Expert opinion on drug safety
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Expert Opin Drug Saf · Jun 2017
Review Comparative StudyClinical pharmacology of neurokinin-1 receptor antagonists for the treatment of nausea and vomiting associated with chemotherapy.
Five NK-1 RA formulations are commercially available to treat the delayed phase of chemotherapy-induced nausea and vomiting (CINV) occurring between days 2-5 post chemotherapy (aprepitant oral capsule and suspension, fosaprepitant intravenous infusion, netupitant/palonosetron capsules and rolapitant tablet) but no direct comparative studies have been conducted to determine their relative clinical utility. Areas covered: Information on pharmacology and safety of the NK-1 RAs derived from PubMed showed that all bind the NK-1 receptor with high affinity and selectivity. There is substantial variation in the disposition and time course in the body of NK-1 RAs because of the differential effects of hepatic metabolism. ⋯ Consequently, aprepitant not only has a much shorter elimination half-life than netupitant and rolapitant but also a more prolific drug interaction profile. All of the NK-1 RAs are efficacious and safe, and are suitable for use in a range of different patient populations, including those with mild or moderate hepatic or renal impairment. Expert opinion: While discovery of NK-1 RAs represents a major breakthrough in CINV control, further work is needed to improve control of chemotherapy-induced nausea.
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Expert Opin Drug Saf · Jun 2017
ReviewClinical pharmacology, efficacy, and safety of selexipag for the treatment of pulmonary arterial hypertension.
Selexipag is the first oral, non-prostanoid, selective prostacyclin receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients. Areas covered: This article reviews the clinical pharmacology, efficacy, and safety of selexipag in the treatment of PAH. Expert opinion: Selexipag is the first oral drug that selectively targets the prostacyclin pathway, and has evidence of long-term efficacy and safety. ⋯ Selexipag has one major metabolite, ACT-333679, which is also a selective IP receptor agonist, with 37-fold higher potency than selexipag. Pharmacokinetic properties of ACT-333679 permit twice-daily dosing of selexipag, providing a more convenient treatment compared to prostacyclin or its analogs. For patients with moderate hepatic impairment a once-daily regimen is recommended.
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Expert Opin Drug Saf · Jun 2017
ReviewThe safety of ustekinumab for the treatment of psoriatic arthritis.
The cytokines interleukin (IL)-12 and IL-23 have been involved in the pathogenesis of psoriasis and psoriatic arthritis. Ustekinumab is a fully human monoclonal antibody targeting the p40 subunit shared by IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 binding to their receptors, blocking the T1 and T17 inflammatory pathways. ⋯ Areas covered: In this review we report the safety data that come from phase II and phase III clinical trials that assay the efficacy and safety of ustekinumab in PsA, including recently published data corresponding to long-term studies. Relevant references were obtained through a literature search in MEDLINE/Pubmed (search strategy: ustekinumab AND psoriatic arthritis) for articles published until November 2016, complemented by a manual search. Expert opinion: In clinical practice, ustekinumab is generally a well-tolerated treatment, and the safety profile in psoriatic arthritis is similar to that reported in plaque psoriasis.