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Portola is pursuing accelerated approval for andexanet alfa and plans to initiate studies on a larger scale in 2014.
Portola Pharmaceuticals announced in late November 2013 that andexanet alfa, its investigational Factor Xa inhibitor antidote, has received breakthrough therapy designation from the FDA. The designation of breakthrough therapy expedites the development and review of drugs for serious or life-threatening conditions. Portola is pursuing accelerated approval for andexanet alfa and plans to initiate studies on a larger scale in 2014.
Recently presented study findings showed that andexanet alfa reversed the effects of apixaban by >90% within two minutes of an initial IV bolus and maintained that level throughout a two-hour infusion. These results came from a comparison of six volunteers given the agent and three controls who received placebo. They were part of a double-blind phase 2 study that randomized 54 volunteers to receive 5 mg apixaban twice daily followed by andexanet alfa at any of several dosages and infusion times. The reported results were for the highest tested bolus dose, 420 mg. No safety issues were identified.
The andexanet alfa molecule largely resembles factor Xa itself and competitively blocks the factor Xa-inhibiting effects of apixaban, rivaroxaban, enoxaparin, edoxaban, and the investigational betrixaban. If approved, andexanet alfa would be the first approved reversal agent for Factor Xa inhibitors.
Source: Stiles S. Portola antidote to Factor Xa inhibitors advances in dosing, safety studies. October 17, 2013. Accessed at Medscape website November 28, 2013.
A retrospective data analysis of 1,745 patients in a Department of Defense database suggests that patients with atrial fibrillation (AF) treated with dabigatran do a better job of taking their medication than do patients treated with warfarin.
The study showed that 63% of patients prescribed dabigatran were taking their medication after one year vs. 39% of patients who were prescribed warfarin. Medication persistence (defined as the duration of time from the initiation of treatment to discontinuation of therapy) was increased in older patients and those with highest stroke risk. It decreased with increasing risk of hemorrhage.
If patients failed to refill a prescription for either drug within an appropriate period (60 days), they were considered to have stopped treatment. Patients who switched from one therapy to the other were also considered discontinued.
Source: Zalesak M, Siu K, Francis K, et al. Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes. 2013;6:5 567-574.
FDA is recommending that healthcare professionals carefully consider the timing of placement and removal of spinal catheters in patients who are on low-molecular-weight heparins. Also recommended is a delay in dosing of these medications for some time after catheter removal to decrease the risk of spinal column bleeding and subsequent paralysis after spinal injections (including epidural procedures and lumbar punctures).
The recommendations are as follows:
· For enoxaparin, placement or removal of a spinal catheter should be delayed for at least 12 hours after administration of prophylactic doses, such as those used for prevention of deep vein thrombosis. Longer delays (24 hours) are appropriate to consider for patients receiving higher therapeutic doses of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily).
· A post-procedure dose of enoxaparin should usually be given no sooner than four hours after catheter removal.
· In all cases, a benefit-risk assessment should consider both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient-risk factors.
Low-molecular-weight heparins already carry a “black-box” warning related to the risk of epidural or spinal hematoma. However, because events continue to happen, the FDA worked with the manufacturer to further evaluate the risk and refine the timing recommendations. These will be added to the manufacturer labeling of all low-molecular-weight heparins.
Source: Low molecular weight heparins: Drug Safety Communication: Recommendations to decrease risk of spinal column bleeding and paralysis. November 6, 2013. Accessed at FDA website November 28, 2013.
Anna D. Garrett is a clinical pharmacist and president of Dr. Anna Garrett (www.drannagarrett.com). Her mission is to help women in midlife maximize their mojo! Contact her at firstname.lastname@example.org.