Evaluation of a simplified pharmacovigilance tool for general practitioners: 5 years of insight.

Spontaneous reporting of adverse drug reactions (ADRs) is the cornerstone of pharmacovigilance. However, major underreporting exists. The main objective of this study was to assess the use of a pharmacovigilance simplified reporting tool (PSRT) by general practitioners (GPs) and, secondarily, to describe the quality of ADR reports during this period. The PSRT was proposed on June 1st, 2015, for the 1290 GPs in the Western Normandy Region. The number and quality of ADRs reported monthly by GPs were prospectively collected from June 1st, 2015, to May 31st, 2020 (Period 2), and compared to those reported during a control period (June 1st, 2010, to May 31st, 2015, Period 1). During all the periods, 920 reports were made by 307 GPs (198 reports in Period 1 and 722 reports in Period 2), with 477 reports (51.8%) using the PSRT. During Period 2, the monthly number of reports was multiplied by 3.5 (p < 0.0001), and the number of GPs was 1.4 compared to that in Period 1 (p = 0.01). Our PSRT showed effectiveness in quantitative and qualitative terms. It must now go further and be integrated into GP software to facilitate ADR reporting nationwide.

[Antidepressive agents and hypertension: A case/no-case study in French pharmacovigilance database]. / Antidépresseurs et hypertension artérielle : étude cas /non-cas dans la base nationale de pharmacovigilance.

INTRODUCTION: Drug-induced hypertension was described with several pharmacological classes. The association between hypertension and antidepressant drugs (AD) is controversial. The objective of this study was to evaluate the link between hypertension and ADs. MATERIALS AND METHODS: A retrospective disproportionality analysis from observations consecutively reported to the French pharmacovigilance database between 1985 and 2020 was performed. The relationship between the suspected ADs and the occurrence of hypertension was assessed by calculating the reporting odds ratio (ROR) in a case/non-case design. A negative (paracetamol) and a positive (celecoxib) control were used to validated this disproportionality method. RESULTS: We compared 6725 cases (including 464 AD-related cases) to 789,483 non-cases (including 56,440 AD-related cases). The reporting of hypertension was significantly associated with serotonin/norepinephrine reuptake inhibitors (SNRI) (ROR 1.43, 95 % CI 1.26-1.64) and monoamine oxidase inhibitors (MAOI) (ROR 6.41, 95 % CI 4.25-9.67) but not with other ADs classes. Concerning ADs analyzed independently of their AD class, a significant signal was observed with many SNRIs (duloxetin, milnacipran and venlafaxin) and with all MAOIs (moclobemide, iproniazide) (ROR between 2.04 and 17.93) but not with others ADs. The ROR value of positive (celecoxib) and negative (paracetamol) controls were ROR=1.53; IC95 %=1.04-2.26 and ROR=0.72; IC95 %=0.65-0.80, respectively. CONCLUSION: We found a significant association between development or worsening of hypertension and SNRIs and MAOIs but not with others ADs, in this study performed in real conditions of life. It is therefore advisable to remain cautious when prescribing ADs and to check systematically for hypertension.

[Acetaminophen induced 5-oxoproline acidosis: An uncommon case of high anion gap metabolic acidosis]. / Acidose à la 5-oxoproline induite par le paracétamol : une cause rare d'acidose métabolique à trou anionique augmenté.

The most common causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis, and intoxications. Nevertheless, clinicians can be faced with unexplained HAGMA, with a need to look for less common etiologies. We describe a case of 5-oxoproline (pyroglutamate) acidosis due to chronic acetaminophen ingestion at therapeutic dose in a 79-year-old inpatient. The pathophysiology of this condition is detailed, with abnormalities in the gamma-glutamyl cycle due to acetaminophen ingestion and severe chronic morbidities, resulting in glutathione and cysteine deficiency and then accumulation of 5-oxoproline. In HAGMA, when usual causes have been excluded, 5-oxoproline acidosis should be suspected in patients with chronic morbidities and acetaminophen ingestion. This diagnosis should be kept in mind because it generally resolves quickly with cessation of acetaminophen and administration of intravenous fluids.

Chemotherapy (platinum and pemetrexed) in combination with erlotinib in non-small cell lung cancer induces major gastrointestinal toxicity: two case reports from the FLARE/GFPC 03-2013 study.

WHAT IS KNOWN AND OBJECTIVE: A randomized phase III study was designed to assess the efficacy and safety of second-line platinum-based chemotherapy with or without erlotinib in non-small cell lung cancer (NSCLC) with EGFR-activating mutation after secondary resistance to EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors). CASE SUMMARY: We report herein two of the first three patients who presented with major gastrointestinal toxicities in the experimental arm of the trial. WHAT IS NEW AND CONCLUSION: Pending further data, it would seem safer to administer EGFR-TKIs and chemotherapy sequentially rather than concomitantly.