Cuprimine (penicillamine)
Also marketed as Depen. An approved treatment for Wilson Disease.
The same compound appears under different names depending on the context. Here is how to identify Penicillamine wherever you encounter it, plus the key facts at a glance.
- Generic name
- Penicillamine
- Brand names
- Cuprimine, Depen
- Drug class
- Copper chelator (oral)
- Manufacturer
- Bausch Health (Cuprimine); Viatris (Depen); generic available
- How it's taken
- Taken by mouth on an empty stomach.
The original copper chelator for Wilson disease, in clinical use since the 1950s. Highly effective at removing copper but limited by a substantial side effect burden, which has driven decades of effort to develop better-tolerated alternatives. Still widely used for initial de-coppering in many centers.
Where Penicillamine fits
Historical first-line de-coppering agent. Many centers now consider trientine (Cuvrior or Syprine/generic) or zinc as alternatives or first-line options for selected patients given penicillamine's tolerability profile, but penicillamine remains a standard option, particularly during the initial de-coppering phase.
How Penicillamine works
Oral copper chelator that binds copper and other heavy metals so they can be excreted in the urine. Penicillamine has been the historical first-line de-coppering agent for Wilson disease since the 1950s.
Side effects and safety
Penicillamine has one of the broader side effect profiles in Wilson disease therapy. Common effects include rash, fever, lymphadenopathy, taste changes, and gastrointestinal upset, especially during initiation. Important serious effects include bone marrow suppression (cytopenias, requiring CBC monitoring), proteinuria from membranous nephropathy, drug-induced lupus and other autoimmune syndromes, myasthenia gravis, and pyridoxine (vitamin B6) deficiency that requires routine supplementation. Paradoxical worsening of neurologic symptoms during the first weeks of therapy can occur in patients with neurologic Wilson disease. Penicillamine has a boxed warning: it should never be used casually, every patient should stay under close supervision by a doctor who knows its risks, and any sign of a side effect should be reported right away. The label says deaths have occurred from aplastic anemia, agranulocytosis, low platelets, Goodpasture's syndrome (a kidney and lung disease) and myasthenia gravis. Urine tests and blood counts are done twice a week for the first month, every 2 weeks for the next 5 months, then monthly, and fever, sore throat, chills, bruising or bleeding should be reported right away. People who had aplastic anemia or agranulocytosis from penicillamine should not take it again. The label also warns about liver injury (liver tests every 3 months in the first year for Wilson disease), pemphigus (a serious blistering skin disease), a rare lung disease called obliterative bronchiolitis, and possible harm to an unborn baby.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Penicillamine
Taken by mouth on an empty stomach. Adult de-coppering doses are typically 1000 to 1500 mg per day divided into 3 to 4 doses, lowered to a maintenance dose (often 750 to 1000 mg per day) once de-coppering is achieved. The label says people with Wilson disease should take 25 mg of pyridoxine (vitamin B6) a day during treatment, because penicillamine raises the need for it. Take penicillamine at least 1 hour before or 2 hours after meals, and at least 1 hour apart from other medicines, food, milk, antacids, zinc or iron.
Availability and cost
Generic versions may be available at a lower cost. Ask your pharmacist.
Help paying for Cuprimine
Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.
- Free medicine program
Brand CUPRIMINE is on the Bausch Health PAP list. Free medicine for eligible patients with limited or no coverage, shipped home for up to 1 year.
For: no insurance, underinsured, Medicaid · source
Good to know: Applies to brand CUPRIMINE only; generic penicillamine and DEPEN (Mylan) are not covered. Bausch left certain federal Medicaid programs on Oct 1, 2025, so Medicaid may not cover Bausch brands; Medicaid patients may get them free through the PAP. A WD Rx Access copay form exists, but its posted terms expired, so current copay help is unconfirmed.
- From a charity · Wilson Disease AssociationWDA Patient Assistance fundApply directly
Pays for: Travel and lodging (up to 7 days) for testing or treatment, for the patient and one companion, up to $2,000 per year.
The foundation says: “Status not shown on page”
How Wilson disease treatments compare
Four FDA-approved medications are available for Wilson disease, plus several investigational programs in late-stage trials. Treatment choice depends on your stage (active de-coppering versus stable maintenance), your tolerance to penicillamine, whether you have neurologic or hepatic features, and your age. This chart summarizes the practical differences between the approved options.
4 FDA-approved wilson disease treatments are available: Cuprimine / Depen (penicillamine, approved 1956); Syprine (trientine hydrochloride, approved 1985); Galzin (zinc acetate, approved 1997); Cuvrior (trientine tetrahydrochloride, approved 2022). Cuprimine / Depen is typically used as historical first-line for active de-coppering. many centers now switch patients off due to side effect burden once stable..
| Drug | How it works | How it’s given | How often | Where you take it | Typical use | FDA approved |
|---|---|---|---|---|---|---|
Cuprimine / Depen penicillamine You are here | Copper chelator — binds copper in the body so it can be flushed out through the urine. The original Wilson disease drug. | Oral capsule or tablet, taken on an empty stomach | 3–4 times daily during de-coppering, lower doses for maintenance | Home (oral) | Historical first-line for active de-coppering. Many centers now switch patients off due to side effect burden once stable. | 1956 |
Syprine trientine hydrochloride | Copper chelator — binds copper for urinary excretion. Generally better tolerated than penicillamine but similar efficacy. | Oral capsule, taken on an empty stomach (capsules require refrigeration) | 2–4 times daily | Home (oral) | Alternative chelator for patients who cannot tolerate penicillamine. Generic versions widely available. | 1985 |
Galzin zinc acetate | Copper absorption blocker — induces a protein in the gut (metallothionein) that traps dietary copper before it can be absorbed. | Oral capsule, taken on an empty stomach (separated from chelators) | 3 times daily | Home (oral) | First-line maintenance therapy in many centers, particularly for presymptomatic patients identified through family screening. | 1997 |
Cuvrior trientine tetrahydrochloride | Copper chelator — same chelating action as Syprine, with a more chemically stable salt formulation that allows simpler storage and twice-daily dosing. | Oral tablet, taken on an empty stomach | Twice daily | Home (oral) | Approved for adults with stable Wilson disease who are de-coppered and tolerant to penicillamine; designed as a maintenance switch option. | 2022 |
This chart summarizes approved Wilson disease treatments to help you understand the landscape. It is not medical advice. Treatment decisions depend on your individual disease stage, prior therapies, tolerability, and lab values for copper control. Investigational programs (ALXN1840, VTX-801, UX701) are not included because they are not yet FDA-approved. Always discuss options with your hepatologist or metabolic specialist.
Development history
Penicillamine was first reported as a copper chelator by John Walshe in 1956 and transformed Wilson disease from a fatal disease into a treatable one. It remained the only Wilson disease drug for nearly 30 years until trientine hydrochloride (Syprine) was approved in 1985, and is still in routine use today.
Explore Wilson Disease trials
Other Wilson Disease treatments
Common questions about Penicillamine
▸What is Penicillamine (Cuprimine)?
The original copper chelator for Wilson disease, in clinical use since the 1950s. Highly effective at removing copper but limited by a substantial side effect burden, which has driven decades of effort to develop better-tolerated alternatives. Still widely used for initial de-coppering in many centers.
▸What is the mechanism of action of Penicillamine?
Oral copper chelator that binds copper and other heavy metals so they can be excreted in the urine. Penicillamine has been the historical first-line de-coppering agent for Wilson disease since the 1950s.
▸What are the side effects of Penicillamine?
Penicillamine has one of the broader side effect profiles in Wilson disease therapy. Common effects include rash, fever, lymphadenopathy, taste changes, and gastrointestinal upset, especially during initiation. Important serious effects include bone marrow suppression (cytopenias, requiring CBC monitoring), proteinuria from membranous nephropathy, drug-induced lupus and other autoimmune syndromes, myasthenia gravis, and pyridoxine (vitamin B6) deficiency that requires routine supplementation. Paradoxical worsening of neurologic symptoms during the first weeks of therapy can occur in patients with neurologic Wilson disease. Penicillamine has a boxed warning: it should never be used casually, every patient should stay under close supervision by a doctor who knows its risks, and any sign of a side effect should be reported right away. The label says deaths have occurred from aplastic anemia, agranulocytosis, low platelets, Goodpasture's syndrome (a kidney and lung disease) and myasthenia gravis. Urine tests and blood counts are done twice a week for the first month, every 2 weeks for the next 5 months, then monthly, and fever, sore throat, chills, bruising or bleeding should be reported right away. People who had aplastic anemia or agranulocytosis from penicillamine should not take it again. The label also warns about liver injury (liver tests every 3 months in the first year for Wilson disease), pemphigus (a serious blistering skin disease), a rare lung disease called obliterative bronchiolitis, and possible harm to an unborn baby.
▸How is Penicillamine taken?
Taken by mouth on an empty stomach. Adult de-coppering doses are typically 1000 to 1500 mg per day divided into 3 to 4 doses, lowered to a maintenance dose (often 750 to 1000 mg per day) once de-coppering is achieved. The label says people with Wilson disease should take 25 mg of pyridoxine (vitamin B6) a day during treatment, because penicillamine raises the need for it. Take penicillamine at least 1 hour before or 2 hours after meals, and at least 1 hour apart from other medicines, food, milk, antacids, zinc or iron.
▸Is Penicillamine FDA approved?
Yes, Penicillamine (Cuprimine) is FDA approved (1970) for the treatment of Wilson Disease.