Carbamazepine 200 Austell 200 mg Tablet

CARBAMAZEPINE 200 AUSTELL is indicated for:

• Epilepsy with motor and psychic manifestations:
• psychomotor or temporal - lobe epilepsy
• generalised tonic - clonic seizure
• mixed forms of seizures
• complex or simple partial seizures (with or without loss of consciousness) with or without secondary generalisation.
• Acute mania and maintenance treatment of bipolar affective disorders to prevent or attenuate recurrence.
• Idiopathic trigeminal neuralgia.
• Idiopathic glossopharyngeal neuralgia.

It is suitable for both monotherapy and combination therapy. It is usually not effective in absences (petit mal) and myoclonic seizures. (See Section 4.4).

Posology

Epilepsy

When possible CARBAMAZEPINE 200 AUSTELL should be prescribed as monotherapy. Treatment should be initiated with low daily dosage, to be slowly increased until an optimal effect is obtained. Determination of plasma levels may help in establishing the optimum dosage. When CARBAMAZEPINE 200 AUSTELL is added to existing anti - epileptic therapy, this should be done gradually while maintaining, or if necessary, adapting the dosage of the other anti - epileptic(s). (See Section 4.5).

Dose for adults

Initially, 100 mg to 200 mg once or twice a day, followed by a slow increase until usually at a level of 400 mg twice or three times a day, the best response is obtained. In some instances 1600 mg in 3 to 4 divided doses may be necessary.

Special populations

Elderly

Due to interactions and different anti - epileptic medicine pharmacokinetics, the dosage of CARBAMAZEPINE 200 AUSTELL should be selected with caution in elderly patients.

Trigeminal Neuralgia

The initial dosage of 200 u2013 400 mg should be slowly raised daily until freedom from pain is achieved (normally at 200 mg 3 u2013 4 times daily, in some instances it may necessitate 1600 mg daily). The dosage should then be gradually reduced to the lowest possible maintenance level. In elderly and particularly sensitive patients (see Section 4.4) an initial dosage of 100 mg twice a day is recommended.

Acute mania and maintenance treatment of (bipolar) affective disorders

Dosage range: Approximately 400 u2013 1600 mg daily, the usual dosage being 400 u2013 600 mg daily given in 2 u2013 3 divided doses. In acute mania, the dosage should be increased rather quickly, whereas small dosage increments are recommended for maintenance therapy of bipolar disorders in order to ensure optimal tolerability.

Method of administration

CARBAMAZEPINE 200 AUSTELL may be taken during, after, or between meals and swallowed with adequate amount of fluid. When the patient is transferred from another anticonvulsant medicine to CARBAMAZEPINE 200 AUSTELL, the dosage of the first should be reduced gradually.

• Known hypersensitivity to carbamazepine, or structurally related medicines e.g. tricyclic antidepressants, or any other component of the CARBAMAZEPINE 200 AUSTELL.
• Patients with atrioventricular block.
• Patients with a history of bone - marrow depression.
• Patients with a history of porphyria (e.g. acute intermittent porphyria, variegate porphyria).
• The use of CARBAMAZEPINE 200 AUSTELL is contra - indicated in combination with monoamine - oxidase inhibitors (MAOls) or within 2 weeks of discontinuation of MAOls (see Section 4.5).
• Carbamazepine passes into the breast milk (about 25 - 60 % of plasma concentration). Mothers taking CARBAMAZEPINE 200 AUSTELL should not breastfeed their infants.
• Previous Stevens - Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

Warnings

Agranulocytosis and aplastic anaemia have been associated with CARBAMAZEPINE 200 AUSTELL. Decreased platelet or white blood cell counts may occur in association with the use of CARBAMAZEPINE 200 AUSTELL. 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 medical practitioner 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). However, treatment with CARBAMAZEPINE 200 AUSTELL should be discontinued if the patient develops leucopenia which is severe, progressive or accompanied by clinical manifestations, e.g. fever or sore throat.

CARBAMAZEPINE 200 AUSTELL 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. CARBAMAZEPINE 200 AUSTELL 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 developments of signs and symptoms of liver dysfunction or active liver disease should be urgently evaluated and treatment CARBAMAZEPINE 200 AUSTELL suspended pending the outcome of the evaluation.

Suicidal ideation and behaviour have been reported in patients treated with anti - epileptic medicines in several indications. A meta - analysis of randomised placebo - controlled trials of anti - epileptic medicines 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 Lyellu2019s syndrome) and Stevens Johnson syndrome (SJS) have been reported with CARBAMAZEPINE 200 AUSTELL. Patients with serious dermatological reactions may require hospitalisation, 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 200 AUSTELL. If signs and symptoms suggestive of severe skin reactions (e.g. SJS, Lyellu2019s syndrome/TEN) appear, CARBAMAZEPINE 200 AUSTELL should be withdrawn at once and alternative therapy should be considered.

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. Tested patients who are found to be negative for HLA - B*1502 have a low risk of SJS, although the reactions may still 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 %. Testing for the presence of HLA - A*3101 allele should be considered in patients with ancestry in genetically at - risk populations (for example, patients of the Japanese and Caucasian populations, patients who belong to the indigenous populations of the Americas, Hispanic populations, people of southern India, and people of Arabic descent), prior to initiating treatment with CARBAMAZEPINE 200 AUSTELL. The use of CARBAMAZEPINE 200 AUSTELL should be avoided in patients who are found to be positive for HLA - A*3101. Screening is generally not recommended for any current CARBAMAZEPINE 200 AUSTELL users, as the risk of SJS/TEN, AGEP, DRESS and maculopapular rash is largely confined to the first few months of therapy, regardless of HLA - A*3101 status.

Other dermatologic reactions

Skin reactions e.g. macular or maculopapular exanthema, can also occur. 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 CARBAMAZEPINE 200 AUSTELL should the reaction worsen with continued use.

The HLA - A*3101 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). However, the HLA - B*1502 allele has not been found to predict the risk of these aforementioned skin reactions.

Hypersensitivity

CARBAMAZEPINE 200 AUSTELL 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.

In general, if signs and symptoms suggestive of hypersensitivity reactions occur, CARBAMAZEPINE 200 AUSTELL 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. Cross - hypersensitivity can occur between carbamazepine and aromatic antiepileptic medicines (e.g. phenytoin, primidone and phenobarbitone).

CARBAMAZEPINE 200 AUSTELL should be used with caution in patients with mixed seizures which include absences, either typical or atypical. In all these conditions, CARBAMAZEPINE 200 AUSTELL may exacerbate seizures. In case of exacerbation of seizures, CARBAMAZEPINE 200 AUSTELL 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 200 AUSTELL may precipitate seizures, therefore carbamazepine withdrawal should be gradual. If treatment with CARBAMAZEPINE 200 AUSTELL has to be withdrawn abruptly in a patient with epilepsy, the changeover to another anti - epileptic medicine should if necessary be effected under the cover of a suitable medicine.

Endocrinological effects

Breakthrough bleeding has been reported in women taking CARBAMAZEPINE 200 AUSTELL while using hormonal contraceptives. The reliability of hormonal contraceptives may be adversely affected by CARBAMAZEPINE 200 AUSTELL and women of child - bearing potential should be advised to consider using alternative forms of birth control while taking CARBAMAZEPINE 200 AUSTELL. Patients taking CARBAMAZEPINE 200 AUSTELL and requiring hormonal contraception should receive a preparation containing not less than 50u03bcg 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; in suspected absorption disorders; in suspected toxicity when more than one medicine is being used (see 4.5).

Precautions

CARBAMAZEPINE 200 AUSTELL 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 medicines, or interrupted courses of therapy with CARBAMAZEPINE 200 AUSTELL. 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 doing 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 200 AUSTELL 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.

Co - administrations 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 200 AUSTELL 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 200 AUSTELL may have to be adjusted.

Carbamazepine is 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 metabolised by CYP3A4 by induction of their metabolism. (See section 4.5)

Falls

CARBAMAZEPINE 200 AUSTELL treatment has been associated with ataxia, dizziness, somnolence, hypotension, confusional state, sedation (see section 4.8) which may lead to falls and, consequently fractures or other injuries. For patients with diseases, conditions, or medication that could exacerbate these effects, complete risk assessment of fall should be considered recurrently for patients on long - term CARBAMAZEPINE 200 AUSTELL treatment.

Women of childbearing potential / Contraception in males and females

Due to enzyme induction, CARBAMAZEPINE 200 AUSTELL may result in a failure of the therapeutic effect of oral contraceptive medicines containing oestrogen and/or progesterone. Women of child - bearing potential should be advised to use alternative contraceptive methods while on treatment with CARBAMAZEPINE 200 AUSTELL.

Pregnancy

Offspring of epileptic mothers are known to be more prone to developmental disorders, including malformations. Developmental disorders and malformations, including spina bifida, and also other congenital anomalies e.g. craniofacial defects such as cleft lip/palate, cardiovascular malformations, hypospadias and anomalies involving various body systems, have been reported in association with the use of CARBAMAZEPINE 200 AUSTELL. Patients should be counselled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening.

- Pregnant women with epilepsy should be treated with special care.

- If women receiving CARBAMAZEPINE 200 AUSTELL became pregnant or plan to become pregnant, or if the need of initiating treatment with CARBAMAZEPINE 200 AUSTELL arises during pregnancy, the expected benefits must be carefully weighed against its possible hazards, particularly in the first 3 months of pregnancy.

- In women of child - bearing potential CARBAMAZEPINE 200 AUSTELL should, wherever possible, be prescribed as monotherapy, because the incidence of congenital abnormalities in the offspring of women treated with combination of antiepileptic medicines is greater than in those of mothers receiving the individual medicines as monotherapy. The risk of malformations following exposure to carbamazepine as polytherapy may vary depending on the specific medicines used and may be higher in polytherapy combinations that include valproate.

- Minimum effective doses should be given and monitoring of plasma levels is recommended. The plasma concentration could be maintained in the lower side of the therapeutic range 4 to 12 micrograms/mL provided seizure control is maintained. There is evidence to suggest that the risk of malformation with carbamazepine may be dose - dependent, i.e. at a dose < 400 mg per day, the rates of malformation were lower than with higher doses of carbamazepine.

- During pregnancy, an effective antiepileptic treatment should not be interrupted, since the aggravation of the illness is detrimental to both the mother and the fetus.

Monitoring and prevention

Folic acid deficiency is known to occur in pregnancy. Antiepileptic medicines have been reported to aggravate deficiency. This deficiency may contribute to the increased incidence of birth defects in the offspring of treated epileptic women. Folic acid supplementation has therefore been recommended before and during pregnancy.

In the neonate

In order to prevent bleeding disorders in the offspring, it has also been recommended that vitamin K1 be given to the mother during the last weeks of pregnancy as well as to the neonate. There have been cases of neonatal seizures and/or respiratory depression associated with maternal CARBAMAZEPINE 200 AUSTELL and other concomitant antiepileptic medicine use. Cases of neonatal vomiting, diarrhoea and/or decreased feeding have also been reported in association with maternal CARBAMAZEPINE 200 AUSTELL use. These reactions may represent a neonatal withdrawal syndrome.

Animal studies have shown reproductive toxicity.

Breastfeeding

Carbamazepine passes into the breast milk (about 25 u2013 60 % of the plasma concentrations). Mothers on CARBAMAZEPINE 200 AUSTELL should not breastfeed their infants.

Fertility

There have been very rare reports of impaired male fertility and/or abnormal spermatogenesis.

The patientu2019s ability to react may be impaired by the medical condition resulting in seizures and adverse reactions including dizziness, drowsiness, ataxia, diplopia, impaired accommodation and blurred vision have been reported with CARBAMAZEPINE 200 AUSTELL, especially at the start of treatment or in connection with dose adjustments. Patients should therefore exercise due caution when driving a vehicle or operating machinery.

a) Summary of the safety profile

Particularly at the start of the treatment with CARBAMAZEPINE 200 AUSTELL, or if the initial dosage is too high, or when treating elderly patients, certain types of adverse reaction occur frequently, e.g. CNS adverse reactions (dizziness, headache, ataxia, drowsiness, fatigue, diplopia), gastrointestinal disturbances (nausea, vomiting), as well as allergic skin reactions. The dose - related adverse reactions usually abate within a few days, either spontaneously or after a transient dosage reduction. The occurrence of CNS adverse reactions may be a manifestation of relative overdosage or significant fluctuation in plasma levels. In such cases it is advisable to monitor the plasma levels and divide the daily dosage into smaller (i.e. 3 - 4) fractional doses.

b) Tabulated list of adverse reactions

The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with carbamazepine. Frequency estimate: Frequent, Less frequent, Not known (cannot be estimated from the available data).

Signs and symptoms

The presenting signs and symptoms of overdosage involves the central nervous, cardiovascular, respiratory systems and the adverse drug reactions mentioned under section 4.8.

Central nervous system: CNS depression; disorientation, depressed level of consciousness, somnolence, agitation, hallucination, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, initially hyper - reflexia, later hyporeflexia; convulsions, psychomotor disturbances, myoclonus, hypothermia, mydriasis.

Respiratory system: Respiratory depression, pulmonary oedema.

Cardiovascular system: Tachycardia, hypotension and at times hypertension, conduction disturbance with widening of QRS complex; syncope in association with cardiac arrest.

Gastro - intestinal system: Vomiting, delayed gastric emptying, reduced bowel motility.

Musculoskeletal system: There have been some cases which reported rhabdomyolysis in association with carbamazepine toxicity.

Renal function: Retention of urine, oliguria or anuria; fluid retention, water intoxication due to ADH - like effect of carbamazepine.

Laboratory findings: Hyponatraemia, possibly metabolic acidosis, possibly hyperglycaemia, increased muscle creatine phosphokinase.

Management/Treatment

There is no specific antidote. Management should initially be guided by the patientu2019s clinical condition; admission to hospital. Measurement of the plasma level to confirm carbamazepine poisoning and to ascertain the size of the overdose. Evacuation of the stomach and administration of activated charcoal. Delay in evacuating the stomach may result in delayed absorption, leading to relapse during recovery from intoxication.

Supportive medical care in an intensive care unit with cardiac monitoring and careful correction of electrolyte imbalance.

Special recommendations: Hypotension, administer dopamine or dobutamine i.v. Disturbances of cardiac rhythm, to be handled on an individual basis. Convulsions, administer a benzodiazepine (e.g. diazepam) or another anti - epileptic, e.g. phenobarbitone (with caution because of increased respiratory depression), or paraldehyde. Hyponatraemia (water intoxication), fluid restriction and slow and careful NaCl 0.9 % infusion i.v. These measures may be useful in preventing brain damage. Charcoal haemoperfusion has been recommended. Forced diuresis, hemodialysis and peritoneal dialysis have been reported to be not effective. Relapse and aggravation of symptomatology on the 2nd and 3rd day after overdose, due to delayed absorption, should be anticipated.