CARBAMAZEPINE ESSENTIAL PHARMA

Posology Carbamazepine Essential Pharma Chewtabs are given orally, usually in two or three divided doses. g. a glass of water. The chewtabs should be chewed before swallowing, preferably with a little liquid to wash down possible remnants of the tablets.

The chewtabs are particularly suitable for children and adults who have difficulty in swallowing tablets. 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. 4). Adults It is advised that with all formulations of carbamazepine, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient.

Carbamazepine Essential Pharma Chewtabs should be taken in a number of divided doses although initially 100-200 mg once or twice daily is recommended. This may be followed by a slow increase until the best response is obtained, often 800-1200 mg daily.

In some instances, 1600 mg or even 2000 mg daily may be necessary. Paediatric population and adolescents It is advised that with all formulations of carbamazepine, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient.

Usual dosage 10-20 mg/kg bodyweight daily taken in several divided doses. Carbamazepine Essential Pharma Chewtabs are not recommended for very young children. 1-5 years: 200 to 400 mg daily (2-4 x 100 mg chewtabs per day, where appropriate).

5-10 years: 400 to 600 mg daily (2-3 x 200 mg chewtabs per day, to be taken in divided doses). 10-15 years: 600 to 1000 mg daily (3-5 x 200 mg chewtabs per day, to be taken in several divided doses). >15 years of age: 800 to 1200 mg daily (same as adult dose).

Maximum recommended dose Up to 6 years of age: 35 mg/kg/day 6-15 years of age: 1000 mg/day >15 years of age: 1200 mg/day. Wherever possible, anti-epileptic agents should be prescribed as the sole anti- epileptic agent but if used in polytherapy the same incremental dosage pattern is advised.

5).

Trigeminal neuralgia:

Slowly raise the initial dosage of 200-400 mg daily until freedom from pain is achieved (normally at 200 mg 3-4 times daily). In the majority of patients, a dosage of 200 mg 3 or 4 times a day is sufficient to maintain a pain free state.

In some instances, doses of 1600 mg carbamazepine daily may be needed. However, once the pain is in remission, the dosage should be gradually reduced to the lowest possible maintenance level. Maximum recommended dose is 1200 mg/day. When pain relief has been obtained, attempts should be made to gradually discontinue therapy, until another attack occurs.

Elderly population Due to drug interactions and different antiepileptic drug pharmacokinetics, the dosage of carbamazepine should be selected with caution in elderly patients. In elderly patients, an initial dose of 100 mg twice daily is recommended.

The initial dosage of 100 mg twice daily should be slowly raised daily until freedom from pain is achieved (normally at 200 mg 3 to 4 times daily). The dosage should then be gradually reduced to the lowest possible maintenance level.

Maximum recommended dose is 1200 mg/day. When pain relief has been obtained, attempts should be made to gradually discontinue therapy, until another attack occurs. For the prophylaxis of manic depressive psychosis in patients unresponsive to lithium therapy Initial starting dose of 400 mg daily, in divided doses, increasing gradually until symptoms are controlled or a total of 1600 mg given in divided doses is reached.

The usual dosage range is 400-600 mg daily, given in divided doses. Renal impairment / Hepatic impairment No data are available on the pharmacokinetics of carbamazepine in patients with impaired hepatic or renal function. Method of administration Oral use.

8. In general, if signs and symptoms suggestive of hypersensitivity reactions occur, carbamazepine 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).

phenytoin, primidone and phenobarbital). Seizures Carbamazepine should be used with caution in patients with mixed seizures which include absences, either typical or atypical. In all these conditions, carbamazepine may exacerbate seizures.

In case of exacerbation of seizures, carbamazepine 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 may precipitate seizures therefore carbamazepine withdrawal should be gradual.

If treatment with carbamazepine 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. Women of childbearing potential Carbamazepine may cause fetal harm when administered to a pregnant woman.

6). Carbamazepine should not be used in women of childbearing potential unless the benefit is judged to outweigh the risks following careful consideration of alternative suitable treatment options. Women of childbearing potential should be fully informed of the potential risk to the fetus if they take carbamazepine during pregnancy.

Before the initiation of treatment with carbamazepine in a woman of childbearing potential, pregnancy testing should be considered. Women of childbearing potential should use highly effective contraception during treatment and for at least two weeks after stopping treatment.

6). 6). Women of childbearing potential should be counselled to contact the doctor immediately if they become pregnant or think they might be pregnant and are taking carbamazepine. Endocrinological effects Breakthrough bleeding has been reported in women taking carbamazepine while using hormonal contraceptives.

The reliability of hormonal contraceptives may be adversely affected by carbamazepine and women of childbearing potential should be advised to consider using alternative forms of birth control while taking carbamazepine. Patients taking carbamazepine and requiring hormonal contraception should receive a preparation containing not less than 50 μg oestrogen or use of some alternative non-hormonal method of contraception should be considered.

5). Precautions Carbamazepine 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.

Baseline and periodic complete urinalysis and BUN determinations are recommended. Hyponatremia Hyponatremia is known to occur with carbamazepine. 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. 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 should be adjusted accordingly and/or the plasma levels monitored. Co-administration of CYP3A4 inducers with […]

Warnings Agranulocytosis and aplastic anaemia have been associated with carbamazepine; however, due to the very low incidence of these conditions, meaningful risk estimates for carbamazepine are difficult to obtain. 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. 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 the physician immediately.

8). g. fever or sore throat. Carbamazepine 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 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.

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. These reactions are estimated to occur in 1 to 6 per 10,000 new users in countries with mainly Caucasian populations.

g. SJS, Lyell's syndrome/TEN) appear, carbamazepine 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 to 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. 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. 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. g. above 15% in the Philippines and Malaysia), testing genetically at risk populations for the presence of HLA-B*1502 may be considered.

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 […]

g. 1. g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda). 5).