Drugs
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Review Meta Analysis
Update on the management of postoperative nausea and vomiting.
New antiemetic drug developments, formulations, guidelines, risk evaluation, and controversies have occurred in the area of postoperative nausea and vomiting (PONV). These developments have helped improve our understanding of the prevention and treatment of PONV in the postanesthesia care unit and after discharge home or to the hospital ward. Antiemetic drug research has resulted in the introduction of the second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron and the neurokinin-1 (NK-1) receptor antagonist aprepitant, as well as new data on existing antiemetics. ⋯ The impact of pharmocogenetics on antiemetic drug metabolism and their resulting efficacy has been correlated with genetic makeup affecting drug response. A discussion of ethics in PONV research has been initiated by the meta-analysis of PONV studies. To help guide antiemetic selection and PONV therapy for clinical practitioners, the Society of Ambulatory Anesthesia (SAMBA) PONV consensus guidelines have been introduced and updated.
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Ivacaftor (Kalydeco™) is a potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first drug that treats an underlying cause of cystic fibrosis to be licensed for use. Ivacaftor increases the open probability (i.e. gating) of CFTR channels with the G551D mutation, thus enhancing chloride transport, and is indicated in a number of countries for the treatment of cystic fibrosis in patients aged ≥6 years who carry this mutation. This review focuses on pharmacological, clinical efficacy and tolerability data relevant to the use of ivacaftor in this indication. ⋯ Ivacaftor was generally well tolerated, with headache, oropharyngeal pain, upper respiratory tract infection and nasal congestion being among the most common adverse events. Thus, ivacaftor expands the current treatment options for patients with cystic fibrosis who have the G551D mutation. Its potential for use in patients with other CFTR mutations is also of interest.
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Ocriplasmin (JETREA(®)) is a recombinant human serine protease plasmin with proteolytic activity against the protein components (e.g. laminin, fibronectin and collagen) of the vitreous and vitreoretinal interface, thereby facilitating vitreous liquefaction and separation of vitreous from the retina. Intravitreal ocriplasmin is indicated for the treatment of symptomatic vitreomacular adhesion (USA) and vitreomacular traction including when associated with a macular hole of diameter ≤400 μm in adult patients (EU). The efficacy of ocriplasmin at the recommended dose of a single 125 μg intravitreal injection was demonstrated in two well-designed pivotal phase III trials of virtually identical design (TG-MV-006 and TG-MV-007) in patients with symptomatic vitreomacular adhesion. ⋯ At day 28, the proportion of eyes achieving total posterior vitreous detachment or nonsurgical closure of macular holes was also significantly greater with ocriplasmin than with placebo. Ocriplasmin was generally well tolerated in these trials, with most ocular adverse events being mild in severity and transient in nature. Current evidence suggests that ocriplasmin is a useful treatment option for patients with symptomatic vitreomacular adhesion.
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The inactivated quadrivalent split-virus seasonal influenza vaccine [Fluarix® quadrivalent, manufactured in Dresden (D-QIV)] contains 15 μg haemagglutinin from each of the four influenza virus strains expected to circulate in the upcoming influenza season. Unlike seasonal trivalent influenza vaccines (TIVs), which have been used previously, quadrivalent influenza vaccines (QIVs) contain two influenza A subtype viruses and two B type viruses. As two different B viruses have co-circulated in recent years, incorporating both B lineages reduces the risk of the dominant B strain not being included in the vaccine. ⋯ D-QIV was generally well tolerated in all age groups studied and, overall, reactogenicity and tolerability were generally similar to observations with TIVs. Quadrivalent influenza vaccines are expected to offer substantial cost-effectiveness benefits in seasons where the B lineage selected for inclusion in TIVs does not match the dominant circulating strain. Thus, by incorporating both circulating influenza B lineages, vaccination with D-QIV is likely to reduce the risk of the dominant circulating B type virus not matching the strain selected for the vaccine and, therefore, more effectively protect target populations from influenza than TIVs.
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Pertuzumab (Perjeta®) is a humanized anti-HER2 monoclonal antibody that binds to the extracellular dimerization subdomain of the HER2 receptor and reduces HER2 intracellular signalling by preventing HER2 from forming heterodimers with other HER receptors. Inhibition of HER2 signalling results in a reduction of tumour cell proliferation, invasiveness and survival. Pertuzumab and trastuzumab bind to different sites on the HER2 receptor and have complementary antitumour activities; they act synergistically in inhibiting the growth of HER2-overexpressing breast cancer cell lines in vitro. ⋯ Pertuzumab in combination with trastuzumab and docetaxel significantly increased independently assessed median progression-free survival (primary endpoint), objective response rate and overall survival compared with placebo in combination with trastuzumab and docetaxel. Pertuzumab had an acceptable tolerability profile when added to trastuzumab and docetaxel in the pivotal CLEOPATRA trial. Thus, pertuzumab is a valuable addition to the growing list of anti-HER2 targeted therapies for breast cancer.