DEPEN
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEPEN (DEPEN).
| Breastfeeding | Penicillamine is excreted into breast milk in low amounts; M/P ratio not well defined. Potential for infant toxicity (e.g., rash, bone marrow suppression). Caution advised; monitor infant for adverse effects. Alternative therapies preferred. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of penicillamine-induced aplastic anemia or agranulocytosis","Pregnancy (relative contraindication due to teratogenicity)","Renal insufficiency (avoid in severe impairment)","Hypersensitivity to penicillamine"]
| 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"] |
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| 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. |