Carbimazole 20mg tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Carbimazole
Available from:
Mawdsley-Brooks & Company Ltd
ATC code:
H03BB01
INN (International Name):
Carbimazole
Dosage:
20mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 06020200

Do not change the dosage without consulting your

doctor first

Some improvement is usually felt within one to three

weeks. However, full beneficial effects usually take

four to eight weeks

In order to maintain control of the thyroid gland, you

may need to continue to take Carbimazole tablets

for several months. Your doctor will decide when

treatment can be stopped. Your doctor may ask you

to have occasional blood tests to help determine

how you are responding to treatment

Radio-iodine is another treatment for hyperthyroidism. If you

need radio-iodine treatment, your doctor will tell you to stop

taking Carbimazole temporarily.

Recommended dose

Adults and the elderly: the recommended starting dose is one to

three 20 mg tablets or four to twelve 5 mg tablets daily. Once control

is achieved your doctor will gradually reduce your dose to one to

three 5 mg tablets each day.

Use in children: the recommended starting dose is three 5 mg

tablets daily.

If you take more Carbimazole than you should

If you take more Carbimazole than you should, contact your doctor

or nearest hospital emergency department immediately. Take the

container and any remaining tablets with you.

If you forget to take Carbimazole

If you forget a dose, take it as soon as you remember. If it is time for

your next dose, take both doses together.

If you have any further questions of the use of this medicine ask

your doctor or pharmacist.

Like all medicines, Carbimazole can cause side effects, although not

everybody gets them.

Serious side effects:

Allergic reactions

If you have an allergic reaction, stop taking Carbimazole and see a

doctor straight away. The signs may include: sudden rash, swelling

or difficulty breathing.

Stop taking Carbimazole and see a doctor straight away if you

notice any of the following side effects:

sore throat

mouth ulcers

high temperature or fever

itching

increased bruising or bleeding tendency

significant tiredness

you are feeling generally unwell or think that you may have an

infection.

In addition, if you experience any of these symptoms while taking

Carbimazole you should also contact your doctor immediately:

muscle pain or weakness

nerve pain

swelling of lymph nodes

swelling of glands in your mouth

feeling faint (low blood sugar)

yellowing of your skin or whites of your eyes.

These could be signs of muscle problems, jaundice or inflammation

of the liver and your doctor may want you to stop taking

Carbimazole and carry out some blood tests on you.

Some tests should be performed to check for bone marrow

depression before restarting your treatment. Bone marrow

depression causes a reduction in the number of blood cells and

reduces the ability to fight infection. If it is not treated as soon as it is

detected the condition can become life-threatening.

Carbimazole can also affect the liver (causing jaundice and

inflammation of the liver) or the muscles. If you experience muscle

aches or pains or notice yellowing of your skin or the whites of your

eyes consult your doctor immediately as, under medical supervision,

the drug should be stopped and blood tests performed.

PACKAGE LEAFLET: INFORMATION FOR THE USER

Carbimazole 5 mg Tablets

Carbimazole 20 mg

Tablets

carbimazole

1.

What Carbimazole is and what it is used for

2.

What you need to know before you take

Carbimazole

3.

How to take Carbimazole

4.

Possible side effects

5.

How to store Carbimazole

6.

Contents of the pack and other information

The name of your medicine is Carbimazole 5 mg Tablets or

Carbimazole 20 mg Tablets (called Carbimazole in this leaflet).

Carbimazole contains the active substance carbimazole.

Carbimazole belongs to a group of medicines called anti-thyroid

agents.

Carbimazole is used to reduce the formation of thyroid hormones in

adults and children with an overactive thyroid gland. The condition is

called hyperthyroidism. Carbimazole is also used in more serious

cases, for example, to restore the normal function of the thyroid

before its partial removal by surgery. It may also be used together

with other treatments for hyperthyroidism.

Do not take Carbimazole

If you are allergic (hypersensitive) to carbimazole, or any of the

other ingredients of this medicine (listed in section 6).

If you have had a serious allergy to other anti-thyroid

medications such as thiamazole, methimazole or propylthiouracil

If you are breast-feeding

If you have a serious blood disorder

If you have a severe liver disorder.

If you had inflammation of the pancreas (acute pancreatitis) after

administration of carbimazole or thiamazole in the past.

Warnings and precautions

Talk to your doctor or pharmacist before taking Carbimazole:

If you are pregnant, think you may be pregnant or are trying to

become pregnant

If you have mild or moderate liver problems

If you have bone marrow depression. Bone marrow depression

causes a reduction in the number of blood cells and reduces the

ability to fight infection

If you are receiving radio-iodine (for thyroid problems)

If you have a swelling in your neck called an intrathoracic goitre.

This may get worse when treatment is first started. Narrowing of

the windpipe (trachea) may occur.

If you are of child-bearing potential. Carbimazole can cause

harm to an unborn baby. If you could get pregnant, use reliable

contraception from the time you start treatment and during

treatment.

If you are allergic to thiamazole, methimazole or propylthiouracil

(other thyroid medications)

If you are lactose intolerant or have any other lactose deficiency

If you are unable to comply with the instructions for use or

cannot be monitored regularly.

Tell your doctor straight away if you develop fever or abdominal

pain, which may be signs of inflammation of the pancreas (acute

pancreatitis). Carbimazole may need to be discontinued.

If you are not sure if the above applies to you, talk to your doctor or

pharmacist before taking Carbimazole.

Children

Do not give this medicine to children under the age of two years

because it may not be safe or effective.

Other medicines and Carbimazole

Please tell your doctor or pharmacist if you are taking, have recently

taken or might take any other medicines.

This includes medicines obtained without a prescription, including

herbal medicines. This is because Carbimazole can affect the way

some medicines work. Also, some medicines can affect the way

Carbimazole works. In particular tell your doctor or pharmacist if you

are taking any of the following:

Theophylline used to treat asthma or breathing problems

Medicines called anticoagulants, which are used to thin the

blood e.g. warfarin

Steroids such as prednisolone

An antibiotic called erythromycin

A medicine for heart failure called digitalis (digoxin)

Medicines for high blood pressure called beta-blockers

Any other medicine that could affect your white blood cell count.

Pregnancy and breast-feeding

Carbimazole can cause harm to an unborn baby.

If you could get pregnant, use reliable contraception from the time

you start treatment and during treatment.

If you are pregnant, think you may be pregnant or are planning to

have a baby, tell your doctor straight away. You treatment with

Carbimazole may need to be continued during pregnancy if the

potential benefit outweighs the potential risk to you and your unborn

baby.

If you are breast-feeding, ask your doctor or pharmacist for advice

before taking this medicine.

You should not breast-feed if you are using Carbimazole. This is

because small amounts may pass into the mother's milk. Ask your

doctor for advice before taking any medicine.

Driving and using machines

You can drive when taking Carbimazole, but do not drive until you

know how it affects you.

Carbimazole contains lactose monohydrate

If your doctor has told you that you have intolerance to some

sugars, contact your doctor before taking this medicine.

Always take Carbimazole exactly as your doctor has told you.

Check with your doctor or pharmacist if you are not sure.

The tablets are to be taken by mouth

The packet containing the silica gel desiccant should not be

swallowed.

You can take the tablets before, after or during meals

The dosage will be decided by your doctor according to your

individual needs, and may be changed at intervals during

treatment

Your doctor may decide to add an additional tablet (L-thyroxine),

to help control your condition

Each day's tablets may be divided into two (morning and

evening) or three daily doses (morning, noon and night)

Other side effects include:

feeling sick

feeling unusually tired

headache

skin rashes, including urticaria (nettle rash)

itching

stomach upset

painful joints.

The following side effects have also been reported:

hair thinning

loss of taste

angioedema, a serious allergic reaction with symptoms that may

include swollen tongue lips, face or throat

Stevens-Johnson syndrome, a serious illness with blistering of

the skin, mouth, eyes and genitals

lung problems, with symptoms that include shortness of breath or

cough

kidney problems, with symptoms that include a reduction of the

amount of urine passed, fluid retention and blood in the urine.

inflammation of the pancreas (acute pancreatitis)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This

includes any possible side effects not listed in this leaflet. You can

also report side effects directly via the Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard or by searching for MHRA Yellow

Card in the Google Play or Apple App store. By reporting side

effects, you can help provide more information on the safety of this

medicine.

Keep this medicine out of the sight and reach of children.

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

container. Keep the bottle tightly closed to protect from light and

moisture.

Do not use after the expiry date which is printed on the carton after

EXP. The expiry date refers to the last day of that month.

Use within 100 days of opening.

Do not throw away any medicines via wastewater or household

waste. Ask your pharmacist how to throw away medicines you no

longer use. These measures will help protect the environment.

What Carbimazole contains

The active ingredient is Carbimazole. Each 5mg tablet contains

5mg carbimazole. Each 20mg tablet contains 20mg carbimazole.

The other ingredients are lactose anhydrous, croscarmellose

sodium and magnesium stearate.

What Carbimazole looks like and contents of the pack

Carbimazole 5 mg tablets are white coloured, round shaped,

uncoated tablets debossed “CARB” on one side and “5” on other

side having diameter about 6.30mm.

Carbimazole 20 mg tablets are white coloured, round shaped,

uncoated tablets debossed “CARB” on one side and “20” on other

side having diameter about 9.60mm.

The pack contains a silica gel desiccant (to keep the tablets dry). Do

not eat the sachet containing the desiccant.

Marketing Authorisation Holder

Activase Pharmaceuticals Limited

11 Boumpoulinas, 1060 Nicosia, Cyprus

Manufacturer

DDSA Pharmaceuticals Limited

84 Pembroke Road, London, W8 6NX, United Kingdom

This leaflet was last revised in 02/2019

A0219-0220/O/PIL/A1

Read all of this leaflet carefully before you start taking

this

medicine

because

it

contains

important

information for you.

- Keep this leaflet. You may need to read it again.

- If you have any further questions, ask your doctor or

pharmacist.

- This medicine has been prescribed for you only. Do

not pass it on to others. It may harm them, even if their

signs of illness are the same as yours.

- If you get any side effects, talk to your doctor or

pharmacist. This includes any possible side effects not

listed in this leaflet. See section 4.

1. WHAT CARBIMAZOLE IS AND WHAT

IT IS USED FOR

2. WHAT YOU NEED TO KNOW BEFORE

YOU TAKE CARBIMAZOLE

3. HOW TO TAKE CARBIMAZOLE

WHAT IS IN THIS LEAFLET

Do not change the dosage without consulting your

doctor first

Some improvement is usually felt within one to three

weeks. However, full beneficial effects usually take

four to eight weeks

In order to maintain control of the thyroid gland, you

may need to continue to take Carbimazole tablets

for several months. Your doctor will decide when

treatment can be stopped. Your doctor may ask you

to have occasional blood tests to help determine

how you are responding to treatment

Radio-iodine is another treatment for hyperthyroidism. If you

need radio-iodine treatment, your doctor will tell you to stop

taking Carbimazole temporarily.

Recommended dose

Adults and the elderly: the recommended starting dose is one to

three 20 mg tablets or four to twelve 5 mg tablets daily. Once control

is achieved your doctor will gradually reduce your dose to one to

three 5 mg tablets each day.

Use in children: the recommended starting dose is three 5 mg

tablets daily.

If you take more Carbimazole than you should

If you take more Carbimazole than you should, contact your doctor

or nearest hospital emergency department immediately. Take the

container and any remaining tablets with you.

If you forget to take Carbimazole

If you forget a dose, take it as soon as you remember. If it is time for

your next dose, take both doses together.

If you have any further questions of the use of this medicine ask

your doctor or pharmacist.

Like all medicines, Carbimazole can cause side effects, although not

everybody gets them.

Serious side effects:

Allergic reactions

If you have an allergic reaction, stop taking Carbimazole and see a

doctor straight away. The signs may include: sudden rash, swelling

or difficulty breathing.

Stop taking Carbimazole and see a doctor straight away if you

notice any of the following side effects:

sore throat

mouth ulcers

high temperature or fever

itching

increased bruising or bleeding tendency

significant tiredness

you are feeling generally unwell or think that you may have an

infection.

In addition, if you experience any of these symptoms while taking

Carbimazole you should also contact your doctor immediately:

muscle pain or weakness

nerve pain

swelling of lymph nodes

swelling of glands in your mouth

feeling faint (low blood sugar)

yellowing of your skin or whites of your eyes.

These could be signs of muscle problems, jaundice or inflammation

of the liver and your doctor may want you to stop taking

Carbimazole and carry out some blood tests on you.

Some tests should be performed to check for bone marrow

depression before restarting your treatment. Bone marrow

depression causes a reduction in the number of blood cells and

reduces the ability to fight infection. If it is not treated as soon as it is

detected the condition can become life-threatening.

Carbimazole can also affect the liver (causing jaundice and

inflammation of the liver) or the muscles. If you experience muscle

aches or pains or notice yellowing of your skin or the whites of your

eyes consult your doctor immediately as, under medical supervision,

the drug should be stopped and blood tests performed.

PACKAGE LEAFLET: INFORMATION FOR THE USER

Carbimazole 5 mg Tablets

Carbimazole 20 mg

Tablets

carbimazole

1.

What Carbimazole is and what it is used for

2.

What you need to know before you take

Carbimazole

3.

How to take Carbimazole

4.

Possible side effects

5.

How to store Carbimazole

6.

Contents of the pack and other information

The name of your medicine is Carbimazole 5 mg Tablets or

Carbimazole 20 mg Tablets (called Carbimazole in this leaflet).

Carbimazole contains the active substance carbimazole.

Carbimazole belongs to a group of medicines called anti-thyroid

agents.

Carbimazole is used to reduce the formation of thyroid hormones in

adults and children with an overactive thyroid gland. The condition is

called hyperthyroidism. Carbimazole is also used in more serious

cases, for example, to restore the normal function of the thyroid

before its partial removal by surgery. It may also be used together

with other treatments for hyperthyroidism.

Do not take Carbimazole

If you are allergic (hypersensitive) to carbimazole, or any of the

other ingredients of this medicine (listed in section 6).

If you have had a serious allergy to other anti-thyroid

medications such as thiamazole, methimazole or propylthiouracil

If you are breast-feeding

If you have a serious blood disorder

If you have a severe liver disorder.

If you had inflammation of the pancreas (acute pancreatitis) after

administration of carbimazole or thiamazole in the past.

Warnings and precautions

Talk to your doctor or pharmacist before taking Carbimazole:

If you are pregnant, think you may be pregnant or are trying to

become pregnant

If you have mild or moderate liver problems

If you have bone marrow depression. Bone marrow depression

causes a reduction in the number of blood cells and reduces the

ability to fight infection

If you are receiving radio-iodine (for thyroid problems)

If you have a swelling in your neck called an intrathoracic goitre.

This may get worse when treatment is first started. Narrowing of

the windpipe (trachea) may occur.

If you are of child-bearing potential. Carbimazole can cause

harm to an unborn baby. If you could get pregnant, use reliable

contraception from the time you start treatment and during

treatment.

If you are allergic to thiamazole, methimazole or propylthiouracil

(other thyroid medications)

If you are lactose intolerant or have any other lactose deficiency

If you are unable to comply with the instructions for use or

cannot be monitored regularly.

Tell your doctor straight away if you develop fever or abdominal

pain, which may be signs of inflammation of the pancreas (acute

pancreatitis). Carbimazole may need to be discontinued.

If you are not sure if the above applies to you, talk to your doctor or

pharmacist before taking Carbimazole.

Children

Do not give this medicine to children under the age of two years

because it may not be safe or effective.

Other medicines and Carbimazole

Please tell your doctor or pharmacist if you are taking, have recently

taken or might take any other medicines.

This includes medicines obtained without a prescription, including

herbal medicines. This is because Carbimazole can affect the way

some medicines work. Also, some medicines can affect the way

Carbimazole works. In particular tell your doctor or pharmacist if you

are taking any of the following:

Theophylline used to treat asthma or breathing problems

Medicines called anticoagulants, which are used to thin the

blood e.g. warfarin

Steroids such as prednisolone

An antibiotic called erythromycin

A medicine for heart failure called digitalis (digoxin)

Medicines for high blood pressure called beta-blockers

Any other medicine that could affect your white blood cell count.

Pregnancy and breast-feeding

Carbimazole can cause harm to an unborn baby.

If you could get pregnant, use reliable contraception from the time

you start treatment and during treatment.

If you are pregnant, think you may be pregnant or are planning to

have a baby, tell your doctor straight away. You treatment with

Carbimazole may need to be continued during pregnancy if the

potential benefit outweighs the potential risk to you and your unborn

baby.

If you are breast-feeding, ask your doctor or pharmacist for advice

before taking this medicine.

You should not breast-feed if you are using Carbimazole. This is

because small amounts may pass into the mother's milk. Ask your

doctor for advice before taking any medicine.

Driving and using machines

You can drive when taking Carbimazole, but do not drive until you

know how it affects you.

Carbimazole contains lactose monohydrate

If your doctor has told you that you have intolerance to some

sugars, contact your doctor before taking this medicine.

Always take Carbimazole exactly as your doctor has told you.

Check with your doctor or pharmacist if you are not sure.

The tablets are to be taken by mouth

The packet containing the silica gel desiccant should not be

swallowed.

You can take the tablets before, after or during meals

The dosage will be decided by your doctor according to your

individual needs, and may be changed at intervals during

treatment

Your doctor may decide to add an additional tablet (L-thyroxine),

to help control your condition

Each day's tablets may be divided into two (morning and

evening) or three daily doses (morning, noon and night)

Other side effects include:

feeling sick

feeling unusually tired

headache

skin rashes, including urticaria (nettle rash)

itching

stomach upset

painful joints.

The following side effects have also been reported:

hair thinning

loss of taste

angioedema, a serious allergic reaction with symptoms that may

include swollen tongue lips, face or throat

Stevens-Johnson syndrome, a serious illness with blistering of

the skin, mouth, eyes and genitals

lung problems, with symptoms that include shortness of breath or

cough

kidney problems, with symptoms that include a reduction of the

amount of urine passed, fluid retention and blood in the urine.

inflammation of the pancreas (acute pancreatitis)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This

includes any possible side effects not listed in this leaflet. You can

also report side effects directly via the Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard or by searching for MHRA Yellow

Card in the Google Play or Apple App store. By reporting side

effects, you can help provide more information on the safety of this

medicine.

Keep this medicine out of the sight and reach of children.

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

container. Keep the bottle tightly closed to protect from light and

moisture.

Do not use after the expiry date which is printed on the carton after

EXP. The expiry date refers to the last day of that month.

Use within 100 days of opening.

Do not throw away any medicines via wastewater or household

waste. Ask your pharmacist how to throw away medicines you no

longer use. These measures will help protect the environment.

What Carbimazole contains

The active ingredient is Carbimazole. Each 5mg tablet contains

5mg carbimazole. Each 20mg tablet contains 20mg carbimazole.

The other ingredients are lactose anhydrous, croscarmellose

sodium and magnesium stearate.

What Carbimazole looks like and contents of the pack

Carbimazole 5 mg tablets are white coloured, round shaped,

uncoated tablets debossed “CARB” on one side and “5” on other

side having diameter about 6.30mm.

Carbimazole 20 mg tablets are white coloured, round shaped,

uncoated tablets debossed “CARB” on one side and “20” on other

side having diameter about 9.60mm.

The pack contains a silica gel desiccant (to keep the tablets dry). Do

not eat the sachet containing the desiccant.

Marketing Authorisation Holder

Activase Pharmaceuticals Limited

11 Boumpoulinas, 1060 Nicosia, Cyprus

Manufacturer

DDSA Pharmaceuticals Limited

84 Pembroke Road, London, W8 6NX, United Kingdom

This leaflet was last revised in 02/2019

A0219-0220/O/PIL/A1

6. CONTENTS OF THE PACK AND OTHER

INFORMATION

5. HOW TO STORE CARBIMAZOLE

4. POSSIBLE SIDE EFFECTS

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Carbimazole 20mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Carbimazole 20mg tablet contains 20mg of carbimazole.

Excipients with known effect: lactose anhydrous 295.750mg.

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablet.

White coloured, round-shaped, uncoated tablets debossed “CARB” on one side and

“20” on the other side having diameter 9.60mm.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Carbimazole is an anti-thyroid agent. It is indicated in adults and children 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.

4.2

Posology and method of administration

Posology

Carbimazole should only be administered if hyperthyroidism has been confirmed by

laboratory tests.

Adults

The initial dose is in the range 20 - 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 - 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 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 - 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

Carbimazole 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).

Paediatric population

Use 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

Method of administration

Oral

4.3

Contraindications

Carbimazole is contraindicated in patients with:

Hypersensitivity to carbimazole or to any of the excipients listed in section

Serious pre-existing haematological conditions

Severe hepatic insufficiency

A history of acute pancreatitis after administration of carbimazole or its

active metabolite thiamazole

4.4

Special warnings and precautions for use

Bone marrow depression including neutropenia, eosinophilia, leucopenia and

agranulocytosis has been reported. Fatalities with carbimazole-induced

agranulocytosis have been reported.

Rare cases of purpura, anaemia, 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.

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 liver disorder.

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.

Carbimazole should be stopped temporarily at the time of administration of radio-

iodine, to avoid thyroid crisis.

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

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.

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).

Carbimazole contains lactose

Patients with rare hereditary problems of galactose intolerance, total lactase

deficiency or glucose-galactose malabsorption should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction

Little is known about interactions.

Interaction studies have not been performed in paediatric patients.

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. Additional monitoring of PT/INR should be considered, especially before

surgical procedures.

The serum levels of theophylline can increase and toxicity may develop if

hyperthyroidic patients are treated with antithyroid medications without reducing the

theophylline dosage.

Co-administration of prednisolone and carbimazole may result in increased clearance

of prednisolone.

Carbimazole may inhibit the metabolism of erythromycin, leading to reduced

clearance of erythromycin.

Serum digitalis (digoxin) levels may be increased when hyperthyroid patients on a

stable digitalis glycoside (digoxin) regimen become euthyroid; a reduced dosage of

digitalis glycosides (digoxin) may be needed.

Hyperthyroidism may cause an increased clearance of beta-adrenergic blockers with a

high extraction ratio. A dose reduction of beta blockers may be needed when a

hyperthyroid patient becomes euthyroid.

4.6

Fertility, pregnancy and lactation

Women of child bearing potential

Women of childbearing potential have to use effective contraceptive measures during

treatment (see section 4.4).

Pregnancy

Hyperthyroidism in pregnant women should be adequately treated to prevent serious

maternal and foetal complications.

Carbimazole is able to cross the human placenta.

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

thyroid hormones. If carbimazole is used during pregnancy, close maternal, foetal and

neonatal monitoring is recommended (see section 4.4).

Breast-feeding

Carbimazole is excreted in breast milk and if treatment is continued during lactation,

the patient should not continue to breast-feed her baby.

Fertility

There are no human data available on the effect of carbimazole on fertility.

4.7

Effects on ability to drive and use machines

Not relevant.

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.

Blood and lymphatic system disorders

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

Immune system disorders

Angioedema and multi-system hypersensitivity reactions such as cutaneous vasculitis,

liver, lung and renal effects occur.

Endocrine disorders

Insulin autoimmune syndrome (with pronounced decline in blood glucose level).

Nervous system disorders

Headache, neuritis, polyneuropathy.

Vascular disorders

Bleeding.

Gastrointestinal disorders

Nausea, mild gastric distress, loss of sense of taste has been observed. Acute salivary

gland swelling.

Acute pancreatitis (frequency not known).

Hepato-biliary 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.

Skin and subcutaneous tissue disorders

Skin 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 disorders

Isolated 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 conditions

Fever, malaise.

Injury, poisoning and procedural complications

Bruising.

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 at www.mhra.gov.uk/yellowcard or search for MHRA

Yellow Card in the Google Play or Apple App Store.

4.9

Overdose

Symptoms

No symptoms are likely from a single large dose.

Management

No specific treatment is indicated.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

ATC Code: H03BB01

Pharmacotherapeutic group: Sulphur-containing imidazole derivatives.

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.

5.2

Pharmacokinetic properties

Absorption

Carbimazole is rapidly metabolised to thiamazole. After oral ingestion, peak plasma

concentrations of thiamazole, the active moiety, occur at 1 to 2 hours.

Distribution

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 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.

Biotransformation

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.

Thiamazole crosses the placenta and appears in breast milk. The plasma:milk ratio

approaches unity.

Elimination

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

Lactose anhydrous

Croscarmellose Sodium

Magnesium Stearate

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

Unopened: 36 months.

In-use: 100 days

6.4

Special precautions for storage

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

closed to protect from light and moisture.

6.5

Nature and contents of container

Carbimazole 20 mg tablets are available in HDPE bottles with polypropylene screw

closure with a sealed liner containing 100 tablets and 1g silica gel desiccant packet.

Each bottle contains 100 tablets. The packet containing the desiccant is not meant to

be consumed.

6.6

Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance

with local requirements.

7

MARKETING AUTHORISATION HOLDER

Activase Pharmaceuticals Ltd.

11 Boumpoulinas

1060 Nicosia

Cyprus

8

MARKETING AUTHORISATION NUMBER(S)

PL 28444/0220

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

11/04/2019

10

DATE OF REVISION OF THE TEXT

02/10/2019

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

1

CARBIMAZOLE 5MG TABLETS

(CARBIMAZOLE)

PL 20620/0005

CARBIMAZOLE 20MG TABLETS

(CARBIMAZOLE)

PL 20620/0006

UK Public Assessment Report

TABLE OF CONTENTS

Lay Summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

Page 13

Summary of Product Characteristics

Page 14

Product Information Leaflets

Page 22

Labelling

Page 24

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

2

CARBIMAZOLE 5MG TABLETS

(CARBIMAZOLE)

PL 20620/0005

CARBIMAZOLE 20MG TABLETS

(CARBIMAZOLE)

PL 20620/0006

LAY SUMMARY

The Medicines and Healthcare products Regulatory Agency (MHRA) granted NRIM

Limited Marketing Authorisations (licences) for the medicinal products Carbimazole

5mg Tablets (PL 20620/0005) and Carbimazole 20mg Tablets (PL 20620/0006) on

February 2008. These are prescription-only medicines (POM) used for the

treatment of thyroid conditions, including hyperthyroidism, where the reduction of

thyroid function is required.

These medicinal products contain the active ingredient carbimazole, which belongs to

a group of medicines called anti-thyroid agents.

The test products were considered to be the same as the reference products

NeoMercazole 5 and NeoMercazole 20 (PL 20072/0013 & 20072/0014, Amdipharm

plc) based on the data submitted by NRIM Limited.

These applications are based on reference products with valid UK licences. No new or

unexpected safety concerns arose from these applications and it was therefore judged

that the benefits of taking Carbimazole 5mg Tablets and Carbimazole 20mg Tablets

outweigh the risks; hence Marketing Authorisations (MAs) have been granted.

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

3

CARBIMAZOLE 5MG TABLETS

(CARBIMAZOLE)

PL 20620/0005

CARBIMAZOLE 20MG TABLETS

(CARBIMAZOLE)

PL 20620/0006

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 4

Pharmaceutical assessment

Page 5

Preclinical assessment

Page 8

Clinical assessment

Page 9

Overall conclusion and risk benefit assessment

Page 12

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

4

INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the MHRA granted

NRIM Limited Marketing Authorisations for the medicinal products Carbimazole

5mg Tablets (PL 20620/0005) and Carbimazole 20mg Tablets (PL 20620/0006) on

February 2008. The products are prescription-only medicines.

These are abridged applications for Carbimazole 5mg Tablets and Carbimazole 20mg

Tablets. These are two strengths of carbimazole, submitted under Article 10.1 of

Directive 2001/83/EC, as amended, claiming to be generic medicinal products of the

reference products NeoMercazole 5 and NeoMercazole 20 (PL 20072/0013 &

20072/0014) respectively, granted to Amdipharm plc on 31/05/2004. PLs 20072/0013

and 20072/0014 were Change of Ownership applications (CoA) from PL 00031/0378

and PL 00031/0379, which were authorised to Roche Products Limited on 15/09/1987

and 20/06/1986 respectively. These were the innovator products. The reference

products have been authorised in the UK for more than 10 years, so the period of data

exclusivity has expired.

Carbimazole 5mg Tablets and Carbimazole 20mg Tablets contain the active

ingredient carbimazole, which is a thyroid reducing agent. The products are indicated

in conditions where reduction of thyroid function is required, including,

hyperthyroidism, preparation for thyroidectomy in hyperthyroidism, and preparation

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

These applications for Carbimazole 5mg Tablets and Carbimazole 20mg Tablets were

submitted at the same time and both depend on the bioequivalence study presented

comparing the applicant’s 20mg product with the reference product NeoMercazole 20,

manufactured by Roche Products Limited. Consequently, all sections of the Scientific

Discussion refer to both products.

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

5

PHARMACEUTICAL ASSESSMENT

ACTIVE SUBSTANCE

Carbimazole

Nomenclature:

INN:

Carbimazole

Chemical name:

Ethyl 3-methyl-2-thioxo-2,3-dihydro-1

H

-imidazole-1-

carboxylate

Structure:

Molecular formula:

Molecular weight:

186.2

CAS No:

22232-54-8

Physical form:

White to yellowish-white crystalline powder

Solubility:

Carbimazole is slightly soluble in water, soluble in acetone and

in alcohol

The active substance, carbimazole, is the subject of a European Pharmacopeia (EP)

monograph.

Synthesis of the drug substance from the designated starting material has been

adequately described and appropriate in-process controls and intermediate

specifications are applied. Satisfactory specifications are in place for all starting

materials and reagents and these are supported by relevant Certificates of Analysis.

Confirmation has been provided that the raw materials, intermediates and auxiliary

agents used in synthesis of the active are not of animal, biological or genetically

modified origin, and therefore comply with the TSE requirements.

An appropriate active substance specification has been provided which is in line with

the EP monograph specification. Analytical methods have been appropriately

validated and are satisfactory for ensuring compliance with the relevant specifications.

Batch analysis data are provided and comply with the proposed specification.

Satisfactory Certificates of Analysis have been provided for reference standards used

by the active substance manufacturer during validation studies.

Active carbimazole is stored in appropriate packaging. It is packed, typically 25 or 50

kg, into double polythene bags as the primary container, secured with tamper evident

liner ties. The bags are then placed inside fibreboard drums as the secondary

container, to which security seals are attached. Specifications and Certificates of

Analysis have been provided for the packaging materials used. The polythene bags in

direct contact with the active substance satisfy Directive 2002/72/EC (as amended),

and are suitable for contact with foodstuffs.

Appropriate stability data have been generated for active substance stored in the

proposed packaging. This data demonstrates the stability of the active substance and

supports a retest period of 4 years when stored in the proposed packaging.

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

6

DRUG PRODUCT

Description and Composition

Carbimazole 5 mg Tablets are white, round, biconvex, uncoated tablets with a score

line on one side and embossed ‘F1’ on the other, whilst Carbimazole 20 mg Tablets

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

the other.

Other ingredients consist of pharmaceutical excipients, namely lactose monohydrate,

maize starch, citric acid monohydrate; and magnesium stearate. Appropriate

justification for the inclusion of each excipient has been provided.

All excipients used comply with their respective European Pharmacopoeia

monographs. Satisfactory Certificates of Analysis have been provided for all

excipients.

The magnesium stearate is of vegetable origin. The only excipient used that contains

material of animal or human origin is lactose monohydrate. A signed TSE / BSE risk-

free declaration has been provided by the manufacturer of lactose monohydrate and is

acceptable.

There were no novel excipients used and no overages.

Dissolution and impurity profiles

Dissolution profiles for the drug products were found to be similar to those for the

reference products, and were satisfactory.

Impurity profiles for the drug products were found to be similar to those for the

reference products, and all the impurities are within the specification limits.

Pharmaceutical development

Details of the pharmaceutical development of the drug products have been supplied

and are satisfactory.

Manufacture

A description and flow-chart of the manufacturing method has been provided.

In-process controls are appropriate considering the nature of the product and the

method of manufacture. Process validation studies have been conducted and are

satisfactory.

Finished product specification

The finished product specifications proposed for both release and shelf life are

acceptable, and provide an assurance of the quality and consistency of the finished

products. Acceptance limits have been justified with respect to conventional

pharmaceutical requirements and, where appropriate, safety. Test methods have been

described and have been adequately validated, as appropriate. Batch data have been

provided and comply with the release specification. Certificates of Analysis have been

provided for any reference standards used.

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

7

Container Closure System

The tablets are presented in polypropylene bottles with child-resistant cap in a pack

size of 100 tablets. The specification for the container, Certificate of Analysis and

analytical methods have been submitted by the finished product manufacturer and

found to be satisfactory. The container complies with EU legislation, Directive

2002/72/EC (as amended), and is suitable for contact with foodstuffs.

Stability

Finished product stability studies have been conducted in accordance with current

guidelines and results were within the proposed specification limits. Based on the

results, a shelf-life of 36 months has been set, which is satisfactory. Storage

conditions are ‘Do not store above 25°C’, ‘Store in the original container’, and ‘Keep

the container tightly closed’.

Bioequivalence Study

A bioequivalence study was presented comparing the test product, Carbimazole 20mg

Tablets, to the reference product, NeoMercazole 20 (manufactured by Roche Products

Limited).

An evaluation of the bioequivalence study is found in the Clinical Assessment section.

Expert Report

A satisfactory expert report is provided, and has been prepared by an appropriately

qualified expert. An appropriate CV for the expert has been supplied.

Product Information

The approved SmPCs, leaflet, and labelling are satisfactory.

Conclusion

The test products are pharmaceutically equivalent to the reference products which

have been licensed in the UK for over 10 years. The drug products correspond to the

current EU definition of a generic medicinal product because they comply with the

criteria of having the same qualitative and quantitative composition in terms of the

active substance and pharmaceutical form. On this basis, and considering the

bioequivalence data provided, the applicant’s claim that Carbimazole 20mg Tablets is

a generic medicinal product of NeoMercazole 20appears justified.

As the test products, Carbimazole 5mg Tablets and Carbimazole 20mg Tablets, meet

the criteria specified in the Note for Guidance on the investigation of bioavailability

and bioequivalence (CPMP/EWP/QWP/1401/98), the results and conclusions of the

bioequivalence studies on the 20mg strength were extrapolated to the 5mg strength

tablets.

All pharmaceutical issues have been resolved and the quality grounds for these

applications are considered adequate. It is recommended that Marketing

Authorisations are granted.

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

8

PRECLINICAL ASSESSMENT

These abridged applications for Carbimazole 5mg Tablets and Carbimazole 2mg

Tablets were submitted according to Article 10.1 of Directive 2001/83/EC, as

amended.

No new preclinical data have been supplied with these applications and none are

required for applications of this type. A preclinical expert report has been written by a

suitably qualified person and is satisfactory.

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

9

CLINICAL ASSESSMENT

INDICATIONS

Carbimazole 5mg Tablets and Carbimazole 20mg Tablets are indicated in conditions

where reduction of thyroid function is required, including hyperthyroidism,

preparation for thyroidectomy in hyperthyroidism, and preparation for, and as

concomitant therapy with, radio-iodine treatment.

The indications are consistent with those for the innovator product and are

satisfactory.

POSOLOGY AND METHOD OF ADMINISTRATION

The posology is consistent with that for the innovator product and is satisfactory.

TOXICOLOGY

No new data has been submitted and none are required for applications of this type.

CLINICAL PHARMACOLOGY

Pharmacodynamics

Carbimazole is a thyroid reducing agent.

Pharmacokinetics

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.

Pharmacokinetics - Bioequivalence study

The applicant presented a single bioequivalence study comparing the test product,

Carbimazole 20 mg Tablets, to the reference product, NeoMercazole 20 (Roche

Products Limited) under fasting conditions. This was a randomised, single-dose,

open-label, crossover, two-treatment, two-period study conducted in 34 healthy adult

male subjects.

Treatment periods 1 and 2 were separated by 9 days for wash out purposes. A total of

16 blood samples were collected at regular intervals up to 24 hours post dosing, which

was adequate to cover AUC

0-∞

. Plasma samples were analysed employing a validated

LC-MS/MS method using MS/MS detection. The pharmacokinetics results were

analysed. The rate and extent of absorption of carbimazole were determined by

analysing the plasma levels of its metabolite, methimazole, using the primary (AUC

, AUC

0-∞

and C

) and secondary variables (T

and k

UKPAR Carbimazole 5mg & 20mg Tablets

PL 20620/0005 & 0006

10

The results of the main pharmacokinetic parameters are summarised below.

Pharmacokinetic results of Methimazole for a randomised single dose crossover study between the test

and reference product. Log transformed. ANOVA. N = 34 healthy adult male subjects, dosed fasted;

t=24 hours. 9 day wash out period

Test parameter

Test product

(geometric mean)

Reference product

(geometric mean)

Ratio

Test/reference x 100

90%

Confidence

intervals

0-24

(ng.h/ml)

2097.07

1964.11

106.77

102.90-110.79

(ng.h/ml)

2319.44

2160.97

107.33

103.37-111.45

(ng/ml)

244.90

225.16

108.77

104.71-112.98

0.10

0.10

(h) *

6.82

6.74

(h) *

0.95

1.40

* Arithmatic values

The 90% confidence intervals for the log-transformed parameters C

, AUC

of Methimazole lie within the range 80-125%, such that the test and reference

products can be considered bioequivalent after a single dose under fasted conditions.

As Carbimazole 5mg Tablets and Carbimazole 20mg Tablets meet the criteria as

specified in the Note for Guidance on the investigation of bioavailability and

bioequivalence (CPMP/EWP/QWP/1401/98), the results and conclusions of the

bioequivalence study on the 20mg strength were extrapolated to the 5mg strength

product.

EFFICACY

No new data are submitted and none are required for applications of this type.

Efficacy is reviewed in the Clinical Expert Report. The reference products are

established and the applications depend upon the bioequivalence study.

SAFETY

No new data are submitted and none are required for applications of this type.

Safety is reviewed in the Clinical Expert Report. The reference products are

established and the applications depend upon the bioequivalence study.

EXPERT REPORT

A satisfactory expert report is provided, and has been prepared by an appropriately

qualified expert. An appropriate CV for the expert has been supplied.

PRODUCT INFORMATION:

Summary of Product Characteristics (SmPC)

The approved SmPCs are consistent with those for the reference products and are

acceptable.

Patient Information Leaflet (PIL)

The PIL is in line with the approved SmPCs and is satisfactory.

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