Journal of clinical pharmacology
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Venetoclax is a selective BCL-2 inhibitor that is approved in the United States for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. The aim of this analysis was to characterize venetoclax pharmacokinetics in the plasma and urine of patients with hematological malignancies and evaluate the effect of dose proportionality, accumulation, weak and moderate CYP3A inhibitors, as well as low- and high-fat meals on venetoclax pharmacokinetics. Patients received a once-daily venetoclax dose of 20 to 1200 mg. ⋯ In summary, venetoclax exhibits a pharmacokinetic profile that is compatible with once-daily dosing with food regardless of fat content. Concomitant use of venetoclax with moderate CYP3A inhibitors should be avoided or venetoclax dose should be reduced during the venetoclax initiation and ramp-up phase in CLL patients. Renal excretion plays a minimal role in the elimination of venetoclax.
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Oxycodone DETERx®(Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended-release, microsphere-in-capsule, abuse-deterrent formulation designed to retain its extended-release properties after tampering (eg, chewing/crushing). This randomized, double-blind, placebo-controlled, triple-dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate-release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. ⋯ Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate-release oxycodone. Study treatments were well tolerated; no subjects experienced serious adverse events. These results demonstrate the lower oral abuse potential of chewed and intact oxycodone DETERx than crushed immediate-release oxycodone.
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Review Meta Analysis
5-HT3 Receptor Antagonists for the Prevention of Perioperative Shivering: A Meta-Analysis.
The aim of this meta-analysis was to evaluate the preventive efficacy and safety of 5-HT3 receptor antagonists (5-HT3 RAs) on perioperative shivering. Relevant databases were searched to identify eligible randomized, controlled trials through January 2016. Primary outcome was the incidence of perioperative shivering, and secondary outcomes were the incidence of safety-related outcomes including postoperative nausea and vomiting (PONV), bradycardia, and hypotension. ⋯ However, they did not show superiority in lowering the rate of bradycardia (RR, 0.75; 95%CI, 0.38 to 1.49; P = 0.42; heterogeneity: I2 = 0%) or hypotension (RR, 0.79; 95%CI, 0.44 to 1.43; P = .44; heterogeneity: I2 = 24%). Trial sequential analysis of primary outcome showed that the required information size was 2634 patients and that the trial sequential monitoring boundary was crossed. Thus, more high-quality randomized, controlled trials with larger sample sizes are still required to draw a definite conclusion about the preventive efficacy of 5-HT3 RAs on perioperative shivering prevention in the future.
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This study investigated postmarketing safety events (PMSEs) for new drugs approved in Brazil and evaluated whether a range of drug characteristics influenced the time between approval and the first PMSE. This retrospective study included new drugs registered between 2003 and 2013 by the National Health Surveillance Agency (ANVISA), which is responsible for medicines approval in Brazil. PMSEs were defined as any drug safety alert or drug withdrawal from the market. ⋯ There was no association between the time to PMSE and the other drug characteristics investigated. This study demonstrated that the frequency of PMSEs for new drugs approved by ANVISA was statistically associated with the existence of an FDA REMS. The time between approval and first PMSE was shorter for drugs with an FDA REMS, and this finding may contribute to improved awareness of the risk/benefit balance required to ensure continued safe and effective use of new drugs.