Phenobarbital with lamotrigine

Valproate Carbamazepine epoxide Diazepam Felbamate Lamotrigine Phenobarbital Risk of toxicity, particularly with phenobarbital including primidone-derived phenobarbital and lamotrigine Inhibition of metabolism of the affected drug. Valproate also displaces diazepam from protein binding sites, affecting relation between total diazepam concentration and effect... 

A 51-year-old woman, who had been seizure-free for 3 years after the removal of a cavernous angioma in her right anterolateral temporal lobe, and who had taken phenobarbital 150 mg/day for 11 years, started reducing the dose and replacing it with lamotrigine. When the dose of phenobarbital reached 60 mg/day (blood concentration 7 gg/ml) with lamotrigine 25 mg bd, complex partial seizures occurred. 

Stopping oral contraceptives - For women not taking carbamazepine, phenytoin, phenobarbital, primidone, or rifampin, the maintenance dose of lamotrigine may need to be decreased by as much as 50% of the maintenance dose with concurrent oral contraceptives. 

With phenytoin, carbamazepine, phenobarbital, primidone, and lamotrigine, hepatotoxicity usually occurs as part of a hypersensitivity reaction, with skin rashes and fever in the early weeks of treatment. More rarely, hepatic disease can develop after many years without signs of hypersensitivity. Once hepatotoxicity develops, mortality... 

Pseudolymphoma and a condition resembling malignant lymphoma occur very rarely with phenytoin (SED-13, 142). There is no evidence of a significant increase in the incidence of other tumors. There have also been reports of pseudolymphoma with other antiepileptic drugs, including carbamazepine (147-149), lamotrigine (150), phenobarbital (151), and valproic acid (151). 

Activated charcoal Carbamazepine Lamotrigine Phenobarbital Phenytoin Valproate With some drugs can be exploited to reduce drug concentrations in overdose Sequestration in the gastrointestinal tract... 

The effects of other antiepileptic drugs on the pharmacokinetics of lamotrigine have been studied in 62 patients with epilepsy (71). Carbamazepine, phenytoin, and phenobarbital, all enzjme inducers, increased the oral clearance of lamotrigine, individually by 58% and in combination by nearly 200%. 

Clinically important, potentially hazardous interactions with carbamazepine, lamotrigine, phenobarbital, phenytoin, pregabalin... 

Decreased effects with rifampin, carbamazepine, cholestyramine, phenytoin, lamotrigine, phenobarbital... 

To date, among the newer-generation agents, only lamotrigine and oxcarbazepine have received Food and Drug Administration (FDA) approval for use as monotherapy in patients with partial seizures. Phenobarbital and primidone are also useful in partial... 

Tonic-clonic seizure As described above for partial with secondarily generalized tonic-clonic seizures except that it is not preceded by a partial seizure. Carbamazepine, phenobarbital, phenytoin, primidone, valproate Lamotrigine, topiramate... 

Primidone use Is associated with decreases In CBZ, lamotrigine, valproate, tiagabine, and zonisamide serum levels. Primidone levels are increased by nicotinamide and Isonlazid. Hydantoins increase the plasma concentrations of primidone, phenobarbital, and PEMA. CBZ Increases levels of phenobarbital derived from primidone. Primidone levels are decreased by succinimides, CBZ, and acetazolamide. 

Methadone levels can be reduced by carbamazepine, phenobarbital or phenytoin. Valproate appears not to interact. An isolated report describes lamotrigine-associated rash and blood dyscrasias, which may have been associated with methadone use. 

Phenobarbital has been associated with reduced lamotrigine serum levels. Phenobarbital and primidone levels were unchanged. 

Furthermore, evidence from clinical studies suggests that levetiraeetam does not affect the serum levels of gabapentin, lamotrigine, phenobarbital, or primidone. In general therefore, no dosage adjustments would seem to be needed if levetiraeetam is used as add-on therapy with any of these drugs. 

It has been suggested that phenobarbital, phenytoin and felbamate compete with mesuximide for the same metabolic mechanisms (hydroxyla-tion) in the liver. As a result each one is metabolised more slowly and therefore their levels increase. Mesuximide appears to increase the clearance of valproate, and lamotrigine (which is principally via glucuronida-tion). 

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