Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal. Therefore, it is mandatory that patients receiving penicillamine therapy remain under close medical supervision throughout the period of drug administration. (See Precautions.)
The most common side-effects are thrombocytopenia and proteinuria.
Thrombocytopenia occurs commonly. It may occur any time during treatment and is usually reversible. Proteinuria occurs in up to 30% of patients and is partially dose-related (see Precautions).
Adverse reactions are ranked under 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), including isolated reports. Not known (where no valid estimate of the incidence has been derived).
Blood and lymphatic system disorders:
Not known: Neutropenia, agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopoenia, sideroblastic anemia, thrombotic thrombocytopenic purpura, red cell aplasia, monocytosis, leukocytosis, eosinophilia, thrombocytosis.
Immune system disorders:
Rare: Allergic reactions including hypersensitivity.
Not known: Drug eruptions which may be accompanied by fever, arthralgia, or lymphadenopathy have occurred.
Metabolism and nutrition disorders:
Not known: Anorexia.
Not known: Confusion.
Nervous system disorders:
Loss of taste, headache, dizziness, tinnitus, optic neuritis and peripheral sensory and motor neuropathies (including polyradiculoneuropathy, i.e. Guillain-Barré syndrome), muscular weakness (with or without peripheral neuropathies), visual and psychic disturbances; mental disorders; agitation, anxiety.
Not known: Abnormal vision.
Ear and labyrinth disorders:
Not known: Pulmonary haemorrhage.
Respiratory, thoracic and mediastinal disorders:
Not known: Dyspnoea, pleural effusion, alveolitis, pulmonary fibrosis, bronchiolitis, pneumonitis.
Rare: Mouth ulceration, stomatitis, glossitis.
Not known: Pancreatitis, nausea, vomiting, diarrhoea, epigastric pain, blunting, diminution cheilosis, gingivostomatitis.
Not known: Cholestatic jaundice.
Skin and subcutaneous tissue disorders:
Rare: Alopecia, pseudoxanthoma elasticum, elastosis perforans, skin laxity.
Not known: Rash, urticarial reactions, epidermolysis bullosa, penicillamine dermopathy, dermatomyositis, pemphigus, Stevens-Johnson syndrome, pruritus, exfoliative dermatitis.
Musculoskeletal, connective tissue and bone disorders:
Not known: Drug induced lupus erythamatosus, myasthenia gravis, polymyositis, rheumatoid arthritis, dystonia.
Renal and urinary disorders:
Very common: Proteinuria.
Not known: Nephrotic syndrome, glomerulonephritis, Goodpasture's syndrome.
Reproductive system and breast disorders:
Rare: Breast enlargement.
General disorders and administration site conditions:
Not known: Fever.
Note: Deaths from agranulocytosis and aplastic anaemia have occurred Nausea, anorexia, fever, rash, vomiting, diarrhoea, headaches, dizziness, abnormal vision and confusion may occur early in therapy especially when full doses are given from the start.
Penicillamine may cause allergic reactions such as urticaria and erythema accompanied by hyperpyrexia. Transient rashes and fever may occur early in therapy; if persistent, antihistamines or temporary withdrawal of treatment with or without a short course of steroids may be necessary. Penicillamine may be re-introduced at a lower dosage. If steroids are given, penicillamine should be reintroduced before steroid withdrawal. Urticarial reactions have been reported (see Precautions).
Reversible loss of taste may occur (See Precautions).
Haematuria may occur rarely, (see Precautions).
A late rash, described as "epidermolysis bullosa" and "penicillamine dermopathy" may occur, after several months or years of therapy and may necessitate discontinuation of treatment.
Breast enlargement has been reported as a rare complication of penicillamine therapy in both women and men (see Precautions).
Neutropenia may occur at any time during treatment and is usually reversible.
Others: Adverse reactions that have been reported rarely include thrombophlebitis; lichen planus; polymyositis; mammary hyperplasia; toxic epidermal necrolysis; anetoderma (cutaneous macular atrophy), thyroiditis. Vasculitis, including fatal renal vasculitis, has also been reported.
Increased skin friability, excessive wrinkling of skin, and development of small white papules at venipuncture and surgical sites have been reported; yellow nail syndrome. Iron deficiency may occur in menstruating women.
The development of septic arthritis in patients with rheumatoid arthritis has been linked to the use of DMARDS, including penicillamine.
Some patients may develop a migratory polyarthralgia, often with objective synovitis.
Deterioration of the neurological symptoms of Wilson's disease (dystonia, rigidity, tremor, dysarthria) have been reported following introduction of penicillamine in patients treated for this condition. This may be a consequence of mobilisation and redistribution of copper from the liver to the brain.