NEOMERCAZOLE Tablet Ref.[49851] Active ingredients: Carbimazole

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

Rare cases of purpura, anaemia, 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.

Following the onset of any signs and symptoms of hepatic disorder (pain in the upper abdomen, anorexia, general pruritus) in patients, the drug should be stopped and liver function tests performed immediately.

Early withdrawal of the drug will increase the chance of complete recovery.

NeoMercazole 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 liver disorder.

Patients unable to comply with the instructions for use or who cannot be monitored regularly should not be treated with NeoMercazole.

Regular full blood count checks should be carried out in patients who may be confused or have a poor memory.

NeoMercazole should be stopped temporarily at the time of administration of radio-iodine, to avoid thyroid crisis.

Precaution should be taken in patients with intrathoracic goitre, which may worsen during initial treatment with NeoMercazole. Tracheal obstruction may occur due to intrathoracic goitre.

The use of carbimazole in non-pregnant women of childbearing potential should be based on individual risk/benefit assessment (see section 4.6).

There is risk of cross-allergy between carbimazole, thiamazole and propylthiouracil.

There have been post-marketing reports of acute pancreatitis in patients receiving carbimazole or its active metabolite thiamazole. In case of acute pancreatitis, carbimazole should be discontinued immediately. Carbimazole must not be given to patients with a history of acute pancreatitis after administration of carbimazole or its active metabolite thiamazole. Re-exposure may result in recurrence of acute pancreatitis, with decreased time to onset.

Women of childbearing potential and pregnancy

Women of childbearing potential have to use effective contraceptive measures during treatment. The use of carbimazole in pregnant women must be based on the individual benefit/risk assessment. If carbimazole is used during pregnancy, the lowest effective dose without additional administration of thyroid hormones should be administered. Close maternal, foetal and neonatal monitoring is warranted (see section 4.6).

NeoMercazole contains lactose

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

NeoMercazole contains sucrose

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Little is known about interactions.

Interaction studies have not been performed in paediatric patients.

Particular care is required in case of concurrent administration of medication capable of inducing agranulocytosis.

Since carbimazole is a vitamin K antagonist, the effect of anticoagulants could be intensified. Additional monitoring of PT/INR should be considered, especially before surgical procedures.

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

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

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

Serum digitalis (digoxin) levels may be increased when hyperthyroid patients on a stable digitalis glycoside (digoxin) regimen become euthyroid; a reduced dosage of digitalis glycosides(digoxin) may be needed.

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.

Women of childbearing potential Women of childbearing potential have to use effective contraceptive measures during treatment (see section 4.4). Pregnancy 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 (thiamazole) 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 (see section 4.4).

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 NeoMercazole 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 to 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.

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

Carbimazole is able to cross the human placenta.

Based on human experience from epidemiological studies and spontaneous reporting, carbimazole is suspected to cause congenital malformations when administered during pregnancy, particularly in the first trimester of pregnancy and at high doses.

Reported malformations include aplasia cutis congenita, craniofacial malformations (choanal atresia; facial dysmorphism), exomphalos, oesophageal atresia, omphalo-mesenteric duct anomaly, and ventricular septal defect.

Carbimazole must only be administered during pregnancy after a strict individual benefit/risk assessment and only at the lowest effective dose without additional administration of thyroid hormones. If carbimazole is used during pregnancy, close maternal, foetal and neonatal monitoring is recommended (see section 4.4).

Breast-feeding

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

Fertility

No fertility data available.

Not relevant.

Adverse reactions usually occur in the first eight weeks of treatment. The most frequently occurring reactions are nausea, headache, arthralgia, mild gastric distress, 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: Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

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, blood cell counts should be performed, particularly where there is any clinical evidence of infection.

^* in these cases, carbimazole should be withdrawn.
^** very rare including isolated reports: severe forms, including generalised dermatitis, have only been described in isolated cases

Paediatric population

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

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 HPRA Pharmacovigilance, Website: www.hpra.ie

Not applicable.