title: Risk factors for hyperammonemia associated with valproic acid therapy in adult epilepsy patients.
abstract: Hyperammonemia is one of the side effects of treatment with valproic acid (VPA), but the risk factors and mechanisms involved remain obscure. This study analyzed the risk factors for hyperammonemia associated with VPA therapy in adult epilepsy patients. A retrospective analysis of 2724 Japanese patients (1217 males and 1507 females aged from 16 to 76years) treated with VPA between January 2006 and December 2010 were analyzed. The ammonia level increased markedly in a VPA dose-dependent manner, and was significantly elevated in patients who also used hepatic enzyme inducers such as phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), and combinations of these drugs. When a blood ammonia level exceeding 200μg/dl was defined as hyperammonemia, the risk factors for hyperammonemia according to multiple regression analysis were a VPA dose >20mg/kg/day (odds ratio (OR): 4.1; 95% confidence interval (CI): 1.6-10.8) and concomitant use of PHT (OR: 11.0; 95% CI: 3.1-38.7), concomitant PB (OR: 4.3; 95% CI: 1.0-17.9), concomitant CBZ (OR: 2.8; 95% CI: 0.6-11.9), and concomitant topiramate (OR: 2.8; 95% CI: 1.2-6.5). Regimens containing multiple inducers were associated with an increased risk of hyperammonemia. Identification of risk factors for hyperammonemia associated with VPA therapy can help to minimize side effects during its clinical use.
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886, Urushiyama, Aoi-ku, Shizuoka-shi, Shizuoka 420-8688 Japan. yamamoty@szec.hosp.go.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Eri
authors.initials: E
authors.lastname: Suzuki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mishima
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid