Epilan

Antiepileptic

Description

Epilan is a combination of two structurally related time-proven antiepileptic drugs having different mechanisms of action. This combination of Phenytoin sodium and Phenobarbitone is used to provide adequate seizure control in patients whose epileptic seizures cannot be controlled by either drug alone.

Indications

EPILAN is indicated for seizure control in patients with generalized tonic-clonic (Grand mal) seizures and complex partial seizures where monotherapy is inadequate.

Recommended Dosage

Adult: 1 tablet 3 or 4 times a day.
Children: Dosage individualized, as per body weight, in the range of phenytoin 4-8 mg/kg/day and phenobarbitone: 3-5 mg/kg/day in 2 or 3 equally divided doses.

Action

The therapeutic rationale for the combination of Phenytoin sodium and Phenobarbitone is based on the following clinical advantages.

  1. As the usage of drug combinations is recognized to be ideal for diseases that require long-term management and multiple drug therapy, the anti-epileptic combination of Phenytoin sodium + Phenobarbitone has been designed to counter the disadvantages of noncompliance and monotherapy inadequacy in achieving total seizure control.
  2. Some epileptic patients do not respond satisfactorily to monotherapy in recommended dosage; this may warrant higher drug dosage which could cause unwelcome side effects. These patients respond satisfactorily when two drugs with different mechanisms of action are used concurrently.

    - Phenytoin has a stabilizing influence on neuronal membrane. It inhibits voltage dependent Na+ channels as a part of its main mode of action; probably of greater importance is its ability to facilitate Na+ extrusion from nerve cells and to prevent intracellular accumulation of this cation during repetitive stimulation. Thus, it selectively inhibits high frequency discharges with little effect on normal neuronal discharges. It also inhibits Ca+ influx during neuronal depolarization.

    - Phenobarbitone has specific anticonvulsant activity which is not entirely dependent on its general CNS depression effect. It mainly facilitates GABA – mediated inhibition of nerve cell activity by binding to GABA receptor-chloride ionophore macromolecular complex. Furthermore, Phenobarbitone also actively reduces nerve cell stimulation by exhibiting anti-glutamate activity. This overall increases the seizure threshold and also limits the spread of seizure discharge.

    Given the different mechanisms of action of Phenytoin and Phenobarbitone, their combined usage offers the benefit of summation of therapeutic effects - a pharmacodynamic advantage.
  3. The summation of desirable therapeutic effects is further strengthened by the fact that there is an attenuated risk-proneness for the development of undesirable drug effects. This is so because such combined usage of Phenytoin and Phenobarbitone does not require higher doses of the individual drugs; hence toxic effects attributable to high doses are averted.
  4. In multiple drug regimens when drugs are used separately, there is always the danger of forgetting and skipping one or more doses of the invaluable antiepileptics. In such situations of poor compliance inadequate seizure control is the unfortunate consequence. Worse still is the scenario, in which, the patient unwittingly compensates for the missed dose by doubling the next dose. This could result in increased incidence of toxic effects. Such undesirable situations in antiepileptic therapy can be averted by combined use of Phenytoin and Phenobarbitone which undoubtedly improves the drug combination’s overall efficacy and safety.
  5. Phenytoin is usually administered to adults in the dose of 100mg b.i.d. upto a maximum of about 400mg/day. Usual adult daily dose of Phenobarbitone is 60-180 mg in divided doses. Given the dosage range of both Phenytoin and Phenobarbitone, the drug combination of Phenytoin sodium 100 mg + Phenobarbitone 30 mg has been diligently designed to meet the criteria of therapeutic efficacy and safety. As this approach does not require higher doses of individual drugs, in contrast to monotherapy, their combined usage overall favours efficacy, safety and patient compliance.
  6. As regards interactions between Phenytoin and Phenobarbitone, the following extract from Martindale; The Complete Drug Reference; 32nd ed:1999, stands to justify the continued therapeutic utility of the said combination. Complex interaction exists between Phenobarbitone and Phenytoin. Phenytoin may cause a rise in plasma concentrations of Phenobarbitone in some patients since the two drugs compete for metabolism by the same enzyme system, but other evidence suggests where this occurs it is rarely of significant magnitude. Similarly, although Phenobarbitone induces the metabolism of Phenytoin it is also, as stated, a competitive inhibitor and in practice the two effects appear to balance out, with rarely any need for dose adjustment. Extrapolation of the above and the empirical clinical data indicate that the apparent interaction between Phenytoin and Phenobarbitone is very seldom clinically significant. Although Phenobarbitone is likely to induce the metabolism of Phenytoin, it is also a competitive inhibitor of Phenytoin metabolism; thus, in clinicalpractice the two opposing effects are evened out, definitively attenuating the concern for dosage adjustments. In light of the above, the drug combination of Phenytoin sodium 100 mg + Phenobarbitone 30 mg is not only pharmacologically appropriate and therapeutically sound but also has the invaluable advantages of effective seizure control, reduced incidence of side effects, economy and better patient compliance.

    7. Safety

    Epilan is generally effective with a desirable tolerability profile. Drug interactions may occur with other antiepileptics and other medications. It is contraindicated in patients with a history of hypersensitivity to either drug, porphyria, restlessness or abnormal reactions to phenobarbitone or other barbiturates, severe renal and hepatic impairment and severe myocardial dysfunction.

    Caution advised in the elderly or severely ill patients, pregnancy, mild to moderate renal or hepatic dysfunction, in alcoholics and drug addicts.

    Use in pregnancy: Congenital deformities may occur with many anticonvulsants. On the other hand, stopping anticonvulsant treatment during pregnancy may result in increased convulsions, abortion and even status epilepticus. The decision to stop or continue Epilan during pregnancy should be taken on an individual patient basis after appropriately weighing the risk-benefit ratio.

    Sedation, irritation, aggressiveness, depression, confusion, rash, dyskinesia, anaemia, hepatitis are known to occur with Epilan occasionally. Gum hyperplasia may occur especially in children. CNS effects include nystagmus, ataxia, vertigo and double vision. Very rarely severe hepatitis, severe skin reactions and agranulocytosis may also occur.

    Presentation

    Available as tablets in 50s/150s/1000s plastic bottles.

    Composition

    Each uncoated tablet of Epilan contains :

    Phenytoin sodium 100 mg
    Phenobarbitone 30 mg

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