{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T13:51:24Z","timestamp":1769521884447,"version":"3.49.0"},"reference-count":0,"publisher":"Canadian Society of Healthcare-Systems Pharmacy","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJHP"],"abstract":"<p><strong>ABSTRACT<\/strong><\/p><p><strong>Background:<\/strong> Coadministration of lorazepam and valproic acid is identified by tertiary references as causing a major drug interaction that requires therapy modification and dosage adjustments. The proposed mechanism involves inhibition of lorazepam glucuronidation via direct inhibition of uridine 5\u2032-diphosphate-glucuronosyltransferase enzymes by valproic acid. However, the clinical significance of this interaction is unclear.<strong> <\/strong><\/p><p><strong>Objectives:<\/strong> To identify site-specific practices and assess clinical responses to the interaction between valproic acid and lorazepam.<\/p><p><strong>Methods:<\/strong> A chart review was conducted for patients over 18 years of age who were admitted, from September 2008 to September 2014 inclusive, to the psychiatry or neurology service at Vancouver General Hospital, Vancouver, British Columbia, and who received concomitant valproic acid and lorazepam therapy.<\/p><p><strong>Results:<\/strong> Of the 30 patients included in the chart review, 12 (40%) received an intervention. A total of 8 (27%) patients experienced an adverse drug reaction (ADR), such as drowsiness and dizziness. Seven of these 8 patients were among those who received an intervention. The mean dosage (\u00b1 standard deviation) of lorazepam was 4.2 \u00b1 1.2 mg per day among patients who experienced an ADR and less than 2 mg per day among those who did not experience an ADR.<\/p><p><strong>Conclusions:<\/strong> The current recommendation from tertiary drug references is to reduce the dose of lorazepam by 50% when this drug is coadministered with valproic acid. However, this recommendation could not be validated through an analysis of patients exposed to this interaction in the clinical setting or through a review of the literature. Further clinical and pharmacokinetic studies are required to determine whether concurrent treatment with lorazepam and valproic acid should be considered as causing a major drug interaction. Until more data are available, clinicians should remain cognizant of the potential for a drug\u2013drug interaction and should use the lowest effective dose of lorazepam when this drug is administered concomitantly with valproic acid.<\/p><p><strong>R\u00c9SUM\u00c9<\/strong><\/p><p><strong>Contexte :<\/strong> Selon des sources tertiaires, la prise concomitante de loraz\u00e9pam et d\u2019acide valpro\u00efque causerait une interaction m\u00e9dicamenteuse grave n\u00e9cessitant un changement au traitement et des ajustements posologiques. Le m\u00e9canisme qui sous-tend cette interaction est l\u2019inhibition de la glucuronoconjugaison du loraz\u00e9pam au moyen de l\u2019inhibition directe des enzymes uridine 5\u2019-diphosphate glucuronosyltransf\u00e9rases par l\u2019acide valpro\u00efque. Cependant, la signification clinique de cette interaction est inconnue.<\/p><p><strong>Objectifs :<\/strong> D\u00e9terminer quelles sont les pratiques particuli\u00e8res \u00e0 l\u2019\u00e9tablissement hospitalier et \u00e9valuer les r\u00e9ponses cliniques \u00e0 l\u2019interaction entre l\u2019acide valpro\u00efque et le loraz\u00e9pam.<\/p><p><strong>M\u00e9thodes :<\/strong> On a men\u00e9 une analyse des dossiers m\u00e9dicaux des patients de plus de 18 ans qui, entre septembre 2008 et septembre 2014 inclusivement, ont \u00e9t\u00e9 admis au service de psychiatrie ou de neurologie de l\u2019H\u00f4pital g\u00e9n\u00e9ral de Vancouver, \u00e0 Vancouver en Colombie-Britannique, et ont re\u00e7u en m\u00eame temps l\u2019acide valpro\u00efque et le loraz\u00e9pam.<\/p><p><strong>R\u00e9sultats :<\/strong> Parmi les 30 patients dont le dossier m\u00e9dical a \u00e9t\u00e9 retenu pour l\u2019analyse, 12 (40 %) ont eu droit \u00e0 une intervention. Un total de 8 (27 %) patients ont subi une r\u00e9action ind\u00e9sirable aux m\u00e9dicaments (RIM), comme de la somnolence et des \u00e9tourdissements. Sept de ces 8 patients appartenaient au groupe qui a eu droit \u00e0 une intervention. La dose quotidienne moyenne de loraz\u00e9pam \u00e9tait de 4,2 \u00b1 1,2 mg chez les patients qui ont subi une RIM et de moins de 2 mg chez ceux qui n\u2019en ont pas subi.<\/p><p><strong>Conclusions :<\/strong> Des sources tertiaires sur les m\u00e9dicaments recommandent actuellement de r\u00e9duire la dose de loraz\u00e9pam de 50 % lorsque ce m\u00e9dicament est administr\u00e9 conjointement avec l\u2019acide valpro\u00efque. Or, cette recommandation n\u2019a pu \u00eatre valid\u00e9e \u00e0 l\u2019aide d\u2019une revue de la litt\u00e9rature ou d\u2019une analyse des dossiers des patients ayant \u00e9t\u00e9 expos\u00e9s \u00e0 une telle interaction m\u00e9dicamenteuse en milieu clinique. De plus amples \u00e9tudes cliniques et pharmacocin\u00e9tiques sont n\u00e9cessaires pour d\u00e9terminer si la prise concomitante de loraz\u00e9pam et d\u2019acide valpro\u00efque peut \u00eatre consid\u00e9r\u00e9e comme une cause d\u2019interaction m\u00e9dicamenteuse grave. D\u2019ici \u00e0 ce qu\u2019ils disposent de plus de donn\u00e9es probantes, les cliniciens doivent demeurer conscients du potentiel d\u2019interaction m\u00e9dicament-m\u00e9dicament et utiliser la plus faible dose efficace de loraz\u00e9pam lorsque ce m\u00e9dicament est pris en concomitance avec l\u2019acide valpro\u00efque.<\/p><\/jats:p>","DOI":"10.4212\/cjhp.v70i3.1656","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T16:20:40Z","timestamp":1499790040000},"source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetic Interactions between Valproic Acid and Lorazepam (PIVOtAL Study): A Review of Site-Specific Practices"],"prefix":"10.4212","volume":"70","author":[{"given":"Joane Y","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony K L","family":"Kiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary H H","family":"Ensom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2732","published-online":{"date-parts":[[2017,6,30]]},"container-title":["The Canadian Journal of Hospital Pharmacy"],"original-title":[],"link":[{"URL":"http:\/\/www.cjhp-online.ca\/index.php\/cjhp\/article\/viewFile\/1656\/2550","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.cjhp-online.ca\/index.php\/cjhp\/article\/viewFile\/1656\/2569","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.cjhp-online.ca\/index.php\/cjhp\/article\/viewFile\/1656\/2569","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T16:20:42Z","timestamp":1499790042000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.cjhp-online.ca\/index.php\/cjhp\/article\/view\/1656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,30]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,6,30]]}},"URL":"https:\/\/doi.org\/10.4212\/cjhp.v70i3.1656","relation":{},"ISSN":["1920-2903","0008-4123"],"issn-type":[{"value":"1920-2903","type":"electronic"},{"value":"0008-4123","type":"print"}],"subject":[],"published":{"date-parts":[[2017,6,30]]}}}