Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug–drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug–drug interactions involving dexamethasone in the clinical setting. We therefore aimed to review the already published evidence for various DDIs involving dexamethasone in vitro in cell culture systems and in vivo in animal models and humans.

Summary: Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life‐threatening disease that may result from drug exposure. We report a case of iTTP occurring in a 39‐year‐old patient, 45 months following introduction of the anti‐CD52 lymphoid cell depleting monoclonal antibody alemtuzumab, to treat a relapsing‐remitting multiple sclerosis. Treatment consisted in plasma exchange, corticosteroids and caplacizumab, allowing clinical remission 3 months after the diagnosis, attested by the absence of thrombocytopenia and recovery of ADAMTS‐13 activity. As other autoimmune disorders, iTTP may occur following alemtuzumab. This diagnosis should be suspected in patients with features of thrombotic microangiopathy following this treatment.