PROPYLTHIOURACIL

Posology Adults:

Management of Hyperthyroidism The initial dose of propylthiouracil is between 300mg and 600mg given as a single daily dose. This dose should be maintained until the patient becomes euthyroid. The dose should then be reduced gradually to a maintenance dose of between 50mg and 150mg, taken as a single daily dose.

Daily doses can be divided if preferred. Preparation for Surgery As for management of hyperthyroidism, until the patient becomes euthyroid. Adjunct to Radioactive Iodine Therapy As for management of hyperthyroidism, for several weeks prior to radio- iodine treatment.

Withdraw propylthiouracil 2 to 4 days before irradiation. The dosage of radio-iodine may need to be adjusted because propylthiouracil may have a radioprotective effect. Management of Thyrotoxic Crisis 200mg every 4 to 6 hours for the first 24 hours, decrease the dose as the crisis subsides.

Elderly The adult dose should apply, but caution is advised in the presence of renal or hepatic impairment, where a dosage reduction may be justified.

Children:

Juvenile Hyperthyroidism Children aged 6 - 10 years: Initial dose of 50-150mg daily.

Children over 10 years:

Initial dose of 150-300mg (or 150mg/m2) daily. Maintenance dose is determined by the patient’s response. Treatment of Hyperthyroidism in Neonates: 5-10mg/kg daily. No other specific children’s doses are known. Method of administration Propylthiouracil is administered by the oral route.

Minor adverse effects of propylthiouracil include: rash, urticaria, pruritus, abnormal hair loss, skin pigmentation, oedema, nausea, vomiting, epigastric distress, loss of taste, arthralgia, myalgia, paresthesia and headache. Leucopenia is a common adverse effect, but it is usually mild and reversible.

Agranulocytosis is the most serious adverse effect of propylthiouracil, but the incidence is very low. It tends to occur within the first two months of therapy and patients over the age of 40 years and receiving larger doses are at greater risk.

Frequency unknown:

Hepatitis, Hepatic Failure Other severe, but infrequent adverse events include: aplastic anaemia; drug fever; lupus-like syndrome; severe hepatic reactions (including encephalopathy, fulminant hepatic necrosis and death); periarteritis; hypoprothrombinaemia; thrombocytopenia and bleeding.

Nephritis, interstitial pneumonitis, cutaneous and systemic vasculitis and polymyositis have also been reported. Hypersensitivity reactions may be associated with the development of anti-neutrophil cytoplasmic antibodies (ANCA). Propylthiouracil-induced hepatoxicity is rare and usually manifests as hepatocellular hepatitis with or without jaundice.

Cholestatic jaundice has also occurred. Adverse liver effects are generally reversible on cessation of propylthiouracil. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Patients should be made aware that the development of certain adverse effects (fever, mouth ulcers, rashes, sore throat) may be an indication of agranulocytosis, a serious reaction to the drug, and they should contact their doctor immediately as treatment should be stopped.

A full blood count should be performed if there is clinical evidence of infection. Likewise propylthiouracil should be used with extreme caution in patients receiving other drugs known to cause agranulocytosis. Use propylthiouracil with caution in patients more than 40 years old.

Decrease the dose of propylthiouracil in renal failure. If the glomerular filtration rate is 10-50ml/min, decrease dose by 25%. If the GFR is <10ml/min decrease dose by 50%. Propylthiouracil may cause hypothrombinaemia and bleeding so prothrombin time should be monitored during therapy, especially prior to surgery.

Discontinue propylthiouracil if clinically important evidence of abnormal liver function occurs. Prolonged therapy and/or excessive doses of propylthiouracil may cause hypothyroidism so thyroid function should be monitored regularly.

Another serious side effect is systemic vasculitis which can occur anytime and up to several years after initiation of treatment with propylthiouracil. Risk of systemic vasculitis may increase with prolonged use. Renal involvement is most common but skin, lung and musculoskeletal systems may also be involved.

In severe cases death can occur. Propylthiouracil should be discontinued promptly and treatment initiated as required. 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. 8). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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