1. Name Of The Medicinal Product
Tegretol® Retard 200mg and 400mg Tablets
2. Qualitative And Quantitative Composition
The active ingredient is 5H-dibenzo[b,f]azepine-5-carboxamide.
Each coated tablet contains 200mg or 400mg carbamazepine Ph.Eur.
3. Pharmaceutical Form
The 200mg tablets are beige-orange, oval, slightly biconvex, coated tablets with a score on each side. One side bears the imprint “H/C”, the other “C/G”.
The 400mg tablets are brownish-orange, oval, slightly biconvex coated tablets with a score on each site. One side bears the imprint “ENE/ENE”, the other “C/G”.
4. Clinical Particulars
4.1 Therapeutic Indications
Epilepsy - generalised tonic-clonic and partial seizures. Tegretol Retard is indicated in newly diagnosed patients with epilepsy and in those patients who are uncontrolled or unable to tolerate their current anti-convulsant therapy.
Note: Carbamazepine 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.
For the prophylaxis of manic-depressive psychoses in patients unresponsive to lithium therapy.
4.2 Posology And Method Of Administration
Tegretol Retard is given orally, generally in the same total daily dose as conventional Tegretol dosage forms but usually in two divided doses. In a few patients when changing from other oral dosage forms of Tegretol to Tegretol Retard the total daily dose may need to be increased, particularly when it is used in polytherapy. When starting treatment with Tegretol Retard 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.
Tegretol Retard (either the whole or half divisible tablet as prescribed), should not be chewed but should be swallowed with a little liquid, before, during or between meals. The divisible tablet presentation enables flexibility of dosing to be achieved.
Before deciding to initiate treatment, patients of Han Chinese and Thai origin should whenever possible be screened for HLA-B*1502 as this allele strongly predicts the risk of severe carbamazepine-associated Stevens-Johnson syndrome (see section 4.4).
Epilepsy:
Adults: It is advised that with all formulations of Tegretol, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient. It may be helpful to monitor the plasma concentration of carbamazepine to establish the optimum dose (see Pharmacokinetics, Precautions and Interactions).
Elderly: Due to the potential for drug interactions, the dosage of Tegretol should be selected with caution in elderly patients.
Children: It is advised that with all formulations of Tegretol, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient. It may be helpful to monitor the plasma concentration of carbamazepine to establish the optimum dose (see Pharmacokinetics, Precautions and Interactions).
Usual dosage 10-20mg/kg bodyweight daily in several divided doses.
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Wherever possible, Tegretol Retard should be used as the sole drug anti-epileptic agent but if used in polytherapy, the same incremental dosage pattern is advised.
When Tegretol 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 (100mg twice daily in elderly patients) 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 1600 Tegretol daily may be needed. However, once the pain is in remission, the dosage should be gradually reduced to the lowest possible maintenance level.
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.
4.3 Contraindications
Known hypersensitivity to carbamazepine or structurally related drugs (e.g. tricyclic antidepressants) or any other component of the formulation.
Patients with atrioventricular block, a history of bone marrow depression or a history of hepatic porphyrias (e.g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda).
The use of Tegretol is not recommended in combination with monoamine oxidase inhibitors (MAOIs) (see section 4.5 Interaction with other medicinal products and other forms of interaction).
4.4 Special Warnings And Precautions For Use
Warnings
Agranulocytosis and aplastic anaemia have been associated with Tegretol; however, due to the very low incidence of these conditions, meaningful risk estimates for Tegretol 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 Tegretol. 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 Tegretol should be discontinued if the patient develops leucopenia which is severe, progressive or accompanied by clinical manifestations, e.g. fever or sore throat. Tegretol 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 Tegretol 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 Tegretol. 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 Tegretol. If signs and symptoms suggestive of severe skin reactions (e.g. SJS, Lyell's syndrome/TEN) appear, Tegretol should be withdrawn at once and alternative therapy should be considered.
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. Whenever possible, these individuals should be screened for this allele before starting treatment with carbamazepine. 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.
It is not definitely known whether all individuals of south east-Asian ancestry are at risk due to lack of data.
The allele HLA-B*1502 has been shown not to be associated to SJS in the Caucasian population.
Mild skin reactions e.g. isolated macular or maculopapular exanthema, can also occur and are mostly transient and not hazardous. They usually disappear within a few days or weeks, either during the continued course of treatment or following a decrease in dosage. However, since it may be difficult to differentiate the early signs of more serious skin reactions from mild transient reactions, the patient should be kept under close surveillance with consideration given to immediately withdrawing the drug should the reaction worsen with continued use.
The HLA-B*1502 allele has not been found to predict risk of less severe adverse cutaneous reactions from carbamazepine, such as anticonvulsant hypersensitivity syndrome or non-serious rash (maculopapular eruption).
Tegretol may trigger hypersensitivity reactions, including multi-organ hypersensitivity reactions, which can affect the skin, liver (including intrahepatic bile ducts), haematopoietic organs and lymphatic system or other organs, either individually or together in the context of a systemic reaction (see section 4.8 Undesirable Effects).
In general, if signs and symptoms suggestive of hypersensitivity reactions occur, Tegretol should be withdrawn immediately.
Patients who have exhibited hypersensitivity reactions to carbamazepine should be informed that 25-30 % of these patients may experience hypersensitivity reactions with oxacarbazepine (Trileptal).
Cross-hypersensitivity can occur between carbamazepine and phenytoin.
Tegretol should be used with caution in patients with mixed seizures which include absences, either typical or atypical. In all these conditions, Tegretol may exacerbate seizures. In case of exacerbation of seizures, Tegretol should be discontinued.
An increase in seizure frequency may occur during switchover from an oral formulation to suppositories.
Abrupt withdrawal of Tegretol may precipitate seizures:
If treatment with Tegretol has to be withdrawn abruptly, the changeover to another anti-epileptic drug should if necessary be effected under the cover of a suitable drug (e.g. diazepam i.v., rectal; or phenytoin i.v.).
Tegretol and oestrogen and/or progestogen preparations
Due to hepatic enzyme induction, Tegretol may cause failure of the therapeutic effect of oestrogen and/or progestogen containing products. This may result in failure of contraception, recurrence of symptoms or breakthrough bleeding or spotting.
Patients taking Tegretol and requiring hormonal contraception should receive a preparation containing not less than 50µg oestrogen or use of some alternative non-hormonal method of contraception should be considered.
Although correlations between dosages and plasma levels of carbamazepine, and between plasma levels and clinical efficacy or tolerability are rather tenuous, monitoring of the plasma levels may be useful in the following conditions: dramatic increase in seizure frequency/verification of patient compliance; during pregnancy; when treating children or adolescents; in suspected absorption disorders; in suspected toxicity when more than one drug is being used (see 4.5 Interaction with other Medicaments and other forms of Interaction).
Precautions
Tegretol 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 Tegretol.
Baseline and periodic complete urinalysis and BUN determinations are recommended.
Tegretol has shown mild anticholinergic activity; patients with increased intraocular pressure should therefore be warned and advised regarding possible hazards.
The possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in mind.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Cytochrome P450 3A4 (CYP 3A4) is the main enzyme catalysing formation of the active metabolite carbamazepine 10, 11-epoxide. Co-administration of inhibitors of CYP 3A4 may result in increased carbamazepine plasma concentrations which could induce adverse reactions. Co-administration of CYP 3A4 inducers might increase the rate of carbamazepine metabolism, thus leading to potential decreases in the carbamazepine serum level and therapeutic effect.
Similarly, discontinuation of a CYP3A4 inducer may decrease the rate of metabolism of carbamazepine, leading to an increase in carbamazepine plasma levels.
Carbamazepine is a potent inducer of CYP3A4 and other phase I and phase II enzyme systems in the liver, and may therefore reduce plasma concentrations of comedications mainly metabolized by CYP3A4 by induction of their metabolism.
Human microsomal epoxide hydrolase has been identified as the enzyme responsible for the formation of the 10,11-transdiol derivative from carbamazepine-10,11 epoxide. Co-administration of inhibitors of human microsomal epoxide hydrolase may result in increased carbamazepine-10,11 epoxide plasma concentrations.
Agents that may raise carbamazepine plasma levels:
Isoniazid, verapamil, diltiazem, ritonavir, dextropropoxyphene, fluoxetine, fluvoxamine, paroxetine, possibly cimetidine, omeprazole, acetazolamide, danazol, nicotinamide (in adults, only in high dosage), trazodone, vigabatrin, macrolide antibiotics (e.g. erythromycin, clarithromycin), azoles (e.g. itraconazole, ketoconazole, fluconazole, voriconazole), loratadine, olanzapine, grapefruit juice, protease inhibitors for HIV treatment (e.g. ritonavir).
Since raised plasma carbamazepine levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Tegretol should be adjusted accordingly and/or the plasma levels monitored.
Agents that may raise the active metabolite carbamazepine-10,11-epoxide plasma levels:
Since raised plasma carbamazepine-10,11-epoxide levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Tegretol should be adjusted accordingly and/or the plasma levels monitored when used concomitantly with the substances described below:
Quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide.
Agents that may decrease carbamazepine plasma levels:
Phenobarbitone, phenytoin and fosphenytoin, primidone or theophylline, aminophylline, rifampicin, cisplatin or doxorubicin and, although the data are partly contradictory, possibly also clonazepam or oxcarbazepine. Mefloquine may antagonise the antiepileptic effect of Tegretol. The dose of Tegretol may consequently have to be adjusted.
Isotretinoin has been reported to alter the bioavailability and/or clearance of carbamazepine and carbamazepine-10, 11-epoxide; carbamazepine plasma concentrations should be monitored.
Serum levels of carbamazepine can be reduced by concomitant use of the herbal remedy St John's wort (Hypericum perforatum).
Effect of Tegretol on plasma levels of concomitant agents:
Carbamazepine may lower the plasma level, diminish or even abolish the activity of certain drugs. The dosage of the following drugs may have to be adjusted to clinical requirement: levothyroxine, clobazam, clonazepam, ethosuximide, primidone, valproic acid, alprazolam, corticosteroids, (e.g. prednisolone, dexamethasone); ciclosporin, digoxin, doxycycline; dihydropyridine derivatives, e.g. felodipine and isradipine; indinavir, saquinavir, ritonavir, haloperidol, imipramine, buprenorphine, methadone, paracetamol, tramadol, products containing oestrogens and/or progestogens (alternative contraceptive methods should be considered) see Section 4.4 “Special Warnings and Precautions for Use”, gestrinone, tibolone, toremifene, theophylline, oral anticoagulants (warfarin and acenocoumarol), lamotrigine, tiagabine, topiramate, bupropion, citalopram, mianserin, sertraline, trazodone, tricyclic antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, oxcarbazapine, olanzapine, quetiapine, itraconazole, imatinib and risperidone.
Plasma phenytoin levels have been reported both to be raised and to be lowered by carbamazepine, and there have been rare reports of an increase in plasma mephenytoin.
Combinations that require specific consideration:
Concomitant use of carbamazepine and levetiracetam has been reported to increase carbamazepine-induced toxicity.
Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.
The combination of lithium and carbamazepine may cause enhanced neurotoxicity in spite of lithium plasma concentrations being within the therapeutic range. Combined use of carbamazepine with metoclopramide or major tranquillisers, e.g. haloperidol, thioridazine, may also result in an increase in neurological side-effects.
Because it (carbamazepine) is structurally related to tricyclic anti-depressants, the use of Tegretol is not recommended in combination with monoamine oxidase inhibitors (MAOIs); before administering Tegretol, MAOIs should be discontinued for a minimum of 2 weeks, or longer if the clinical situation permits.
Concomitant medication with Tegretol and some diuretics (hydrochlorothiazide, furosemide) may lead to symptomatic hyponatraemia.
Carbamazepine 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, like other psychoactive drugs, may reduce alcohol tolerance. It is therefore advisable for the patient to abstain from alcohol.
4.6 Pregnancy And Lactation
Pregnancy
In animals (mice, rats and rabbits) oral administration of carbamazepine during organogenesis led to increased embryo mortality at a daily doses which caused maternal toxicity (above 200mg/kg b.w. daily i.e. 20 times the usual human dosage). In the rat there was also some evidence of abortion at 300mg/kg body weight daily. Near-term rat foetuses showed growth retardation, again at maternally toxic doses. There was no evidence of teratogenic potential in the three animal species tested but, in one study using mice, carbamazepine (40-240 mg/kg b.w. daily orally) caused defects (mainly dilatation of cerebral ventricles in 4.7% of exposed foetuses as compared with 1.3% in controls).
Pregnant women with epilepsy should be treated with special care.
In women of childbearing age Tegretol should, 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.
If women receiving Tegretol become pregnant or plan to become pregnant, or if the problem of initiating treatment with Tegretol arises during pregnancy, the drug's potential benefits must be carefully weighed against its possible hazards, particularly in the first three months of pregnancy. Minimum effective doses should be given and monitoring of plasma levels is recommended.
During pregnancy, an effective antiepileptic treatment must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the fetus.
Offspring of epileptic mothers with untreated epilepsy are known to be more prone to developmental disorders, including malformations. The possibility that carbamazepine, like all major antiepileptic drugs, increases the risk has been reported, although conclusive evidence from controlled studies with carbamazepine monotherapy is lacking. However, there are reports on developmental disorders and malformations, including spina bifida, and also other congenital anomalies e.g. craniofacial defects, cardiovascular malformations, hypospadias and anomalies involving various body systems, have been reported in association with Tegretol. Patients should be counselled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening.
Folic acid deficiency is known to occur in pregnancy. Antiepileptic 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 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 a few cases of neonatal seizures and/or respiratory depression associated with maternal Tegretol 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 Tegretol use. These reactions may represent a neonatal withdrawal syndrome.
Use during lactation:
Carbamazepine 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 Tegretol may breast-feed their infants, provided the infant is observed for possible adverse reactions (e.g. excessive somnolence, allergic skin reaction).
Fertility:
There have been very rare reports of impaired male fertility and/or abnormal spermatogenesis.
4.7 Effects On Ability To Drive And Use Machines
The patient's ability to react may be impaired by dizziness and drowsiness caused by Tegretol, 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.
4.8 Undesirable Effects
Particularly at the start of treatment with Tegretol, 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.
Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: very common (> 1/10) common (> 1/100, < 1/10); uncommon (> 1/1000, < 1/100); rare (> 1/10,000, < 1/1,000); very rare (< 1/10,000), including isolated reports.
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* In some Asian countries also reported as rare. See also section 4.4 Special warnings and precautions for use.
4.9 Overdose
Signs and symptoms
The presenting signs and symptoms of overdosage involve the central nervous, cardiovascular or respiratory systems.
Central nervous system: CNS depression; disorientation, 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.
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.
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 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:
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 antiepileptic, 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, haemodialysis, 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.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Therapeutic class: Anti-epileptic, neurotropic and psychotropic agent; (ATC Code: N03 AF01). 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, the active substance of Tegretol, has only been partially elucidated. Carbamazepine 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.
5.2 Pharmacokinetic Properties
Absorption
Carbamazepine is almost completely absorbed but the rate of absorption from the tablets is slow and may vary amongst the various formulations and between patients. Peak concentrations of active substance in the plasma are attained within 24 hours of administration of single dose of Tegretol Retard tablets.
The retard formulation shows about 15% lower bioavailability than standard preparations due mainly to the considerable reduction in peak plasma levels occasioned by controlled release of the same dosage of carbamazepine. Plasma concentrations show less fluctuation but auto-induction of carbamazepine occurs as with standard carbamazepine preparations.
The bioavailability of Tegretol in various oral formulations has been shown to lie between 85-100%.
Ingestion of food has no sign
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