Xarelto

xareltoXarelto is the brand name of the anti-coagulant medication, rivaroxaban.  It is a blood-thinner or oral anti-coagulant that is manufactured by Bayer HealthCare, the pharmaceutical division of Bayer AG, a Germany-based healthcare products manufacturer.  It is marketed in the United States by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, the largest manufacturer of pharmaceuticals and medical products in the world.

Xarelto is used to treat patients who have had blood clots such as deep vein thrombosis and pulmonary embolism to prevent them from reoccurring.  It is also used to reduce the risk of blood clot formation and stroke in patients with atrial fibrillation or rapid heartbeat that is not related to a heart valve problem and in patients who have had knee or hip replacement surgery.

Xarelto is a competitor drug of Pradaxa (dabigatran etexilate) which is manufactured by another German drug maker, Boehringer-Ingelheim but Pradaxa works differently than Xarelto.  Xarelto and Pradaxa were meant to replace older anticoagulants such as heparin and warfarin (Coumadin) without requiring laboratory testing of the drug’s clotting ability in a specific patient at a particular dose.

The anti-coagulant market is currently thought to be worth over $10 billion per year and Xarelto generated sales of over $1.3 billion worldwide in 2013 and is expected to generate up to four times that amount in 2014.  Only three years after its approval by the Food and Drug Administration, it is the #1 prescribed novel oral anticoagulant in the US.

The US marketer of Xarelto, Johnson & Johnson, and its subsidiary, Janssen Pharmaceuticals has an estimated yearly revenue of $71 billion.

Xarelto is the subject of lawsuits that have already been filed even though the medication has only been available in the United States since July of 2011.  Lawsuits have claimed injuries caused by internal bleeding including some cases which may result in death.

What is Xarelto

Xarelto is an anticoagulant that works differently from other medications on the market.  It acts by decreasing the production of thrombin, a naturally occurring chemical produced to form the “fibers” in blood clots that stop bleeding.  Thrombin production is decreased because Xarelto inhibits Factor Xa, which is a co-factor that is needed for the body to create thrombin.

Xarelto is a new type of anticoagulant that has been designed to use a “set” dose for all patients with a specific medical disorder.  Older anticoagulants such as warfarin or Coumadin required dietary changes and frequent laboratory testing on blood to confirm how well the medication was working.  Medication dosing would be adjusted based on how long it took for the patient’s blood to begin clotting.

Another type of blood thinner, enoxaparin (Lovenox) works differently than Xarelto.  Like Xarelto, it does not require laboratory testing but requires daily injections as the medication is not available as an oral medication.

Xarelto is available as an oral tablet and does not require laboratory testing and does not require dietary adjustments.  This also means that the patient is not required to have check-ups as frequently and may go longer in between physician visits.  Lack of physician interaction may contribute to the development of serious side effects.

In addition, Xarelto is much more expensive than older medications and may cost more than $300 per month vs. less than $20 per month for warfarin.

Xarelto was shown in a clinical study of over 9,500 patients to be more effective than the medication enoxaparin (Lovenox), an injectable blood thinner when used to prevent blood clots after patients have had knee or hip replacement surgery.

Results of a study comparing Xarelto to warfarin use in more than 14,000 patients with Atrial fibrillation showed that Xarelto worked as well as warfarin.  Xarelto had a lower risk of bleeding in the brain but had a risk of overall bleeding that was the same as warfarin.  The pharmaceutical companies, Bayer and Johnson & Johnson had requested that Xarelto claims could say the medication was better than warfarin in stroke prevention but this request was rejected by the FDA who stated that study results showed it was just as effective but not better than warfarin.

Xarelto was first approved in July of 2011 to reduce the risk of blood clots which may cause deep vein thrombosis (DVT) or pulmonary embolism (PE) after a patient has had hip or knee replacement surgery.  In November of the same year, it was approved to reduce the risk of stroke in patients with Atrial Fibrillation that was not related to a valve defect.

In 2012, the medication received fast-track approval for treatment of PE and DVT and to reduce the risk of re-developing the conditions.  The manufacturers of Xarelto also requested approval for the treatment of Acute Coronary Syndrome but was rejected by the FDA in June of 2012.

Xarelto is available in 10 mg, 15 mg and 20 mg tablets and is prescribed to be taken once or twice daily with the amount determined by the reason for use.

Xarelto Side Effects and Drug Interactions

Like most drugs, Xarelto has a number of side effects and drug interactions.  Some of these side effects are minor but some are serious and may even become life threatening.

Common Side Effects

Xarelto may cause side effects which are bothersome and may require medical treatment but are usually not life threatening such as:

  • Nausea and vomiting
  • Headache
  • Low blood pressure
  • Dizziness
  • Muscle pain
  • Swelling or edema

Other side effects may indicate minor bleeding but need to be treated by a medical practitioner such as:

  • Hemorrhaging of the eye (bleeding)
  • Nose bleed
  • Rectal bleeding
  • Gastrointestinal bleeding (tarry stool)
  • Urogenital (urinary or genital) bleeding
  • Bruising

Serious Side Effects of Xarelto

Xarelto may also cause more serious side effects, usually related to internal bleeding and the inability to form blood clots at all.  Severe and serious side effects have contributed to the occurrence of death in some patients.

An internal bleed may develop in any part of the body and will continue until the drug is discontinued and cleared from the system.  Unlike other anticoagulant medications such as enoxaparin and warfarin, there is no antidote for Xarelto related bleeding.

Bleeding may become a serious or life threatening condition if it occurs close to a major organ like the lungs, kidneys, liver, or brain.  Uncontrolled bleeding will mean that the organ is not receiving adequate blood flow to provide oxygen and nutrients and may cause significant organ damage.

In addition, uncontrolled internal bleeding may cause blood pooling within the abdominal and other areas which can result in additional risks such as pain, organ compression, and infection.

Symptoms of uncontrolled bleeding may include:

  • Reduced platelet levels or other blood count abnormalities
  • Abnormal liver function
  • Unexplained bruising
  • Neurological abnormalities such as symptoms of stroke
  • Sudden or extreme tiredness
  • Sudden or extreme dehydration
  • Loss of skin color
  • Abdominal swelling

Any symptoms of bleeding should be immediately reported to a medical professional.

Xarelto Black Box Warning

Prescribing information for Xarelto includes a “black box warning” which is the most serious warning that can be given by the FDA.  The black box warning is placed in a box, surrounded by a thick black border at the top of prescribing information so that it will be clearly identified to practitioners before prescribing Xarelto.

The black box warning on Xarelto includes information about the increased risk of blood clot formation after Xarelto is discontinued.  It also warns of an increased risk of the development of a spinal or epidural hematoma (blood pool) after a patient has had a spinal procedure such as epidural or spinal anesthesia.  Effects of the hematoma may be permanent and cause paralysis.

Xarelto Drug Interactions

Xarelto may also interact with certain medications.  These medications will usually increase the risk of developing a bleed by increasing the activity of Xarelto or will make Xarelto less effective which will increase the chance of developing an unexpected clot.

Medications that increase the bleeding risk include:

  • Antibiotics such as clarithromycin
  • Antifungals such as fluconazole
  • Antivirals such as ritonavir
  • Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen, naproxen, diclofenac and etodolac

Medications that increase the risk of clot formation include:

  • Anticonvulsants such as phenytoin or carbamazepine
  • Antivirals such as rifampicin
  • Herbal medications such as St. Johns Wort

Other Xarelto Risks

Renal Impairment – Patients with decreased kidney function may experience an increased risk of bleeding, particularly when taken with certain medications such as diazepam (Valium), verapamil (Calan, Verelan, Covera or Isoptin), or erythromycin.

Hepatic Impairment – Patients with significantly decreased liver function may experience an increased risk of bleeding and use should be avoided.  Patients with liver-related clotting disorders should not use Xarelto.

Pregnancy and Nursing – Xarelto has been classified as a Category C medication by the FDA.  Category C indicates that no adequate studies have been done in humans but animal studies have shown an increased risk to the fetus.  Animal studies in rabbits and rats have shown an increased risk of miscarriage and maternal bleeding.  Xarelto should only be used in pregnant women if the benefits clearly outweigh the potential risk to the fetus and mother.  Bleeding experienced during pregnancy or in emergency delivery may not be easily reversed.

It is not known if Xarelto is safe in nursing women but it has been shown to be excreted in the milk of animals that were nursing.  Women who are nursing will need to decide if Xarelto should be discontinued or if the mother should discontinue nursing.

Incorrect Dosing Information of Xarelto

The healthcare provider website for Xarelto listed incorrect dosing information which was corrected on March 19, 2014.  A “Dear Healthcare Professional” Letter was issued in June of 2014 indicating that incorrect information was included on both the mobile and desktop versions of the Xarelto professionals website www.xareltohcp.com which gives prescribing and other information intended to be viewed by healthcare professionals such as physicians and pharmacists.

Xarelto Lawsuit

According to Reuters News, Bayer has recently admitted to facing up to nine lawsuits regarding the use of Xarelto in the U.S even though the drug has only been available since 2011.

The FDA received 680 serious adverse event reports for the first quarter of 2013 regarding Xarelto use.  According to the Institute for Safe medicine practices, Xarelto adverse events have now outpaced those of another new anti-coagulant, Pradaxa which also faces a number of lawsuits regarding bleeding events.  Boehringer-Ingelheim expects to pay over $650 million to settle an estimated 4000 Pradaxa lawsuits.

The lawsuits regarding injury caused by Xarelto include one filed in the U.S. District Court for the District of Vermont on July 25, 2014 by the family of a man experienced uncontrolled brain bleeding, resulting in his death after using Xarelto.  He had only taken the medication for 10 days when the irreversible bleeding incident occurred.

Lawyers for the plaintiff claim that the companies (Bayer and Johnson & Johnson) failed to adequately warn and withheld information from consumers and the healthcare community about the risks of Xarelto and the lack of an antidote.  Many additional Xarelto lawsuits are expected.

View Sources
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