Drugs
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Dexmedetomidine (Dexdor(®)) is a highly selective α2-adrenoceptor agonist. It has sedative, analgesic and opioid-sparing effects and is suitable for short- and longer-term sedation in an intensive care setting. In the randomized, double-blind, multicentre MIDEX and PRODEX trials, longer-term sedation with dexmedetomidine was noninferior to midazolam and propofol in terms of time spent at the target sedation range, as well as being associated with a shorter time to extubation than midazolam or propofol, and a shorter duration of mechanical ventilation than midazolam. ⋯ Dexmedetomidine had beneficial effects on delirium in some randomized, controlled trials (e.g. patients receiving dexmedetomidine were less likely to experience delirium than patients receiving midazolam, propofol or remifentanil and had more delirium- and coma-free days than patients receiving lorazepam). Intravenous dexmedetomidine had an acceptable tolerability profile; hypotension, hypertension and bradycardia were the most commonly reported adverse reactions. In conclusion, dexmedetomidine is an important option for sedation in the intensive care setting.
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Oral naltrexone extended-release/bupropion extended-release (naltrexone ER/bupropion ER; Contrave(®), Mysimba(™)) is available as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial body mass index (BMI) of ≥ 30 kg/m(2) (i.e. obese) or a BMI of ≥ 27 kg/m(2) (i.e. overweight) in the presence of at least one bodyweight-related comorbidity, such as type 2 diabetes mellitus, hypertension or dyslipidaemia. In 56-week phase III trials in these patient populations, oral naltrexone ER/bupropion ER 32/360 mg/day was significantly more effective than placebo with regard to percentage bodyweight reductions from baseline and the proportion of patients who achieved bodyweight reductions of ≥ 5 and ≥ 10%. ⋯ Naltrexone ER/bupropion ER was generally well tolerated in phase III trials, with nausea being the most common adverse event. Thus, naltrexone ER/bupropion ER 32/360 mg/day as an adjunct to a reduced-calorie diet and increased physical activity, is an effective and well tolerated option for chronic bodyweight management in obese adults or overweight adults with at least one bodyweight-related comorbidity.
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Eluxadoline (Viberzi(™)), developed by Actavis (now Allergan), is an orally administered, first-in-class compound that functions as both a µ-opioid receptor agonist and a δ-opioid receptor antagonist, and is indicated for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D) in adults. The agent was originally developed by Janssen Pharmaceutica. Eluxadoline has been approved in the US, and submissions to other global authorities are being contemplated or planned. This article summarizes the milestones in the development of eluxadoline leading to this first approval for IBS-D.
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Review
Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir: A Review in Chronic HCV Genotype 1 Infection.
A fixed-dose tablet comprising ombitasvir (an NS5A replication complex inhibitor), paritaprevir (an NS3/4A protease inhibitor) and ritonavir (a cytochrome P450 inhibitor) taken in combination with dasabuvir (an NS5B polymerase inhibitor) is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in several countries, including the USA (copackaged as Viekira Pak(™)) and those of the EU (Viekirax(®) and Exviera(®)). In phase II and III trials, this interferon-free regimen, taken ± ribavirin, provided high rates of sustained virological response 12 weeks post-treatment in adults with chronic HCV genotype 1a or 1b infection, including those with compensated cirrhosis, liver transplants or HIV-1 co-infection. The regimen was generally well tolerated, with nausea, insomnia, asthenia, pruritus, other skin reactions and fatigue being among the most common tolerability issues. Thus, ombitasvir/paritaprevir/ritonavir plus dasabuvir is an effective interferon-free, direct-acting antiviral regimen for use ± ribavirin in a broad range of adults chronically infected with HCV genotype 1.
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Ibrutinib (Imbruvica®) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton's tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK. Oral ibrutinib is indicated for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) or chronic lymphocytic leukaemia (CLL) and for the treatment of patients with CLL and a chromosome 17 deletion (del 17p) or TP53 mutation. This article summarizes pharmacological, efficacy and tolerability data relevant to the use of ibrutinib in these indications. ⋯ In addition, ibrutinib significantly prolonged progression-free survival and significantly improved the partial response rate and overall survival in patients with relapsed/refractory CLL (RESONATE study), including in those with del 17p, a subgroup with a poor prognosis. Ibrutinib had an acceptable tolerability profile in these studies with <10% of patients discontinuing treatment because of adverse events. Given its efficacy and tolerability, once-daily, oral ibrutinib is an emerging treatment option for patients with relapsed/refractory MCL or CLL and CLL patients with del 17p or TP53 mutation.