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. |
| Molecular Weight | 588.72 (penicillin G procaine: C29H38N2O8S, MW 588.72) |
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 | Crosses placenta; generally considered low risk, but use only if clearly needed due to risk of altered gut flora and rare allergic reactions. No known teratogenicity. |
| 2nd trimester | Generally safe; use during pregnancy not associated with major malformations. Administer with caution in case of maternal penicillin allergy. |
| 3rd trimester | Considered safe; may rarely cause neonatal diarrhea or candidiasis due to alteration of infant gut flora. No known fetal harm. |
Clinical note
Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.
| FDA category | Human |
| Placental transfer | Readily crosses the placenta; achieves therapeutic levels in fetal serum. Considered safe for use during pregnancy when indicated. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Diarrhea |
| Serious Effects |
Known hypersensitivity to penicillins or procaineSevere allergy to cephalosporins (cross-sensitivity risk)History of immediate allergic reaction (e.g., anaphylaxis) to beta-lactam agents
| 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. |
| Food/Dietary | No significant food interactions. However, avoid alcohol as it may increase side effects like dizziness or gastrointestinal upset. |
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| Breastfeeding |
| Penicillin G procaine is excreted into breast milk in small amounts (less than 10% of maternal dose). Concentrations are low, and adverse effects in nursing infants are rare. Monitor for possible rash, diarrhea, or alteration of intestinal flora. Compatible with breastfeeding when clinically indicated. |
| Lactation Rating | L1 (Compatible) |
| Teratogenic Risk | 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. |
| Clinical Pearls | Penicillin G procaine is a long-acting intramuscular formulation used primarily for syphilis and other susceptible infections. Due to procaine component, it is contraindicated in patients with procaine allergy. Always confirm lack of allergy to both penicillin and procaine. Administer deep IM in the gluteal region; avoid intravascular injection to prevent procaine toxicity or Jarisch-Herxheimer reaction. Monitor for procaine reactions (e.g., anxiety, confusion, seizures) particularly in elderly or those with renal impairment. Not for IV use. |
| Patient Advice | This medication is given as an injection into your muscle, usually in the buttock. · You may experience pain, swelling, or redness at the injection site. · Report any signs of allergic reaction such as rash, itching, swelling, or difficulty breathing immediately. · You might develop a reaction called Jarisch-Herxheimer reaction (fever, chills, muscle aches) within 24 hours, especially if being treated for syphilis; this is not an allergic reaction but notify your doctor. · Avoid driving or operating machinery if you feel dizzy or anxious after the injection. · Complete the full course of injections even if you feel better. |