PENICILLIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENICILLIN (PENICILLIN).
Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation and autolysin activation, leading to cell lysis.
| Metabolism | Primarily renally excreted unchanged; minor hepatic metabolism to penicilloic acid. |
| Excretion | Primarily renal (60-80% unchanged via glomerular filtration and tubular secretion); biliary/fecal excretion accounts for 10-20%. |
| Half-life | 0.5-1.0 hours in normal renal function; prolonged to 7-10 hours in anuria. Dose adjustment required in renal impairment. |
| Protein binding | Approximately 60% bound to serum albumin (primarily) and other proteins. |
| Volume of Distribution | 0.3-0.5 L/kg; primarily confined to extracellular fluid; limited CNS penetration except with inflamed meninges. |
| Bioavailability | Oral: 30-50% (acid-labile, food decreases absorption); IM: 60-80%; IV: 100%. |
| Onset of Action | IV: immediate; IM: 15-30 min; oral: 30-60 min. |
| Duration of Action | 2-4 hours for short-acting formulations; prolonged with probenecid (increases half-life by 30-50%). |
| Molecular Weight | 356.38 |
Penicillin G: 2-4 million units IV every 4-6 hours; Penicillin V: 250-500 mg orally every 6 hours for mild to moderate infections.
| Dosage form | FOR SOLUTION |
| Renal impairment | For Penicillin G: CrCl >50 mL/min: 2-4 million units every 4-6 hours; CrCl 10-50 mL/min: 2-4 million units every 6-8 hours; CrCl <10 mL/min: 2-4 million units every 8-12 hours. For Penicillin V: No adjustment needed for mild impairment; CrCl <10 mL/min: use with caution and monitor. |
| Liver impairment | No dose adjustment required for Child-Pugh Class A or B. For Child-Pugh Class C, use with caution and monitor for adverse effects; no specific dose reduction recommended. |
| Pediatric use | Neonates (0-7 days): 50,000-100,000 units/kg/day IV divided every 12 hours; Neonates (8-28 days): 75,000-150,000 units/kg/day IV divided every 8 hours; Infants and children: 100,000-250,000 units/kg/day IV divided every 4-6 hours for severe infections; Oral Penicillin V: 25-50 mg/kg/day divided every 6-8 hours. |
| Geriatric use | No specific dose adjustment based on age alone; adjust for renal function per renal adjustment guidelines. Start at lower end of dosing range due to possible decreased renal function; monitor for CNS toxicity with high doses. |
| 1st trimester | Penicillin is generally considered safe in the first trimester. Numerous studies show no increased risk of major birth defects. Use only if clearly needed. |
| 2nd trimester | Penicillin is generally safe in the second trimester, with low risk of fetal harm. Commonly used to treat infections during pregnancy. |
| 3rd trimester | Penicillin is generally safe in the third trimester. Avoid high doses near delivery due to risk of altering fetal gut flora, but low risk overall. |
Clinical note
Comprehensive clinical and safety monograph for PENICILLIN (PENICILLIN).
| Placental transfer | Penicillin crosses the placenta to a variable degree. Transfer is generally low to moderate, but can be higher at term. Concentrations in fetal serum are typically lower than maternal serum. |
| Breastfeeding | Penicillin is excreted into breast milk in low amounts. It is generally considered compatible with breastfeeding, as the small amount ingested by the infant is unlikely to cause adverse effects. However, monitor for potential allergic reactions or diarrhea in the infant. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to penicillinsHistory of severe immediate hypersensitivity reaction (e.g., anaphylaxis) to beta-lactam antibiotics
| Precautions | Severe hypersensitivity reactions (anaphylaxis) can occur, especially in patients with penicillin allergy., Serious skin reactions (e.g., Stevens-Johnson syndrome) have been reported., Clostridium difficile-associated diarrhea (CDAD) may occur., Renal impairment requires dose adjustment., Neurologic adverse effects (e.g., seizures) with high doses or renal failure. |
| Food/Dietary | Penicillin absorption is not significantly affected by food. However, acidic beverages (e.g., fruit juice, carbonated drinks) may degrade penicillin in the stomach; avoid taking with such drinks. No specific dietary restrictions. |
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| Lactation Rating | L1 |
| Teratogenic Risk | Penicillin is generally considered safe during pregnancy. No increased risk of congenital anomalies has been observed across all trimesters. At therapeutic doses, fetal risks are minimal. However, caution is advised with high doses near delivery due to risk of fetal methemoglobinemia or hemolytic anemia in G6PD deficiency. |
| Fetal Monitoring | Monitor maternal renal and hepatic function with prolonged therapy. In pregnancy, assess fetal growth and well-being via ultrasound if treatment is extended. No specific fetal monitoring required for short courses. Observe for signs of maternal allergic reactions or superinfection. |
| Fertility Effects | No negative effects on human fertility reported. Penicillins do not alter spermatogenesis or oocyte function. No evidence of impaired fecundity in animal studies. |
| Clinical Pearls | Penicillin is bactericidal against gram-positive cocci (e.g., Streptococcus pyogenes, Streptococcus pneumoniae) and some gram-negative cocci (e.g., Neisseria meningitidis). It is ineffective against beta-lactamase-producing organisms. Always check for penicillin allergy before administration; cross-reactivity with cephalosporins is low but present. Use with caution in renal impairment as excretion is primarily renal. For syphilis, penicillin G is the drug of choice; treat neurosyphilis with high-dose intravenous penicillin G. |
| Patient Advice | Complete the full course of penicillin even if you feel better. · Take penicillin exactly as prescribed; do not skip doses. · Report any signs of allergic reaction (rash, hives, itching, difficulty breathing) immediately. · Penicillin may be taken with or without food; avoid acidic beverages like fruit juice within 1 hour of dosing. · Store penicillin in a cool, dry place; some liquid forms require refrigeration. |