- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Excipients with known effect:Lactose Anhydrous (125.35 mg per tablet)For a full list of excipients see section 6.1.
Older peopleNo 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).
Paediatric populationUse in children and adolescents (3 to 17 years of age) The usual initial daily dose is 15 mg per day adjusted according to response.Use in children (2 years of age and under) Safety and efficacy of carbimazole in children below 2 years of age have not been evaluated systematically. Use of carbimazole in children below 2 years of age is therefore not recommended.
AdultsThe initial dose is in the range 20 mg to 60 mg, 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 5 mg to 15 mg per day, which may be taken as a single daily dose. Therapy should be continued for at least six 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 mg to 60 mg per day, and supplemental L-thyroxine, 50 mcg to 150 mcg per day, is administered concomitantly, in order to prevent hypothyroidism. Therapy should be continued for at least six months and up to 18 months. Where a single dosage of less than 20 mg is recommended, it is intended that carbimazole 5 mg tablets should be taken.
Method of administrationOral
PregnancyCarbimazole 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 (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 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.
Breast-feedingCarbimazole is excreted in milk and if treatment is continued during lactation the patient should not continue to breast-feed her baby.
Paediatric populationFrequency, type and severity of adverse reactions in children appear to be comparable with those in adults.
Blood and lymphatic system disordersBone 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 disordersAngioedema and multi-system hypersensitivity reactions such as cutaneous vasculitis, liver, lung and renal effects occur.
Endocrine disordersInsulin autoimmune syndrome (with pronounced decline in blood glucose level).
Nervous system disordersHeadache, neuritis, polyneuropathy.
Gastrointestinal disordersNausea, mild gastrointestinal disturbance.Loss of sense of taste has been observed.Acute salivary gland swelling.
Hepatobiliary disordersHepatic 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.
Skin and subcutaneous tissue disordersSkin 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 disordersIsolated 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 conditionsFever, malaise.Injury, poisoning and procedural complicationsBruising.
Reporting of suspected adverse reactionsReporting 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 the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.
SymptomsNo symptoms are likely from a single large dose.
TreatmentNo specific treatment is indicated.
Mechanism of action: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.
AbsorptionCarbimazole is rapidly metabolised to thiamazole. After oral ingestion, peak plasma concentrations of thiamazole, the active moiety, occur at 1 to 2 hours
DistributionThe total volume of distribution of thiamazole is 0.5 1/kg. Thiamazole is concentrated in the thyroid gland. This intrathyroidal concentration of thiamazole has the effect of prolonging its activity. 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.
BiotransformationThiamazole 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. Thiamazole crosses the placenta and appears in breast milk. The plasma milk ratio approaches unity.
EliminationOver 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.
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