Carbimazole

Carbimazole tablets should be used with caution in patients with mild-moderate hepatic insufficiency. If abnormal liver function is discovered, the treatment should be stopped. The half-life may be prolonged due to the liver disorder.

Hyperthyroidism may cause an increased clearance of beta-adrenergic blockers with a high extraction ratio. A dose reduction of beta blockers may be needed when a hyperthyroid patient becomes euthyroid.

Carbimazole may inhibit the metabolism of erythromycin, leading to reduced clearance of erythromycin.

Co-administration of prednisolone and carbimazole may result in increased clearance of prednisolone.

There is a risk of cross-allergy between carbimazole, the active metabolite thiamazole (methimazole) and propylthiouracil.

The serum levels of theophylline can increase and toxicity may develop if hyperthyroidic patients are treated with antithyroid medications without reducing the theophylline dosage.

Carbimazole crosses the placenta but, provided the mother’s dose is within the standard range and her thyroid status is monitored; there is no evidence of neonatal thyroid abnormalities. Studies have shown that the incidence of congenital malformations is greater in the children of mothers whose hyperthyroidism has remained untreated than in those who have been treated with carbimazole.

However, cases of congenital malformations have been observed following the use of carbimazole or its active metabolite methimazole during pregnancy.

A causal relationship of these malformations, especially choanal atresia and aplasia cutis congenita (congenital scalp defects), to transplacental exposure to carbimazole and methimazole cannot be excluded.

Therefore the use of carbimazole in non-pregnant women of childbearing potential should be based on individual risk/benefit assessment.

Cases of renal, skull, cardiovascular congenital defects, exomphalos, gastrointestinal malformation, umbilical malformation and duodenal atresia have also been reported. Therefore, carbimazole should be used in pregnancy only when propylthiouracil is not suitable.

If carbimazole is used in pregnancy, the dose must be regulated by the patient’s clinical condition. The lowest dose possible should be used, and this can often be discontinued three or four weeks before term, in order to reduce the risk of neonatal complications.

The blocking-replacement regimen should not be used during pregnancy since very little thyroxine crosses the placenta in the last trimester.

Carbimazole is excreted in milk and if treatment is continued during lactation the patient should not continue to breast-feed her baby.

Not relevant.

Adverse reactions usually occur in the first eight weeks of treatment. The most common minor reactions are nausea, headache, arthralgia, mild gastrointestinal disturbance, skin rashes and pruritus. These reactions are usually self-limiting and may not require withdrawal of the drug.

The undesirable effects are listed below by system organ class and the following frequency convention: Not known (cannot be estimated from the available data).

Blood and lymphatic system disorders: Bone marrow depression including neutropenia, eosinophilia, leucopenia and agranulocytosis has been reported. Fatalities with carbimazole-induced agranulocytosis have been reported.

Rare cases of pancytopenia/aplastic anaemia and isolated thrombocytopenia have also been reported. Additionally, very rare cases of haemolytic anaemia have been reported.

Patients should always be warned about the onset of sore throats, bruising or bleeding, mouth ulcers, fever and malaise and should be instructed to stop the drug and to seek medical advice immediately. In such patients, white blood cell counts should be performed immediately, particularly where there is any clinical evidence of infection.

Generalised lymphadenopathy.

Immune system disorders: Angioedema and multi-system hypersensitivity reactions such as cutaneous vasculitis, liver, lung and renal effects occur.

Endocrine disorders: Insulin autoimmune syndrome (with pronounced decline in blood glucose level).

Nervous system disorders: Headache, neuritis, polyneuropathy.

Vascular disorders: Bleeding.

Gastrointestinal disorders: Nausea, mild gastrointestinal disturbance. Loss of sense of taste has been observed. Acute salivary gland swelling. Acute pancreatitis.

Hepatobiliary disorders: Hepatic disorders, including abnormal liver function tests, hepatitis, cholestatic hepatitis, cholestatic jaundice and most commonly jaundice, have been reported; in these cases carbimazole should be withdrawn.

Skin and subcutaneous tissue disorders: Skin rashes, pruritus, urticaria. Hair loss has been occasionally reported.

Severe cutaneous hypersensitivity reactions have been reported in both adult and paediatric patients, including Stevens-Johnson syndrome (very rare including isolated reports: severe forms, including generalised dermatitis, have only been described in isolated cases).

Musculoskeletal and connective tissue disorders: Isolated cases of myopathy have been reported. Patients experiencing myalgia after the intake of carbimazole should have their creatine phosphokinase levels monitored

General disorders and administration site conditions: Fever, malaise.

Injury, poisoning and procedural complications: Bruising.

Paediatric population

Frequency, type and severity of adverse reactions in children appear to be comparable with those in adults.