Risk factors for hyperammonemia associated with valproic acid therapy in adult epilepsy patients

Changing incidence of hyperammonemia in Japan from 2006 to 2013: expansion of new antiepileptic drugs reduces the risk of hyperammonemia

“…1). Among these inducers, concomitant use of PHT was the strongest risk factor for hyperammonemia (Table 2), confirming our previous findings [5,6]. Tseng et al [21] performed a prospective study of 158 patients using VPA and similarly reported that concomitant PHT or PB was a significant risk factor.…”

“…Recently, we studied a large cohort of 2724 adult patients and 1753 pediatric patients on VPA therapy Electronic supplementary material The online version of this article (doi:10.1007/s00228-015-1939-3) contains supplementary material, which is available to authorized users. and identified the following risk factors for hyperammonemia: VPA dose, age, female gender, and concomitant use of enzymeinducing AEDs [inducers included phenytoin (PHT), phenobarbital (PB), primidone, and carbamazepine (CBZ)] or carbonic anhydrase inhibitors (CAIs) such as zonisamide (ZNS) and topiramate (TPM) [5,6]. Among the inducers, concomitant use of PHT and PB was associated with a marked increase in the risk of hyperammonemia by about 5-to 10-fold and 3-to 7-fold, respectively, and poly-inducer regimens including PHT resulted in the highest risk of hyperammonemia.…”

Increased Occurrence of Valproic Acid-Induced Hyperammonemia in Carriers of T1405N Polymorphism in Carbamoyl Phosphate Synthetase 1 Gene

“…Both heterozygous and homozygous carrier states of the T1405N polymorphism and concomitant administration of two or more anticonvulsants with VPA were shown previously to be independent risk factors for developing HA in the relatively small cohort of patients ( N = 79) from Japan and single case report from our laboratory [4, 5]. In the recent larger study, Yamamoto et al identified several other risk factors for HA in PWE, including VPA dose and use of hepatic enzyme inducers, although genetic polymorphism was not analyzed in this study [6]. Built on the previous reports, we hypothesized that in a Caucasian population of patients without liver failure and treated with VPA, genetically determined variations in CPS1 function would be associated with increased incidence of HA.…”

Valproate-induced hyperammonaemic encephalopathy in a neonate: Treatment with carglumic acid

“…On the other hand, mild elevations in the level of ammonia that did not cause any symptoms have been observed in patients treated with VA in whom medication did not need to be discontinued. Some anticonvulsant drugs, such as phenobarbital, phenytoin, carbamazepine, and topiramate, increase the toxicity of VA. 15 OTC deficiency (an X-linked disease) is the most common inherited cause of hyperammonaemia. 14 Several factors may be associated to the development of VHE, but the most important are polytherapy and deficiency of ornithine transcarbamylase (OTC) and of carnitine.…”