ANTITHYROX Tablet

Carbimazole is an anti-thyroid agent. It is indicated in all conditions where reduction of thyroid function is required.

Such conditions are:

- Hyperthyroidism.

- Preparation for thyroidectomy in hyperthyroidism.

- Therapy prior to and post radio-iodine treatment.

Dosage and Administration

Adult:

The initial dose is in the range 20mg to 60mg, taken as 2-3 divided doses. The dose should be titrated against thyroid function until the patient is euthyroid in order to reduce the risk of over-treatment and resultant hypothyroidism.

Subsequent therapy may then be administered in one of two ways.

Maintenance regimen: Final dosage is usually in the range 5-15mg per day, which may be taken as a single daily dose. Therapy should be continued for at least 6 months and up to 18 months. Serial thyroid function monitoring is recommended, together with appropriate dosage modification in order to maintain a euthyroid state.

Blocking-replacement regimen: dosage is maintained at the initial level, i.e. 20-60mg per day, and supplement L-thyroxine, 50-150mg per day, is administered concomitantly, in order to prevent hypothyroidism. Therapy should be continued for at least 6 months and up to 18 months. Where a single dosage of less than 20mg is recommended, it is intended that carbimazole 5mg tablets should be taken.

Elderly:

No special dosage regimen is required, but care should be taken to observe the contraindications and warnings as it has been reported that the risk of a fatal outcome to neutrophil dyscrasias may be greater in the elderly (aged 65 or over)

Children:

The usual initial daily dose is 15mg per day adjusted according to response.

Hypersensitivity to carbimazole or other thiourea antithyroid agents.

Carbimazole should be given with the utmost caution, or not at all, if there is any degree of tracheal obstruction, as high dosages may produce thyroid enlargement and obstructive symptoms may become marked.

Adverse reactions usually occur in the first 8 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.

Blood and lymphatic system disorders

Bone marrow depression including neutropenia, eosinophilia, leucopenia, 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, 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.

Nervous system disorders

Headache

Gastrointestinal system disorders

Nausea, mild gastrointestinal disturbance.

Loss of sense of taste has been observed.

General disorders and administration site conditions

Fever, Malaise

Hepato-biliary system disorders

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

Injury, poisoning and procedural complications

Bruising

Skin and subcutaneous tissue disorders

Skin rashes, pruritus, urticaria. Hair loss has been occasionally reported.

Musculoskeletal system disorders

Isolated cases of myopathy have been reported. Patients experiencing myalgia after the intake of Carbimazole should have their creatine phosphokinase levels monitored.

Hypersensitivity and allergic reaction

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

Vascular Disorders

Bleeding.

Carbimazole may interact adversely with other medicines. Iodine or iodine excess may decrease the response to Carbimazole, requiring an increase in dosage or longer duration of therapy with antithyroid agents. Amiodarone contains 37% iodine by weight, and therefore its use significantly increases iodine intake, iodine deficiency may increase response to antithyroid agents, requiring a decrease in dosage or shorter duration of therapy.

As thyroid and metabolic status of patient decreases toward normal, response to oral anticoagulants may decrease, however, if thionamide-induced hypoprothrombinemia occurs, anticoagulant effect may be enhanced. Adjustment of oral anticoagulant dosage on the basis of prothrombin time is recommended. Serum concentrations of digoxin and digitoxin have been reported to increase as the thyroid and metabolic status of patients taking antithyroid agents decreased, reduction in dosage of any digitalis glycoside may be necessary as patients become euthyroid. Antithyroid agents may decrease thyroidal uptake of sodium iodideⅠ131, a rebound increase in uptake may occur up to 5 days after sudden withdrawal of Carbimazole.

Laboratory value alterations:

With diagnostic test results: Carbimazole may decrease thyroidal uptake of sodium iodideⅠ123 or Ⅰ131, or pertechnetate, withdrawal of Carbimazole 5 days or more before radioactive iodine uptake tests is necessary to prevent interference.

With physiology laboratory test values: ALT(SGPT) serum concentrations, Alkaline phosphatase serum concentrations, AST(SGOT) serum concentrations, Bilirubin serum concentrations, LDH serum concentrations and PT may be increased, and may indicate hepatoxicity and be associated with splenomegaly.

Pregnancy

(see the package insert about the details.)

Carbimazole should be used in pregnancy only when propylthiouracil is not suitable.

If carbamazole is used in pregnancy, the dose of carbimazole tablets must be regulated by the patient’s clinical condition. The lowest dose possible should be used, and this can often be discontinued 3-4 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.

Lactation

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

As fatal cases of agranulocytosis with carbimazole have been reported and early treatment of agranulocytosis is essential, it is important that patients should always be warned about the onset of sore throats, bruising or bleeding, mouth ulcers, fever, 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, 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.

Carbimazole tablets should be stopped temporarily at the time of administration of radio-iodine (to avoid thyroid crisis).

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

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

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

Antithyroid Agent

Carbimazole, a thionamide, is a pro-drug, which undergoes rapid and virtually complete metabolism to the active metabolite, thiamazole, also known as Methimazole. The method of action is believed to be inhibition of the organification of iodide and the coupling of iodothyronine residues, which in turn suppress the synthesis of thyroid hormones.