Reality of drug-induced erythema multiforme: A French pharmacovigilance study.

BACKGROUND: Since the 2002 SCAR study, erythema multiforme (EM), a post-infectious disease, has been distinguished from Stevens-Johnson syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported in the French pharmacovigilance database (FPDB). OBJECTIVES: To describe EM reported in the FPDB and to compare the quality and the characteristics of the reports. METHODS: This retrospective observational study selected all EM cases reported in the FPDB over two periods: period 1 (P1, 2008-2009) and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of clinically typical EM and/or validated by a dermatologist; 2) a reported date of onset of the reaction; and 3) a precise chronology of drug exposure. Cases were classified confirmed EM (typical acral target lesions and/or validation by a dermatologist) and possible EM (not-otherwise-specified target lesions, isolated mucosal involvement, doubtful with SJS). We concluded possible drug-induced EM when EM was confirmed, with onset ranging from 5 to 28 days without an alternative cause. RESULTS: Among 182 selected reports, 140 (77%) were analyzed. Of these, 67 (48%) presented a more likely alternative diagnosis than EM. Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32), 36 (49%) had a probable non-drug cause and 28 (38%) were associated with only drugs with an onset time ≤4 days and/or ≥29 days. Possible drug-induced EM was retained in 9 cases (6% of evaluable reports). Etiological work-up was more often performed in period 2 than 1 (53.1% vs 29.3%, P=0.04), and the time to onset from 5 to 28 days was more frequent in period 2 (59.2% vs 40%, P=0.04). CONCLUSIONS: This study suggests that possible drug-induced EM is rare. Many reports describe "polymorphic" rashes inappropriately concluded as EM or post-infectious EM with unsuitable drug accountability subject to protopathic bias.

Calcium channel blocker exposure and psoriasis risk: Pharmacovigilance investigation and literature data.

INTRODUCTION: Evidence regarding a possible association between psoriatic manifestations and use of calcium channel blockers (CCBs) is sparse. Currently, psoriatic manifestations are not listed in the summary of product characteristics (SmPC) of CCBs. In this context, we aimed to investigate the association between psoriasis and CCB exposure. METHODS: We reviewed spontaneous reports recorded in the French national pharmacovigilance database (FPVD) between 1985 and 2019. The association between CCB exposure and risk of psoriasis was assessed using the case/non-case method. We also analyzed literature data. RESULTS: Ninety-four reports of psoriatic manifestations after CCB exposure were recorded in the FPVD. Both induction and exacerbation cases were observed. Time to onset was less than 2 years in 64% of reports and outcome was favorable in 71% of reports after CCB discontinuation. These features were concordant with those of literature reports. The reporting odds ratio (ROR) was 2.45 (95% CI 1.99-3.02). Concomitant use of betablockers or angiotensin II receptor blockers did not interact with the association between CCB exposure and psoriasis risk. The ROR for the stratum "use of angiotensin converting enzyme inhibitors" (ACEI) was 2.14 (95% CI 1.29-3.55), while the ROR for the stratum ACEI non-use was 0.12 (95% CI 0.10-0.15). Large-scale epidemiologic studies were focused only on first diagnoses and did not include exacerbations; psoriasis risk was therefore probably underestimated. CONCLUSION: We found a statistically significant association between CCB exposure and psoriasis risk, which constitutes a safety signal. This risk is a class effect, time to onset is mostly less than 2 years and outcome is favorable after CCB discontinuation. Psoriasis should be mentioned in the SmPCs of all CCBs, and healthcare workers should be aware of this risk. Attention should be paid to patients taking CCB and ACEI concomitantly.

Drug interactions related to self-medication: a French pharmacovigilance database study.

Self-medication (SM) is a common practice perceived by patients as harmless which can, however, entail health risks. The aim of the study was to identify drug-drug interactions (DDIs) involving SM drugs leading to adverse drug reactions (ADRs) in the National French Pharmacovigilance Database. All ADR reports from 1 January 1985 to 31 July 312018, coded as 'interaction' and 'self-medication', were selected and studied. Patient characteristics, the level and type of interaction, and the therapeutic classes of the drugs were examined. Adverse drug reactions were analysed and classified according to the system organ classes of the Medical Dictionary for Regulatory Activities. One hundred and three reports totalling 158 ADRs (71% severe cases) were included; 153 DDIs (59.5% pharmacodynamic) involving 234 drugs were identified. The latter included 119 SM drugs (51% available on prescription), mainly analgaesics, anti-inflammatory drugs, dietary supplements and antibiotics. Haemostasis disorders and renal failure were the most frequently reported ADRs. The analysis of reference documents raised concerns on the lack of information provided by package leaflets. In conclusion, the present study highlights the risks of medically unapproved re-use of prescription drugs or the consumption of dietary supplements without monitoring possible interactions and ADRs. Patient awareness could be improved by more regular updates of medication package inserts.