Pradox 25/Pradox 50/Pradox 100 Drug Interactions

(For purposes of this section, a no effect dose is defined as a ≤15% change.)
Effects of other AEDs on Topiramate: Phenytoin and Carbamazepine decrease the plasma concentration of Topiramate. The addition or withdrawal of Phenytoin of Carbamazepine to Topiramate therapy may require an adjustment in dosage of the latter. This should be done by titrating to clinical effect. The addition or withdrawal of Valproic acid dose not produce clinically significant changes in plasma concentrations of Topiramate and, therefore, does not warrant dosage adjustment of Topiramate.
The results of these interactions are summarized as follows: See Table 4.

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Effects of Topiramate on other AEDs: The addition of Topiramate to other AEDs (Phenytoin, Carbamazepine, Valproic acid, Phenobarbital, Primidone) has no effect on their steady-state plasma concentrations, except in the occasional patient, where the addition of Topiramate to Phenytoin may result in an increase of plasma concentrations of Phenytoin. This is possibly due to inhibition of a specific enzyme polymorphic isoform (CYP2C19). Consequently, any patient on Phenytoin showing clinical signs or symptoms of toxicity should have Phenytoin levels monitored.
A pharmacokinetic interaction of patients with epilepsy indicated the addition of Topiramate to Lamotrigine had no effect on steady state plasma concentration of Lamotrigine at Topiramate doses of 100 to 400 mg/day. In addition, there was no change in steady state plasma concentration of Topiramate during or after removal of Lamotrigine treatment (mean dose of 327 mg/day).
Other drug interactions: Digoxin: When Topiramate is added or withdrawn in patients on Digoxin therapy, careful attention should be given to the routine monitoring of serum Digoxin.
Central Nervous System (CNS) depressants: It is recommended that Topiramate not be used concomitantly with alcohol or other CNS depressant drugs.
Oral contraceptives: The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with Topiramate. Patients taking Estrogen-containing contraceptives should be asked to report any change in their bleeding patterns. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding.
Lithium: Lithium levels should be monitored when co-administered with Topiramate.
Risperidone: There were no clinically significant changes in the systemic exposure of the Risperidone total active moiety or of Topiramate, therefore this interaction is not likely to be of clinical significance.
Hydrochlorothiazide (HCTZ): The addition of HCTZ to Topiramate therapy may require an adjustment of the Topiramate dose. The steady-state pharmacokinetics of HCTZ were not significantly influenced by the concomitant administration of Topiramate. Clinical laboratory results indicated decreases in serum potassium after Topiramate or HCTZ administration, which were greater when HCTZ and Topiramate were administered in combination.
Metformin: The clinical significance of the effect of Topiramate on Metformin pharmacokinetics is unclear. Oral plasma clearance of Topiramate appears to be reduced when administered with Metformin. The extent of change in the clearance is unknown. The clinical significance of the effect of Metformin on Topiramate pharmacokinetics is unclear. When Topiramate is added or withdrawn in patients on Metformin therapy, careful attention should be given to the routine monitoring for adequate control of their diabetic disease state.
Pioglitazone: When Topiramate is added to Pioglitazone therapy or Pioglitazone is added to Topiramate therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.
Glyburide: The steady-state pharmacokinetics of Topiramate were unaffected by concomitant administration of Glyburide. When Topiramate is added to Glyburide therapy or Glyburide is added to Topiramate therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.
Other forms of interactions: Agents predisposing to nephrolithiasis: Topiramate when used concomitantly with other agents predisposing to nephrolithiasis may increase the risk of nephrolithiasis. While using Topiramate, agents like these should be avoided since they may create a physiological environment that increases the risk of renal stone formation.
Valproic acid: Concomitant 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.
This adverse reaction is not due to a pharmacokinetic interaction.
Hypothermia, defined as an unintentional drop in body core temperature to <35°C, has been reported in association with concomitant use of Topiramate and Valproic acid (VPA) both in conjunction with hyperammonemia and in the absence of hyperammonemia. This adverse event in patients using concomitant Topiramate and Valproate can occur after starting Topiramate treatment or after increasing the daily dose of Topiramate.
Vitamin K-antagonist anticoagulant medications: Decreased Prothrombin Time/International Normalized Ratio (PT/INR) responses have been reported following concomitant administration of Topiramate with Vitamin K-antagonist anticoagulant medications. Closely monitor INR during concomitant administration of Topiramate therapy with Vitamin K-antagonist anticoagulant medications.