Primidone Felbamate

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]... 

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

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. 

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. 

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. 

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... 

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... 

Carbamazepine, phenytoin, phenobarbital and primidone, felbamate, oxcarbazepine, and topiramate stimulate the metabolism of oral contraceptive steroids. 

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... 

Felbamate causes a moderate increase in plasma phenobarbital levels (including those derived from primidone), which has resulted in phenobarbital toxicity. 

An established interaction. If felbamate is added to established treatment with phenobarbital or primidone, particularly in patients already taking substmtial doses, monitor well for any evidence of increased adverse effects (drowsiness, lethargy, anorexia, ataxia) and reduce the dosages of the phenobarbital or primidone if necessary. 

None of the interactions between the benzodiazepines and antiepileptics described here appear to be of major clinical importance, with the possible exception of the interaction between clobazam and felbamate. If both drugs are given be aware that additive sedative or other adverse effects may occur. This may also be possible in some rare cases with chlordiazepoxide or clobazam and phenobarbital clonazepam and lamotrigine or primidone and clorazepate and primidone. 

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. 

Nephrolithiasis, urinary crystals or debris Aciclovir, amoxicillin, atazanavir [17],ciprofloxacin, ephedrine/guaifenesin, floctafenine [18], indinavir [19], magnesium trisilicate, methotrexate, primidone, sulfasalazine [20], sulfonamides, triamterene [21,22] ceftriaxone [23,24] felbamate [25] ketamine [26] Djenkol beans [27] Microscopy, infrared spectroscopy. X-ray diffraction, mass spectroscopy... 

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