Neutropenia and agranulocytosis

Doctors are reminded of the importance of recognising bone marrow suppression induced by carbimazole and propylthiouracil, and the need to stop treatment promptly.

1. Patients should be asked to report symptoms and signs suggestive of infection, especially sore throat, mouth ulcers and high fever.
2. A white blood cell count should be performed if there is any clinical evidence of infection
3. Carbimazole and propylthiouracil should be stopped promptly pending results of clinical or laboratory evidence of neutropenia

Carbimazole

• Tablets 5mg, 20mg (£1.81 = 100 x 5mg)

Indications

• Hyperthyroidism

Dose

• 15 to 40mg daily; higher doses should be prescribed under specialist supervision only. This dose is continued until the patient becomes euthyroid, usually after 4 to 8 weeks and the dose is then gradually reduced to a maintenance dose of 5 to 15mg. Therapy is usually given for 12 to 18 months

Notes

1. MHRA Drug Safety Update (February 2019): Carbimazole: increased risk of congenital malformations; strengthened advice on contraception
   1. Carbimazole is associated with an increased risk of congenital malformations when used during pregnancy, particularly in the first trimester of pregnancy and at high doses (15 mg or more of carbimazole daily)
   2. Women of childbearing potential should use effective contraception during treatment with carbimazole
   3. Carbimazole should only be considered in pregnancy after a thorough individual assessment of benefits and risks of treatment, and only at the lowest effective dose without additional administration of thyroid hormones; close maternal, foetal, and neonatal monitoring is recommende
2. See resources for: contraception for drugs with teratogenic potential, and prescribing in pregnancy and lactatio
3. MHRA Drug Safety Update (February 2019): Carbimazole: risk of acute pancreatitis
   1. Cases of acute pancreatitis have been reported very infrequently during treatment with carbimazole
   2. If acute pancreatitis occurs, stop carbimazole treatment immediately
   3. Do not use carbimazole in patients with a history of acute pancreatitis in association with previous treatment
   4. Re-exposure may result in life-threatening acute pancreatitis with a decreased time to onset

Propylthiouracil

• Tablets 50mg (£5.47 = 56 tablets)

Indications

• Hyperthyroidism

Dose

• Propylthiouracil should only be used as second-line therapy due to rare reports of fulminant hepatic toxicity. An exception is early pregnancy when it is first-line treatment, because carbimazole use in early pregnancy may be associated with foetal congenital abnormalities
• 200 to 400mg daily in divided doses in adults and this dose is maintained until the patient becomes euthyroid; the dose may then be gradually reduced to a maintenance dose of 50 to 150mg daily in divided doses

Notes:

1. Patients receiving propylthiouracil should be told how to recognise signs of liver disorder and advised to seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, jaundice, dark urine, or pruritus develop.

Aqueous iodine oral solution

• Solution, also known as Lugol's iodine

Sodium perchlorate

• Liquid 300mg in 1ml (approximately 20mg per drop) (unlicensed preparation)