Topiramate/valproate semisodium interaction
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Hyperammonaemic encephalopathy: case report A 31-year-old woman developed hyperammonaemic encephalopathy during concomitant treatment with valproate semisodium [Depakote] and topiramate [duration of treatment to reaction onset not stated]. The woman, who had a history of migraine, borderline personality disorder and bipolar disorder with psychotic features, reported a "manic episode on Christmas Eve" and started receiving oral valproate semisodium 500mg twice a day; she was also receiving oral topiramate 45mg at bedtime for migraine headaches, citalopram and quetiapine. Two weeks after valproate semisodium initiation, she presented with irritation, somnolence, dysarthria and ataxia and reported the presence of ‘voices’ telling her to hurt herself 2 days earlier. Depakote was discontinued and the woman was taken to an emergency room where she was hospitalised. Liver function tests were normal. However, she had a mildly elevated valproate concentration (104.0 µg/mL) and an elevated plasma ammonia level (41.52 mmol/L). She was diagnosed with valproate-induced hyperammonaemic encephalopathy. One day after admission and Depakote cessation, her symptoms resolved and she had a plasma ammonia level of 31.66 mmol/L. Author comment: "The synergistic effects of topiramate may relate to its ability to inhibit carbonic anhydrase. . . Also, topiramate can inhibit glutamine synthetase activity in the brain, leading to locally increased levels of ammonia . . . However, because it is based on limited case reports, the existence of synergism between valproate and topiramate must remain impressionistic." Deutsch SI, et al. Valproate-induced hyperammonemic encephalopathy and normal liver functions: Possible synergism with topiramate. Clinical Neuropharmacology 32: 350-352, No. 6, Nov-Dec 2009. Available from: URL: http:// 803007396 dx.doi.org/10.1097/WNF.0b013e3181ac3615 - USA
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Reactions 20 Mar 2010 No. 1293
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