New prothrombin complex concentrate approved for acute bleeding

August 15, 2013

The FDA has approved a new plasma-derived product for the urgent reversal of vitamin-K antagonist (VKA) anticoagulation in adults with acute major bleeding.

The FDA has approved a new plasma-derived product for the urgent reversal of vitamin-K antagonist (VKA) anticoagulation in adults with acute major bleeding.

The new product, Kcentra, offers an additional option to address the problem of acute bleeding in patients who are receiving chronic anticoagulation therapy with warfarin and other VKA anticoagulants. The current standard of care in the U.S. for reversal of VKA therapy in patients with acute major bleeding includes withdrawal of VKA therapy, vitamin K administration, and administration of plasma.

Prothrombin complex concentrate (PCC) can be used more quickly than plasma to reverse the effect of VKA anticoagulants. Unlike plasma, it does not require blood-group typing or thawing. In addition, it is given in a lower volume than plasma, which is important in patients who may not be able to tolerate a large volume of plasma. As with plasma, PCC is given together with vitamin K.

Kcentra is the first four-factor PCC in the United States approved for urgent reversal of VKA (e.g., warfarin) therapy in patients with acute major bleeding. Other PCCs licensed in the United States are indicated for the treatment of hemophilia B.

PCCs are not approved for reversal of target-specific anticoagulants. There are case reports of use for this purpose, and there has been some success noted. However, the data are too limited to determine the efficacy and safety in this situation.

Kcentra carries a boxed warning on the label stating there is a risk for blood clots. Clinicians should monitor patients receiving the product for signs and symptoms of thromboembolic events.

Source: http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM351877.pdf

Dabigatran has new boxed warning

The manufacturer of dabigatran (Boehringer Ingelheim) has added a new boxed warning that stopping the drug may increase the risk of stroke in patients with non-valvular atrial fibrillation. This issue is already mentioned in the package labeling, but the move is designed to heighten the awareness of prescribers when it comes to the potential serious consequences of leaving patients without anticoagulation during times of transition (e.g. switch back to warfarin or interruption for procedures).

The warning also spotlights the importance of patient education with target-specific anticoagulants. The consequences of nonadherence with the medications can be devastating, and pharmacists have a critical role in contributing to successful outcomes with new anticoagulants. Patients need a thorough understanding of the consequences of missing doses or stopping the medication without consulting their prescriber.

A number of anticoagulation clinics are adding target-specific anticoagulant consultations to the menu of services they provide. Patients receive extensive education and periodic follow-up calls to ensure they are tolerating therapy and adhering to the prescribed regimen.

Source: www.pradaxapro.com/.

Rivaroxaban approved for ACS use in Europe

The European Commission has given approval to rivaroxaban for secondary prevention in adult patients who have had biomarker-confirmed acute coronary syndrome (ACS). The indication is for 2.5 mg twice daily in combination with standard antiplatelet therapy.

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) had recommended the rivaroxaban approval for ACS in March, based largely on the ATLAS ACS 2 TIMI 51 trial, which randomized more than 15,000 patients. In the trial, the 2.5-mg twice-daily dose was associated with a reduction in overall and cardiovascular mortality vs. placebo, despite an increased risk of bleeding and intracranial hemorrhage (ICH). The 5-mg dose also tested in the trial, however, was associated with an increased bleeding risk that outweighed the drug's benefits.

Approval for the ACS indication has been more of a challenge for the new generation of oral anticoagulants than approval for other indications. The FDA delayed its ruling on rivaroxaban for ACS secondary prevention pending submission of more safety data.

Source: http://www.medscape.com/viewarticle/804734