Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy

Christie M Mock, Kristen H Schwetschenau
American Journal of Health-system Pharmacy: AJHP 2012 January 1, 69 (1): 35-9

PURPOSE: The use of levocarnitine for the treatment of valproic-acid-induced hyperammonemic encephalopathy (VHE) is reviewed.

SUMMARY: VHE is generally characterized by an acute onset of impaired consciousness, focal neurologic symptoms, and increased seizure frequency. The exact mechanism of VHE is unclear but relates to the accumulation of toxic valproic acid metabolites and elevated ammonia levels. Carnitine is an essential cofactor in the proper metabolism of valproic acid and ammonia elimination. A lack of carnitine is thought to contribute to hyperammonemia. Valproic acid is thought to increase renal metabolism of glutamate and may contribute to ammonia production. Levocarnitine, the active isomer of carnitine, has been used to treat VHE resulting from valproic acid overdose as well as usual dosages of valproic acid. A literature search of PubMed was conducted for all English-language articles published from 1948 to May 2011 regarding the use of levocarnitine for VHE. Search terms included levocarnitine, l-carnitine, valproic acid, and hyperammonemia encephalopathy. Although large, randomized controlled trials of levocarnitine treatment in VHE are lacking, levocarnitine has been shown to be generally safe and effective in retrospective trials and case reports. Overall, there is more literature supporting the use of levocarnitine in VHE associated with acute overdose than with short- or long-term treatment with usual dosages of valproic acid. No adverse events related to levocarnitine therapy were reported in any of the literature reviewed. Prospective trials are needed to further support the efficacy and safety of levocarnitine in the treatment of VHE.

CONCLUSION: Levocarnitine may be effective and appears to be safe in the treatment of VHE.

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