| Serious Effects |
["Hypersensitivity to penicillins","Hypersensitivity to procaine","Neonates (due to procaine toxicity risk)"]
| Precautions | ["Severe hypersensitivity reactions (anaphylaxis) can occur; monitor for 30 minutes after injection.","Procaine toxicity (CNS stimulation, seizures) with inadvertent intravascular injection.","Use with caution in renal impairment (dosage adjustment required).","Pseudomembranous colitis due to Clostridium difficile overgrowth.","Jarisch-Herxheimer reaction in syphilis treatment."] |
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| Penicillin G procaine is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and there are no adequate well-controlled studies in pregnant women. However, because animal reproduction studies are not always predictive of human response, it should be used during pregnancy only if clearly needed. There is no evidence of teratogenicity in humans, but theoretical risk of allergic reaction exists. No specific fetal risks have been identified in any trimester. |
| Fetal Monitoring | Monitor for signs of allergic reaction (rash, urticaria, anaphylaxis) in the mother. Fetal monitoring is not routinely required, but assess for potential adverse effects such as intrauterine growth restriction if high doses are used. For maternal therapy, monitor renal function and electrolyte balance due to procaine component. |
| Fertility Effects | No known adverse effects on fertility. Animal studies have not shown impaired fertility. In humans, no data suggest negative impact on reproductive function. |