Topiramate administration

Deutsch SI, Schwartz BL, Rosse RB, Mastropaolo J, Marvel CL, et al. 2003. Adjuvant topiramate administration A pharmacologic strategy for addressing NMDA receptor hypofunction in schizophrenia. Clin Neuropharmacol 26... 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

MefaboZ/sm/Excref/on- Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose). The mean plasma elimination half-life is 21 hours after single or multiple doses. Overall, plasma clearance is approximately 20 to 30 mL/min following oral administration. 

Hyperammonemia and encephalopathy associated with concomitant valproic acid use Administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. In most cases, symptoms and signs abated with discontinuation of either drug. 

An 11-year-old boy with refractory partial epilepsy who had been taking topiramate 300 mg/day for 13 months developed hyperventilation. He had a hyperchloremic metabolic acidosis with partial respiratory compensation. The hyperventilation and acidosis resolved after the administration of sodium bicarbonate and reduction of the dose of topiramate. 

Laskey AL, Korn DE, Moorjani Bl, Patel NC, Tobias JD. Central hyperventilation related to administration of topiramate. Pediatr Neurol 2000 22(4) 305-8. 

Areas J, Ferrer T, Roche MC, Martinez-Bermejo A, Lopez-Martin V. Hypohidrosis related to the administration of topiramate to children. Epilepsia 2001 42(10) 1363-5. 

Topiramate is routinely administered orally, absorbed rapidly, and metabolized minimally, but its disposition is affected by CyP 2C19. Serum concentrations of other anticonvulsant drugs are not significantly affected by the concurrent administration of topiramate, with the exception in individual patients on phenytoin who exhibit increased phenytoin plasma concentrations after addition of topiramate. Co-administration of phenytoin or carbamazepine decreases topiramate serum concentrations. Changes in cotherapy with phenytoin or carbamazepine (e.g., addition or withdrawal) for patients stabilized on topiramate therapy may require topiramate dose adjustment. As with other... 

Dosing and Administration. Topiramate should be titrated slowly in order to avoid adverse events. Starting doses are 12.5 to 50 mg/day, increasing by 12.5 to 50 mg/day every week or every other week. The minimally effective dose of topiramate is approximately 200 mg/day. For patients on other AEDs, doses of greater than 600 mg/day do not appear to lead to improved efficacy and may cause increased adverse effects however, higher doses may prove beneficial to individual patients who tolerate them. Monotherapy doses as high as 1000 mg/day have been well tolerated and effective in some patients. 

Phenobarbital, phenytoin, and valproic acid may increase the metabolism of carbamazepine by inducing CYP3A4 carbamazepine may enhance the biotransformation of phenytoin. Concurrent administration of carbamazepine may lower concentrations of valproic acid, lamotrigine, tiagabine, and topiramate. Carbamazepine reduces both the plasma concentration and therapeutic effect of haloperidol. The metabolism of carbamazepine may be inhibited by propoxyphene, erythromycin, cimetidine, fluoxetine, and isoniazid. 

PHARMACOKINETICS Topiramate is rapidly absorbed after oral administration, exhibits little (10-20%) binding to plasma proteins, and is mainly excreted unchanged in the urine. Its tj is -1 day. Reduced plasma concentrations of estradiol occur with concurrent topiramate, suggesting that low-dose oral contraceptives should be avoided in this setting. 

Absorption of topiramate is rapid and unaffected by food intake, with peak plasma concentrations being achieved approximately 2 hours after administration of a 400 mg dose. Metabolism of topiramate is not extensive and its oral plasma clearance is slow, with approximately 70% of an administered dose being eliminated unchanged by the kidneys. When used as monotherapy, topiramate has a... 

The anticonvulsant action of valproate may prevent ECT treatment from being effective by preventing seizure activity. This is also a theoretical/practical concern with carbamazepine, gabapentin, lamotrigine, and topiramate. As a rule of thumb, the co-administration of an anticonvulsant and ECT should be considered very cautiously ... 

Liang, L., Wang, H., Bhatt, P.P., Veiira, M.L. Sustained-release formulations of topiramate for oral administration, WO 2008061226 A3, 2008,58pp. 

Body temperature In an analysis performed using the US Food and Drug Administration s Adverse Events Reporting System database, hypothermia was associated with concomitant administration of topiramate and valproic acid in patients who tolerated either drug alone (see also Topiramate ) [326 ]. 

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