Felbamate Carbamazepine

Felbamate Carbamazepine Risk of toxicity due to concomitant rise in carbamazepine epoxide concentration and pharmacodynamic interaction Induction of carbamazepine metabolism, possible inhibition of epoxide hydrolase and pharmacodynamic interaction... 

Acetazolamide, allopurinol, aspirin, captopril, carbamazepine, chloramphenicol, chlorpromazine, dapsone, felbamate, gold salts, metronidazole, methimazole, penicillamine, pentoxifylline, phenothiazines, phenytoin, propylthiouracil, quinidine, sulfonamide antimicrobials, sulfonylureas, and ticlopidine... 

Anticonvulsants (barbiturates, including phenobar-bital and primidone carbamazepine felbamate phenytoin topiramate vigabatrin)... 

Egnell, A.-C., Houston, B. and Boyer, S. (2003) in vivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine. The Journal of Pharmacology and Experimental Therapeutics, 305, 1251-1262. 

Drugs that may affect valproic acid include carbamazepine, charcoal, chlorpromazine, cholestyramine, cimetidine, erythromycin, ethosuximide, felbamate, lamotrigine, phenytoin, rifampin, and salicylates. Drugs that may be affected by valproic acid include carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, phenytoin, tolbutamide, tricyclic antidepressants, warfarin, and zidovudine. 

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

Drugs that can decrease carbamazepine serum levels include charcoal, cisplatin, doxorubicin, felbamate, hydantoins, rifampin, phenobarbital, primidone, theophylline. The serum levels of oral contraceptives, haloperidol, bupropion, anticoagulants, felbamate, valproic acid, felodipine, tricyclic antidepressants, acetaminophen, ziprasidone, voriconazole, topiramate, tiagabine, olanzapine, and lamotrigine can be lowered by carbamazepine. 

II.e. 5.2. Interactions between first and second generation AEDs. Felbamate raises plasma concentrations of phenytoin, valproic acid and carbamazepine. Clearance of tiagabine, topiramate and zon-isamide is increased in the presence of an enzyme inducer. Vigabatrin reduces phenytoin concentrations after 4-5 weeks of comedication (via an unknown mechanism). For tiagabine, the elimination half-life may be reduced by 2-3 hours in the presence of an enzyme-induction AED. Lamotrigine elimination is slower if given with valproic acid. Topiramate reduces elimination of phenytoin. 

Type I Block SRF by enhancing sodium channel inactivation Phenytoin Carbamazepine Oxcarbazepine Lamotrigine Felbamate ... 

While its mechanism of action has not been clearly established, felbamate shows some activity as an inhibitor of voltage-dependent sodium channels in a manner similar to that of phenytoin and carbamazepine. Felbamate also interacts at the strychnine-insensitive glycine recognition site on the NMDA receptor-ionophore complex. Whether this effect is important to its anticonvulsant activity is not clear. 

Felbamate appears to have multiple mechanisms of action. It produces a use-dependent block of the NMDA receptor, with selectivity for the NR1-2B sub-type. It also potentiates GABAa receptor responses. Felbamate has a half-life of 20 hours (somewhat shorter when administered with either phenytoin or carbamazepine) and is metabolized by hydroxylation and conjugation a significant percentage of the drug is excreted unchanged in the urine. When added to treatment with other antiseizure drugs, felbamate increases plasma phenytoin and valproic acid levels but decreases levels of carbamazepine. 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Partial seizures Carbamazepine Phenytoin Lamotrigine Valproic acid Oxcarbazepine Gabapentin Topiramate Levetiracetam Zonisamide Tiagabine Primidone, phenobarbital Felbamate... 

For simple and complex partial seizures and secondary generalized tonic-clonic seizures, the first line drugs are - carbamazepine, valproate and phenytoin. Second line drugs include - acetazolamide, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxacarbamazepine, primidone, tiagabine, topiramate and vigabactin. 

For atypical absence, tonic and clonic seizures, first line treatment is with valproate and second line with acetazolamide, carbamazepine, clobazam, clonazepam, ethosuximide, felbamate, lamotrigine, oxacarbamazepine, phenobarbitone, phenytoin, primidone or topiramate. 

Mode of action. The specific site of action of felbamate is unknown. There is experimental evidence that felbamate blocks NMDA receptors, but less potently than carbamazepine, ethosuximide, phenytoin or valproate. It also modulates sodium channel conductance but does not enhance GABAergic function. In addition to its protective action against chemically induced seizures felbamate has also been shown to have a neuroprotective action in models of hypoxic ischaemia as induced by bilateral carotid ligation. 

In addition to phenytoin, carbamazepine, and lamotrigine, metabolically optimized analogs of these drugs, such as fosphenytoin and oxcarbazepine, show clinical promise. Other anticonvulsants that block sodium channels, among several mechanisms of action, include zonisamide, felbamate, topiramate, and valproate (Fig. 5). 

Drug interactions involving AEDs are shown in Table 52-5. Phenobarbital, phoiytom, primidone and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate gjucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzjrme systems and displaces some drugs from plasma albumin. Felbamate and topiramate can act as inducers with some isoforms and inhibitors with others. 

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... 

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