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 |
| Molecular Weight | 781.96 |
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 | Contraindicated; risk of fetal nephrotoxicity and ototoxicity. Avoid unless life-threatening infection with no alternative. |
| 2nd trimester | Contraindicated; risk of fetal nephrotoxicity and ototoxicity. Avoid unless life-threatening infection with no alternative. |
| 3rd trimester | Contraindicated; risk of fetal nephrotoxicity and ototoxicity. Avoid unless life-threatening infection with no alternative. |
Clinical note
Comprehensive clinical and safety monograph for PERMAPEN (PERMAPEN).
| Placental transfer | Crosses placenta; achieves fetal serum concentrations approximately 30-50% of maternal levels. Accumulates in fetal kidneys and cochlea. |
| Breastfeeding | Excreted into breast milk in low concentrations; however, due to potential for infant gut flora alteration and risk of ototoxicity/nephrotoxicity, alternative agents are preferred. Use only if clearly needed and monitor infant for diarrhea, rash, or candidiasis. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to any aminoglycosideMyasthenia gravisPre-existing severe renal impairment (CrCl <30 mL/min) without dose adjustment capabilityConcurrent use with potent diuretics (especially loop diuretics) or other nephrotoxic/ototoxic drugs
| 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) |
| Food/Dietary | No significant food interactions. Alcohol consumption may exacerbate gastrointestinal side effects; avoid for 48 hours post-injection. |
Loading safety data…
| Lactation Rating | L4 (Hazardous) |
| 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. |
| 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. |
| Clinical Pearls | PENICILLIN G BENZATHINE (Bicillin L-A) is the only benzathine penicillin formulation; do not confuse with procaine penicillin. Administer deep IM in the upper outer quadrant of the gluteus maximus; do not administer IV or intra-arterially. Verify patient history of anaphylactic penicillin allergy. In syphilis treatment, a single dose of 2.4 million units is recommended for early stages; three doses at one-week intervals for late latent syphilis. Monitor for Jarisch-Herxheimer reaction within 24 hours. For rheumatic fever prophylaxis, administer every 3-4 weeks. Avoid in neonates due to risk of intra-arterial injection. Shake vial vigorously to create a milky suspension before use. |
| Patient Advice | This medication is an antibiotic used to treat bacterial infections like syphilis and to prevent rheumatic fever. · You will receive this as an injection into a muscle, usually the buttock; do not massage the injection site. · Common side effects include pain at the injection site, nausea, and headache. · Report any severe allergic reactions immediately: difficulty breathing, rash, itching, or swelling of the face or mouth. · You may experience a Jarisch-Herxheimer reaction within 24 hours (fever, chills, muscle aches); this is temporary and treatable. · Avoid alcohol for at least 48 hours after injection to reduce side effects. · Keep all follow-up appointments, especially for syphilis serology. · Inform your healthcare provider if you are pregnant or breastfeeding. |