Penicillamine

CUPRIMINE

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Pronunciation: pen-i-SIL-a-meen

Penicillamine ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Penicillamine ballicule

What it isChelator of copper and heavy metals; Wilson disease, cystinuria and lead poisoning.

Why this oneIt is the long-established oral treatment for Wilson disease and reduces cystine stone formation.

What limits itParadoxical neurological worsening early in Wilson disease. Myelosuppression, proteinuria and drug-induced autoimmunity; pyridoxine is co-given.

Penicillamine molecular structure (skeletal formula) — Molecular structure: Penicillamine

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk4 / 4

Legacy pregnancy categoryC

Defining liabilitySerious infection, cytopenias, hepatic injury and malignancy risk require laboratory and clinical monitoring.

FDA label

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BOXED WARNING Serious, potentially fatal toxicity; use only under close, continuous physician supervision and warn patients to report toxicity promptly.

FDA dosing	Population	Start	Target	Max
Wilson's disease	adult	250 mg QD (if intolerant) up to 750 mg-1.5 g/day	0.75-1.5 g/day	2 g/day
Cystinuria	adult	250 mg QD, increase gradually	2 g/day QID	4 g/day
Cystinuria	pediatric		30 mg/kg/day divided QID
Rheumatoid arthritis	adult	125-250 mg QD	500-750 mg/day	~1.5 g/day

Titration RA: increase by 125-250 mg/day at 1-3 month intervals.

Renal Undefined

Hepatic Undefined

Doses <=500 mg/day may be given once daily; >500 mg/day must be divided.

Instructions

Take on empty stomach, >=1 h before or 2 h after meals, and >=1 h apart from any other drug, food, or milk
Supplement pyridoxine (increased requirement)
Cystinuria: drink copiously incl. ~1 pint at bedtime and once overnight; retain bedtime dose if reducing
After interrupted therapy, reintroduce cautiously at a lower dose

Available strengths

cap 250 mg
tab 250 mg

Contraindications

Pregnancy (except Wilson's disease or certain cystinuria patients)
Nursing mothers should not breastfeed during therapy
Prior penicillamine-related aplastic anemia or agranulocytosis (do not restart)
Rheumatoid arthritis patients with history/evidence of renal insufficiency

Cautions

Bone marrow depression - aplastic anemia, agranulocytosis, thrombocytopenia, leukopenia (fatalities reported)
Proteinuria/hematuria progressing to nephrotic syndrome (immune complex glomerulopathy)
Autoimmune syndromes: pemphigus, myasthenia gravis, Goodpasture's, drug-induced lupus, polymyositis
Increased pyridoxine requirement

Adverse reactions

GI upset - anorexia, nausea, vomiting, diarrhea (17%)
Taste blunting/loss (12%)
Proteinuria (6%)
Rash, generalized pruritus (5%)
Thrombocytopenia (4%)
Leukopenia (2%)

Pregnancy Pregnancy Category D.

Lactation Do not nurse during penicillamine therapy.

Cost

Penicillamine (CUPRIMINE)

Strength		#/mo	generic $/mo	CostPlus
250 mg	cap	30 qd		offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Penicillamine is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Generic entry2019

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Self-check

Penicillamine: What paradoxical early effect can occur in Wilson disease?
Neurological worsening.
Penicillamine: Which vitamin is co-given?
Pyridoxine.