Topiramat ve Valproik asit etkileşimi

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease.

In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, valproic acid oral solution should only be used after other anticonvulsants have failed.

Hyperammonemia and hyperammonemic encephalopathy; measure ammonia level if unexplained lethargy and vomiting or changes in mental status, and also with concomitant topiramate use; consider discontinuation of valproate therapy (5.6, 5.9, 5.10)

This adverse reaction can also occur in patients using concomitant topiramate with valproate after starting topiramate treatment or after increasing the daily dose of topiramate [see Drug Interactions (7.3) ].

Topiramate Concomitant administration of valproate and topiramate has been associated with hyperammonemia with and without encephalopathy [see Contraindications (4) and Warnings and Precautions (5.6, 5.9, 5.10 ) ].

Dose-related hyperammonemia was also seen in pediatric patients 1 to 24 months of age treated with topiramate and concomitant valproic acid for partial-onset epilepsy and this was not due to a pharmacokinetic interaction.

Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, topiramate extended-release capsules should be used with extreme caution if used in combination with alcohol and other CNS depressants.

Hypothermia has been reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use ( 5.14 )

Hyperammonemia and Encephalopathy (Without and With Concomitant Valproic Acid Use) Topiramate treatment can cause hyperammonemia with or without encephalopathy [see Adverse Reactions (6.2) ] .

Hyperammonemia has been reported more frequently when topiramate is used concomitantly with valproic acid.