Topiramateinteractions

Contraceptives: decreased contraceptive efficacy and increased breakthrough bleeding, especially at doses greater than 200 mg/day Monitor lithium levels if lithium is used with high-dose TOPAMAX

7.1 Antiepileptic

Drugs Concomitant administration of phenytoin or carbamazepine with TOPAMAX resulted in a clinically significant decrease in plasma concentrations of topiramate when compared to TOPAMAX given alone. A dosage adjustment may be needed. Concomitant administration of valproic acid and TOPAMAX has been associated with hypothermia and hyperammonemia with and without encephalopathy. Examine blood ammonia levels in patients in whom the onset of hypothermia has been reported.

7.2 Other Carbonic

Anhydrase Inhibitors Concomitant use of topiramate, a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., zonisamide or acetazolamide) may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation. Therefore, patients given TOPAMAX concomitantly with another carbonic anhydrase inhibitor should be monitored particularly closely for the appearance or worsening of metabolic acidosis.

7.3 CNS Depressants

Concomitant administration of TOPAMAX and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, TOPAMAX should be used with extreme caution if used in combination with alcohol and other CNS depressants.

7.4 Contraceptives

The possibility of decreased contraceptive efficacy and increased breakthrough bleeding may occur in patients taking contraceptive products with TOPAMAX. Patients taking estrogen-containing or progestin-only contraceptives should be asked to report any change in their bleeding patterns. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding.

7.5 Hydrochlorothiazide (HCTZ)

Topiramate C max and AUC increased when HCTZ was added to TOPAMAX. The clinical significance of this change is unknown. The addition of HCTZ to TOPAMAX may require a decrease in the TOPAMAX dose. 7.6 Pioglitazone A decrease in the exposure of pioglitazone and its active metabolites were noted with the concurrent use of pioglitazone and TOPAMAX in a clinical trial. The clinical relevance of these observations is unknown; however, when TOPAMAX is added to pioglitazone therapy or pioglitazone is added to TOPAMAX therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.

7.7 Lithium

An increase in systemic exposure of lithium following TOPAMAX doses of up to 600 mg/day can occur. Lithium levels should be monitored when co-administered with high-dose TOPAMAX.

7.8 Amitriptyline

Some patients may experience a large increase in amitriptyline concentration in the presence of TOPAMAX and any adjustments in amitriptyline dose should be made according to the patient's clinical response and not on the basis of plasma levels.