Clinical pharmacology : advances and applications
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Carfilzomib, a selective proteasome inhibitor approved in the USA in 2012, is a single agent for relapsed and refractory multiple myeloma. Carfilzomib is administered as a 2-10-minute infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle at a starting dose of 20 mg/m(2) for cycle 1 and a target dose of 27 mg/m(2) thereafter. In the pivotal Phase II study (PX-171-003-A1), carfilzomib 20/27 mg/m(2) provided durable responses in a heavily pretreated population with relapsed and refractory multiple myeloma (n=266), with an overall response rate of 22.9% and a median duration of response of 7.8 months. ⋯ New or worsening peripheral neuropathy was infrequent (13.9% overall, 1.3% grade 3, no grade 4). This review discusses findings of the integrated safety analysis and provides practical experience from a single institution in managing treatment-related and disease-related adverse events. Individualized treatment with proactive management of side effects and complications allows patients with advanced multiple myeloma to remain on carfilzomib for extended periods.
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In severe alcohol withdrawal (AW), benzodiazepines may be inadequate to control symptoms. In many situations, benzodiazepine dosing escalates despite no additional efficacy and introduces potential toxicities. Severe cases of AW may require additional agents to control symptoms. Case reports and studies have shown benefits with dexmedetomidine and propofol in severe AW, but these agents have not been compared with one another. This study compares the effects of dexmedetomidine and propofol on benzodiazepine and haloperidol utilization in patients with AW. ⋯ In patients with severe AW who require sedation, both dexmedetomidine and propofol have unique and advantageous properties. Both agents appear to have equivalent efficacy in reducing AW-related symptoms and benzodiazepine and haloperidol requirements. These results should be validated in a larger, prospective trial.