Drug information of Penicillamine

Penicillamine

Drug group:

Penicillamine is a chelating (KEE-late-ing) agent that binds to excess copper and removes it from the blood stream. In certain conditions, excess copper can build up in the blood stream, leading to tissue damage throughout the body.
Penicillamine is used to remove excess copper in people with an inherited condition called Wilson's disease. Penicillamine is also used to reduce urine levels of an amino acid called cystine, which can cause stones to form in the kidneys and bladder in people with an inherited condition called cystinuria.
Penicillamine is also used to treat severe rheumatoid arthritis after other medicines have been tried without success. Penicillamine is not approved to treat juvenile rheumatoid arthritis.

Mechanism of effect

Chelates with lead, copper, mercury and other heavy metals to form stable, soluble complexes that are excreted in urine; depresses circulating IgM rheumatoid factor, depresses T-cell but not B-cell activity; combines with cystine to form a compound which is more soluble, thus cystine calculi are prevented

Pharmacodynamic

Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy.

Pharmacokinetics

Absorption: Rapid but incomplete; 40% to 70%.Metabolism: Hepatic (small amounts metabolized to s-methyl-d-penicillamine).
Excretion: Urine (primarily as disulfides). Onset of Action: Rheumatoid arthritis: 2 to 3 months; Wilson disease: 1 to 3 months.
Time to Peak: Serum: 1 to 3 hours.
Half-Life Elimination: 1.7 to 7 hours (Roberts 2008). Protein Binding: >80% to albumin and ceruloplasmin

Dosage

Usual Adult Dose for Wilson's Disease
Initial dose: 0.75 to 1.5 grams/day that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about three months.
Maintenance dose: The optimal maintenance dosage can be determined by measurement of urinary copper excretion and determination of free copper in the serum. It is seldom necessary to exceed a dosage of 2 g/day.
Usual Adult Dose for Cystinuria
Usual adult dose: 2 grams/day with a range of 1 to 4 grams/day. The total daily dose should be divided into four doses. If four equal doses are not feasible, give the larger portion at bedtime.
Usual Adult Dose for Rheumatoid Arthritis
Initial dose: Begin with a single daily dose of 125 mg or 250 mg, which is thereafter increased at one to three month intervals, by 125 mg or 250 mg/day, as patient response and tolerance indicate.
Maintenance dose: The maintenance dosage must be individualized, and may require adjustment during the course of treatment. Many patients respond satisfactorily to a dosage within the 500 to 750 mg/day range.
Usual Pediatric Dose for Wilson's Disease
Initial dose: 0.75 to 1.5 grams/day that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about three months.
Maintenance dose: The optimal maintenance dosage can be determined by measurement of urinary copper excretion and determination of free copper in the serum. It is seldom necessary to exceed a dosage of 2 g/day.
Usual Pediatric Dose for Cystinuria
Usual pediatric dose: 30 mg/kg/day. The total daily dose should be divided into four doses. If four equal doses are not feasible, give the larger portion at bedtime.
Usual Pediatric Dose for Rheumatoid Arthritis
Initial dose: Begin with a single daily dose of 125 mg or 250 mg, which is thereafter increased at one to three month intervals, by 125 mg or 250 mg/day, as patient response and tolerance indicate.
Maintenance dose: The maintenance dosage must be individualized, and may require adjustment during the course of treatment. Many patients respond satisfactorily to a dosage within the 500 to 750 mg/day range.

Drug contraindications

Pregnancy , Renal dysfunction , Lactation

Alerts

1- Penicillamine has been associated with fatalities due to agranulocytosis, aplastic anemia, and thrombocytopenia. Discontinue therapy for WBC <3500/mm3. Withhold therapy at least temporarily for platelet counts <100,000/mm3 or a progressive fall in WBC or platelets in 3 successive determinations, even though values may remain within the normal range. Monitor for signs/symptoms of leukopenia and thrombocytopenia.
2- Penicillamine has been associated with myasthenic syndrome, and in some cases, progression to myasthenia gravis. Resolution of symptoms has been observed in most cases following discontinuation of therapy.
3- Use with caution in the elderly; may be more susceptible to skin rash and/or taste alterations.
4- Drug fever: Drug fever may be observed, usually 2-3 weeks after therapy initiation. Discontinue use in patients with rheumatoid arthritis, Wilson’s disease, or cystinuria who develop a marked febrile response. Consider alternative therapy for patients with rheumatoid arthritis due to high incidence of fever reoccurrence with penicillamine rechallenge. May resume therapy at a reduced dose in Wilson’s disease or cystinuria upon resolution of fever; dose should then be gradually titrated to effective dose.
5- Penicillamine has been associated with fatalities due to Goodpasture's syndrome. Discontinue therapy immediately in patients with abnormal urinary findings in association with hemoptysis and pulmonary infiltrates on chest x-ray.
6- Pemphigus: May occur early or late in therapy; discontinue use with suspicion of pemphigus. May treat with high-dose corticosteroids alone, or in conjunction with an immunosuppressant; treatment duration can range from weeks to >1 year.
7- Proteinuria/hematuria: Proteinuria or hematuria may develop; monitor for membranous glomerulopathy which can lead to nephrotic syndrome. In rheumatoid arthritis patients, discontinue if gross hematuria or persistent microscopic hematuria develop and discontinue therapy or reduce dose for proteinuria that is either >1 g/day or progressively increasing. Dose reduction may lead to resolution of proteinuria.

Points of recommendation

Drink liberally.
• Food reduces availability, take on an empty stomach.

Pregnancy level

D

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