[Analysis of regulatory status changes of drugs in France: 2010-2019]. / Analyse des modifications de statut réglementaire des médicaments en France : 2010­2019.

OBJECTIVES: The existence of borderline products between the status of a medicinal product and other less regulated products allows some products to have different statuses or even to change from one status to another. In order to quantify these changes, a review of medicines that have changed from drug status to other statuses (medical device, cosmetic product or food supplement) in France between 2010 and 2019 was performed. METHOD: The lists of medicinal products with archived or revoked marketing authorization (MA) from the French National Authority's Register of Medicinal Products were analyzed in order to identify the medicinal products withdrawn from the market between January 1, 2010 and September 30, 2019 that could be considered as products with a "potential for status change". Then, we searched on the official websites of the MA holders and other firms, for a possible return to the market with a different status, marketed by the same firm (self-change of status) or a different firm (hetero-change of status). RESULTS: Out of a list of 206 drugs identified as "with potential for status change", we detected a total of 101 status changes, including 36 auto-changes and 65 hetero-changes. These changes mainly concern vitamin or herbal drugs later marketed as food supplements (30 cases of auto-changes and 60 cases of hetero-changes). There are also 6 cases of switching to cosmetic product and 5 cases of switching to medical device. CONCLUSION: The existence of no clear distinction between the different statuses of health products facilitates their status changes. The increasing shift from "medicines" to less regulated products, the trivialization of their use by the public and their increasing consumption make them a fundamental issue of social pharmacology, requiring to raise the awareness of consumers and health professionals.

Pharmacovigilance, risks and adverse effects of self-medication.

Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.

Adverse drug reactions to self-medication: a study in a pharmacovigilance database.

Although self-medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self-medication recorded in the Midi-Pyrénées PharmacoVigilance between 2008 and 2014. Self-medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three-forth of the ADRs were 'serious'. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy-homeopathy accounted for 9.1% of drugs.

Nitric oxide inhibits spleen cell proliferative response after burn injury by inducing cytostasis, apoptosis, and necrosis of activated T lymphocytes: role of the guanylate cyclase.

We previously showed that an overproduction of nitric oxide (NO) by macrophages was responsible for the collapse of lymphoproliferative responses after burn injury in rats. First, we demonstrate here that 10 days post-burn, the inhibition of splenocyte response to concanavalin-A results from cytostatic, apoptotic, and necrotic effects of NO on activated T cells. This was evidenced by various criteria at the levels of DNA, mitochondria, and plasma membrane. Inhibition of NO synthase by S-methylisothiourea (10 microM) normalized all the parameters. Second, we show that two soluble guanylate cyclase (sGC) inhibitors, LY83583 and ODQ, restored the proliferative response in a concentration-dependent manner. LY83583 (0.5 microM) rescued T cells from apoptosis. Similar results were obtained with KT5823 (5 microM) a specific inhibitor of protein kinase G (PKG). In contrast, neither LY83583 nor KT5823 inhibited NO-induced necrosis. These results suggest that NO blocked T cells in the G1 phase and induced apoptosis through a sGC-PKG-dependent pathway and necrosis through an independent one.