MEIZINE

Posology Meizine/Carbamazepine Prolonged-release tablets is given orally, generally in the same total daily dose as conventional Carbamazepine dosage forms but usually in two divided doses. In a few patients when changing from other oral dosage forms of Carbamazepine to Meizine/Carbamazepine Prolonged-release tablets the total daily dose may need to be increased, particularly when it is used in polytherapy.

When starting treatment with Meizine/Carbamazepine Prolonged-release tablets in monotherapy, 100-200mg once or twice daily is recommended. This may be followed by a slow increase in dosage until the best response is obtained, often 800- 1200mg daily.

In some instances, 1600mg or even 2000mg daily may be necessary. Not all dose regimens can be administered with this strength. Other formulations may need to be used for the administration of the 100 mg minimum daily dose. 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:

It is advised that with all formulations of Meizine/Carbamazepine, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient.

Elderly population (65 years or above):

Due to the potential for drug interactions, the dosage of Meizine/Carbamazepine should be selected with caution in elderly patients.

Children and adolescents:

It is advised that with all formulations of Meizine/Carbamazepine, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient. Usual dosage 10-20mg/kg bodyweight daily taken in several divided doses.

Age Up to 5 years:

Meizine/Carbamazepine Prolonged-release tablets are not recommended 5-10 years: 400-600 mg daily 10-15 years: 600-1000 mg >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, Meizine/Carbamazepine Prolonged-release tablets should be used as the sole drug anti-epileptic agent but if used in polytherapy, the same incremental dosage pattern is advised. 5 Interaction with other medicinal products and other forms of interaction).

Trigeminal neuralgia:

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

In some instances, doses of 1600mg Meizine/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 (65 years or above):

Dosage in Trigeminal neuralgia: Due to drug interactions and different anti-epileptic drug pharmacokinetics, the dosage of Meizine/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 400mg daily, in divided doses, increasing gradually until symptoms are controlled or a total of 1600mg given in divided doses is reached.

The usual dosage range is 400- 600mg daily, given in divided doses.

Special populations:

Renal impairment / Hepatic impairment: No data are available on the pharmacokinetics of carbamazepine in patients with impaired hepatic or renal function. Method of administration Meizine/Carbamazepine Prolonged-release tablets is given orally, and should not be chewed but should be swallowed with a little liquid, before, during or between meals.

). g. fever or sore throat. Meizine/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 Meizine/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 Meizine/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 Meizine/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, Meizine/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 1-6 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%). 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.

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.

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 […]

Warnings Agranulocytosis and aplastic anaemia have been associated with Meizine/Carbamazepine; however, due to the very low incidence of these conditions, meaningful risk estimates for Meizine/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 Meizine/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 Undesirable Effects). g. fever or sore throat. Meizine/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 Meizine/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 Meizine/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 Meizine/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, Meizine/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 1-6 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 […]

1. g. tricyclic antidepressants). g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda). The use of Meizine/Carbamazepine is contraindicated in combination with monoamine oxidase inhibitors (MAOIs) (see section