PENICILLAMINE

Posology a) Rheumatoid Arthritis Adults A daily dose of 125 - 250 mg per day is recommended for the first month, increasing by the same amount every four to twelve weeks until remission occurs. The minimum maintenance dose to achieve suppression of symptoms should be used and treatment should be discontinued if no improvement occurs within 12 months.

Improvement may not occur for some months. The usual maintenance dose is 500 mg to 750 mg daily. However, up to 1500 mg daily may be required. Reduction in maintenance dosage by 125 mg to 250 mg every 12 weeks may be attempted after a period of 6 months continuous remission.

Elderly The initial dose should not exceed 125 mg daily for the first month, increasing by similar increments every four to twelve weeks until the minimum maintenance dose to supress symptoms is reached. 4). Paediatric population The usual maintenance dose is 15 to 20 mg/kg/day.

5 to 5 mg/kg/day) and increased every four weeks over a period of three to six months. Patients with Renal impairment Penicillamine therapy should be initiated at a low dose with intervals between dose increase of at least twelve weeks.

Fortnightly monitoring for toxicity is mandatory throughout treatment for rheumatoid arthritis. b) Wilsons Disease Patients must be maintained in negative copper balance and the minimum dose of Penicillamine required to achieve this should be given.

Adults 1500 mg to 2000 mg daily in divided doses. Dose reduction may be attempted when remission occurs, decreasing to 750 mg to 1000 mg per day. It is advisable that a dose of 2000 mg per day should not be continued for more than 12 months.

Elderly 20 mg/kg/day in divided doses adjusting the dose minimal level necessary to control disease. Paediatric population 20 mg/kg/day in two or three divided doses, given 1 hour before meals. For older children (>12 years) the usual maintenance dose is 750 mg to 1000 mg daily.

Patients with Renal impairment Extra precautions should be taken to monitor for adverse effects in patients with Wilson’s disease and renal insufficiency. c) Cystinuria The lowest effective dose should be used and this is determined by quantitative amino acid chromatography of urine.

(i) Dissolution of cystine stones Adults 1000 mg to 3000 mg daily, in divided doses. Cystine levels in urine should not exceed 200 mg/litre. (ii) Prevention of cystine stones Adults 500 mg to 1000 mg at bedtime. Maintenance of adequate fluid intake (not less than 3 litres/day is important).

The most common of all side-effects are thrombocytopenia and proteinuria. Thrombocytopenia occurs commonly. The reaction may occur at any time during treatment and is usually reversible. 4). Adverse reactions are ranked under the heading of frequency, the most frequent first, using the following convention: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000) and not known (frequency cannot be estimated from the available data).

The incidence and severity of some of the adverse reactions, noted below, varies according to the dosage and nature of the disease under treatment.

Blood and lymphatic system disorders Common:

Not known: Thrombocytopenia. Neutropenia 8, agranulocytosis 1, aplastic anaemia 1, haemolytic anaemia, leucopenia.

Immune system disorders Rare:

Allergic reactions including hypersensitivity.

Metabolism and nutrition disorders Not known:

Anorexia 2.

Nervous system disorders Not known:

Loss of taste 4.

Vascular disorders Not known:

Pulmonary haemorrhage, vasculitis.

Respiratory, thoracic and mediastinal disorders Not known:

Inflammatory conditions of the respiratory tract such as bronchiolitis, pneumonitis, yellow nail syndrome.

Gastrointestinal disorders Rare:

Mouth ulceration, stomatitis.

Full blood and platelet counts should be performed and renal function should be assessed prior to treatment with penicillamine. 8). Urinalysis should be carried out weekly at first, and following each increase in dose, then monthly, although longer intervals may be adequate for cystinuria and Wilson’s disease.

Increasing or persistent proteinuria may necessitate withdrawal of therapy. During the first eight weeks of therapy full blood counts should be carried out weekly or fortnightly and also in the week after any increase in dose, otherwise monthly thereafter.

In cystinuria or Wilson’s disease, longer intervals may be adequate. If platelets fall below 120,000 per mm3 or white blood cells below 2,500 per mm3, or if three consecutive falls are noted within the normal range, withdrawal of treatment should be considered.

When counts return to normal, treatment may be restarted at a reduced dosage, but should be permanently withdrawn on recurrence of leucopenia or thrombocytopenia. Penicillamine may potentiate the bone marrow suppression caused by clozapine.

2). Especially careful monitoring is necessary in older people since increased toxicity has been observed in this patient population regardless of renal function. 5). Penicillamine should be used with caution in patients who have had adverse reactions to gold.

Concomitant or previous treatment with gold may increase the risk of side effects with penicillamine treatment. 5). Penicillamine should not be used in patients who are receiving concurrently antimalarial drugs such as hydroxychloroquine phosphate, chloroquine.

5). 5). 8). Reversible loss of taste may occur. 8). 8). A late rash, described as acquired epidermolysis bullosa and penicillamine dermopathy, may occur after several months or years of therapy. 8). 8). Danazol has been used successfully to treat breast enlargement which does not regress on drug discontinuation.

1. Agranulocytosis, aplastic anaemia or severe thrombocytopenia due to penicillamine. Lupus erythematosus. Moderate or severe renal impairment.