Drug General Information (ID: DDI4G2IFZ8)
Drug Name			Topiramate		Drug Info		Valproic acid		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anticonvulsants				Anticonvulsants
Structure

Mechanism of Topiramate-Valproic acid Interaction (Severity Level: Moderate)
Increased risk of hyperammonemia Click to Show/Hide Mechanism Graph
Drug Name		Topiramate				Valproic acid
Mechanism		Hyperammonemia				Hyperammonemia
Key Mechanism Factor 1
		Factor Name		Hyperammonemia
		Factor Description		Hyperammonemia is a metabolic disorder characterized by elevated levels of ammonia. The most common manifestations of hyperammonemia are neurological signs and symptoms that may be acute or chronic, depending on the underlying abnormality, and severe life-threatening complications such as cerebral edema and brain herniation can occur.
Mechanism Description		Increased risk of hyperammonemia by the combination of Topiramate and Valproic acid

Recommended Action
Management		Pharmacologic response to topiramate and valproic acid should be monitored more closely following addition or withdrawal of one or the other drug. Dose adjustments may be required if an interaction is suspected. Patients should be advised to notify their physician if they experience loss of seizure control. Patients should also be monitored for clinical symptoms of hyperammonemic encephalopathy, which often include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting. Monitoring of ammonia levels should be considered if such symptoms occur. Signs and symptoms usually abate with discontinuation of either drug. Discontinuation of topiramate or valproic acid should be considered if hypothermia occurs. Patients should be monitored for symptoms such as lethargy, confusion, coma, and cardiovascular or respiratory system changes.

References
1	Bourgeois BF "Drug interaction profile of topiramate." Epilepsia 37(suppl 2 (1996): s14-7. [PMID: 8641241]
2	May TW, Rambeck B, Jurgens U "Serum concentrations of topiramate in patients with epilepsy: influence of dose, age, and comedication." Ther Drug Monit 24 (2002): 366-74. [PMID: 12021627]
3	Product Information. Topamax (topiramate). Ortho Pharmaceutical Corporation, Raritan, NJ.
4	Rosenfeld WE, Liao S, Kramer LD, et al "Comparison of the steady-state pharmacokinetics of topiramate and valproate in patients with epilepsy during monotherapy and concomitant therapy." Epilepsia 38 (1997): 324-33. [PMID: 9070595]