Drugs
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Upadacitinib (Rinvoq™), an orally-administered Janus kinase 1 (JAK-1) inhibitor, is being developed by AbbVie for the treatment of rheumatoid arthritis. In August 2019, based on positive results from multinational phase III trials conducted in patients with rheumatoid arthritis, upadacitinib received marketing approval in the USA for the treatment of moderately to severely active rheumatoid arthritis and an inadequate response or intolerance to methotrexate. This article summarizes the milestones in the development of upadacitinib leading to this first approval for the treatment of rheumatoid arthritis.
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Review
Leave it to Lefamulin: A Pleuromutilin Treatment Option in Community-Acquired Bacterial Pneumonia.
Lefamulin (BC-3781) is the first systemic pleuromutilin antibiotic found to be safe and effective in the treatment of community-acquired bacterial pneumonia (CABP) in humans. This novel antibiotic was developed to combat the increasing incidence of bacterial resistance to current therapies. As the first semisynthetic pleuromutilin for systemic use in humans, lefamulin has demonstrated efficacy against the most common bacteria responsible for CABP, including strains exhibiting resistance to macrolides, fluoroquinolones, tetracyclines, vancomycin, and beta-lactams. ⋯ Two phase III trials (LEAP-1 and LEAP-2) have demonstrated similar findings, meeting non-inferiority criteria for CABP with a minimal side-effect profile. Pharmacokinetic and pharmacodynamic evaluations have shown sufficient drug levels in plasma, subcutaneous adipose tissue, skeletal muscle, and epithelial lining fluid, warranting further investigation for other clinical uses. Lefamulin was approved by the United States Food and Drug Administration (FDA) on 19 August 2019 for the treatment of CABP.
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Emicizumab (Hemlibra®), a recombinant, humanized, bispecific monoclonal antibody, restores the function of missing activated factor VIII (FVIII) by bridging FIXa and FX to facilitate effective haemostasis in patients with haemophilia A. Subcutaneous emicizumab is approved in several countries, including in the USA and Japan, for the routine prophylaxis of bleeding episodes in patients with haemophilia A with or without FVIII inhibitors. ⋯ Emicizumab was also associated with beneficial effects on health-related quality of life and health status, and was generally well tolerated. In view of its convenient route of administration and versatile dosage regimens (maintenance dose of once every 1, 2 or 4 weeks), emicizumab provides an effective and generally well-tolerated alternative to conventional FVIII replacement products for the prophylaxis of bleeding episodes in patients with haemophilia A, regardless of the presence or absence of inhibitors.
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Lusutrombopag (Mulpleta®), an orally bioavailable, small molecule thrombopoietin receptor agonist, is approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. In placebo-controlled phase 3 clinical trials, lusutrombopag significantly increased the proportion of patients who did not require a platelet transfusion prior to the procedure or rescue therapy for bleeding up to 7 days after the scheduled procedure. ⋯ Lusutrombopag is well tolerated, with headache being the most common adverse reaction in lusutrombopag recipients in clinical trials. Thus, lusutrombopag represents a promising emerging therapeutic option for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.
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Naloxone is a well-established essential medicine for the treatment of life-threatening heroin/opioid overdose in emergency medicine. Over two decades, the concept of 'take-home naloxone' has evolved, comprising pre-provision of an emergency supply to laypersons likely to witness an opioid overdose (e.g. peers and family members of people who use opioids as well as non-medical personnel), with the recommendation to administer the naloxone to the overdose victim as interim care while awaiting an ambulance. There is an urgent need for more widespread naloxone access considering the growing problem of opioid overdose deaths, accounting for more than 100,000 deaths worldwide annually. ⋯ New legislation in different countries permits over-the-counter sales or other prescription-free methods of provision. However, access remains uneven with take-home naloxone still not provided in many countries and communities, and with ongoing barriers contributing to implementation inertia. Take-home naloxone is an important component of the response to the global overdose problem, but greater commitment to implementation will be essential, alongside improved affordable products, if a greater impact is to be achieved.