Vrignaud Laura, Simon Corinne, Agier Marie Sara, Théophile Hélène, Gras-Champel Valérie, Beau-Salinas Frédérique, Lengellé Céline, Jonville-Béra Annie Pierre
Centre régional de pharmacovigilance, centre-Val-de-Loire, service de pharmacosurveillance, CHRU de Tours, 37044 Tours, France.
Centre régional de pharmacovigilance, département de pharmacologie médicale, CHU de Bordeaux, 33000 Bordeaux, France.
Therapie. 2019 Oct;74(5):513-519. doi: 10.1016/j.therap.2019.02.006. Epub 2019 Mar 31.
The adverse reaction profile of alitretinoin, a retinoid indicated in severe topical corticosteroid-refractory chronic hand eczema, is similar to that of other oral retinoids, especially isotretinoin. The objective of this study was to detect new adverse effects (not listed) of alitretinoin and to estimate the number of pregnancies exposed.
All cases of ADR reported in France with alitretinoin between October 1st, 2012 and February 29th, 2016 were analysed.
During the 41 months of follow-up, 52 cases of serious adverse drug reaction (ADR) and 88 cases of non-serious and unexpected ADR were notified. The most frequent serious ADRs were psychiatric, neurological and dermatological. Psychiatric disorders, mainly depression and suicidal ideation represented 23% of serious ADRs. New adverse drug reactions were detected: myocardial infarction, pancreatitis and digestive haemorrhage. Three pregnancies exposed during the teratogenic risk period, were registered.
The safety profile of alitretinoin matches that of other retinoids. However, the rate of psychiatric disorders appears to be high. Otherwise, the risk of myocardial infarction in patients with cardiovascular risk factor should be considered as a safety concern. It could be explained by the hyperlipemic effects of alitretinoin and studies suggest a cardiovascular risk with retinoids through their effects on lipids (class effect), especially for patients with others cardiovascular risk factors. Pancreatitis and digestive hemorrhage are described with isotretinoin. The rate of reporting of pregnancy induced by a non-compliance with the Pregnancy Prevention Program is near the rate observed with isotretinoin. The high incidence of serious ADR and the non-application of pregnancy prevention program lead the French National Agency for Medicines to limit the first prescription of alitretinoin to dermatologists.
阿利维A酸是一种用于治疗严重的外用皮质类固醇难治性慢性手部湿疹的维甲酸类药物，其不良反应谱与其他口服维甲酸类药物相似，尤其是异维A酸。本研究的目的是检测阿利维A酸新的不良反应（未列出的）并估算暴露于该药物的妊娠数量。
分析了2012年10月1日至2016年2月29日期间法国上报的所有使用阿利维A酸的药物不良反应（ADR）病例。
在41个月的随访期间，共通报了52例严重药物不良反应（ADR）和88例非严重且意外的ADR。最常见的严重ADR为精神、神经和皮肤方面的。精神障碍，主要是抑郁和自杀意念，占严重ADR的23%。检测到了新的药物不良反应：心肌梗死、胰腺炎和消化道出血。记录了在致畸风险期有3例妊娠暴露。
阿利维A酸的安全性与其他维甲酸类药物相当。然而，精神障碍的发生率似乎较高。此外，有心血管危险因素的患者发生心肌梗死的风险应作为安全问题予以考虑。这可能是由阿利维A酸的高脂血症作用所解释的，并且研究表明维甲酸类药物通过其对脂质的影响（类效应）存在心血管风险，尤其是对于有其他心血管危险因素的患者。胰腺炎和消化道出血在异维A酸使用中也有描述。因未遵守妊娠预防计划导致的妊娠报告率接近异维A酸观察到的比率。严重ADR的高发生率以及妊娠预防计划未得到执行导致法国国家药品管理局将阿利维A酸的首次处方限制于皮肤科医生。
