This information is intended for use by health professionals

1. Name of the medicinal product

Carbimazole 20mg Tablets

2. Qualitative and quantitative composition

Each tablet contains Carbimazole Ph. Eur. 20mg

Excipients with known effect:

Each tablet also contains lactose monohydrate. For full list of excipients, see section 6.1

3. Pharmaceutical form

Tablet

Tablets are white, round, biconvex, uncoated tablets with a score line on one side and plain on the other

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.

1. Hyperthyroidism.

2. Preparation for thyroidectomy in hyperthyroidism.

3. Preparation for, and as concomitant therapy with, radio-iodine treatment.

4.2 Posology and method of administration

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

Adults

The initial dose is in the range 20 - 60mg 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 - 15mg per day, which may be taken as a single daily dose. Therapy should be continued for at least six, 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 supplemental l-thyroxine, 50 - 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 contra-indications and warnings.

Children

The usual initial daily dose is 15mg per day.

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Serious, pre-existing haematological conditions.

- Severe hepatic insufficiency.

- Patients with a history of acute pancreatitis after administration of carbimazole or its active metabolite thiamazole.

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

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.

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 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.

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, total 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.

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

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).

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 patients are treated with antithyroid medications without reducing the theophylline dosage.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

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

Pregnancy

Carbimazole is able to cross the human 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.

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

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).

The blocking-replacement regimen should not be used during pregnancy since very little thyroxine crosses the placenta in the last trimester.

Breast-feeding

Carbimazole is secreted in breast 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 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.

Paediatric population

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

The frequencies are defined as follows:

Very common: ≥1/10

Common: ≥1/100, <1/10

Uncommon: ≥1/1000, <1/100

Rare: ≥1/10 000, <1/1000

Very rare: <1/10 000

Not known: cannot be estimated from the available data

Blood and lymphatic system disorders

Rare: pancytopenia/aplastic anaemia

Very rare: haemolytic anaemia, thrombocytopenia

Not known: bone marrow depression including neutropenia, eosinophilia, leukopenia, and agranulocytosis has been reported. Fatalities with carbimazole-induced agranulocytosis 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 immediately, particularly where there is any clinical evidence of infection. Generalised lymphadenopathy.

Endocrine disorders

Not known: Insulin autoimmune syndrome (with pronounced decline in blood glucose level).

Nervous system disorders

Not known: Headache, neuritis, polyneuropathy.

Gastro-intestinal system disorders

Not known: Nausea, mild gastric distress. Loss of sense of taste has been observed. Acute salivary gland swelling. Acute pancreatitis

General disorders and administration site conditions

Not known: Fever, Malaise

Hepatobiliary disorders

Not known: 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

Not known: Bruising

Skin and subcutaneous tissue disorders

Very rare: 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).

Not known: Skin rashes, pruritus, urticaria. Hair loss has been occasionally reported.

Musculoskeletal and connective tissue disorders

Not known: Isolated cases of myopathy have been reported. Patients experiencing myalgia after the intake of carbimazole should have their creatine phosphokinase levels monitored.

Immune system disorders

Not known: Angioedema and multi-system hypersensitivity reactions such as cutaneous vasculitis, liver, lung and renal effects occur.

Vascular Disorders

Not known: Bleeding

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 the Yellow Card Scheme (Website: www.mhra.gov.uk/yellowcard) or search for MHRA Yellow Card in the Google Play or Apple App Store.

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

Pharmacotherapeutic group: Carbimazole is a thyroid reducing agent.

ATC code: H03BB01

5.2 Pharmacokinetic properties

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.

5.3 Preclinical safety data

Not relevant.

6. Pharmaceutical particulars
6.1 List of excipients

Lactose monohydrate

Maize Starch

Citric acid monohydrate

Magnesium stearate

6.2 Incompatibilities

Not applicable

6.3 Shelf life

36 months

6.4 Special precautions for storage

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

6.5 Nature and contents of container

Tablets are packed in a PP or HDPE container with child resistant cap (built in 2gm silica gel) containing 100 tablets.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Accord Healthcare Limited

Sage House

319 Pinner Road

North Harrow

Middlesex

HA1 4HF

United Kingdom

8. Marketing authorisation number(s)

PL 20075/1163

9. Date of first authorisation/renewal of the authorisation

18/02/2008

10. Date of revision of the text

25/03/2019