Cancer Treatment Today » Anti-coagulation

Xarelto

M Levin, MD — Thu, 29 Nov 2012 14:42:55 +0000

Xarelto is the first oral blood thinner approved for anti-coagulation in 60 years, since Warfarin (coumadin) was approved. A variety of injectable options are available; however, the oral route is preferred by many physicians and patients. Xarelto joins the much older Coumadin as an oral medication. Previouwly Xarelto was only approved for Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation. In November 2012, the U.S. Food and Drug Administration expanded the approved use of Xarelto (rivaroxaban) to include treating deep vein thrombosis (DVT) or pulmonary embolism (PE), and to reduce the risk of recurrent DVT and PE following initial treatment. .

The approval was approved based on three clinical studies that showed it to be as effective as the enoxaparin and coumadin for treating DVT and PE. With these results, when oral preparations are preferred for tratment of DVT or PE, Xarelto appears to have an advantage over injectable anticoagulants.

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Genetic test for Coumadin

M Levin, MD — Sun, 16 Sep 2012 20:32:25 +0000

Warfarin (Coumadin®) dose is sometimes difficult to adjust. Now there is a genetic tests that can identify people who have an increased response to conventional doses of Coumadin, which can cause bleeding. The labeling for a popular formulation of warfarin was revised in August 2007 and February 2010 to include information about how the three most widely studied pharmacogenetic mutations (CYP2C9*2, CYP2C9*3, and VKORC1 -1639G>A) affect dose requirements (NDA 9-218/S-105). The Warfarin-Sensitivity test idendifies that most common mutations that affect warfarin metabolism. CYP2C9 genotype accounts for up to 18% of the variability in warfarin dosing, VKORC1 genotype accounts for up to 29% of the variability in warfarin dosing. Combining genotypes with clinical factors may account for 50-70% of variability in warfarin dosing.

Approval was based on a study involved 896 participants with an average age of 65 who were members of prescription benefit plans managed by Medco. Hospitalization rates for this group were matched against a historical control group of 2,688 individuals. Researchers collected DNA from either blood or buccal cells and determined patients’ genotypes for the CYP2C9 and VKORC genetic variants. Mutations in the CYP2C9 gene have been associated with decreased warfarin metabolism, while mutations in the VKORC1 gene are associated with warfarin sensitivity. Based on each individual’s genotype, clinicians used a dosing algorithm to determine that person’s initial dose. The study followed patients for 6 months after the start of their treatment. Compared with the control group, the genotyped patients had 31% fewer hospitalizations overall and 28% fewer hospitalizations for bleeding or thromboembolism during the follow-up period. The study results were first reported at theAmericanCollegeof Cardiology’s annual meeting in March of 2010 and are available online: J Am Coll Cardiol (doi:10.1016/j.jacc.2010.03.009).

This is the relevant information from the label for Warfarin: ”

The dose of COUMADIN must be individualized by monitoring the PT/INR. Not all factors causing warfarin dose variability are known. The maintenance dose needed to achieve a target PT/INR is influenced by:

Clinical factors including age, race, body weight, sex, concomitant medications, and comorbidities and
Genetic factors (CYP2C9 and VKORC1 genotypes).

Select the starting dose based on the expected maintenance dose, taking into account the above factors. Routine use of loading doses is not recommended as this may increase hemorrhagic and other complications and does not offer more rapid protection against clot formation. If the patient’s CYP2C9 and VKORC1 genotypes are not known, the initial dose of COUMADIN is usually 2 to 5 mg per day. Modify this dose based on consideration of patient-specific clinical factors. Consider lower initiation doses for elderly and/or debilitated patients.

The patient’s CYP2C9 and VKORC1 genotype information, when available, can assist in selection of the starting dose. Table 5 of the Prescribing Information describes the range of stable maintenance doses observed in multiple patients having different combinations of CYP2C9 and VKORC1 gene variants. Consider these ranges in choosing the initial dose.”

Some physians argue that this test should not routinely obtained and that only if it is “available” should it play a role in dose modification. I do not find this a credible interpretation of the Prescribing Information langauge. Considering that the label of Warfarin includes CYP2c9 testing, this test should be considered medically necessary.

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Pradaxa

M Levin, MD — Thu, 09 Aug 2012 18:34:56 +0000

Dabigatran (Pradaxa ) is an oral anticoagulant from the class of the direct thrombin inhibitors. It is oral and offers an alternative to warfarin. Unlike warfarin(Coumadin) it does not require frequent blood tests for international normalized ratio (INR) monitoring while offering similar results in terms of efficacy. On the other hand, there is no specific way to reverse the anticoagulant effect of dabigatran in the event of a major bleeding event, unlike warfarin. The U.S. Food and Drug Administration (FDA) approved Pradaxa on October 19, 2010, for prevention of stroke in patients with non-valvular atrial fibrillation. On December 7, 2011, the FDA initiated an investigation into serious bleeding events associated with dabigatran stating that the “FDA is working to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of Pradaxa [RE-LY trial].”

It is far from clear that it is a better alternative than older anti-coagulants in the settings of chemotherapy of stem cell transplantation.

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Home treatment of DVT

M Levin, MD — Wed, 20 Jun 2012 18:25:21 +0000

Deep Venous Thrombosis is a common problem and its treatment usually starts with a hospitalization for IV heparin. Home treatment of newly diagnoses DVT would be a boon to patients and reduce costs of the overburdened health care system. Four criteria can be used to identify patients with DVT for whom outpatient treatment might not be appropriate: presence of massive DVT, presence of symptomatic pulmonary embolism, high risk of bleeding with anticoagulant therapy, and presence of other conditions or other factors that warrant in-hospital care. This is an extensively studied subject and at this point, limited literature evidence suggests that home management is cost effective and preferred by patients.

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