Stephan Moll, MD writes…
Today is a very exciting day for patients with blood clots and for health care professionals looking after such patients: the oral blood thinner Xarelto® (Rivaroxaban) was FDA approved today (Nov 2nd, 2012) for the use in patients with DVT (deep vein thrombosis) and PE (pulmonary embolism). The FDA announcement can be read, here. Why is this exciting? Because therapy with Xarelto is much easier than the often cumbersome therapy with warfarin. The reasons for this are discussed below.
A. The Scientific Data that led to the FDA approval
Xarelto was compared with warfarin in three large clinical trials and was found to (a) be at least as effective as warfarin in preventing further (recurrent) clots, and (b) cause similar amounts of major bleeding as warfarin [reference 1,2]. In short: Xarelto is at least as effective and safe as warfarin.
B. The Advantages of Xarelto
1. No INR monitoring: Warfarin needs frequent testing of its blood thinning effect to determine what dose a patient needs – Xarelto does not. This is because Xarelto leads to a predictable blood-thinning effect and, thus, no monitoring of INR or other coagulation tests is needed. Every patient needs the same dose:
- 15 mg twice daily with food for the first 3 weeks after an acute DVT or PE,
- 20 mg once daily with food after those first 3 weeks and for the long-term prevention of another clot.
2. Eat what you want: Warfarin’s blood thinning effect is influenced by vitamin K in the diet, such as salads and green vegetables. Therefore, patients on warfarin need to watch what they eat and need to be consistent in their dietary vitamin K intake. Xarelto, on the other hand, is not influenced by vitamin K and, therefore, patients can eat what they want.
3. Fully active within 2 to 4 hours: Warfarin takes at least 5 days after starting it to reach its full blood thinning effect. Therefore, patients who start warfarin need to be treated with an additional blood thinner during those first 5 or more days; these additional blood thinners need to be injected underneath the skin (low molecular weight heparins, such as Enoxaparin [Lovenox] or Dalteparin [Fragmin]) or into a vein (heparins). That is complex, and cumbersome. Xarelto, on the other hand, leads to full blood thinning effect within 2 to 4 hours being taken; thus, there is no need for the initial injections with an additional blood thinner. That simplifies treatment tremendously.
4. Gone in less than 2 days after stopping the drug: Prior to surgeries or procedures like colonoscopies, blood thinners often have to be stopped. As warfarin’s blood thinning effect sticks around for several days after it has been stopped, discontinuation 5- 7 days before surgeries is typically needed. Xarelto, on the other hand, is relatively quickly out of the system. Discontinuation 24 to 36 hours before surgeries is typically enough. That makes management around times of surgeries or procedures much easier.
5. Drug interactions: Warfarin is notorious for being influenced by other medications: many medications increase the INR, i.e. increase warfarin’s blood thinning effect; many decrease the INR, i.e. “thicken the blood”. This leads to the need for more frequent INR blood testing and warfarin dose adjustments when a patient starts other medications, such as antibiotics. Xarelto is influenced by much fewer other medications.
6. Cost: Initiation of warfarin therapy with initial bridging therapy with low molecular weight heparin (LMWH, e.g. enoxaparin = Lovenox; Dalteparin = Fragmin; etc.) can be quite expensive, as LMWH is so expensive. Also, copay for clinic visits for INR monitoring can be expensive for the patient on warfarin. Whether Xarelto is more, equally, or less expensive than warfarin therapy depends on a patient’s co-pay. A patient who is considering switching to Xarelto should contact his/her insurance carrier to find out what the co-pay would be.
C. The Disadvantages of Xarelto
- Xarelto is still a relatively new drug. However, it has been used (a) by more than 35,000 patients over the last several years in the clinical trials that have lead to the FDA approval in the various indications, as well as (b) by many patients worldwide since its approval in the various indications. Since 2008, Xarelto has been approved by the regulatory agencies as follows:
- for DVT prevention after orthopedic surgeries in Canada and Europe in September 2008, and in the U.S. in July 2011;
- for irregular heart beat (atrial fibrillation) in the U.S. Nov 2011, and in Europe in December 2011;
- for treatment of DVT in Europe in December 2011, and for DVT and PE in the U.S. today (Nov 2nd, 2012).
D. “Should I be on Xarelto?”
- Patients who have marked kidney impairment or liver disease should NOT be treated with Xarelto, as the drug is cleared by the kidney and liver.
- Patients who are on certain medications that interfere with Xarelto (some anti-seizure medications; certain drugs used to treat fungal infections, HIV, or other infections) should NOT take the drug. These drugs are listed in the Xarelto Patient Medication Guide and on the Xarelto package insert-full prescribing information .
- Pregnant women should not be on Xarelto.
- For cancer patients with DVT or PE the first choice of blood thinner continues to be low molecular weight heparin, not warfarin or Xarelto.
Patients who can consider Xarelto therapy fall into one of two groups:
1) Patients with previous clot (“I have had a clot [DVT or PE] and am on warfarin – should I switch to Xarelto?”)
- Certainly, Xarelto is an attractive option for the patient who is presently on warfarin for a history of DVT or PE, but does not tolerate warfarin well or finds warfarin cumbersome to take and monitor because of fluctuating INRs, significant side effects (hair loss, fatigue) or difficulty getting to an anticoagulation clinic and monitoring the INR. In this situation the approved and appropriate dose of Xarelto is 20 mg once daily with food.
- However, Xarelto is also an attractive treatment option for any patient with DVT and PE who is presently on warfarin therapy. The appropriate Xarelto dose in these patients is 20 mg once daily with food.
2) Patients with new clot (“I have just been diagnosed with a new blood clot [DVT or PE] – Should I be treated with warfarin or Xarelto?”
One of the beauties of Xarelto is that it is so quickly active after oral intake (within 2-4 hours), and can be taken by the patient with a newly diagnosed DVT or PE right of the bat without the need for initial injections of blood thinners (such as Lovenox = enoxaparin or Fragmin = Dalteparin). The appropriate Xarelto dose in these patients is 15 mg twice daily with food for the first 3 weeks after the acute clot, and then 20 mg once daily with food.
E. What Should I do now?
There is no rush to act. However, if a patient is interested in considering switching to Xarelto, the classic advice applies: “You should talk to your doctor!”
- The Einstein Investigators: Oral Rivaroxaban for symptomatic venous thromboembolism. New Engl J Med 2010;363:2499-510.
- The Einstein Investigators: Oral Rivaroxaban for the treatment of symptomatic pulmonary embolism. New Engl J Med 2012;366:1287-97.
- Turpie AG et al. Rivaroxaban for the prevention of venous thromboembolism after hip and knee arthroplasty. Pooled analysis of four studies. Thromb Haemost, 2011;105:444-453.
Disclosure: I have consulted for Janssen (U.S. distributor of Xarelto) and Boehringer-Ingelheim (company making Pradaxa).
Last updated: Nov 2nd, 2012
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