Penicillamine
Penicillamine is a potent **chelating agent** primarily utilized in veterinary medicine for the management of **copper-storage hepatopathies**, particularly in susceptible dog breeds like Bedlington Terriers, Labrador Retrievers, and Dalmatians. Key clinical highlights: * **Slow Onset**: Clinical improvement in copper-associated hepatopathy may require weeks to months of continuous therapy. * **Versatility**: Beyond copper, it is effective for long-term oral treatment of lead or mercury poisoning, and for the dissolution/prevention of **cystine urolithiasis**. * **Anti-fibrotic Properties**: May offer benefits in chronic hepatitis by inhibiting collagen crosslinking, though the required doses are often poorly tolerated. > **Clinical Pearl**: Because penicillamine can chelate dietary minerals, it should not be administered concurrently with zinc or vitamin-mineral supplements unless specifically staggered under a strict protocol.
Mechanism: Penicillamine exerts its effects through multiple distinct mechanisms depending on the target condition: * **Heavy Metal Chelation**: Contains sulfhydryl groups that bind to heavy metals (copper, lead, iron, mercury) โ forms stable, water-soluble complexes โ facilitates rapid excretion via the kidneys. * **Cystine Urolithiasis**: Combines chemically with cystine via a disulfide interchange reaction โ forms a stable, highly soluble penicillamine-cysteine mixed disulfide complex โ readily excreted in urine, preventing stone formation. * **Antirheumatic Activity**: Mechanism is not fully elucidated, but it improves lymphocyte function and decreases **IgM rheumatoid factor** and immune complexes in serum and synovial fluid. * **Antifibrotic Activity**: Inhibits **lysyl oxidase** and collagen crosslinking โ renders newly synthesized collagen more susceptible to enzymatic degradation.
Dosing by species
- Lead poisoning ยท 125 mg q12h PO for 5 days. ยท PO ยท q12h ยท 5 days ยท After initial therapy with CaEDTA and if blood lead is greater than 0.2 ppm at 3-4 weeks post-treatment.
- Copper toxicity ยท 52 mg/kg daily for 6 days ยท PO ยท q24h ยท 6 days ยท FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Copper toxicity ยท 26-52 mg/kg PO once daily for 6 days. ยท PO ยท q24h ยท 6 days
- Lead or mercury toxicity ยท 110 mg/kg PO for 1-3 weeks. ยท PO ยท Unknown ยท 1-3 weeks ยท Must clear GI tract of toxic metal before therapy.
- Adjunctive treatment of lead poisoning ยท 55 mg/kg PO q12h for 1-2 weeks. ยท PO ยท q12h ยท 1-2 weeks ยท Suggested to combine CaEDTA and penicillamine for several days until symptoms dissipate followed by a 3-6 week treatment with penicillamine.
- Lead or mercury toxicity ยท 110 mg/kg PO for 1-3 weeks. ยท PO ยท Unknown ยท 1-3 weeks ยท To prevent continued metal absorption, must clear GI tract of toxic metal before therapy. FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Copper toxicity ยท 52 mg/kg daily for 6 days ยท PO ยท q24h ยท 6 days ยท FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
Routes of administration
Contraindications
- Patients with a history of penicillamine-related blood dyscrasias
- Presence of lead in the gastrointestinal tract (can enhance absorption)
- Pregnancy (unless benefits outweigh teratogenic risks)
- Moderate to marked renal impairment
- History of penicillamine-related blood dyscrasias
Adverse effects
- Nausea
- Vomiting
- Depression
- Anorexia
- Dietary mineral deficiencies (zinc, iron, copper, calcium) with long-term use
- Fever (rare)
- Lymphadenopathy (rare)
- Skin hypersensitivity reactions (rare)
- Immune-complex glomerulonephropathy (rare)
- Teratogenicity
- Pyrexia
- Nephrotic syndrome
- Leucopenia (human data)
- Thrombocytopenia (human data)
- Lymphadenopathy (human data)
- Skin hypersensitivity reactions (human data)
Drug interactions
- 4-Aminoquinoline drugs (e.g., chloroquine, quinacrine) ยท Concomitant administration may increase the risks for severe dermatologic adverse effects.
- Oral Cations (Zinc, Iron, Calcium, Magnesium) ยท May decrease the effectiveness of penicillamine if given orally together due to chelation in the gut.
- Food and Antacids ยท The amount of penicillamine absorbed from the GI tract may be reduced by concurrent administration.
- Gold Compounds ยท May increase the risk of hematologic and/or renal adverse reactions.
- Immunosuppressant drugs (e.g., cyclophosphamide, azathioprine) ยท May increase the risk of hematologic and/or renal adverse reactions.
- Phenylbutazone ยท May increase the risk of hematologic and/or renal adverse reactions.
- Antacids ยท Decreased gastrointestinal absorption of penicillamine ยท moderate
- Food ยท Decreased gastrointestinal absorption of penicillamine ยท moderate
- Iron salts ยท Decreased gastrointestinal absorption of penicillamine ยท moderate
- Zinc salts ยท Decreased gastrointestinal absorption of penicillamine ยท moderate
- Cytotoxic drugs ยท Increased renal and haematological adverse effects ยท major
- NSAIDs ยท Increased risk of renal damage ยท major
Monitoring
- Clinical efficacy (e.g., resolution of neurologic signs in lead poisoning)
- Liver enzymes (ALT) and liver copper levels via biopsy (for hepatopathy)
- Urinalysis and stone dissolution (for cystine urolithiasis)
- Complete blood count (CBC) and urinalysis to monitor for rare blood dyscrasias or glomerulonephropathy
- Full blood count (weekly initially)
- Urinalysis (weekly initially)
- Renal function
- Dietary mineral levels (zinc, iron, copper, calcium) during long-term use
Overdose
No specific acute toxic dose has been established for penicillamine. Toxic effects generally occur in patients taking the drug chronically. Any relationship of toxicity to dose is unclear; patients on small doses may develop toxicity. Management of overdose would be largely supportive and symptomatic.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.