Carbamazepine 125mg suppositories

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

Buy It Now

Active ingredient:
Carbamazepine
Available from:
Essential Pharma Ltd
ATC code:
N03AF01
INN (International Name):
Carbamazepine
Dosage:
125mg
Pharmaceutical form:
Suppository
Administration route:
Rectal
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 04080100; GTIN: 5060334120213
Authorization number:
; PL 41871/0011

Read the complete document

Package Leaflet: Information for the User

Carbamazepine Essential Pharma

125 and 250 mg Suppositories

(carbamazepine)

What you need to know about Carbamazepine Essential

Pharma Suppositories

Your doctor has decided that you need this medicine to help

treat your condition.

Please read this leaflet carefully before you start to use the

suppositories. It contains important information.

Keep the

leaflet in a safe place because you may want to read it again.

If you have any other questions, or if there is something you

don’t understand, please ask your doctor or pharmacist.

This medicine has been prescribed for you. Never give it to

someone else. It may not be the right medicine for them even if

their symptoms seem to be the same as yours.

If any of the side effects gets serious, or if you notice any side

effects not listed in this leaflet, please tell your doctor or

pharmacist.

In this leaflet:

1. What Carbamazepine Essential Pharma Suppositories are

and what they are used for

2. Things to consider before you are treated with

Carbamazepine Essential Pharma Suppositories

3. How to use Carbamazepine Essential Pharma Suppositories

4. Possible side effects

5. How to store Carbamazepine Essential Pharma Suppositories

6. Further information

1. What Carbamazepine Essential Pharma

Suppositories are and what they are used for

Carbamazepine, the active ingredient in Carbamazepine

Essential Pharma Suppositories, is an anti-convulsant medicine

(prevents fits).

Carbamazepine Essential Pharma Suppositories are used to

treat some forms of epilepsy. They are useful in the short term,

(maximum 7 days), for patients who cannot take medicines by

mouth, e.g. after surgery or if unconscious.

2. Things to consider before you are treated with

Carbamazepine Essential Pharma Suppositories

Some people MUST NOT have Carbamazepine Essential

Pharma Suppositories. Make sure your doctor knows if;

you think you may be hypersensitive (allergic) to

carbamazepine or similar drugs such as oxcarbazepine

(Trileptal), or to any of a related group of drugs known as

tricyclic antidepressants (such as amitriptyline or

imipramine). If you are allergic to carbamazepine there is a

one in four (25%) chance that you could also have an allergic

reaction to oxcarbazepine.

you think you may be allergic to any of the other ingredients

of Carbamazepine Essential Pharma Suppositories (these are

listed at the end of the leaflet). Signs of a hypersensitivity

reaction include swelling of the face or mouth (angioedema),

breathing problems, runny nose, skin rash, blistering or

peeling,

you have any heart problems,

you have ever had problems with your bone marrow,

you have a blood disorder called porphyria,

you have taken drugs called monoamine oxidase inhibitors

(MAOIs), used to treat depression, within the last 14 days.

A small number of people being treated with anti-epileptics

such as carbamazepine have had thoughts of harming or killing

themselves. If at any time you have these thoughts,

immediately contact your doctor.

Serious skin rashes (Stevens- Johnson syndrome, toxic

epidermal necrolysis) have been reported with the use of

carbamazepine. Frequently, the rash can involve ulcers of the

mouth, throat, nose, genitals and conjunctivitis (red and swollen

eyes). These serious skin rashes are often preceded by

influenza-like symptoms fever, headache, body ache (flu-like

symptoms). The rash may progress to widespread blistering and

peeling of the skin. The highest risk for occurrence of serious

skin reactions is within the first months of treatment.

These serious skin reactions can be more common in people

from some Asian countries. The risk of these reactions in

patients of Han Chinese or Thai origin may be predicted by

testing a blood sample of these patients. Your doctor should be

able to advise if a blood test is necessary before taking

carbamazepine.

If you develop a rash or these skin symptoms, stop taking

carbamazepine and contact your doctor immediately.

You should also ask yourself these questions before you have

Carbamazepine Essential Pharma Suppositories. If the answer

to any of these questions is YES, discuss your treatment with

your doctor or pharmacist because Carbamazepine Essential

Pharma Suppositories might not be the right medicine for you.

Are you pregnant or planning to become pregnant?

Are you breastfeeding?

Do you suffer from the sort of epilepsy where you get mixed

seizures which include absences?

Do you have any mental illness?

Are you allergic to an epilepsy medicine called phenytoin?

Do you have liver problems?

Do you have kidney problems associated with low sodium

blood level or do you have kidney problems and you are

taking certain medicines that lower sodium blood levels

(diuretics such as hydrochlorothiazide, furosemide)?

Are you elderly?

Isotretinoin (a medicine for the treatment of acne).

Metoclopramide or aprepitant (anti-sickness medications).

Acetazolamide (a medicine to treat glaucoma - increased

pressure in the eye).

Danazol or gestrinone (treatments for endometriosis).

Theophylline or aminophylline (used in the treatment of

asthma).

Ciclosporin, tacrolimus or sirolimus (immunosuppressants,

used after transplant operations, but also sometimes in the

treatment of arthritis or psoriasis).

Drugs to treat schizophrenia (e.g. paliperidone, aripiprazole).

Cancer drugs (e.g. temsirolimus, cyclophasphamide,

lapatinib).

The anti-malarial drug, mefloquine.

Drugs to treat HIV.

Levothyroxine (used to treat hypothyroidism).

Tadalafil (used to treat impotence).

Albendazole (used to treat worms).

Bupropion (used to help stop smoking).

A herbal remedy called St John’s Wort or Hypericum.

Drugs or supplements containing Vitamin B (nicotinamide).

Pregnancy and breastfeeding

You must discuss your epilepsy treatment with your doctor well

before you become pregnant. If you do get pregnant you must

tell the doctor straightaway. It is important that your epilepsy

remains well controlled, but, as with other anti-epilepsy

treatments, there is a risk of harm to the foetus. Make sure you

are very clear about the risks and the benefits of being treated

with Carbamazepine Essential Pharma Suppositories.

Mothers being treated with Carbamazepine Essential Pharma

Suppositories can breastfeed their babies, but you must tell the

doctor as soon as possible if you think that the baby is suffering

side effects such as excessive sleepiness, skin reaction or yellow

skin and eyes, dark urine or pale stools.

Will there be any problems with driving or using machinery?

Carbamazepine Essential Pharma Suppositories can make you

feel dizzy or drowsy, or may cause blurred vision, double vision,

or you may have a lack of muscular coordination, especially at

the start of treatment or when the dose is changed. If you are

affected in this way, or if your eyesight is affected, you should

not drive or operate machinery.

Other special warnings

Drinking alcohol may affect you more than usual. Discuss

whether you should stop drinking with your doctor.

Eating grapefruit, or drinking grapefruit juice, may increase

your chance of experiencing side effects.

Your doctor may want you to have a number of blood tests

before you are treated with Carbamazepine and sometimes

during your treatment. This is quite usual and nothing to

worry about.

3. How to use Carbamazepine Essential Pharma

Suppositories

The doctor will tell you the dose you need. Always follow

his/her instructions carefully. The dose will be on the

pharmacist’s label. Check the label carefully. It is important

to use the suppositories at the right times. If you are not sure,

ask your doctor or pharmacist. Keep using the suppositories

for as long as you have been told, unless you have any

problems. In that case, check with your doctor.

Suppositories are designed to be inserted into the back passage

(rectum). Never take them by mouth.

For how to insert the suppositories see the end of the leaflet.

Your doctor will work out the dose that you need. It varies from

person to person.

Do you have any eye problems such as glaucoma (increased

pressure in the eye) or do you have difficulty retaining your

urine?

Are you taking other medicines?

Because of the way that Carbamazepine Essential Pharma

works, it can affect, and be affected by, lots of other things that

you might be eating or medicines that you are taking. It is very

important to make sure that your doctor knows all about what

else you are taking, including anything that you have bought

from a chemist or health food shop. It may be necessary to

change the dose of some medicines, or stop taking something

altogether.

Tell the doctor if you are taking:

Hormone contraceptives, e.g. pills, patches, injections or

implants. Carbamazepine Essential Pharma affects the way

the contraceptive works in your body, and you may get

breakthrough bleeding or spotting. It may also make the

contraceptive less effective and there will be a risk of getting

pregnant. Your doctor will be able to advise you about this,

and you should think about using other contraceptives.

Hormone Replacement Therapy (HRT). Carbamazepine

Essential Pharma can make HRT less effective.

Any medicines for depression or anxiety.

Corticosteroids (‘steroids’). You might be taking these for

inflammatory conditions such as asthma, inflammatory

bowel disease, muscle and joint pains.

Anticoagulants to stop your blood clotting.

Antibiotics to treat infections including skin infections and TB

(e.g. ciprofloxacillin).

Antifungals to treat fungal infections.

Painkillers containing paracetamol, dextropropoxyphene,

tramadol, methadone or buprenorphine.

Other medicines to treat epilepsy.

Medicines for high blood pressure or heart problems.

Antihistamines (medicines to treat allergy such as hayfever,

itch, etc).

Diuretics (water tablets).

Car125-250mgSupp-PL-UK-3

11pt

News Gothic MT Bold Condens

18PT

Cimetidine or omeprazole (medicines to treat gastric ulcers).

Will there be any problems with driving or using machinery?

Carbamazepine Essential Pharma Suppositories can make you

feel dizzy or drowsy, or may cause blurred vision, double vision,

or you may have a lack of muscular coordination, especially at

the start of treatment or when the dose is changed. If you are

affected in this way, or if your eyesight is affected, you should

not drive or operate machinery.

Other special warnings

Drinking alcohol may affect you more than usual. Discuss

whether you should stop drinking with your doctor.

Eating grapefruit, or drinking grapefruit juice, may increase

your chance of experiencing side effects.

Your doctor may want you to have a number of blood tests

before you are treated with Carbamazepine and sometimes

during your treatment. This is quite usual and nothing to

worry about.

3. How to use Carbamazepine Essential Pharma

Suppositories

The doctor will tell you the dose you need. Always follow

his/her instructions carefully. The dose will be on the

pharmacist’s label. Check the label carefully. It is important

to use the suppositories at the right times. If you are not sure,

ask your doctor or pharmacist. Keep using the suppositories

for as long as you have been told, unless you have any

problems. In that case, check with your doctor.

Suppositories are designed to be inserted into the back passage

(rectum). Never take them by mouth.

For how to insert the suppositories see the end of the leaflet.

Your doctor will work out the dose that you need. It varies from

person to person.

The maximum dose is 1,000 mg per day. Elderly people might

need a lower dose.

What if you forget a dose?

If you forget to take a dose, take one as soon as you remember.

If it is nearly time for your next dose, though, just take the next

dose and forget about the one you missed.

Using too many suppositories

If you accidentally insert too many suppositories, or if anyone

swallows any suppositories, tell your doctor or your nearest

hospital casualty department. Take your pack with you so that

people can see what medicine you are having.

4. Possible side effects

Carbamazepine Essential Pharma Suppositories do not usually

cause problems, but like all medicines, they can sometimes

cause side effects.

Some side effects can be serious

Stop using the suppositories and tell your doctor straight away

if you notice:

Serious skin reactions such as rash, red skin, blistering of the

lips, eyes or mouth, or skin peeling accompanied by fever.

These reactions may be more frequent in patients of Chinese

or Thai origin

Mouth ulcers or unexplained bruising or bleeding

Sore throat or high temperature, or both

Yellowing of your skin or the whites of your eyes

Swollen ankles, feet or lower legs

Any signs of nervous illness or confusion

Pain in your joints and muscles, a rash across the bridge of

the nose and cheeks and problems with breathing (these

may be the signs of a rare reaction known as lupus

erythematosus)

Fever, skin rash, joint pain, and abnormalities in blood and

liver function tests (these may be the signs of a multi-organ

sensitivity disorder)

Bronchospasm with wheezing and coughing, difficulty in

breathing, feeling faint, rash, itching or facial swelling (these

may be the signs of a severe allergic reaction)

Pain in the area near the stomach.

The side effects listed below have also been reported.

More than 1 in 10 people have experienced:

Leucopenia (a reduced number of the cells which fight infection

making it easier to catch infections); dizziness and tiredness;

feeling unsteady or finding it difficult to control movements;

feeling or being sick; changes in liver enzyme levels (usually

without any symptoms); skin reactions which may be severe.

Up to 1 in 10 people have experienced:

Changes in the blood including an increased tendency to bruise

or bleed; fluid retention and swelling; weight increase; low

sodium in the blood which might result in confusion; headache;

double or blurred vision; dry mouth; rectal irritation.

Up to 1 in 100 people have reported:

Abnormal involuntary movements including tremor or tics;

abnormal eye movements; diarrhoea; constipation.

Up to 1 in 1,000 people have reported:

Disease of the lymph glands; folic acid deficiency; a generalised

allergic reaction including rash, joint pain, fever, problems with

the liver, kidneys and other organs; hallucinations; depression;

loss of appetite; restlessness; aggression; agitation; confusion;

speech disorders; numbness or tingling in the hands and feet;

muscle weakness; high blood pressure (which may make you

feel dizzy, with a flushed face, headache, fatigue and

nervousness); low blood pressure (the symptoms of which are

feeling faint, light headed, dizzy, confused, having blurred

vision); changes to heart beat; stomach pain; liver problems

including jaundice; symptoms of lupus.

Up to 1 in 10,000 people have reported:

Changes to the composition of the blood including anaemia;

porphyria; meningitis; swelling of the breasts and discharge of

milk which may occur in both male and females; abnormal

thyroid function tests; osteomalacia (which may be noticed as

pain on walking and bowing of the long bones in the legs);

osteoporosis; increased blood fat levels; taste disturbances;

conjunctivitis; glaucoma; cataracts; hearing disorders; heart and

circulatory problems including deep vein thrombosis (DVT), the

symptoms of which could include tenderness, pain, swelling,

warmth, skin discoloration and prominent superficial veins; lung

or breathing problems; severe skin reactions including

Stevens-Johnson syndrome (these reactions may be more

frequent in patients of Chinese or Thai origin); sore mouth or

tongue; liver failure; increased sensitivity of the skin to sunlight;

alterations in skin pigmentation; acne; excessive sweating; hair

loss; increased hair growth on the body and face; muscle pain

or spasm; sexual difficulties which may include reduced male

fertility, loss of libido or impotence; kidney failure; blood spots in

the urine; increased or decreased desire to pass urine or

difficulty in passing urine.

The following have also been reported, but the frequency cannot

be estimated from the available information:

Severe skin reactions, accompanied by feeling unwell and

changes in blood results. Diarrhoea, abdominal pain, and fever

(signs of inflammation of the colon), reactivation of herpes virus

infection (can be serious when immune system is depressed),

complete loss of nails, fracture, decrease in the measure of the

bone density, drowsiness, memory loss, purple or

reddish-purple bumps that may be itchy.

Do not be alarmed by this list. Most people use

Carbamazepine Essential Pharma Suppositories without any

problems.

If any of the symptoms become troublesome, or if you notice

anything else not mentioned here, please go and see your

doctor. He/she may want to give you a different medicine.

There have been reports of bone disorders including osteopenia

and osteoporosis (thinning of the bone) and fractures.

Check with your doctor or pharmacist if you are on long-term

antiepileptic medication, have a history of osteoporosis, or take

steroids.

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. By reporting side

effects you can help provide more information on the safety of

this medicine.

5.

How to store Carbamazepine Essential Pharma

Suppositories

Protect from heat (store below 30ºC).

Keep out of the reach and sight of children.

Do not use the suppositories after the expiry date which is

printed on the outside of the pack.

If your doctor tells you to stop using the suppositories, please

take any left over back to your pharmacist to be destroyed. Do

not throw them away with your normal household water or

waste. This will help to protect the environment.

6. Further information

The suppositories are white or off-white in colour and come in

two strengths. The active ingredient is carbamazepine, and they

also contain the inactive ingredients hydroxypropyl

methylcellulose and suppository mass 15. The lower dose

contains 125 mg of carbamazepine and the suppository weighs

about 1 gram. The higher dose contains 250 mg of

carbamazepine and the suppository weighs about 2 grams.

There are 5 suppositories in each pack.

Marketing Authorisation Holder:

Essential Pharma Ltd, 7 Egham Business Village, Crabtree

Road, Egham, Surrey, TW20 8RB, United Kingdom.

Manufacturer

Delpharm Huningue SAS - Huningue

26 rue de la Chapelle,

68330 Huningue

France

How to insert the suppositories

Empty your bowels before

inserting a suppository.

Wash your hands.

Take out the strip of suppositorie

and tear off one along the

perforation.

Tear the foil wrapping apart at the

notch and take out the

suppository.

Lie on one side with your knees

pulled up towards your chest.

Gently push the suppository

pointed end first into your back

passage (rectum) with your finger.

Push the suppository in as far as

possible as shown in the diagram.

Lower your legs and, if possible, stay still for a few minutes.

If you feel as if you need to push the suppository out, try to

resist this by lying still with your buttocks pressed together. It

is important to keep the suppository in the rectum to allow it

to melt and the medicine to be absorbed. Pushing the

suppository high into the rectum with your finger will help to

reduce this feeling.

Wash your hands.

The procedure is the same for a child. Once they have emptied

their bowels, get them to lie down on their front or side. Gently

push the suppository into the child’s back passage until it

disappears. Try and stop the child moving around for a few

minutes to reduce the risk of the suppository coming out.

If a doctor or nurse is giving the suppository to an unconscious

patient, the procedure will be similar to that described above.

This leaflet was revised in August 2016.

Car125-250mg-Supp-PL-UK-3

Read the complete document

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Carbamazepine Essential Pharma 125mg Suppositories

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

The active ingredient is 5H-dibenzo[b,f]azepine-5-carboxamide (carbamazepine).

Each suppository contains 125 mg carbamazepine Ph.Eur.

3

PHARMACEUTICAL FORM

White to practically white, torpedo shaped suppositories

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Epilepsy - generalised tonic-clonic and partial seizures.

Note: Carbamazepine Essential Pharma is not usually effective in absences (petit mal)

and myoclonic seizures. Moreover, anecdotal evidence suggests that seizure

exacerbation may occur in patients with atypical absences.

No clinical data are available on the use of Carbamazepine Essential Pharma

Suppositories in indications other than epilepsy.

4.2

Posology and method of administration

Before deciding to initiate treatment, patients of Han Chinese and Thai origin should

whenever possible be screened for HLA-B*1502 as this allele strongly predicts the

risk of severe carbamazepine-associated Stevens-Johnson syndrome (See information

on genetic testings and cutaneous reactions in section 4.4).

Epilepsy:

The dose of carbamazepine should be adjusted to the needs of the individual patient

to achieve adequate control of seizures. Determination of plasma levels may help in

establishing the optimum dosage. In the treatment of epilepsy, the dose of

carbamazepine usually requires total plasma-carbamazepine concentrations of about 4

to 12 micrograms/mL (17 to 50 micromoles/litre) (see warnings and precautions).

Adults, Elderly, Children and Adolescents: 125mg and 250mg suppositories are

available for short-term use as replacement therapy (maximum period recommended:

7 days) in patients for whom oral treatment is temporarily not possible, for example

in post-operative or unconscious subjects.

When switching from oral formulations to suppositories the dosage should be

increased by approximately 25% (the 125 and 250mg suppositories correspond to 100

and 200mg tablets respectively). Carbamazepine Essential Pharma Suppositories have

been shown to provide plasma levels which are well within the therapeutic range (see

Pharmacokinetics).

Where Suppositories are used the maximum daily dose is limited to 1000mg (250mg

qid at 6 hour intervals, see Pharmacokinetics).

No clinical data are available on the use of suppositories in indications other than

epilepsy.

Due to the potential for drug interactions, the dosage of Carbamazepine Essential

Pharma should be selected with caution in elderly patients.

When Carbamazepine Essential Pharma is added to existing antiepileptic therapy, this

should be done gradually while maintaining or, if necessary, adapting the dosage of

the other antiepileptic(s) (see 4.5 Interaction with other Medicaments and other forms

of Interaction).

Route of administration: Rectal.

Special populations

Renal impairment / Hepatic impairment

No data are available on the pharmacokinetics of carbamazepine in patients with

impaired hepatic or renal function.

4.3

Contraindications

Known hypersensitivity to carbamazepine or structurally related drugs (e.g. tricyclic

antidepressants) or any other component of the formulation.

Patients with atrioventricular block, a history of bone marrow depression or a history

of hepatic porphyrias (e.g. acute intermittent porphyria, variegate porphyria,

porphyria cutanea tarda).

The use of Carbamazepine Essential Pharma is contraindicated in combination with

monoamine oxidase inhibitors (MAOIs) (see section 4.5 Interaction with other

medicinal products and other forms of interaction).

4.4

Special warnings and precautions for use

Warnings

Agranulocytosis and aplastic anaemia have been associated with Carbamazepine

Essential Pharma; however, due to the very low incidence of these conditions,

meaningful risk estimates for Carbamazepine Essential Pharma are difficult to obtain.

The overall risk in the general untreated population has been estimated at 4.7 persons

per million per year for agranulocytosis and 2.0 persons per million per year for

aplastic anaemia.

Decreased platelet or white blood cell counts occur occasionally to frequently in

association with the use of Carbamazepine Essential Pharma. Nonetheless, complete

pre-treatment blood counts, including platelets and possibly reticulocytes and serum

iron, should be obtained as a baseline, and periodically thereafter.

Patients and their relatives should be made aware of early toxic signs and symptoms

indicative of a potential haematological problem, as well as symptoms of

dermatological or hepatic reactions. If reactions such as fever, sore throat, rash,

ulcers in the mouth, easy bruising, petechial or purpuric haemorrhage appear, the

patient should be advised to consult his physician immediately.

If the white blood cell or platelet count is definitely low or decreased during

treatment, the patient and the complete blood count should be closely monitored (see

Section 4.8 Undesirable Effects). However, treatment with Carbamazepine Essential

Pharma should be discontinued if the patient develops leucopenia which is severe,

progressive or accompanied by clinical manifestations, e.g. fever or sore throat.

Carbamazepine Essential Pharma should also be discontinued if any evidence of

significant bone marrow depression appears.

Liver function tests should also be performed before commencing treatment and

periodically thereafter, particularly in patients with a history of liver disease and in

elderly patients. The drug should be withdrawn immediately in cases of aggravated

liver dysfunction or acute liver disease.

Some liver function tests in patients receiving carbamazepine may be found to be

abnormal, particularly gamma glutamyl transferase. This is probably due to hepatic

enzyme induction. Enzyme induction may also produce modest elevations in alkaline

phosphatase. These enhancements of hepatic metabolising capacity are not an

indication for the withdrawal of carbamazepine.

Severe hepatic reactions to carbamazepine occur very rarely. The development of

signs and symptoms of liver dysfunction or active liver disease should be urgently

evaluated and treatment with Carbamazepine Essential Pharma suspended pending

the outcome of the evaluation.

Suicidal ideation and behaviour have been reported in patients treated with anti-

epileptic agents in several indications. A meta-analysis of randomised placebo

controlled trials of anti-epileptic drugs has also shown a small increased risk of

suicidal ideation and behaviour. The mechanism of this risk is not known and the

available data do not exclude the possibility of an increased risk for carbamazepine.

Therefore patients should be monitored for signs of suicidal ideation and behaviours

and appropriate treatment should be considered. Patients (and caregivers of patients)

should be advised to seek medical advice should signs of suicidal ideation or

behaviour emerge.

Serious dermatological reactions, including toxic epidermal necrolysis (TEN: also

known as Lyell’s syndrome) and Stevens Johnson syndrome (SJS) have been reported

very rarely with Carbamazepine Essential Pharma. Patients with serious

dermatological reactions may require hospitalization, as these conditions may be life-

threatening and may be fatal. Most of the SJS/TEN cases appear in the first few

months of treatment with Carbamazepine Essential Pharma. These reactions are

estimated to occur in 1 to 6 per 10,000 new users in countries with mainly Caucasian

populations. If signs and symptoms suggestive of severe skin reactions (e.g. SJS,

Lyell's syndrome/TEN) appear, Carbamazepine Essential Pharma should be

withdrawn at once and alternative therapy should be considered.

Cutaneous reactions

Serious and sometimes fatal cutaneous reactions including toxic epidermal necrolysis

(TEN) and Stevens-Johnson syndrome (SJS) have been reported during treatment

with carbamazepine. These reactions are estimated to occur in 1-6 per 10 000 new

users in countries with mainly Caucasian populations, but the risk in some Asian

countries is estimated to be about 10 times higher.

There is growing evidence of the role of different HLA alleles in predisposing

patients to immune-mediated adverse reactions (see section 4.2).

HLA-B*1502 allele - in Han Chinese, Thai and other Asian populations

HLA-B*1502 in individuals of Han Chinese and Thai origin has been shown to be

strongly associated with the risk of developing Stevens-Johnson syndrome (SJS)

when treated with carbamazepine. The prevalence of HLA-B*1502 carrier is about

10% in Han Chinese and Thai populations. Whenever possible, these individuals

should be screened for this allele before starting treatment with carbamazepine (see

section 4.2). If these individuals test positive, carbamazepine should not be started

unless there is no other therapeutic option. Tested patients who are found to be

negative for HLA-B*1502 have a low risk of SJS, although the reactions may still

very rarely occur.

There are some data that suggest an increased risk of serious carbamazepine-

associated TEN/SJS in other Asian populations. Because of the prevalence of this

allele in other Asian populations (e.g. above 15% in the Philippines and Malaysia),

testing genetically at risk populations for the presence of HLA-B*1502 may be

considered.

The prevalence of the HLA-B*1502 allele is negligible in e.g. European descent,

African, Hispanic populations sampled, and in Japanese and Koreans (< 1%).

HLA-A*3101 allele - European descent and Japanese populations

There are some data that suggest HLA-A*3101 is associated with an increased risk of

carbamazepine induced cutaneous adverse drug reactions including SJS, TEN, Drug

rash with eosinophilia (DRESS), or less severe acute generalized exanthematous

pustulosis (AGEP) and maculopapular rash (see section 4.8) in people of European

descent and the Japanese.

The frequency of the HLA-A*3101 allele varies widely between ethnic populations.

HLA-A*3101 allele has a prevalence of 2 to 5% in European populations and about

10% in Japanese population.

The presence of HLA-A*3101 allele may increase the risk for carbamazepine induced

cutaneous reactions (mostly less severe) from 5.0% in general population to 26.0%

among subjects of Northern European ancestry, whereas its absence may reduce the

risk from 5.0% to 3.8%.

There are insufficient data supporting a recommendation for HLA-A*3101 screening

before starting carbamazepine treatment.

If patients of European descent or Japanese origin are known to be positive for HLA-

A*3101 allele, the use of carbamazepine may be considered if the benefits are

thought to exceed risks.

Other dermatologic reactions

Mild skin reactions e.g. isolated macular or maculopapular exanthema, can also occur

and are mostly transient and not hazardous. They usually disappear within a few days

or weeks, either during the continued course of treatment or following a decrease in

dosage. However, since it may be difficult to differentiate the early signs of more

serious skin reactions from mild transient reactions, the patient should be kept under

close surveillance with consideration given to immediately withdrawing the drug

should the reaction worsen with continued use.

The HLA-B*1502 allele has not been found to predict risk of less severe adverse

cutaneous reactions from carbamazepine, such as anticonvulsant hypersensitivity

syndrome or non-serious rash (maculopapular eruption).

Hypersensitivity

Carbamazepine Essential Pharma may trigger hypersensitivity reactions, including

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), reactivation of

HHV6 associated with DRESS, a delayed multi-organ hypersensitivity disorder with

fever, rash, vasculitis, lymphadenopathy, pseudo lymphoma, arthralgia, leukopenia,

eosinophilia, hepato-splenomegaly, abnormal liver function tests and vanishing bile

duct syndrome (destruction and disappearance of the intrahepatic bile ducts), that may

occur in various combinations. Other organs may also be affected (e.g. lungs,

kidneys, pancreas, myocardium, colon) see section 4.8 Undesirable Effects.

In general, if signs and symptoms suggestive of hypersensitivity reactions occur,

Carbamazepine Essential Pharma should be withdrawn immediately.

Patients who have exhibited hypersensitivity reactions to carbamazepine should be

informed that 25-30 % of these patients may experience hypersensitivity reactions

with oxacarbazepine (Trileptal).

Cross-hypersensitivity can occur between carbamazepine and phenytoin.

Carbamazepine Essential Pharma should be used with caution in patients with mixed

seizures which include absences, either typical or atypical. In all these conditions,

Carbamazepine Essential Pharma may exacerbate seizures. In case of exacerbation of

seizures, Carbamazepine Essential Pharma should be discontinued.

An increase in seizure frequency may occur during switchover from an oral

formulation to suppositories.

Dose reduction and withdrawal effects:

Abrupt withdrawal of Carbamazepine Essential Pharma may precipitate seizures

therefore carbamazepine withdrawal should be gradual. If treatment with

Carbamazepine Essential Pharma has to be withdrawn abruptly in a patient with

epilepsy, the changeover to another anti-epileptic drug should if necessary be effected

under the cover of a suitable drug.

Endocrinological effects

Breakthrough bleeding has been reported in women taking Carbamazepine Essential

Pharma while using hormonal contraceptives. The reliability of hormonal

contraceptives may be adversely affected by Carbamazepine Essential Pharma and

women of childbearing potential should be advised to consider using alternative

forms of birth control while taking Carbamazepine Essential Pharma.

Patients taking Carbamazepine Essential Pharma and requiring hormonal

contraception should receive a preparation containing not less than 50µg oestrogen or

use of some alternative non-hormonal method of contraception should be considered.

Monitoring of plasma levels

Although correlations between dosages and plasma levels of carbamazepine, and

between plasma levels and clinical efficacy or tolerability are rather tenuous,

monitoring of the plasma levels may be useful in the following conditions: dramatic

increase in seizure frequency/verification of patient compliance; during pregnancy;

when treating children or adolescents; in suspected absorption disorders; in suspected

toxicity when more than one drug is being used (see 4.5 Interaction with other

Medicaments and other forms of Interaction).

Precautions

Carbamazepine Essential Pharma should be prescribed only after a critical benefit-

risk appraisal and under close monitoring in patients with a history of cardiac, hepatic

or renal damage, adverse haematological reactions to other drugs, or interrupted

courses of therapy with Carbamazepine Essential Pharma.

Baseline and periodic complete urinalysis and BUN determinations are

recommended.

Hyponatremia

Hyponatremia is known to occur with carbamazepine. In patients with pre-existing

renal conditions associated with low sodium or in patients treated concomitantly with

sodium-lowering medicinal products (e.g. diuretics, medicinal products associated

with inappropriate ADH secretion), serum sodium levels should be measured prior to

initiating carbamazepine therapy. Thereafter, serum sodium levels should be

measured after approximately two weeks and then at monthly intervals for the first

three months during therapy, or according to clinical need. These risk factors may

apply especially to elderly patients. If hyponatraemia is observed, water restriction is

an important counter-measurement if clinically indicated.

Hypothyroidism

Carbamazepine may reduce serum concentrations of thyroid hormones through

enzyme induction requiring an increase in dose of thyroid replacement therapy in

patients with hypothyroidism. Hence thyroid function monitoring is suggested to

adjust the dosage of thyroid replacement therapy.

Anticholinergic effects

Carbamazepine Essential Pharma has shown mild anticholinergic activity; patients

with increased intraocular pressure and urinary retention should therefore be closely

observed during therapy (see section 4.8).

Psychiatric effects

The possibility of activation of a latent psychosis and, in elderly patients, of

confusion or agitation should be borne in mind.

Interactions

Co-administration of inhibitors of CYP3A4 or inhibitors of epoxide hydrolase with

carbamazepine can induce adverse reactions (increase of carbamazepine or

carbamazepine-10,11 epoxide plasma concentrations respectively). The dosage of

Carbamazepine Essential Pharma should be adjusted accordingly and/or the plasma

levels monitored.

Co-administration of CYP3A4 inducers with carbamazepine may decrease

carbamazepine plasma concentrations and its therapeutic effect, while discontinuation

of a CYP3A4 inducer may increase carbamazepine plasma concentrations. The

dosage of Carbamazepine Essential Pharma may have to be adjusted.

Carbamazepine is a potent inducer of CYP3A4 and other phase I and phase II enzyme

systems in the liver, and may therefore reduce plasma concentrations of co-

medications mainly metabolized by CYP3A4 by induction of their metabolism. See

section 4.5 Interactions.

Female patients of childbearing potential should be warned that the concurrent use of

Carbamazepine Essential Pharma with hormonal contraceptives may render this type

of contraceptive ineffective (see sections 4.5 Interactions and 4.6 Pregnancy and

lactation). Alternative non-hormonal forms of contraception are recommended when

using Carbamazepine Essential Pharma.

4.5

Interaction with other medicinal products and other forms of interaction

Cytochrome P450 3A4 (CYP 3A4) is the main enzyme catalysing formation of the

active metabolite carbamazepine 10, 11-epoxide. Co-administration of inhibitors of

CYP 3A4 may result in increased carbamazepine plasma concentrations which could

induce adverse reactions. Co-administration of CYP 3A4 inducers might increase the

rate of carbamazepine metabolism, thus leading to potential decreases in the

carbamazepine serum level and therapeutic effect.

Similarly, discontinuation of a CYP3A4 inducer may decrease the rate of metabolism

of carbamazepine, leading to an increase in carbamazepine plasma levels.

Carbamazepine is a potent inducer of CYP3A4 and other phase I and phase II enzyme

systems in the liver, and may therefore reduce plasma concentrations of

comedications mainly metabolized by CYP3A4 by induction of their metabolism.

Human microsomal epoxide hydrolase has been identified as the enzyme responsible

for the formation of the 10,11-transdiol derivative from carbamazepine-10,11

epoxide. Co-administration of inhibitors of human microsomal epoxide hydrolase

may result in increased carbamazepine-10,11 epoxide plasma concentrations.

Interactions resulting in a contraindication

The use of Carbamazepine Essential Pharma is contraindicated in combination with

monoamine-oxidase inhibitors (MAOIs); before administering Carbamazepine

Essential Pharma MAOIs should be discontinued for a minimum of 2 weeks, or

longer if the clinical situation permits (see contraindications).

Agents that may raise carbamazepine plasma levels:

Since raised plasma carbamazepine levels may result in adverse reactions (e.g.

dizziness, drowsiness, ataxia, diplopia), the dosage of Carbamazepine Essential

Pharma should be adjusted accordingly and/or the plasma levels monitored when

used concomitantly with the substances described below:

Analgesics, anti-inflammatory drugs: dextropropoxyphene.

Androgens: danazol.

Antibiotics: macrolide antibiotics (e.g. erythromycin, clarithromycin), ciprofloxacine.

Antidepressants: fluoxetine, fluvoxamine, paroxetine, trazodone.

Antiepileptics: vigabatrin.

Antifungals: azoles (e.g. itraconazole, ketoconazole, fluconazole, voriconazole).

Alternative anti-convulsants may be recommended in patients treated with

voriconazole or itraconazole.

Antihistamines: loratadine.

Antipsychotics: olanzapine.

Antituberculosis: isoniazid.

Antivirals: protease inhibitors for HIV treatment (e.g. ritonavir).

Carbonic anhydrase inhibitors: acetazolamide.

Cardiovascular drugs: diltiazem, verapamil.

Gastrointestinal drugs: possibly cimetidine, omeprazole.

Other interactions: grapefruit juice, nicotinamide (only in high dosage).

Agents that may raise the active metabolite carbamazepine-10,11-epoxide plasma

levels:

Since raised plasma carbamazepine-10,11-epoxide levels may result in adverse

reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Carbamazepine

Essential Pharma should be adjusted accordingly and/or the plasma levels monitored

when used concomitantly with the substances described below:

Quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide.

Agents that may decrease carbamazepine plasma levels:

The dose of Carbamazepine Essential Pharma may have to be adjusted when used

concomitantly with the substances described below:

Antiepileptics:

oxcarbazepine, phenobarbital, phenytoin (to avoid phenytoin

intoxication and subtherapeutic concentrations of carbamazepine it is recommended

to adjust the plasma concentration of phenytoin to 13 micrograms /mL before adding

carbamazepine to the treatment) and fosphenytoin, primidone, and, although the data

are partly contradictory, possibly also clonazepam.

Antineoplastics: cisplatin or doxorubicin.

Antituberculosis: rifampicin.

Bronchodilatators or anti-asthma drugs: theophylline, aminophylline.

Dermatological drugs: isotretinoin.

Other interactions: herbal preparations containing St John's wort (Hypericum

perforatum).

Effect of Carbamazepine Essential Pharma on plasma levels of concomitant

agents:

Carbamazepine may lower the plasma level, diminish or even abolish the activity of

certain drugs. The dosage of the following drugs may have to be adjusted to clinical

requirement:

Analgesics, anti-inflammatory agents: buprenorphine, methadone, paracetamol (long

term administration of carbamazepine and paracetamol (acetaminophen) may be

associated with hepatotoxicity), tramadol.

Antibiotics: doxycycline, rifabutin.

Anticoagulants: oral anticoagulants (e.g. warfarin and acenocoumarol).

Antidepressants: bupropion, citalopram, mianserin, sertraline, trazodone, tricyclic

antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine).

Antiemetics: aprepitant

Antiepileptics: clobazam, clonazepam, ethosuximide, lamotrigine, oxcarbazepine,

primidone, tiagabine, topiramate, valproic acid, zonisamide. To avoid phenytoin

intoxication and subtherapeutic concentrations of carbamazepine it is recommended

to adjust the plasma concentration of phenytoin to 13 micrograms /mL before adding

carbamazepine to the treatment. There have been rare reports of an increase in plasma

mephenytoin levels.

Antifungals: itraconazole, voriconazole. Alternative anti-convulsants may be

recommended in patients treated with voriconazole or itraconazole.

Antihelmintics: albendazole.

Antineoplastics: imatinib, cyclophosphamide, lapatinib, temsirolimus.

Antipsychotics: clozapine, haloperidol and bromperidol, olanzapine, quetiapine,

risperidone, aripiprazole, paliperidone.

Antivirals: protease inhibitors for HIV treatment (e.g. indinavir, ritonavir, saquinavir).

Anxiolytics: alprazolam.

Bronchodilatators or anti-asthma drugs: theophylline.

Contraceptives: hormonal contraceptives (alternative contraceptive methods should

be considered).

Similar products

Search alerts related to this product

View documents history

Share this information