DEPEN
Clinical safety rating
cautionComprehensive clinical and safety monograph for DEPEN (DEPEN).
Penicillamine is a chelating agent that forms soluble complexes with heavy metals (e.g., copper, mercury, lead) and promotes their renal excretion. In rheumatoid arthritis, it reduces rheumatoid factor and immune complexes, and inhibits collagen cross-linking.
| Metabolism | Penicillamine is metabolized via oxidation to disulfides. It is primarily excreted in urine as unchanged drug and metabolites. |
| Excretion | Renal: 50% as unchanged drug; biliary/fecal: minor, <5%. |
| Half-life | 1.5-4 hours; prolonged to 6-12 hours in renal impairment; clinical context: dosing interval adjustments needed in CKD. |
| Protein binding | 80%; primarily to albumin. |
| Volume of Distribution | 0.1-0.4 L/kg; indicates limited extravascular distribution, mainly confined to plasma and interstitial fluid. |
| Bioavailability | Oral: 40-70% (variable due to food and formulation). |
| Onset of Action | Oral: 1-2 hours for chelation effect in Wilson disease; IV: immediate for heavy metal chelation. |
| Duration of Action | 4-6 hours for chelation effect; may persist up to 12 hours in renal impairment. |
| Molecular Weight | 135.23 |
250 mg orally 4 times daily, target dose 1000-1500 mg/day in divided doses.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: 250 mg every 8-12 hours; GFR 15-29 mL/min: 250 mg every 12-24 hours; GFR <15 mL/min: 250 mg every 24 hours or avoid use. |
| Liver impairment | No adjustment recommended for mild to moderate impairment (Child-Pugh A or B); avoid use in severe impairment (Child-Pugh C) due to increased risk of hepatotoxicity. |
| Pediatric use | Children >1 year: 10-15 mg/kg/day divided every 6-8 hours, maximum 500 mg/day. |
| Geriatric use | Start at lower end of dosing range (250 mg twice daily) due to age-related renal function decline; monitor renal function and adjust based on creatinine clearance. |
| 1st trimester | Risk of congenital anomalies, especially orofacial clefts and neural tube defects. |
| 2nd trimester | Risk of fetal hepatotoxicity and intrauterine growth restriction. |
| 3rd trimester | Risk of neonatal hepatotoxicity and coagulopathy. |
Clinical note
Comprehensive clinical and safety monograph for DEPEN (DEPEN).
| Placental transfer | Crosses placenta; fetal concentrations can reach maternal levels after multiple doses. |
| Breastfeeding | Not recommended due to excretion into breast milk and risk of neonatal hepatotoxicity. |
| Lactation Rating | L5 |
| Teratogenic Risk | Penicillamine (Depen) is associated with severe fetal malformations including cutis laxa and skeletal abnormalities when used during pregnancy. First trimester exposure carries highest risk; use is contraindicated unless necessary for maternal conditions like Wilson's disease or cystinuria. Second and third trimester use may cause fetal connective tissue disorders. |
| Fetal Monitoring | Monitor maternal renal function, CBC, and urinalysis monthly. Fetal ultrasound for skeletal anomalies. In Wilson's disease, monitor serum copper levels and neurological status. |
| Fertility Effects | No significant adverse effects on fertility reported in humans. Animal studies suggest no impairment. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to penicillamineHistory of penicillamine-induced aplastic anemia or agranulocytosisPregnancy (relative contraindication, but may be used for Wilson disease with caution)
| Precautions | Bone marrow suppression (leukopenia, thrombocytopenia, aplastic anemia), Proteinuria and nephrotic syndrome, Autoimmune reactions (lupus-like syndrome, myasthenia gravis), Hepatotoxicity, Severe skin reactions (e.g., pemphigus, Stevens-Johnson syndrome), Monitor renal function, blood counts, and urinalysis regularly |
| Food/Dietary | Avoid foods high in copper (e.g., liver, shellfish, nuts, chocolate, mushrooms) during treatment for Wilson disease. For cystinuria, maintain high fluid intake (at least 3-4 liters/day) and reduce sodium and animal protein to decrease cystine excretion. Vitamin B6 supplementation may be needed as DEPEN can increase pyridoxine requirements. |
| Clinical Pearls | DEPEN (penicillamine) is a chelating agent used for Wilson disease, cystinuria, and rheumatoid arthritis. Monitor for proteinuria and hematuria due to immune complex nephropathy. Cross-sensitivity with penicillin possible. Administer on empty stomach for Wilson disease; with meals for cystinuria to reduce GI upset. Avoid concomitant use with other nephrotoxic drugs. |
| Patient Advice | Take DEPEN on an empty stomach at least 1 hour before or 2 hours after meals, unless otherwise directed for cystinuria. · Do not skip doses; consistent intake is critical for Wilson disease to prevent copper accumulation. · Report any signs of infection, unusual bleeding, skin rash, or changes in urine color or output immediately. · Avoid alcohol completely as it may increase risk of liver toxicity. · Use effective contraception during therapy as DEPEN can cause fetal harm. · Have regular blood and urine tests as ordered to monitor for side effects. |
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