PROPYLTHIOURACIL Tablet Ref.[8060] Active ingredients: Propylthiouracil

Because of the risk of agranulocytosis it is advised that patients should be warned to report to their doctor in the event of a sore throat, fever, mouth ulcers, bruising, malaise, non-specific illness or other symptoms of infection immediately. A full blood count should be performed and treatment should be discontinued immediately if there is clinical or laboratory evidence of neutropenia.

The prothrombin time should be monitored during therapy, especially prior to surgery, because propylthiouracil may cause thrombocytopenia.

Some cases of severe hepatic reactions, both in adults and children, including fatal cases and cases requiring a liver transplant have been reported with propylthiouracil. Time to onset has varied but in a majority of cases the liver reaction occurred within 6 months. If significant hepatic enzyme abnormalities develop during treatment with propylthiouracil the drug should be discontinued immediately (see 4.8).

Propylthiouracil should be used with caution in patients with renal impairment or hepatic disease (see 4.2 Posology and Method of Administration). Patients should be advised of the symptoms of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc) and told to report them immediately. The occurrence of hepatic necrosis may have fatal consequences (see section 4.8, Undesirable effects).

Drug induced changes in thyroid status may affect the dosage requirements for theophylline, digoxin or beta-blockers. The doses of theophylline, digoxin or beta-blockers may need to be reduced as thyroid function returns to normal.

Pre-treatment with propylthiouracil may reduce the effectiveness of radio-iodine (¹³¹I) therapy for hyperthyroidism. This is supported by four studies one of which, a randomised study in 80 patients, showed an approximate halving of cure rate one year after ¹³¹I therapy in patients pre-treated with propylthiouracil.

Women of childbearing potential

Women of childbearing potential should be informed about the potential risks of propylthiouracil use during pregnancy.

Pregnancy

Hyperthyroidism in pregnant women should be adequately treated to prevent serious maternal and foetal complications.

Propylthiouracil is able to cross the human placenta and in high doses may cause foetal goitre and hypothyroidism.

Animal studies are insufficient with respect to reproductive toxicity. Epidemiological studies provide conflicting results regarding the risk of congenital malformations.

Individual benefit/risk assessment is necessary before treatment with propylthiouracil during pregnancy. Propylthiouracil should be administered during pregnancy at the lowest effective dose without additional administration of thyroid hormones. If propylthiouracil is used during pregnancy, close maternal, foetal and neonatal monitoring is recommended.

Lactation

Propylthiouracil also transfers to breast milk but this does not preclude breast-feeding. Neonatal development and infant thyroid function should be closely monitored. The lowest effective dose should be used.

None known.

Blood and lymphatic system: Reversible leucopenia. Rarely, agranulocytosis, thrombocytopenia, leucopenia, aplastic anaemia, pancytopenia. A rare complication of therapy is a tendency to haemorrhage associated with hypoprothrombinaemia which may be controlled by the administration of phytomenadione.

Ear and labyrinth disorders: Rarely, hearing impairment may occur with propylthiouracil. The impairment usually becomes less marked after withdrawal of the drug.

Gastrointestinal: Nausea, gastrointestinal disturbances, taste perversion. Rarely vomiting.

General: Fever.

Hepatobiliary: Jaundice (usually cholestatic), hepatic necrosis (sometimes with fatal consequences), encephalopathy. More commonly, asymptomatic liver function test abnormalities (increased serum bilirubin, Alanine transaminase and/or alkaline phosphatase concentrations), which are reversible on dose reduction or discontinuation of treatment, may occur with propylthiouracil.

Frequency unknown: Hepatitis, hepatic failure.

Immune system: Interstitial pneumonitis, alveolar haemorrhage, lymphadenopathy, arthritis, nephritis, vasculitis and lupus erythematosus-like syndromes have occurred in some patients taking thiourea antithyroid drugs. An immune mechanism has been proposed. There have also been rare reports of acute glomerulonephritis. Hypersensitivity reactions may also be associated with the development of antineutrophil cytoplasmic antibodies (ANCA).

Musculoskeletal: Myopathy, arthralgia,

Nervous system: Headache.

Skin: Mild papular skin rashes, pruritus, urticaria, alopecia, cutaneous vasculitis.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

None known.