Pharmacokinetic Interactions between Valproic Acid and Lorazepam (PIVOtAL Study): A Review of Site-Specific Practices

Tang, Joane Y; Kiang, Tony K. L.; Ensom, Mary H H

doi:10.4212/cjhp.v70i3.1656

Cited by 6 publications

(9 citation statements)

References 17 publications

(29 reference statements)

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“…Despite its safety profile, VA’s common side effects include dry mouth, nausea, and vomiting. One of the rare, but potentially life-threatening side effect of VA is hyperammonemia [ 5 ]. VA-induced hyperammonemia usually presents as lethargy, vomiting, or any focal neurologic deficit [ 6 ] and is usually due to VA’s toxic metabolite-induced inhibition of N-acetyl glutamate synthetase (NAGS), a rate-limiting enzyme of the urea cycle.…”

Section: Introductionmentioning

confidence: 99%

Carglumic Acid Treatment of a Patient with Recurrent Valproic Acid-induced Hyperammonemia: A Rare Case Report

Sattar¹,

Wasiq²,

Yasin³

et al. 2018

Cureus

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Valproic acid, first manufactured as an anticonvulsant, is commonly used to treat both neurological and psychiatric conditions. A rare and deadly side effect of this medication is hyperammonemia, presenting as lethargy, confusion, seizure, and, ultimately, coma. In rare circumstances, hyperammonemia can be recurrent and devastating, especially in patients with an underlying N-acetyl glutamate synthase (NAGS) deficiency, as the valproic acid can enhance this enzyme deficiency and inhibit the conversion of ammonia into urea in the liver. For these subtypes of patients, the United States Food and Drug Administration (US FDA) has recently approved carglumic acid, a medication that can act as a scavenger by effectively increasing the levels of NAGS, ultimately enhancing the conversion of ammonia to urea. In our case report, we have mentioned a patient with treatment-resistant bipolar disorder, who presented with elevated ammonia levels secondary to valproic acid treatment. Valproic acid was the only drug that was effective in his case, so we initiated therapy to reduce his elevated ammonia levels. After a thorough evaluation, we found the patient had a genetic NAGS deficiency. Carglumic acid was initiated and proved efficacious in our patient.

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Section: Introductionmentioning

confidence: 99%

Carglumic Acid Treatment of a Patient with Recurrent Valproic Acid-induced Hyperammonemia: A Rare Case Report

Sattar¹,

Wasiq²,

Yasin³

et al. 2018

Cureus

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“…As such, kratom may precipitate interactions with drugs that undergo glucuronidation, including lorazepam, which is extensively conjugated to the inactive 3‐O‐phenolic glucuronide in the liver 46 . The UGT inhibitor valproate has been shown to decrease the oral clearance of lorazepam and increase systemic concentrations of lorazepam 47 …”

Section: Discussionmentioning

confidence: 99%

An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021

Ndungu

Taneja

et al. 2023

Clinical Translational Sci

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Kratom is a widely used Asian botanical that has gained popularity in the United States due to a perception that it can treat pain, anxiety, and opioid withdrawal symptoms. The American Kratom Association estimates 10-16 million people use kratom. Kratom-associated adverse drug reactions (ADRs) continue to be reported and raise concerns about the safety profile of kratom. However, studies are lacking that describe the overall pattern of kratom-associated adverse events and quantify the association between kratom and adverse events. ADRs reported to the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021 were used to address these knowledge gaps. Descriptive analysis was conducted to analyze kratom-related adverse reactions. Conservative pharmacovigilance signals based on observed-to-expected ratios with shrinkage were estimated by comparing kratom to all other natural products and drugs. Based on 489 deduplicated kratom-related ADR reports, users were young (mean age 35.5 years), and more often male (67.5%) than female patients (23.5%). Cases were predominantly reported since 2018 (94.2%). Fiftytwo disproportionate reporting signals in 17 system-organ-class categories were generated. The observed/reported number of kratom-related accidental death reports was 63-fold greater than expected. There were eight strong signals related to addiction or drug withdrawal. An excess proportion of ADR reports were about kratom-related drug complaints, toxicity to various agents, and seizures.

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“…In theory, this interaction could lead to toxicity. Several small, randomized, or non-randomized controlled trials investigated the clinical relevance of VPA-LZP interaction [4]. Clinical signs in these studies included mostly dizziness or drowsiness.…”

Section: Discussionmentioning

confidence: 99%

Stupor in a catatonic patient due to an interaction between high-dose lorazepam and valproic acid: a case report

Neeling

Paesschen

2021

Acta Neurol Belg

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Pharmacokinetic Interactions between Valproic Acid and Lorazepam (PIVOtAL Study): A Review of Site-Specific Practices

Cited by 6 publications

References 17 publications

Carglumic Acid Treatment of a Patient with Recurrent Valproic Acid-induced Hyperammonemia: A Rare Case Report

Carglumic Acid Treatment of a Patient with Recurrent Valproic Acid-induced Hyperammonemia: A Rare Case Report

An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021

Stupor in a catatonic patient due to an interaction between high-dose lorazepam and valproic acid: a case report

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