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Janus kinase inhibitors (JAKi), such as tofacitinib, baricitinib, upadacitinib or ruxolitinib, are small molecules active on specific intracellular targets and used orally for the treatment of autoimmune or myeloproliferative diseases. Their remarkable therapeutic efficacy is offset by a significant risk of toxicities, essentially dose-dependent and a variable pharmacokinetic profile. The JAKi represent a new therapeutic armamentarium for treating autoimmune, myeloproliferative and inflammatory diseases (incl. COVID-19), but require thorough treatment individualization and close monitoring. Therapeutic Drug Monitoring (TDM) of JAKi could allow a personalized prescription and improve the efficacy-toxicity profile., Competing Interests: Le Pr Yves Chalandon déclare les conflits d’intérêts suivant en relation avec cet article : membre de l’Advisory Board et Travel Support de Novartis et Incyte. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

As a result of advances in pharmacogenomics (PGx), the paradigm that a single dose of a drug is extrapolated to an entire population is set to change. Personalising drug prescriptions according to individual genomic determinants would make it possible to increase the effectiveness and tolerance of treatments. In Switzerland, any doctor can prescribe validated PGx tests for five actionable drugs : abacavir, carbamazepine, thiopurines [azathioprine], fluoropyrimidines [5-FU, capecitabine] and irinotecan. Such an approach presupposes that PGx data are shared with trained clinicians and that prescribing aids can guide them., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

New direct-acting antivirals (DAA) against hepatitis C virus (HCV) have led to a therapeutic revolution in HCV management and virological cure rates approaching 100% while potentially avoiding significant complications of HCV (first cause of liver transplantation). We estimated the price of sustained virological response (SVR) depending on treatment strategy and patient profile. Costs of treatment with recent DAAs being so high, the accessibility to those drugs for the majority of subjects is hitherto limited to advanced stages of hepatitis C. This current situation increases the inequity and strengthens the dominant position of insurers and pharmaceutical companies with a rationing of care. We suggest herein global approaches from a population-level and health-care perspective aiming to reduce the prevalence, morbidity, and mortality related to HCV.

The aim of this article is to help primary care teachers to instruct students' recommendations for drug prescription. Teaching drug prescription covers many aspects of primary care physicians' profession: establishing the correct diagnosis, choosing the appropriate treatment for any individual patient, negotiating with the patient concrete ways of taking the treatment, handling the necessary pharmacologic knowledge or existing tools that help treatment choice and communicating efficiently with the patient. The WHO 6-step method is presented. It helps to clarify the complexity of medical prescription so as to make it understandable for the student.

Cardiovascular morbidity and mortality are higher in psychiatric patients than in the general population. In schizophrenic patients without cardiovascular history, long QT interval is a major risk factor for torsades de pointe and for sudden death. QT interval prolongation is a severe and underestimated dose-dependent adverse reaction triggered by several psychotropic drugs and by clinical situations such as polymedication, methadone maintenance treatment, electrolytic disturbances, cardiovascular history and congenital long QT syndromes. Systematic measurement of QT interval is recommended when psychotropic medications known to prolong it are introduced, as well as in clinical situations at risk. Stereoselective R-methadone administration (chiral switching) contributes to reduce the risk of QT prolongation.

Adverse drug reactions (ADR) have increasing clinical implications and are a permanent challenge for general practitioners. Data suggest that ADR cause 3 to 18% of all hospital admissions with potentially serious consequences. Polymedication, female sex, multiple pathologies with age-related changes are predisposing factors. Antihypertensive drugs with a low bioavailability, a high protein binding capacity and specific elimination pathways are particularly prone to pharmacokinetic interactions. ACE-inhibitors, atenolol, moxonidine and diuretics have few pharmacokinetic interactions. Calcium channel blockers and beta-blockers are associated with an increased risk of pharmacokinetic drug-drug interactions. Diltiazem and verapamil are particularly prone to interactions, as they strongly inhibit the elimination of drugs undergoing the CYP3A4 and P-glycoprotein pathways.

The HMG-CoA reductase inhibitors have similar therapeutic targets and indications. However, their potential pharmacokinetic drug-drug interaction profile may play a significant role in their safety profile in polymedicated and polymorbid patients and can serve as a selection criterion. If their utility is clearly demonstrated in selected conditions, their safety profile remains of concern. Beside dose-related hepatic and muscular injury, other rare and important adverse drug reactions have been reported after prolonged administration such as polyneuropathy, fibrotic interstitial pulmonary disease and lupus-like syndrome. Teratogenicity has also been associated with statin therapy.