Phenobarbital Felbamate

Tiagabine, unlike carbamazepine and oxcarbazepine, felbamate, phenobarbital, phenytoin, and topiramate, does not affect the metabolism of oral contraceptive steroids (29). 

Romanyshjm, L.A. Wichmann, J.K. Kucharczyk, N. Shumaker, R.C. Ward, D. Sofia, R.D. Simultaneous determination of felbamate, primidone, phenobarbital, carbamazepine, two carbamazepine metabolites, phenytoin, and one phenytoin metabolite in human plasma by hig -performance liquid chromatography. Ther.Drug Monit., 1994,16,90-99 [plasma extracted metabolites, felbamate, phenobarbital, primidone column temp 40-50 LOQ 195-391 ng/mL simultaneous acetaminophen, aspirin, brompheniramine, caffeine, chlorpheniramine, dextromethorphan, dimethadione, ethosuximide, ethotoin, ibuprofen, iministUbene, mephenytoin, mephobarbital, metharbital, methsuximide, para-methadione, phenacemide, phensuximide, phenylpropanolamine, theophylline, trimethadione noninterfering clonazepam valproic acid]... 

Carbamazepine levels are increased by CYP3A4 inhibitors (cimetidine, macrolides, diltiazem, fluoxetine, ketoconazole, verapamil, valproate) levels are decreased by CYP3A4 inducers (cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline). Carbamazepine may increase levels of clomipramine, phenytoin, and primidone and lithium toxicity may decrease levels of phenytoin, warfarin, oral contraceptives, doxycycline, theophylline, haloperidol, alprazolam, clozapine, ethosuximide, and valproate may interfere with other anticonvulsants. 

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 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. 

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... 

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

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. 

Potschka H, Fedrowitz M, Loscher W (2002) P-Glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood-brain barrier Evidence from microdialysis experiments in rats. Neurosci Lett 327 173-176. 

Phenobarbital Phenytoin Primidone Felbamate Lamotrigine Tiagabide Topiramate Valproate Zonisamide Clobazam Clonazepam Diazepam usually compensated by the effect of the added drug risk of toxicity when interfering drug is discontinued drug... 

Felbamate Clonazepam Diazepam Phenobarbital Phenytoin Valproate High risk of toxicity with phenytoin, phenobarbital, and valproate Inhibition of metabolism of the affected drug... 

Gamma-vinyl GABA Phenytoin Phenobarbital Felbamate Interaction inconsistent and usually of little clinical relevance Unknown... 

Felbamate is a metabolic inhibitor and significantly increases blood concentrations of phenobarbital (SEDA-19, 69) (SEDA-20, 61). 

Increased effects (P450 3A4 inhibitors) cimetidine, danazol, diltiazem, erythromycin, troleandomycin, clarithromycin, fluoxetine, isoniazid, niacinamide, nicotinamide, propoxyphene, ketoconazole, itraconazole, verapamil,and valproate Decreased effects (P450 3A4 inducers) cisplatin, doxorubicin, felbamate, rifampin, phenobarbital, phenytoin, primidone, theophylline... 

Importantly, Loscher et al. found that carbamazepine, felbamate, gabapentin, lamotrigine, phenobarbital, and topiramate are substrates of ABCBl (P-gp) [38]. Crowe et al. also studied the transport of a variety of antiepileptic drugs including vigabatrin, gabapentin, phenobarbitone, lamotrigine, phenytoin, carbamazepine, and acetazolamide in colorectal tumor-derived Caco-2 cell monolayers. They found that only one antiepileptic, acetazolamide, is a weak ABCBl substrate [39]. 

Drug Interactions. Phenobarbital is a potent enzyme inducer and may increase the elimination of any drug metabolized by CYP450-or UGT-mediated metabolism. Valproic acid, phenytoin, felbamate, cimetidine, and chloramphenicol inhibit phenobarbital metabolism, necessitating a decrease in dose. Ethanol increases the metabolism of phenobarbital. ... 

Anticonvulsants (barbiturates, including phenobarbital and primidone carbamazepine felbamate phenytoin Possible decreased contraceptive effect Avoid simultaneous use use alternative contraceptive (DMPA) for patients with seizure disorder... 

Barbiturates phenobarbital 1 Benzodiazepines alprazolam, diazepam, i lorazepam, oxazepam Carbamazepine, ethosuximide, valproic acid, phenytoin, diazepam, lorazepam, gabapentin, lamotrigine, felbamate, topiramate, tiagabin, vigabatrin... 

Activation of these ligand-gated channels enables sodium and calcium influx and potassium efflux, facilitating depolarization. Blockade of the NMDA receptor by felbamate or of the AMPA/KA receptor by phenobarbital and topiramate inhibits depolarization (Fig. 20.3). 

Valproate, a substrate for hepatic CYP2C19 and CYP2C9, has an extensive pattern of drug interactions. It increases the plasma concentrations of lamotrigine, CBZ, and phenobarbital and the free fraction of phenytoin by either displacing these drugs from plasma proteins or inhibiting their metabolism. Phenytoin, phenobarbital, and CBZ cause decreased plasma concentrations of valproate, whereas felbamate increases valproate levels. 

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