Xarelto: an overhyped medication

Xarelto (Rivaroxaban) is a new blood thinner marketed in the US by Bayer and Janssen. It pertains to the Novel Oral Anticoagulant (NOAC) drug category, and its sales increased significantly over the course of a few years. Thanks to its anticoagulant action, Xarelto stops the formation of blood clots and prevents their growth inside our body. Its primary indication is the treatment of Venous Thromboembolism (VTE) and pulmonary embolism (PE) and the prevention of stroke in patients with non-valvular atrial fibrillation (Afib). Many other anticoagulants are available in the market, and the safety of some of them has been established over the course of many years. Some examples are Coumadin (warfarin), heparins and Plavix (clopidogrel). All these medications effectively treated millions of patients for more than 40 years (especially Warfarin).

Why the need for a new drug then? The first reason was to avoid the various dietary restriction that patients under treatment with Warfarin had to endure. Because of its mechanism of action, this blood thinner may interact with many alimentary sources of Vitamin K, such as spinach, kale or broccoli, which may inactivate it. A second limitation lies is the fact that the older medications need to be constantly monitored to assess their effectiveness and check their safety by properly adjusting the dosage. This is generally achieved by performing regular blood tests in a clinic or doctor’s office, even if some home-monitoring devices do exist. NOACs like Xarelto instead boast a new mechanism of action instead that free the patients from any kind of dietary restrtiction. They do not need any kind of check also, so they can just skip the annoying trip to the blood clinic.

The negative aspect of all blood thinners is the risk of severe adverse reactions that can pose a serious threat to a patient’s life, like uncontrolled bleeding and internal hemorrhages. Even a minor trauma like a fall can lead to an emergency hospitalization. A patient’s life can be usually saved if he’s quickly administered an intravenous antidote like Vitamin K or with the infusion of fresh platelets. This is not true for rivaroxaban and the other NOACs however, since nothing can reverse their effects leaving the doctors unarmed in case of an accidental bleeding event. Pradaxa (dabigatran), a drug that shares many similarities with Xarelto, accounted for almost 4,000 adverse reaction reports in 2011, including more than 500 patient deaths. No other drug reached the same amount of reports of stroke (644 cases), acute renal failure (291) and hemorrhage (2,367). Many trials showed that rivaroxaban and the other NOACs were also associated to a higher risk of bleeding, showing that they are not as safe as they were initially advertised. Xarelto side effects include bleeding from needle injections or wounds, unusual bleeding (rectum, mouth and nose) easy bruising, and unstoppable bleedings. However, the absence of a proper agent to revers its effect may transform even a simple gastrointestinal ulcer in a lethal accident. Many international agencies determined that the various NOACs should be considered high-risk, and even the Food and Drugs Administration advised caution to doctors and patients.

Rivaroxaban is widely advertised as the improved standard of care for many conditions, boasting its “simple dosing” and “superior efficacy”. Even worse than this, Bayer and Janssen claimed for years that this drug showed a more “favourable safety profile” compared to Warfarin. Several commercials featuring famous personalities like Arnold Palmer, Kevin Nealon and Brian Vickers talked over many consumers into buying this dangerous drug. The group of VIPs speak about their love for life and golf as well, thanking Xarelto since their life vastly improved by using it. No more dietary restrictions nor blood monitoring, sitting on their comfortable bench they just discuss about their quality of life with no blood monitoring and no dietary restriction required. Nealon spouts one of the saddest punchline ever heard since we now know how many patients died because of the side effects of this drug. “Golf clinic or blood clinic? Ooh, that’s a tough one”. But what if one of them slips out during their golf course and starts bleeding? No antidote could ever save their lives. The most appropriate punchline should be “Emergency room or morgue? Ooh, that’s a tough one”.

The NOACs have been marketed as a superior alternative to other anticoagulants. But is this true? One thing is sure: their price is significantly higher than their competitors, more than ten times over. Xarelto is priced at $3,000 a year per patient, while warfarin just costs $200. Originally marketed in 2010, NOACs rapidly substituted Warfarin in just a couple of years, even if the older drug has been safely used for several decades. According to a study published in the American Journal of Medicine, NOACs accounted for 62 percent of all blood thinner prescriptions in 2013. However, they represented the vast majority (98 percent) of total blood thinner-related drug expenditure. The price itself is significant as explained by Dr. Niteesh K. Choudhry, MD, the author of the study. In just 6 months the cost for initiating a new treatment with a NOAC was $900 higher compared to other anticoagulants. Many patients defined as low-risk for stroke or atrial fibrillation received a prescription for these drugs, even if their risks of a bleeding accident is superior to the danger of other fatal accidents related to their conditions. The yearly revenues coming from the Xarelto market are impressive. The anticoagulant market is wort over $10 billion, so it’s easy to understand why several pharmaceutical companies became so gredy that they didn’t care about patient’s safety anymore. Back in 2014, Boehringer Ingelheim had to defend its reputation after more than 4,000 lawsuits were filed against it. Plaintiffs held them responsible of several death and serious injuries after patients who took their drug Pradaxa suffered of life-threatening bleeding accidents. Eventually, the Big Pharma agreed to pay a $650 million fine and settled down the litigation. The claimed that the money paid diverted a lot of time and resources from newer research and patient care, yet that price was still too small compared to the impressive number of lives lost because of their drug lack of safety.

 

Article written by Dr. Claudio Butticè, Pharm.D.

REFERENCES

  1. Nihar R. Desai, Alexis A. Krumme, Sebastian Schneeweiss, et al. Patterns of Initiation of Oral Anticoagulants in Patients with Atrial Fibrillation— Quality and Cost Implications. Am J Med. 2014 Nov;127(11):1075-82.e1.
  2. U.S. Food and Drug Administration: “Xarelto Full Prescribing Information” (Accessed August 2015)
  3. Siebelt F, et al. June 14, 2014. “Bayer faces law suits in United States over Xarelto: paper” Reuters. (Accessed July 2015)
  4. Institute for Safe Medication Practices (ISMP) “Monitoring FDA MedWatch Reports – Anticoagulants the Leading Reported Drug Risk in 2011.” (Accessed September 2015)
  5. Alexander T. Cohen, Theodore E. Spiro, Harry R. Büller, et al. Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients. N Engl J Med 2013; 368:513-523. DOI: 10.1056/NEJMoa1111096