A Massive Venlafaxine Intoxication: Evolution of Cardiac Toxicity with Venlafaxine and O-Desmethylvenlafaxine Elimination Kinetics: A Grand Round.

BACKGROUND: This study presents the case of a 19-year-old woman who attempted suicide by ingesting 11.25 g of venlafaxine (V). She was admitted to the hospital with severe biventricular dysfunction, progressing to cardiac arrest requiring extracorporeal circulatory life support for 11 days. The pharmacokinetics of venlafaxine during impaired cardiac output and the effect of its active metabolite, the O-desmethylvenlafaxine (ODV), are currently not very well understood. METHODS AND RESULTS: Serum concentrations of V and ODV were monitored twice daily for 3 weeks. The maximum concentrations of venlafaxine and ODV were at 14 hours after ingestion, with 29,180 mcg/L for V and 5399 mcg/L for ODV. Half-lives increased, requiring 2 weeks to eliminate the drug. The left ventricular ejection fraction significantly improved when V + ODV was below 1000 mcg/L and remained altered until the ODV concentrations were lower than 400 mcg/L. CONCLUSIONS: This report, with complete elimination kinetic of V and ODV in a monodrug intoxication, provides information about the modification of pharmacokinetics in the case of an overdose managed by extracorporeal circulatory life support, the cardiac toxicity of ODV, and the value of the toxic threshold for the active moiety.

What Is the Therapeutic Reference Range for Levetiracetam? Grand Round/A Case Study.

ABSTRACT: The Therapeutic Drug Monitoring guidelines of Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie had proposed a therapeutic reference range of 10-40 mg/L for levetiracetam in 2011. In the first version of the 2017 update, it was changed to 20-40 mg/L; however, 5 months later, in an erratum version, it was changed back to 10-40 mg/L. In this study, the authors agree with the range to 10-40 mg/L but discuss to what extent a wider interval may be proposed for certain patients.

Self-poisoning with 60 tablets of Apixaban, a pharmacokinetics case report.

A 67-year-old man was admitted to the emergency department about 5 h after deliberate self-poisoning with 300 mg of Apixaban. The clinical examination did not show any organ dysfunctions or haemorrhagic signs, and the patient's life was not in danger. The first analysis, upon admission, showed a concentration of 2655 µg l-1 of Apixaban. The Cmax was observed 17 h after the intake (3654 µg l-1 ), about four times the classical Tmax value (median [range]: 4 h [2-4]). The Apixaban was then eliminated following a first order elimination with a calculated half-life of 10.8 h. The anti-Xa activity seems to be linearly related to concentration up to 4000 µg l-1 . This report suggests that the use of activated charcoal should be effective up to 17 h after a massive intake.

Unsuccessful Suicide Attempt With Tiapride.

To the best of our knowledge, no case has been published in the literature that reports an overdose of tiapride, either alone or in combination with other drugs. We report a self-poisoning case in an 18-year-old girl, with approximately 10 times the usual daily dose (ie, 2.5 g). Although the blood concentration was 20/30-fold higher than usually observed after therapeutic drug intakes (17,300 mcg/L), the patient remained almost asymptomatic.

[Therapeutic drug monitoring of cyamemazine: How to interpret a concentration? A review of literature]. / Suivi thérapeutique pharmacologique de la cyamémazine : comment interpréter une concentration ? Une revue de la littérature.

Cyamemazine is the most prescribed antipsychotic drug in France, often in combination with another antipsychotic, for its sedative and anxiolytic component. Providing to physicians serum concentrations of cyamemazine in different contexts (compliance checking, ineffectiveness, adverse effects, intoxication, modification of pharmacokinetic parameters…) requires to interpret them correctly. This article presents an update on how to interpret a concentration of cyamemazine, wich remains poorly documented. The anxiolysis occurs at steady-state serum trough concentrations of 4 to 5µg/L; the antipsychotic effect from 18-20µg/L. Cyamemazine is not a drug with a narrow therapeutic window and concentrations up to 400µg/L may be sought in cases of partial efficacy; concentrations of 1800µg/L might be fatal; lower concentrations might be fatal if association with high others concentrations of drugs.

[Therapeutic drug monitoring of antidepressants: Why venlafaxine is the most monitored drug? A review of literature]. / Suivi thérapeutique pharmacologique des antidépresseurs : pourquoi la venlafaxine est le médicament le plus surveillé ? Une revue de la littérature.

Venlafaxine is the third most frequently prescribed antidepressant in France the last decade, with about 400,000 daily doses. Therapeutic drug monitoring (TDM) of this medication, by measuring the active moiety venlafaxine (V) and O-desmethylvenlafaxine (ODV), is recommended (level of recommendation 2). However, this antidepressant seems to be the one for which clinicians most often use TDM, much more frequently than escitalopram, which is more prescribed and for which TDM is also recommended. The main goal of this review is to provide an update on the TDM of venlafaxine: its therapeutic interval, its level of recommendation and the origin of its "success". From the literature does not enable to define a therapeutic interval for the active moiety V+ODV, that is to say a steady-state trough concentration allowing a clinical response without toxicity. Nevertheless, a target concentration from 100 to 400µg/L is certainly relevant for the majority of patients without any pharmacodynamic resistance ; though a greater concentration could result in an earlier response or could be required for a clinical response in a minority of patients. A patient with no clinical response despite a concentration greater than 1000µg/L should be proposed another antidepressant. Measurement of the ODV/V ratio is also a useful tool, values below 0.3 usually reflecting a slow metabolizer phenotype for cytochrome P-450 2D6, which is more at risk of adverse effects. Research for this phenotype probably explains many prescriptions for TDM.

Infectious risk of biological drugs vs. traditional systemic treatments in moderate-to-severe psoriasis: a cohort analysis in the French insurance database.

The aim of this study was to compare the infectious risk between a group of psoriasis patients treated by biological drugs (BD) and a group treated by traditional systemic treatments (TST). We built a retrospective observational cohort study from the French health insurance database in the Midi-Pyrénées area (2.9 million inhabitants, southwest of France) using data from 01/01/2010 to 12/31/2013. We compared the infectious risk between 'exposed' patients treated with BD (adalimumab, etanercept, infliximab, or ustekinumab) and 'unexposed' patients treated by TST (phototherapy, acitretin, methotrexate, or cyclosporine). We realized a survival analysis on the first infectious event, defined as an anti-infective drug delivery or a hospital diagnosis of infection. We selected 101 'exposed' and 788 'unexposed' patients. In our multivariate Cox model, 'exposure' did not seem to decrease the time frame of the first infectious event compared with 'nonexposure' (HR = 0.94, P = 0.62). Among all treatment, the safest seemed to be ustekinumab while the least safe was etanercept. We found factors statistically associated with the risk of infection: gender (female vs. male), economic deprivation, chronic hepatitis B or C, history of cancer, at least one infectious event, and the number of different drugs during the 6-month period before the study. We did not find any difference of infective risk between the BD and the TST. This result enhances the recent PSONET registries conclusions.