Carbamazepine Oral Suspension USP 100mg/5ml Taj Pharma

1. Name of the medicinal product

Carbamazepine Taj Pharma 100mg/5ml Oral Suspension

2. Qualitative and quantitative composition

Carbamazepine TAJ PHARMA 100mg/5ml Oral Suspension
Each 5ml Oral suspension contains:
Carbamazepine USP 100mg
Excipients: QS.

Excipients with known effect: Sorbitol  and orange yellow S

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Oral Suspension.

4. Clinical particulars

• Therapeutic indications

Carbamazepine Taj Pharma is indicated for

• epilepsy (generalised tonic-clonic and partial seizures)

Note: Carbamazepine Taj 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.

• the paroxysmal pain of trigeminal neuralgia
• the prophylaxis of manic-depressive psychosis in patients unresponsive to lithium therapy.

Posology and method of administration

Posology

Since a given dose of Carbamazepine Taj Pharma oral suspension will produce higher peak levels than the same dose in tablet form, it is advisable to start with low doses of the liquid and to increase them slowly so as to avoid adverse effects on the central nervous system such as dizziness and lethargy.

When switching a patient from tablets to liquid the same overall dose may be used but in smaller, more frequent, doses.

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 Taj Pharma-associated Stevens-Johnson syndrome (see information on genetic testings and cutaneous reactions in section 4.4).

Epilepsy

The dose of Carbamazepine Taj Pharma 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 Taj Pharma usually requires total plasma-Carbamazepine Taj Pharma 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 Carbamazepine Taj Pharma, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient.

Carbamazepine Taj Pharma should be taken in a number of divided doses although initially 100-200mg once to twice daily is recommended. This may be followed by a slow increase until the best response is obtained, often 800-1200mg daily. In some instances, 1600mg or even 2000mg daily may be necessary.

Elderly

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

Paediatric population

It is advised that with all formulations of Carbamazepine Taj Pharma, 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 in several divided doses.

Maximum recommended dose

Wherever possible anti-epileptic agents should be prescribed as the sole drug anti-epileptic agent but if used in polytherapy, the same incremental dosage pattern is advised.

When Carbamazepine Taj 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).

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 Carbamazepine Taj Pharma 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 1200mg/day. When pain relief has been obtained, attempts should be made to gradually discontinue therapy, until another attack occurs.

Elderly

Dosage in Trigeminal neuralgia

Due to drug interactions and different antiepileptic drug pharmacokinetics, the dosage of Carbamazepine Taj Pharma should be selected with caution in elderly patients.

In elderly patients, an initial dose of 100mg twice daily is recommended. The initial dosage of 100mg twice daily should be slowly raised daily until freedom from pain is achieved (normally at 200mg 3 to 4 times daily). The dosage should then be gradually reduced to the lowest possible maintenance level. Maximum recommended dose is 1200mg/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 Taj Pharma in patients with impaired hepatic or renal function.

Method of administration

Carbamazepine Taj Pharma oral suspension is given orally, usually in two or three divided doses. Carbamazepine Taj Pharma oral suspension (oral suspension should be shaken before use) may be taken during, after or between meals.

• Contraindications

• known hypersensitivity to Carbamazepine Taj Pharma or structurally related drugs (e.g. tricyclic antidepressants) or any of the excipients listed in section 6.1
• patients with atrioventricular block, a history of bone marrow depression or a history of hepatic porphyria (e.g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda)
• The use of Carbamazepine Taj Pharma is contraindicated in combination with monoamine oxidase inhibitors (MAOIs) (see section 4.5 Interaction with other medicinal products and other forms of interaction).
  • Special warnings and precautions for use

Warnings

Agranulocytosis and aplastic anaemia have been associated with Carbamazepine Taj Pharma; however, due to the very low incidence of these conditions, meaningful risk estimates for Carbamazepine Taj 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 Taj 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 Taj Pharma should be discontinued if the patient develops leukopenia which is severe, progressive or accompanied by clinical manifestations, e.g. fever or sore throat. Carbamazepine Taj 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 Taj Pharma 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 Taj Pharma.

Severe hepatic reactions to Carbamazepine Taj Pharma occur very rarely. The development of signs and symptoms of liver dysfunction or active liver disease should be urgently evaluated and treatment with Carbamazepine Taj 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 Taj Pharma.

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 Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN: also known as Lyell’s syndrome) have been reported very rarely with Carbamazepine Taj 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 Taj 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 Taj 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 Taj Pharma. 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 Taj Pharma. 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 Taj Pharma (see section 4.2). If these individuals test positive, Carbamazepine Taj Pharma 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 Taj Pharma-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 Taj Pharma 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 Taj Pharma 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 Taj Pharma treatment.

If patients of European descent or Japanese origin are known to be positive for HLA-A*3101 allele, the use of Carbamazepine Taj Pharma 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 Taj Pharma, such as anticonvulsant hypersensitivity syndrome or non-serious rash (maculopapular eruption).

Hypersensitivity

Carbamazepine Taj 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 Taj Pharma should be withdrawn immediately.

Patients who have exhibited hypersensitivity reactions to Carbamazepine Taj Pharma should be informed that 25-30% of these patients may experience hypersensitivity reactions with oxacarbazepine (Trileptal).

Cross-hypersensitivity can occur between Carbamazepine Taj Pharma and phenytoin.

Carbamazepine Taj Pharma should be used with caution in patients with mixed seizures which include absences, either typical or atypical. In all these conditions, Carbamazepine Taj Pharma may exacerbate seizures. In case of exacerbation of seizures, Carbamazepine Taj 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 Taj Pharma may precipitate seizures therefore Carbamazepine Taj Pharma withdrawal should be gradual. If treatment with Carbamazepine Taj 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 Taj Pharma while using hormonal contraceptives. The reliability of hormonal contraceptives may be adversely affected by Carbamazepine Taj Pharma and women of childbearing potential should be advised to consider using alternative forms of birth control while taking Carbamazepine Taj Pharma.

Patients taking Carbamazepine Taj Pharma 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.

Monitoring of plasma levels

Although correlations between dosages and plasma levels of Carbamazepine Taj Pharma, 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 Taj 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 Taj Pharma.

Baseline and periodic complete urinalysis and BUN determinations are recommended.

Hyponatremia

Hyponatremia is known to occur with Carbamazepine Taj Pharma. 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 Taj Pharma 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 Taj Pharma 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 Taj 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 Taj Pharma can induce adverse reactions (increase of Carbamazepine Taj Pharma or Carbamazepine Taj Pharma-10,11 epoxide plasma concentrations respectively). The dosage of Carbamazepine Taj Pharma should be adjusted accordingly and/or the plasma levels monitored.

Co-administration of CYP3A4 inducers with Carbamazepine Taj Pharma may decrease Carbamazepine Taj Pharma plasma concentrations and its therapeutic effect, while discontinuation of a CYP3A4 inducer may increase Carbamazepine Taj Pharma plasma concentrations. The dosage of Carbamazepine Taj Pharma may have to be adjusted.

Carbamazepine Taj Pharma 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 Taj 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 Taj Pharma.

This product contains the colouring orange yellow S. It may cause allergic reactions.

This product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This product contains potassium sorbate. Each 5ml of suspension contains less than 1 mmol (39mg) of potassium, i.e. essentially “potassium free”.

• Interaction with other medicinal products and other forms of interaction

Cytochrome P4503A4 (CYP3A4) is the main enzyme catalysing formation of the active metabolite Carbamazepine Taj Pharma 10, 11-epoxide. Co-administration of inhibitors of CYP3A4 may result in increased plasma concentrations which could induce adverse reactions. Co-administration of CYP3A4 inducers might increase the rate of Carbamazepine Taj Pharma metabolism, thus leading to potential decreases in the Carbamazepine Taj Pharma serum level and therapeutic effect.

Similarly, discontinuation of a CYP3A4 inducer may decrease the rate of metabolism of Carbamazepine Taj Pharma, leading to an increase in Carbamazepine Taj Pharma plasma levels.

Carbamazepine Taj Pharma 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 Taj Pharma-10,11 epoxide. Co-administration of inhibitors of human microsomal epoxide hydrolase may result in increased Carbamazepine Taj Pharma-10,11 epoxide plasma concentrations.

Interactions resulting in a contraindication

The use of Carbamazepine Taj Pharma is contraindicated in combination with monoamine-oxidase inhibitors (MAOIs); before administering Carbamazepine Taj 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 Taj Pharma plasma levels

Since raised plasma Carbamazepine Taj Pharma levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Carbamazepine Taj Pharma should be adjusted accordingly and/or the plasma levels monitored when used concomitantly with the substances described below:

Agents that may raise the active metabolite Carbamazepine Taj Pharma-10,11-epoxide plasma levels

Since raised plasma Carbamazepine Taj Pharma-10,11-epoxide levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Carbamazepine Taj 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 Taj Pharma plasma levels

The dose of Carbamazepine Taj Pharma may have to be adjusted when used concomitantly with the substances described below:

Effect of Carbamazepine Taj Pharma on plasma levels of concomitant agents

Carbamazepine Taj Pharma 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:

Combinations that require specific consideration

Concomitant use of Carbamazepine Taj Pharma and levetiracetam has been reported to increase Carbamazepine Taj Pharma-induced toxicity.

Concomitant use of Carbamazepine Taj Pharma and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.

The combination of lithium and Carbamazepine Taj Pharma may cause enhanced neurotoxicity in spite of lithium plasma concentrations being within the therapeutic range. Combined use of Carbamazepine Taj Pharma with metoclopramide or major tranquillisers, e.g. haloperidol, thioridazine, may also result in an increase in neurological side-effects.

Concomitant medication with Carbamazepine Taj Pharma and some diuretics (hydrochlorothiazide, furosemide) may lead to symptomatic hyponatraemia.

Carbamazepine Taj Pharma may antagonise the effects of non-depolarising muscle relaxants (e.g. pancuronium). Their dosage should be raised and patients monitored closely for a more rapid recovery from neuromuscular blockade than expected.

Carbamazepine Taj Pharma, like other psychoactive drugs, may reduce alcohol tolerance. It is therefore advisable for the patient to abstain from alcohol.

Interference with serological testing

Carbamazepine Taj Pharma may result in false positive perphenazine concentrations in HPLC analysis due to interference.

Carbamazepine Taj Pharma and the 10,11-epoxide metabolite may result in false positive tricyclic antidepressant concentration in fluorescence polarized immunoassay method.

• Fertility, pregnancy and lactation

Pregnancy

Offspring of epileptic mothers with untreated epilepsy 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 clept lip/palate, cardiovascular malformations, hypospadias and anomalies involving various body systems, have been reported in association with the use of Carbamazepine Taj Pharma. Patients should be counselled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening. Based on data in a North American pregnancy registry, the rate of major congenital malformations, defined as a structural abnormality with surgical, medical, or cosmetic importance, diagnosed within 12 weeks of birth was 3.0% (95% CI 2.1 to 4.2%) among mothers exposed to Carbamazepine Taj Pharma monotherapy in the first trimester and 1.1% (95% CI 0.35 to 2.5%) among pregnant women not taking any antiepileptic drug (relative risk 2.7, 95% CI 1.1 to 7.0).

Taking these data into consideration:

• pregnant women with epilepsy should be treated with special care
• if women receiving Carbamazepine Taj Pharma become pregnant or plan to become pregnant, or if the problem of initiating treatment with Carbamazepine Taj Pharma arises during pregnancy, the drug’s expected benefits must be carefully weighed against its possible hazards, particularly in the first 3 months of pregnancy
• in women of childbearing potential Carbamazepine Taj Pharmashould, wherever possible, be prescribed as monotherapy, because the incidence of congenital abnormalities in the offspring of women treated with a combination of antiepileptic drugs is greater than in those of mothers receiving the individual drugs as monotherapy. The risk of malformations following exposure to Carbamazepine Taj Pharma as polytherapy may vary depending on the specific drugs 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 Taj Pharma may be dose-dependent i.e. at a dose < 400mg per day, the rates of malformation were lower than with higher doses of Carbamazepine Taj Pharma.
• patients should be counseled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening
• during pregnancy, an effective antiepileptic treatment should not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.

Monitoring and prevention

Folic acid deficiency is known to occur in pregnancy. Anti-epileptic drugs 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 K_1, be given to the mother during the last weeks of pregnancy as well as to the neonate.

There have been a few cases of neonatal seizures and/or respiratory depression associated with maternal Carbamazepine Taj Pharma and other concomitant antiepileptic drug use. A few cases of neonatal vomiting, diarrhoea and/or decreased feeding have also been reported in association with maternal Carbamazepine Taj Pharma use. These reactions may represent a neonatal withdrawal syndrome.

Women of child-bearing potential and contraceptive measures

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

Breast-feeding

Carbamazepine Taj Pharma passes into the breast milk (about 25-60% of the plasma concentrations). The benefits of breast-feeding should be weighed against the remote possibility of adverse effects occurring in the infant. Mothers taking Carbamazepine Taj Pharma may breast-feed their infants, provided the infant is observed for possible adverse reactions (e.g. excessive somnolence, allergic skin reaction). There have been some reports of cholestatic hepatitis in neonates exposed to Carbamazepine Taj Pharma during antenatal and or during breast-feeding. Therefore breast-fed infants of mothers treated with Carbamazepine Taj Pharma should be carefully observed for adverse hepatobiliary effects.

Fertility

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

• Effects on ability to drive and use machines

The patient’s 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 reported with Carbamazepine Taj Pharma, 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.

• Undesirable effects

Summary of the safety profile

Particularly at the start of treatment with Carbamazepine Taj Pharma, or if the initial dosage is too high, or when treating elderly patients, certain types of adverse reaction occur very commonly or commonly, 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.

Tabulated summary of adverse drug reactions compiled from clinical trials and from spontaneous reports

Adverse drug reactions from clinical trials are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10) common (≥1/100, <1/10), uncommon (≥1/1.000, <1/100), rare (≥1/10.000, </1.000), very rare (<1/10.000), not known (cannot be estimated from the available data).

*In some Asian countries also reported as rare. See also section 4.4 Special warnings and precautions for use.

**Additional adverse drug reactions from spontaneous reports (frequency not known)

The following adverse drug reactions have been derived from post-marketing experience with Carbamazepine Taj Pharma via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness.

There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with Carbamazepine Taj Pharma. The mechanism by which Carbamazepine Taj Pharma affects bone metabolism has not been identified.

There is increasing evidence regarding the association of genetic markers and the occurrence of cutaneous ADRs such as SJS, TEN, DRESS, AGEP and maculopapular rash. In Japanese and European patients, these reactions have been reported to be associated with the use of Carbamazepine Taj Pharma and the presence of the HLA-A*3101 allele. Another marker, HLA-B*1502 has been shown to be strongly associated with SJS and TEN among individuals of Han Chinese, Thai and some other Asian ancestry (see sections 4.2 and 4.4 for further information).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Overdose

Signs and symptoms

The presenting signs and symptoms of overdosage involve 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 hyperreflexia, 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 Taj Pharma toxicity.

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

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

Treatment

There is no specific antidote.

Management should initially be guided by the patient’s clinical condition; admission to hospital. Measurement of the plasma level to confirm Carbamazepine Taj Pharma poisoning and to ascertain the size of the overdose.

Evacuation of the stomach, gastric lavage, 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

Charcoal haemoperfusion has been recommended. Hemodialysis is the effective treatment modality in the management of the Carbamazepine Taj Pharma overdose.

Relapse and aggravation of symptomatology on the 2nd and 3rd day after overdose, due to delayed absorption, should be anticipated.

5. Pharmacological properties
   • Pharmacodynamic properties

Pharmacotherapeutic group: Anti-epileptic, neurotropic and psychotropic agent;

Dibenzazepine derivative.

As an antiepileptic agent its spectrum of activity embraces: partial seizures (simple and complex) with and without secondary generalisation; generalised tonic-clonic seizures, as well as combinations of these types of seizures.

The mechanism of action of Carbamazepine Taj Pharma, the active substance of Carbamazepine Taj Pharma, has only been partially elucidated. Carbamazepine Taj Pharma stabilises hyperexcited nerve membranes, inhibits repetitive neuronal discharges, and reduces synaptic propagation of excitatory impulses. It is conceivable that prevention of repetitive firing of sodium-dependent action potentials in depolarised neurons via use- and voltage-dependent blockade of sodium channels may be its main mechanism of action.

Whereas reduction of glutamate release and stabilisation of neuronal membranes may account for the antiepileptic effects, the depressant effect on dopamine and noradrenaline turnover could be responsible for the antimanic properties of Carbamazepine Taj Pharma.

• Pharmacokinetic properties

Absorption

Carbamazepine Taj Pharma is absorbed almost completely but relatively slowly from the tablets. The conventional tablets yield mean peak plasma concentrations of the unchanged substance within 12 hours (liquid 2 hours) following single oral doses. With respect to the amount of active substance absorbed, there is no clinically relevant difference between the oral dosage forms. After a single oral dose of 400mg Carbamazepine Taj Pharma (tablets) the mean peak concentration of unchanged Carbamazepine Taj Pharma in the plasma is approx. 4.5μg/ml.

The bioavailability of Carbamazepine Taj Pharma in various oral formulations has been shown to lie between 85-100%.

Ingestion of food has no significant influence on the rate and extent of absorption, regardless of the dosage form of Carbamazepine Taj Pharma.

Steady-state plasma concentrations of Carbamazepine Taj Pharma are attained within about 1-2 weeks, depending individually upon auto-induction by Carbamazepine Taj Pharma and hetero-induction by other enzyme-inducing drugs, as well as on pre-treatment status, dosage, and duration of treatment.

Different preparations of Carbamazepine Taj Pharma may vary in bioavailability; to avoid reduced effect or risk of breakthrough seizures or excessive side effects, it may be prudent to avoid changing the formulation.

Distribution

Carbamazepine Taj Pharma is bound to serum proteins to the extent of 70-80%. The concentration of unchanged substance in cerebrospinal fluid and saliva reflects the non-protein bound portion in plasma (20-30%). Concentrations in breast milk were found to be equivalent to 25-60% of the corresponding plasma levels.

Carbamazepine Taj Pharma crosses the placental barrier. Assuming complete absorption of Carbamazepine Taj Pharma, the apparent volume of distribution ranges from 0.8 to 1.9 l/kg.

Biotransformation

Carbamazepine Taj Pharma is metabolised in the liver, where the epoxide pathway of biotransformation is the most important one, yielding the 10, 11-transdiol derivative and its glucuronide as the main metabolites.

Cytochrome P450 3A4 has been identified as the major isoform responsible for the formation of Carbamazepine Taj Pharma 10, 11-epoxide from Carbamazepine Taj Pharma. Human microsomal epoxide hydrolase has been identified as the enzyme responsible for the formation of the 10,11-transdiol derivative from Carbamazepine Taj Pharma-10,11 epoxide. 9-Hydroxy-methyl- 10-carbamoyl acridan is a minor metabolite related to this pathway. After a single oral dose of Carbamazepine Taj Pharma about 30% appears in the urine as end-products of the epoxide pathway.

Other important biotransformation pathways for Carbamazepine Taj Pharma lead to various monohydroxylated compounds, as well as to the N-glucuronide of Carbamazepine Taj Pharma produced by UGT2B7.

Elimination

The elimination half-life of unchanged Carbamazepine Taj Pharma averages approx. 36 hours following a single oral dose, whereas after repeated administration it averages only 16-24 hours (auto-induction of the hepatic mono-oxygenase system), depending on the duration of the medication. In patients receiving concomitant treatment with other enzyme-inducing drugs (e.g. phenytoin, phenobarbitone), half-life values averaging 9-10 hours have been found.

The mean elimination half-life of the 10, 11-epoxide metabolite in the plasma is about 6 hours following single oral doses of the epoxide itself.

After administration of a single oral dose of 400mg Carbamazepine Taj Pharma, 72% is excreted in the urine and 28% in the faeces. In the urine, about 2% of the dose is recovered as unchanged drug and about 1% as the pharmacologically active 10, 11-epoxide metabolite.

Characteristics in patients

The steady-state plasma concentrations of Carbamazepine Taj Pharma considered as “therapeutic range” vary considerably inter-individually; for the majority of patients a range between 4-12 μg/ml corresponding to 17-50 μmol/l has been reported. Concentrations of Carbamazepine Taj Pharma 10, 11-epoxide (pharmacologically active metabolite): about 30% of Carbamazepine Taj Pharma levels.

Owing to enhanced Carbamazepine Taj Pharma elimination, children may require higher doses of Carbamazepine Taj Pharma (inmg/kg) than adults to maintain therapeutic concentrations.

There is no indication of altered pharmacokinetics of Carbamazepine Taj Pharma in elderly patients as compared with young adults.

No data are available on the pharmacokinetics of Carbamazepine Taj Pharma in patients with impaired hepatic or renal function.

• Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, local tolerance, genotoxicity and carcinogenic potential. Reproductive toxicity studies in animals were insufficient to rule out a teratogenic effect of Carbamazepine Taj Pharma in humans.

Carcinogenicity

In rats treated with Carbamazepine Taj Pharma for two years, there was an increased incidence of hepatocellular tumours in females and benign testicular tumours in males. However, there is no evidence to date that these observations are of any relevance to the therapeutic use of Carbamazepine Taj Pharma in humans.

Reproductive toxicity

In animals studies in mice, rats and rabbits oral administration of Carbamazepine Taj Pharma during organogenesis led to increased embryo-fetal mortality and fetal growth retardation at daily doses which were associated with maternal toxicity (above 200mg/kg/day). Carbamazepine Taj Pharma was teratogenic in a number of studies, particularly in mice, however showed no or only minor teratogenic potential at doses relevant to humans. In a reproduction study in rats, nursing offspring demonstrated a reduced weight gain at a maternal dosage level of 192mg/kg/day.

Fertility

In chronic toxicity studies dose related testicular atrophy and aspermatogenesis occurred in rats receiving Carbamazepine Taj Pharma. The safety margin for this effect is not known.

6. Pharmaceutical particulars
   • List of excipients

Sucralose, Poloxamer 188, Xanthan gum, Potassium sorbate, Propylene glycol, Citric acid monohydrate, Orange yellow S, Sorbitol , Natural and artificial flavour orange, Water, purified.

• Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

• Shelf life

2 years

• Special precautions for storage

Do not store above 25°C.

Keep the bottle tightly closed between doses.

• Nature and contents of container

PET/Glass bottles using a polypropylene child resistant plastic cap.

Pack sizes: 300ml & 500ml.

Not all pack sizes may be marketed.

• Special precautions for disposal and other handling

No special requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com

Carbamazepine Taj PharmaOral Suspension USP 100mg/5ml

Package leaflet: Information for the patient

Carbamazepine Taj Pharma 100mg/5ml Oral Suspension

Carbamazepine Taj Pharma

Read all of this leaflet carefully before you take this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Carbamazepine Taj Pharma is and what it is used for
2. What you need to know before you take Carbamazepine Taj Pharma
3. How to take Carbamazepine Taj Pharma
4. Possible side effects
5. How to store Carbamazepine Taj Pharma
6. Contents of the pack and other information
7. What Carbamazepine Taj Pharma is and what it is used for

Carbamazepine Taj Pharma is a pale orange suspension that contains Carbamazepine Taj Pharma, the active ingredient. Carbamazepine Taj Pharma is an anti-convulsant medicine (prevents fits), it can also modify some types of pain and can control mood disorders.

Carbamazepine Taj Pharma is used

• To treat some forms of epilepsy
• To treat a painful condition of the face called trigeminal neuralgia
• To help control serious mood disorders when some other medicines don’t work.

2. What you need to know before you take Carbamazepine Taj Pharma

Do not take Carbamazepine Taj Pharma

• If you are allergic to Carbamazepine Taj Pharma 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) or any of the other ingredients of this medicine (listed in section 6). If you are allergic to Carbamazepine Taj Pharma there is a one in four (25%) chance that you could also have an allergic reaction to oxcarbazepine
• if you have any heart problems
• if you have ever had problems with your bone marrow
• if you have a blood disorder called porphyria (an inherited enzyme disorder)
• If you have taken drugs called monoamine oxidase inhibitors (MAOIs), used to treat depression, within the last 14 days.

Warnings and precautions

Talk to your doctor or pharmacist before taking Carbamazepine Taj Pharma if

• you suffer from the sort of epilepsy where you get mixed seizures which include absences
• you have any mental illness
• you are allergic to phenytoin (another epilepsy medicine)
• you have liver problems
• 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)
• you are elderly
• you have eye problems such as glaucoma (increased pressure in the eye)
• you have difficulty retaining urine

A small number of people being treated with anti-epileptics such as Carbamazepine Taj Pharma 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 Taj Pharma. 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 Taj Pharma.

If you develop a rash or these skin symptoms, stop taking Carbamazepine Taj Pharma and contact your doctor immediately.

Other medicines and Carbamazepine Taj Pharma

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Taking some medicines together can be harmful. Remember that the doctor at the hospital may not have been informed if you have recently begun a course of treatment for another illness. In particular tell your doctor if you are taking

• hormone contraceptives, e.g. pills, patches, injections or implants. Carbamazepine Taj Pharma affects the way 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 such as tibolone. Carbamazepine Taj Pharma can make HRT less effective
• drugs to treat depression or anxiety, such as lithium, alprazolam, viloxazine, fluoxetine, desipramine, fluvoxamine
• medicines to treat mental illness (including schizophrenia), e.g. clozapine, olanzapine, risperidone, haloperidol, thioridazine, paliperidone or aripiprazole
• 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, such as warfarin
• antibiotics and medicines to treat TB (tuberculosis) such as doxycycline, rifampicin, erythromycin, clarithromycin, or isoniazid
• antifungals to treat fungal infections such as itraconazole, fluconazole, ketoconazole or voriconazole
• painkillers containing paracetamol, dextropropoxyphene, tramadol, methadone or buprenorphine
• other antiepileptics such as clobazam, clonazepam, phenytoin, phenobarbitone, primidone, tiagabine, lamotrigine, topiramate, ethosuximide, valproic acid, felbamate or oxcarbazepine
• medicines to treat blood pressure or heart problems, such as digoxin, felodipine, nifedipine, nilvadipine, verapamil or diltiazem
• antihistamines (medicines to treat allergies) such as loratadine or terfenadine
• diuretics (‘water’ tablets) e.g. furosemide, hydrochlorothiazide
• cimetidine or omeprazole (medicines to treat gastric ulcers)
• isotretinoin (medicine for the treatment of acne)
• aprepitant or metoclopramide (medicines often used to treat sickness)
• acetazolamide (medicine to treat glaucoma – increased pressure in the eye)
• danazol or gestrinone (medicines for the treatment of endometriosis)
• theophylline or aminophylline (medicines for the treatment of asthma)
• cyclosporin, tacrolimus or sirolimus (immunosuppressants, medicines used after transplant operations, but also sometimes in the treatment of arthritis or psoriasis)
• medicines to treat cancer such as toremifene, cisplatin or doxorubicin
• anti-malaria medicine mefloquine (medicine used to treat malaria)
• medicines to treat HIV known as protease inhibitors such as indinavir, saquinavir or ritonavir
• thyroxine (medicine used to treat hypothyroidism)
• tadalafil (medicine used to treat impotence)
• albendazole (medicine used to treat worms)
• bupropion (medicine used to help stop smoking)
• a herbal remedy St. John’s wort (Hypericum perforatum)
• medicines or supplements containing vitamin B such as nicotinamide.

Carbamazepine Taj Pharma with food, drink and alcohol

Drinking alcohol may affect you more than usual. Discuss with your doctor whether you should stop drinking.

Eating grapefruit, or drinking grapefruit juice, may increase your chance of experiencing side effects. You can take Carbamazepine Taj Pharma  during, after or between meals.

Pregnancy and breast-feeding

You must discuss your epilepsy treatment with your doctor well before you become pregnant. If you do get pregnant while you are taking Carbamazepine Taj Pharma  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 taking Carbamazepine Taj Pharma .

If you are taking Carbamazepine Taj Pharma  you can breast-feed your 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.

Driving and using machines

Carbamazepine Taj Pharma  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.

Carbamazepine Taj Pharma contains sorbitol, potassium sorbate and orange yellow S

This medicine contains:

• If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
• potassium sorbate. Each 5ml of suspension contains less than 1 mmol (39mg) of potassium, i.e. essentially “potassium free”.
• orange yellow S, which may cause allergic reactions.

3. How to take Carbamazepine Taj Pharma

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is:

Epilepsy

• Adults: The usual dose is 800-1,200mg a day, although higher doses may be necessary
• Elderly: You might need a lower dose.
• Children aged up to and over 1 year: usually 10-20mg/kg body weight daily in several divided doses. Your doctor will tell you how much liquid the child should take.

Trigeminal neuralgia

The usual dose is 600-800mg a day. The maximum dose is 1,200mg a day. If you are elderly you might require a lower dose. Once the pain is controlled, your doctor will probably reduce the dose.

Mood swings

The usual dose is 400-600mg a day.

Method of administration

Your doctor will usually start Carbamazepine Taj Pharma  at a fairly low dose which can then be increased to suit you individually. The dose needed varies between patients. Shake the bottle before you measure out your dose. You are usually told to take a dose two or three times a day. Carbamazepine Taj Pharma  is given orally, either before, during or between meals.

If you take more Carbamazepine Taj Pharma than you should

If you accidentally take too much Carbamazepine Taj Pharma, tell your doctor or your nearest hospital casualty department. Take your medicine pack with you so that people can see what you have taken.

If you forget to take Carbamazepine Taj Pharma

If you forget to take a dose, take one as soon as you remember. Do not take a double dose to make up for a forgotten dose.

If you stop taking Carbamazepine Taj Pharma

Do not stop taking your medicine suddenly, as this may result in you having a seizure. Only stop taking your medicine if your doctor tells you to do so.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

If you develop any of the following side effects, stop taking Carbamazepine Taj Pharma and contact your doctor immediately

• 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.
• changes in the blood, including unexplained bleeding or bruising, or making it easier to catch infections with mouth ulcers, sore throat, or high temperature
• liver problems or failure, including jaundice with 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
• severe skin reactions, accompanied by feeling unwell and changes in blood results
• reactivation of herpes virus infection (can be serious when immune system is depressed).

The following side effects have also been reported

Very common (may affect more than 1 in 10 people):

• dizziness
• drowsiness
• 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, including urticaria (hives), which may be severe.

Common (may affect up to 1 in 10 people):

• fluid retention and swelling
• weight increase
• low sodium in the blood which might result in confusion
• headache
• double or blurred vision
• Dry mouth.

Uncommon (may affect up to 1 in 100 people):

• abnormal involuntary movements including tremor or tics
• abnormal eye movements
• diarrhoea

Rare (may affect up to 1 in 1,000 people):

• disease of the lymph glands
• folic acid deficiency (can be detected with a blood test by your doctor)
• 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 in heart beat
• stomach pain.

Very rare (may affect up to 1 in 10,000 people):

• changes to the composition of the blood including anaemia
• porphyria
• meningitis (inflammation of the brain lining)
• 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 (brittle bones)
• increased blood fat levels
• taste disturbances
• conjunctivitis (red eyes)
• glaucoma (increased pressure in the eyes)
• 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
• sore mouth or tongue
• increased sensitivity of the skin to light
• changes in skin colour (alteration in skin pigments)
• 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.

Not known (frequency cannot be estimated from the available data):

• diarrhoea, abdominal pain and fever (signs of inflammation of the colon)
• complete loss of nails
• fracture
• decrease in the measure of the bone density
• memory loss
• Purple or reddish-purple bumps that may be itchy.

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, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Carbamazepine Taj Pharma

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

Store below 25°C. Keep the bottle tightly closed between doses.

Do not use this medicine after the expiry date which is stated on the label. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Carbamazepine Taj Pharma contains

• The active substance is Carbamazepine Taj Pharma. 5ml of suspension contains 100mg of Carbamazepine Taj Pharma.
• The other ingredients are: poloxamer 188, sucralose, xanthan gum, potassium sorbate, propylene glycol, citric acid monohydrate, orange yellow S, sorbitol, natural and artificial flavour orange and water, purified.

What Carbamazepine Taj Pharma looks like and content of the pack

Bottles with a child resistant plastic cap.

Pack sizes: 300ml and 500ml.

Not all pack sizes may be marketed.

Manufactured in India by:
CEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com