Amdipharm Limited

NeoMercazole 5 mg Tablets

¹Each NeoMercazole 5 mg Tablets contains carbimazole 5 mg.

Each tablet contains Lactose monohydrate 30.0 mg and Sucrose 139.39 mg

For full list of excipients, see section 6.1

Tablet.

Pink, circular biconvex tablet, imprinted with 'Neo 5' on the obverse and plain on the reverse.

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

1. Hyperthyroidism.

2. Preparation for thyroidectomy in hyperthyroidism.

3. ²Therapy prior to and post radio-iodine treatment.

NeoMercazole should only be administered if hyperthyroidism has been confirmed by laboratory tests.

Adults

The initial dose is in the range 20 – 60 mg and 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 – 15 mg per day, which may be taken as a single daily dose. Therapy should be continued for at least six, and up to eighteen months.

Serial thyroid function 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 – 60 mg per day, and supplemental l-thyroxine, 50 – 150 mcg per day, is administered concomitantly, in order to prevent hypothyroidism. Therapy should be continued for at least six months, and up to eighteen months.

Where a single dosage of less than 20 mg is recommended, it is intended that NeoMercazole 5 mg Tablets should be taken.

Elderly

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

Children

The usual initial daily dose is 15 mg per day.

NeoMercazole is contraindicated in patients with:

• Hypersensitivity to carbimazole or to any of the excipients

• Serious pre-existing haematological conditions

• Severe hepatic insufficiency

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, 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.

Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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.

Little is known about interactions.

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.

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 to whom treatment with carbimazole has been given.

However, very rare 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, 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 of NeoMercazole 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.

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

No studies on the effects on the ability to drive and use machines have been performed.

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.

Blood and lymphatic system disorders

Bone marrow depression including neutropenia, eosinophilia and agranulocytosis have been reported. Fatalities with carbimazole induced agranulocytosis have been reported. Rare cases of purpura, anaemia, pancytopenia/aplastic anaemia, neutropenia, leucopenia 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, blood cell counts should be performed, particularly where there is any clinical evidence of infection.

Nervous system disorders

Headache.

Gastro-intestinal system disorders

Nausea, mild gastric distress, 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 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 NeoMercazole 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 can occur.

Vascular Disorders

Bleeding.

No symptoms are likely from a single large dose, and so no specific treatment is indicated.

Carbimazole is a thyroid reducing agent.

Carbimazole is rapidly metabolised to methimazole. The mean peak plasma concentration of methimazole is reported to occur one hour after a single dose of carbimazole. The apparent plasma half-life of methimazole is reported as 6.4 hours.

Not relevant.

Lactose monohydrate

Starch maize

Gelatin

Magnesium stearate

Sucrose

Acacia

Talc

Red Iron oxide (E172)

Not applicable.

³ 3 years

Do not store above 25°C. Store in the original container.

NeoMercazole tablets are available in HDPE bottles with a low density polyethylene tamper evident snap-fit closure. Each bottle contains 100 tablets.

No special requirements.

Amdipharm Limited

Temple Chambers

3 Burlington Road

Dublin 4

Ireland

PA 1142/2/1

Date of first authorisation: 13 March 1995

Date of last renewal: 13 March 2010

May 2011

¹ PA 1142/2/1 – CRN 2078794; 6/05/2011

² PA 1142/2/1-2046497-2046504; 11/08/2008

³ PA 1142/2/1- 2055337;04/09/2008