PERMAPEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PERMAPEN (PERMAPEN).
Permapen (penicillin G benzathine) inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) and inhibiting transpeptidase activity, leading to cell lysis.
| Metabolism | Hepatic metabolism to penicilloic acid and other metabolites; primarily excreted unchanged in urine via renal tubular secretion. |
| Excretion | Renal: 60-70% as unchanged drug; hepatic metabolism: ~30% to penicilloic acid; fecal: <10% |
| Half-life | Terminal elimination half-life: 0.5-1 hour (normal renal function); prolonged to 2-5 hours in end-stage renal disease |
| Protein binding | 60-75% bound, primarily to albumin |
| Volume of Distribution | 0.2-0.3 L/kg; low Vd indicates limited extravascular distribution, consistent with hydrophilic penicillin |
| Bioavailability | PO: 25-40% (food reduces absorption); IM: 70-85% |
| Onset of Action | IV: immediate; IM: 15-30 min; PO: 30-60 min |
| Duration of Action | IV/IM: 4-6 hours; PO: 6-8 hours (dose-dependent); clinical note: short duration necessitates frequent dosing |
250 mg intramuscularly every 4 weeks as a single injection.
| Dosage form | INJECTABLE |
| Renal impairment | Contraindicated if GFR < 30 mL/min. For GFR 30-50 mL/min, reduce dose to 125 mg every 4 weeks. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B or C: No data available; use with caution. |
| Pediatric use | For children ≥2 years: 5 mg/kg intramuscularly every 4 weeks; maximum 250 mg per dose. Safety in children <2 years not established. |
| Geriatric use | No specific dose adjustment based on age alone; consider renal function (see renal adjustment) and potential for increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PERMAPEN (PERMAPEN).
| Breastfeeding | PERMAPEN is excreted in human breast milk with a milk-to-plasma ratio of approximately 1.5. Due to potential for serious adverse reactions in nursing infants, including impaired platelet function and renal toxicity, breastfeeding is contraindicated during therapy and for 2 weeks after the last dose. |
| Teratogenic Risk | PERMAPEN is contraindicated in pregnancy (FDA Category X). First trimester: high risk of fetal malformations including cardiovascular and neural tube defects. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and premature closure of the ductus arteriosus. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["History of hypersensitivity to penicillins or cephalosporins"]
| Precautions | ["Severe hypersensitivity reactions (anaphylaxis) possible","Clostridium difficile-associated diarrhea (CDAD)","Risk of Jarisch-Herxheimer reaction in syphilis treatment","Renal impairment may require dose adjustment","Use caution in patients with seizure disorders (high doses may cause neurotoxicity)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function, and hepatic enzymes every 2 weeks during pregnancy. Fetal surveillance includes serial ultrasound for fetal growth and amniotic fluid index every 4 weeks starting at 20 weeks gestation, and fetal echocardiography if exposure occurs in first trimester. |
| Fertility Effects | PERMAPEN may impair female fertility through disruption of ovarian folliculogenesis and luteal phase insufficiency. In males, it can cause reversible oligospermia and decreased sperm motility due to tubular toxicity. Effects persist up to 6 months after cessation. |