|Both the frequency and severity of many side-effects and adverse reactions to penicillamine are found to be dose-related and vary according to the nature of the disease under treatment, hence the importance of initiating therapy at low doses and gradually increasing the quantity of drug given to optimum level.The most common side-effects are thrombocytopenia and proteinuria. Thrombocytopenia occurs commonly. It may occur any time during treatment and is usually reversible (see Section 4.4 Special Warnings and Precautions for use). Proteinuria occurs in up to 30% of patients and is partially dose-related (see Section 4.4 Special Warnings and Precautions for use).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:Common: ThrombocytopeniaNot known: Neutropenia8, agranulocytosis1, aplastic anaemia1, haemolytic anaemia, leucopoenia
Immune system disorders:Rare: Allergic reactions including hypersensitivity
Metabolism and nutrition disorders:Not known: Anorexia2
Psychiatric disorders:Not known: Confusion2
Nervous system disorders:Not known: Loss of taste4, headache2, dizziness2
Eye disorders:Not known: Abnormal vision2
Ear and labyrinth disorders:Rare: Deafness
Vascular disorders:Not known: Pulmonary haemorrhage
Respiratory, thoracic and mediastinal disorders:Not known: Dyspnoea, pleural effusion, alveolitis, pulmonary fibrosis, bronchiolitis, pneumonitis
Gastrointestinal disorders:Rare: Mouth ulceration, stomatitis, glossitisNot known: Pancreatitis, nausea2, vomiting2, diarrhoea2
Hepatobiliary disorders:Not known: Cholestatic jaundice
Skin and subcutaneous tissue disorders:Rare: Alopecia, pseudoxanthoma elasticum, elastosis perforans, skin laxityNot known: Rash2, urticarial reactions3, epidermolysis bullosa6, penicillamine dermopathy6, dermatomyositis, pemphigus, Stevens-Johnson syndrome.
Musculoskeletal, connective tissue and bone disorders:Not known: Drug induced lupus erythamatosus, myasthenia gravis, polymyositis, rheumatoid arthritisRenal and urinary disorders:Very common: Proteinuria Rare: Haematuria5Not known: Nephrotic syndrome, glomerulonephritis, Goodpasture's syndrome
Reproductive system and breast disorders:Rare: Breast enlargement7
General disorders and administration site conditions:Not known: Fever21Deaths from agranulocytosis and aplastic anaemia have occurred2Nausea, anorexia, fever, rash, vomiting, diarrhoea, headaches, dizziness, abnormal vision and confusion may occur early in therapy especially when full doses are given from the start3Penicillamine 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 Section 4.4, Special Warnings and Precautions for Use).4Reversible loss of taste may occur (See section 4.4 Special Warnings and Precautions for Use).5Haematuria may occur rarely, (see section 4.4 special warnings and precautions for use).6A late rash, described as "epidermolysis bullosa" and "penicillamine dermopathy" may occur, after several months or years of therapy and may necessitate discontinuation of treatment.7Breast enlargement has been reported as a rare complication of penicillamine therapy in both women and men (see Section 4.4, Special Warnings and Precautions for Use).8 Neutropenia may occur at any time during treatment and is usually reversibleIron 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 (see section 4.4 Special warnings and Precautions for use)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 (see Section 4.4 Special warnings and Precautions for use).