1. Name Of The Medicinal Product
Carbimazole 5mg tablets
2. Qualitative And Quantitative Composition
Each tablet contains 5mg of carbimazole
For a full list of excipients see section 6.1
3. Pharmaceutical Form
Tablet
Pale pink, uncoated, round, biconvex tablets marked with LINK C5 on one side and a scoreline on the reverse.
4. Clinical Particulars
4.1 Therapeutic Indications
Carbimazole is an anti-thyroid agent. It is indicated in all conditions where reduction of thyroid function is required.
Such conditions are:
1. Hyperthyroidism.
2. Preparation for thyroidectomy in hyperthyroidism.
3. Therapy prior to and post radio-iodine treatment.
4.2 Posology And Method Of Administration
Carbimazole should only be administered if hyperthyroidism has been confirmed by laboratory tests.
Adult:
The initial dose is in the range 20mg to 60mg, taken as two to three 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 5mg to 15mg per day, which may be taken as a single daily dose. Therapy should be continued for at least six months and up to eighteen 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. 20mg to 60mg per day, and supplemental L-thyroxine, 50mcg to 150mcg 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 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 dyscrasia may be greater in the elderly (aged 65 or over).
Children:
The usual initial daily dose is 15mg per day adjusted according to response.
4.3 Contraindications
Carbimazole 5mg tablets are contraindicated in patients with a previous history of adverse reactions to carbimazole or to any of the excipients listed in section 6.1 List of Excipients.
Serious, pre-existing haematological conditions, severe hepatic insufficiency.
4.4 Special Warnings And Precautions For Use
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 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.
Carbimazole 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.
Precaution should be taken in patients with intrathoracic goitre, which may worsen during initial treatment with Carbimazole. 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 a risk of cross-allergy between carbimazole, the active metabolite thiamazole (methimazole) and propylthiouracil.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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.
4.6 Pregnancy And Lactation
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, 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 congenital (congential 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 Special warnings and precautions for use).
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 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 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.
4.7 Effects On Ability To Drive And Use Machines
The effect on the ability to drive and use machines is not known.
4.8 Undesirable Effects
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.
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
4.9 Overdose
No symptoms are likely from a single large dose and so no specific treatment is indicated.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
ATC Code: H03B B01 - a thyroid reducing 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.
5.2 Pharmacokinetic Properties
Carbimazole is rapidly metabolised to thiamazole. The mean peak plasma concentration of thiamazole is reported to occur one hour after a single dose of thiamazole.
After oral ingestion, peak plasma concentrations of thiamazole, the active moiety, occur at 1 to 2 hours. The total volume of distribution of thiamazole is 0.5 l/kg. Thiamazole is concentrated in the thyroid gland. This intrathyroidal concentration of thiamazole has the effect of prolonging the activity of carbimazole. However, thiamazole has a shorter half-life in hyperthyroid patients than in normal controls and so more frequent initial doses are required while the hyperthyroidism is active.
Thiamazole is moderately bound to plasma proteins.
Carbimazole has a half-life of 5.3 to 5.4 hours. It is possible that the plasma half-life may also be prolonged by renal or hepatic disease. See Section 4.2. Posology and method of administration.
Thiamazole crosses the placenta and appears in breast milk. The plasma:milk ratio approaches unity.
Over 90% of orally administered carbimazole is excreted in the urine as thiamazole or its metabolites. The remainder appears in faeces. There is 10% enterohepatic circulation.
5.3 Preclinical Safety Data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Anhydrous lactose,
Croscarmellose sodium
Iron oxide (red) (E172)
Magnesium stearate
6.2 Incompatibilities
None known
6.3 Shelf Life
36 months
6.4 Special Precautions For Storage
Do not store above 25°C. Store the blisters in the original package.
6.5 Nature And Contents Of Container
The tablets are supplied in white, opaque 250 micron thermoformed PVC blister packs sealed with 20 micron lacquered aluminium foil containing 28, 56, 100 or 112 tablets (not all pack sizes may be marketed).
The heatseal coating lacquer of the aluminium foil consists of a PVC/PVAC co-polymer and polymethacrylate, with the outer side being a heat resistant lacquer based on polyester.
6.6 Special Precautions For Disposal And Other Handling
No special requirements.
7. Marketing Authorisation Holder
Archimedes Pharma UK Ltd
250 South Oak Way
Green Park
Reading
Berkshire
RG2 6UG
UK
8. Marketing Authorisation Number(S)
PL 12406/0021
9. Date Of First Authorisation/Renewal Of The Authorisation
08/05/2008
10. Date Of Revision Of The Text
08/05/2008
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