Penicillamine
D-Penicillamine, beta,beta-Dimethylcysteine, D-3-Mercaptovaline
Also known as: Depen · Cuprimine · Pendramine · D-Penicillamine · beta,beta-Dimethylcysteine · D-3-Mercaptovaline · penicillaminum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Copper-associated hepatopathy | 10-15 mg/kg PO q12h on an empty stomach. Do not give concurrently with any medication, including zinc or a vitamin-mineral supplement. | PO | q12h | — | 🌎 NA |
| Copper-associated hepatopathy | 15 mg/kg PO twice daily 30 minutes before meals. Give supplemental pyridoxine. Chelate at least 6 months, and then use a second liver biopsy to determine efficacy and chronic treatment plan. | PO | q12h | At least 6 months | 🌎 NA |
| Copper-associated hepatopathy | 10-15 mg/kg PO two times a day 30 minutes prior to food. Start low and increase. | PO | q12h | — | 🌎 NA |
| Copper-associated hepatopathy | 15 mg/kg PO twice daily on an empty stomach. | PO | q12h | — | 🌎 NA |
| Cystine urolithiasis | 15 mg/kg: PO twice daily. If nausea and vomiting occur, mix with food or give at mealtime. Some dogs may need to have the dosage slowly increased to full dose in order to tolerate the drug. | PO | q12h | — | 🌎 NA |
| Cystine urolithiasis | 15 mg/kg: PO twice daily with food | PO | q12h | — | 🌎 NA |
| Lead poisoning | 110 mg/kg/day, PO divided q6-8h for 1-2 weeks. If vomiting, depression, and anorexia occur, may reduce dose to 33-55 mg/kg/day divided q6-8h, which should be better tolerated. | PO | q6-8h | 1-2 weeks | 🌎 NA |
| Lead poisoning | 110 mg/kg/day divided q6-8h PO 30 minutes before feeding for 1-2 weeks. If vomiting a problem may premedicate with dimenhydrinate (2-4 mg/kg PO). Alternatively, may give 33-55 mg/kg/day divided as above. | PO | q6-8h | 1-2 weeks | 🌎 NA |
| Copper storage disease / Copper-associated hepatopathy | Dose not specified in monograph | PO | Not specified | Long-term (weeks to months) | 🌍 EU |
| Cystinuria | Dose not specified in monograph | PO | Not specified | Not specified | 🌍 EU |
| Lead toxicity | Dose not specified in monograph | PO | Not specified | Long-term | 🌍 EU |
- Copper-associated hepatopathy: If patient is zinc intolerant, use chronic penicillamine at a dose restriction of 50%. Do not use chelation and zinc together.
- Lead poisoning: After initial therapy regimen with CaEDTA and if continued therapy is desired at home.
- Lead poisoning: As an alternate or adjunct to CaEDTA. Dissolving medication in juice may facilitate administration.
- Copper storage disease / Copper-associated hepatopathy: Not helpful in an acute crisis. Pretreat with antiemetics 30-60 mins before if poorly tolerated.
- Cystinuria: Decreases cystine excretion by forming soluble complex.
- Lead toxicity: Used when injecting EDTA is too difficult or long-term chelation is required.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Lead poisoning | 125 mg q12h PO for 5 days. | PO | q12h | 5 days | 🌎 NA |
- Lead poisoning: After initial therapy with CaEDTA and if blood lead is greater than 0.2 ppm at 3-4 weeks post-treatment.
Birds
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive treatment of lead poisoning | 55 mg/kg PO q12h for 1-2 weeks. | PO | q12h | 1-2 weeks | 🌎 NA |
- Adjunctive treatment of lead poisoning: Suggested to combine CaEDTA and penicillamine for several days until symptoms dissipate followed by a 3-6 week treatment with penicillamine.
Cattle
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Lead or mercury toxicity | 110 mg/kg PO for 1-3 weeks. | PO | Unknown | 1-3 weeks | 🌎 NA |
- Lead or mercury toxicity: 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.
Sheep
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Copper toxicity | 52 mg/kg daily for 6 days | PO | q24h | 6 days | 🌎 NA |
| Copper toxicity | 26-52 mg/kg PO once daily for 6 days. | PO | q24h | 6 days | 🌎 NA |
| Lead or mercury toxicity | 110 mg/kg PO for 1-3 weeks. | PO | Unknown | 1-3 weeks | 🌎 NA |
- Copper toxicity: FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Lead or mercury toxicity: Must clear GI tract of toxic metal before therapy.
Goats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Copper toxicity | 52 mg/kg daily for 6 days | PO | q24h | 6 days | 🌎 NA |
| Copper toxicity | 26-52 mg/kg PO once daily for 6 days. | PO | q24h | 6 days | 🌎 NA |
| Lead or mercury toxicity | 110 mg/kg PO for 1-3 weeks. | PO | Unknown | 1-3 weeks | 🌎 NA |
- Copper toxicity: FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Lead or mercury toxicity: Must clear GI tract of toxic metal before therapy.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
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 of action
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) → forms stable, water-soluble complexes → facilitates rapid excretion via the kidneys.
- Cystine Urolithiasis: Combines chemically with cystine via a disulfide interchange reaction → forms a stable, highly soluble penicillamine-cysteine mixed disulfide complex → 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 → renders newly synthesized collagen more susceptible to enzymatic degradation.
Safety & warnings
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
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)
- Lupus-like reactions (human data)
Precautions
Penicillamine is contraindicated in patients with a history of penicillamine-related blood dyscrasias. Warning: Penicillamine potentially can cause enhanced absorption of lead from the gastrointestinal tract. If lead is still present in the gut (e.g., visible on radiographs), it should NOT be administered until the GI tract is cleared. Use with caution in pregnant animals due to known teratogenic potential (FDA Category D).
Drug interactions
Concomitant administration may increase the risks for severe dermatologic adverse effects.
May decrease the effectiveness of penicillamine if given orally together due to chelation in the gut.
The amount of penicillamine absorbed from the GI tract may be reduced by concurrent administration.
May increase the risk of hematologic and/or renal adverse reactions.
May increase the risk of hematologic and/or renal adverse reactions.
May increase the risk of hematologic and/or renal adverse reactions.
Decreased gastrointestinal absorption of penicillamine
Decreased gastrointestinal absorption of penicillamine
Decreased gastrointestinal absorption of penicillamine
Decreased gastrointestinal absorption of penicillamine
Increased renal and haematological adverse effects
Increased risk of renal damage
Increased risk of renal damage
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
Pharmacokinetics
Absorption
In humans, well absorbed after oral administration. Peak serum levels occur about one hour after dosing. Food decreases bioavailability.
Distribution
Crosses the placenta. Otherwise, little information is known about its distribution.
Metabolism
Penicillamine that is not complexed with either a metal or cystine is thought to be metabolized by the liver.
Elimination
Excreted in the urine and feces.
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.
Available products
Formulations
- Titratable Oral Tablets: 250 mg
- Oral Capsules: 125 mg, 250 mg
- 125 mg oral tablet
- 250 mg oral tablet
Veterinary
- None
Human-labeled
- Penicillamine Titratable Oral Tablets: 250 mg (scored); Depen (Wallace)
- Penicillamine Oral Capsules: 125 mg & 250 mg; Cuprimine (Aton Pharma)
- Pendramine 125 mg tablets
- Pendramine 250 mg tablets
- Penicillamine 125 mg tablets
- Penicillamine 250 mg tablets
Regulatory status
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Penicillamine should be stored at room temperature (15-30°C). The capsules should be stored in tight containers; tablets in well-closed containers.
Client information
Penicillamine is used to help your pet's body eliminate toxic levels of metals (like copper or lead) or to dissolve certain types of bladder stones.
- Administration: This drug should preferably be given on an empty stomach, at least 30 minutes before feeding, to ensure it is absorbed properly.
- Managing Side Effects: If your pet develops vomiting or loss of appetite, contact your veterinarian. They may suggest:
- Dividing the daily dose into smaller, more frequent doses.
- Temporarily reducing the dose and gradually increasing it.
- Giving the medication with a small amount of food (e.g., cheese or bread) to settle the stomach, though this may slightly reduce absorption.
- Do not give this medication at the same time as vitamin/mineral supplements (especially those containing zinc or iron) or antacids, as they will bind to the drug and stop it from working.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.