PENICILLIN G SODIUM
Clinical safety rating: safe
Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.
Penicillin G inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and activating autolytic enzymes.
| Metabolism | Primarily eliminated unchanged by renal tubular secretion; minor hepatic metabolism to penicilloic acid (inactive). |
| Excretion | Primarily renal (60-90% unchanged) via glomerular filtration and tubular secretion; minor biliary/fecal (<10%). |
| Half-life | 30-60 minutes in normal renal function; prolonged to 7-10 hours in anuria. |
| Protein binding | 60-80% bound to serum albumin. |
| Volume of Distribution | 0.3-0.5 L/kg; approximates extracellular fluid volume, limited CNS penetration unless inflamed meninges. |
| Bioavailability | IM: 60-80%; oral: <30% (not clinically used). |
| Onset of Action | IM: 15-30 minutes; IV: immediate; oral: not applicable (acid-labile). |
| Duration of Action | IM: 4-6 hours; IV: 2-4 hours depending on dose and renal function. |
| Molecular Weight | 356.37 |
2-4 million units intravenously every 4 hours for moderate to severe infections; up to 24 million units/day for severe infections (e.g., meningitis, endocarditis).
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: administer every 6-8 hours; CrCl <10 mL/min: administer every 8-12 hours. For high-dose therapy (e.g., >10 million units/day), reduce dose by 50% when CrCl <10 mL/min. |
| Liver impairment | No significant hepatic metabolism; dose adjustment not required for Child-Pugh Class A, B, or C. Monitor for electrolyte disturbances with high doses. |
| Pediatric use | Neonates: 50,000-100,000 units/kg/day divided every 12 hours (postnatal age ≤7 days, weight ≤2 kg) to every 8 hours (older neonates). Infants/children: 100,000-250,000 units/kg/day divided every 4-6 hours; maximum 24 million units/day. For meningitis: 300,000-400,000 units/kg/day divided every 4-6 hours. |
| Geriatric use | Initiate at lowest recommended adult dose (2 million units IV every 4 hours) with careful renal function monitoring. Adjust dose based on CrCl as per renal adjustment. Monitor for neurotoxicity (seizures) at high doses or with decreased renal function. |
| 1st trimester | Crosses placenta; use only if clearly needed. No evidence of teratogenicity in humans. |
| 2nd trimester | Considered safe; no known fetal harm. |
| 3rd trimester | Considered safe; no known fetal harm. |
Clinical note
Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.
| FDA category | Human |
| Placental transfer | Crosses placenta; achieves therapeutic concentrations in fetal serum and amniotic fluid. |
| Breastfeeding | Excreted in breast milk in low concentrations; generally considered compatible with breastfeeding. Monitor infant for rash, diarrhea, or candidiasis. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to penicillinsHistory of immediate hypersensitivity reaction (e.g., anaphylaxis) to beta-lactam antibiotics
| Precautions | Severe hypersensitivity reactions (anaphylaxis) can occur; cross-sensitivity with cephalosporins., Use with caution in renal impairment (dose adjustment required)., Prolonged use may lead to superinfection., Neurologic adverse effects (seizures) with high doses, especially in renal failure., Jarisch-Herxheimer reaction when treating syphilis. |
| Food/Dietary | No significant food interactions. However, avoid alcohol as it may reduce drug effectiveness and slow recovery. |
Loading safety data…
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | Penicillin G is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and no adequate controlled studies in pregnant women exist. Across all trimesters, no known teratogenic effects have been reported; risk is considered low. |
| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal renal function if used for prolonged periods or at high doses due to potential electrolyte imbalances from sodium content. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies have not shown impaired fertility. |
| Clinical Pearls | Administer IV only; IM can cause severe pain and sterile abscess. Contraindicated in patients with immediate hypersensitivity to penicillins. Perform skin testing prior to use in suspected allergy. Monitor renal function as clearance is primarily renal. For neurosyphilis, use high doses (18–24 million units/day). Use within 24 hours after reconstitution due to rapid loss of potency. |
| Patient Advice | Complete the full course of antibiotics even if you feel better. · Report any rash, hives, or difficulty breathing immediately. · This medication is given intravenously, not by mouth. · May cause diarrhea; contact your doctor if persistent or bloody. · Inform your doctor if you are pregnant, breastfeeding, or have kidney disease. |