Xarelto

Xarelto Side Effects

The side effects of Xarelto (rivaroxaban) include uncontrollable bleeding that may become apparent due to symptoms such as coughing up or vomiting blood, headaches, red or black stool, and spinal and epidural blood clots after a spinal tap or epidural. The U.S. Food & Drug Administration (FDA) has challenged several of Johnson & Johnson’s claims and advertising, finding that the company did not warn consumers adequately about Xarelto’s side effects, but Johnson & Johnson and its subsidiary Janssen Pharmaceuticals continue to promote the anticoagulant as safe and effective.1 Below are some of the serious side effects of Xarelto.

Uncontrollable Bleeding

The most common and possibly life-threatening side effect of Xarelto is an increased risk of excessive bleeding. According to the anticoagulant’s medication guide, such bleeding can cause a range of related problems, such as bruising easily, and may even lead ultimately to death. The risk of bleeding may worsen if Xarelto is taken in conjunction with other medications (see list below).2

Because an antidote for Xarelto and other Factor Xa inhibitors does not currently exist, severe bleeding that occurs as a side effect cannot be effectively counteracted. In contrast, warfarin (another common anticoagulant) can be counteracted with vitamin K or plasma products.3

Spinal and Epidural Blood Clots

Patients who take Xarelto may be put at an additional risk of clots in certain circumstances. In particular, patients who have a spinal tap or who receive a spinal anesthetic (frequently called an epidural) may form a blood clot around the brain or spinal cord.4 These types of clots are very serious and may result in a stroke, long-term or permanent paralysis, and damage throughout the body.5

Examples of treatments and conditions that could cause blood clots to form in patients who are taking Xarelto include:

  • Epidural catheters used to deliver certain medications to the body through the back
  • Non-steroidal anti-inflammatory drugs (NSAIDs) or other medications intended to prevent blood clots
  • A personal health history that includes problems with or frequent spinal punctures or epidural procedures
  • Spinal surgery or other problems related to the spine6

Wound Complications with Xarelto

Xarelto is sometimes given as a prophylactic to prevent deep-vein thrombosis and pulmonary embolism (PE) for patients who undergo either a total knee or total hip arthroplasty.

Several studies suggest that Xarelto administered after such surgeries tends to result in higher rates of wound complication than when total-hip and total-knee arthroplasty patients are prophylactically treated with low-molecular-weight heparin or other forms of thromboprophylaxis, such as aspirin and compression stockings, and DVT compression pumps.

In 2011, Jensen et al. found that when comparing 489 patients who received a low-molecular-weight heparin and underwent a total hip or knee replacement versus 559 patients who received Xarelto, there were statistically significantly more wound complications that necessitated a return to the operating room for the patients given Xarelto as thromboprophylaxis.7

In 2012, Jameson and his team of researchers found significantly fewer wound complications in a low-molecular-weight heparin group of lower limb arthroplasty patients, 2.81 percent compared with 3.85 percent for those who took rivaroxaban.8 The authors point out, citing another study that found an estimated $108-worth of savings per patient given Xarelto for thromboprophylaxis following total hip or knee arthroplasty, that “the higher cost burden of prolonged wound drainage would offset the apparent savings…even before additional treatment costs such as revision for infection are considered.”

In 2013, Rath led a team in prospectively comparing 266 knee arthroplasty patients who received prophylactic doses of rivaroxaban with a retrospective control group of 596 patients who did not. They found only two control group patients, but seven patients given rivaroxaban, suffered wound complications that necessitated return to the operating room, with wound oozing, dehiscence (rupture) and hematoma (pooling of blood) being the most common complications. The researcher’s results add “to the concerns raised regarding the true benefit of rivaroxaban as an agent of choice for routine use in lower limb arthroplasty.”9

There was a Xarelto manufacturer-sponsored clinical trial that examined the safety and efficacy of Xarelto for thromboprophylaxis after total knee arthroplasty versus enoxaparin, a low-molecular-weight heparin. One of the members of the steering committee for the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 4 trial, wrote an editorial in the New England Journal of Medicine in 2008 voicing his concerns about the fact that the study “did not measure the surgical outcomes, such as wound healing, drainage, infection, range of motion, and chronic pain.” This orthopedic surgeon, Dr. Paul Lotke of the University of Pennsylvania, concluded that because of these shortcomings he “would not recommend [Xarelto] for my patients.”10

At the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS), Dr. Olubusola Brimmo presented his team’s findings from the study “Rivaroxaban Use for Thrombosis Prophylaxis is an Independent Risk Factor for Early Periprosthetic Joint Infections.”11 The study found that patients who took Xarelto after total hip arthroplasty (THA) or total knee arthroplasty (TKA) had a significantly higher incidence of deep surgical site infections. The study examined 480 patients treated with other medications and 159 patients treated with Xarelto.

At the same conference, Washington University School of Medicine physician Dr. Robert L. Barrack participated in the Symposium on Hot Topics and Controversies in Primary Total Hip Arthroplasty. His presentation was titled “Aspirin and Mechanical Compression Sleeves are Best for Most.”12 He presented a review of literature indicating that for most patients who undergo TKA or THA, in cases where patients do not have major risk factors for thromboembolic events, mechanical compression and prescribing aspirin should suffice for thromboprophylaxis. Dr. Barrack’s presentation called attention to an important issue: that considerable physician debate exists as to whether the use of aggressive pharmacoprophylaxis, such as new oral anticoagulants like Xarelto, is necessary for the vast majority of patients after joint replacement surgery.

In late 2015, Brimmo and a team of colleagues published a study in The Journal of Arthroplasty that retrospectively examined the incidence of deep surgical site infections within 30 days in patients who had THA or TKA. Two groups were created; patients received either rivaroxaban or another type of medication, such as enoxaparin, aspirin or warfarin. All patients in the study also received compression devices for their legs and were mobilized early in an effort to further prevent DVT. The groups did not differ in their demographic characteristics.  The authors calculated that receiving Xarelto after THA or TKA carried a relative risk of infection of 10.7 when compared to patients who received other types of pharmacological thromboprophylaxis.13

Wound complications following total hip or total knee arthroplasty Xarelto can include:

  1. Prolonged and excessive drainage
  2. Infection
  3. Leakage
  4. Hematoma
  5. Reduced range of motion
  6. Site-specific chronic pain

Reoperation can be required to address these Xarelto wound complications.

Other Xarelto Side Effects

The Xarelto label lists other adverse reactions that have been voluntarily reported in patients taking Xarelto:

  • Agranulocytosis – a serious state in which the body’s white blood cells count is depleted
  • Jaundice – yellowing of the skin caused by high levels of bilirubin in the blood
  • Anaphylactic reaction or shock – a serious, systemic allergic reaction
  • Stevens-Johnson syndrome – a life-threatening skin condition
  • Hemiparesis – weakness on one side of the body

Other serious side effects of Xarelto may exist that have not yet been reported or identified.

Patients who take Xarelto should contact their doctor immediately if they experience any of the following symptoms:

  • Bleeding unexpectedly or for an extended period of time
  • Coughing up or vomiting blood
  • Stool that is black, bright red or looks like tar
  • Headaches or sensations that leave you dizzy or weakened
  • Wounds that swell, drain excessively, or become more painful

Drug Interactions

Xarelto is one of several types of blood-thinning drugs known as Factor Xa inhibitors. The side effects of Xarelto, including both heavy bleeding and life-endangering blood clots in the spine following epidural or spinal tap, may intensify if Xarelto is taken with other anticoagulants or drugs.

If you take any of the drugs or supplements listed below, you should inform your doctor immediately before taking Xarelto.14

Generic DrugBrand Name(s)

aspirin N/A – sold under many brand names
clopidogrel Plavix
conivaptan Vaprisol
heparin N/A
rifampin Rifadin, Rifater, Rifamate
rifapentine Priftin
romiplostim Nplate
St. John’s wort N/A
warfarin Coumadin, Jantoven


Also, the following classes of drugs may exacerbate Xarelto’s side effects or change the amount of Xarelto present in the body:

Drug ClassExample(s)

Antifungals itraconazole (Sporanox), ketoconazole (Nizoral, Onmel)
Barbiturates phenobarbital (Solfoton)
Heart or blood pressure medications reserpine, diltiazem (Cartia, Cardizem), dronedarone (Multaq), felodipine (Plendil), quinidine (Quin-G), verapamil (Calan, Covera, Isoptin, Verelan)
HIV medications ritonavir (Norvir, Kaletra)
Seizure medications carbamazepine (Carbatrol, Equetro, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenytoin (Dilantin), or primidone (Mysoline)
Non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others
Salicylates aspirin, Nuprin Backache Caplet, Kaopectate, KneeRelief, Pamprin Cramp Formula, Pepto-Bismol, Tricosal, Trilisate, and others

 

  1. Department of Health and Human Services. Letter to Johnson & Johnson. (June 6, 2013.) NDA# 202439/MA# 215. Reference ID: 3320499 
  2. Janssen Pharmaceuticals. “Medication Guide: Xarelto.” (Revised March 2014) Accessed Dec. 16, 2014. 
  3. Haverkamp D, Hutten BA, Büller HR, et al. “The use of specific antidotes as a response to bleeding complications during anticoagulant therapy for venous thromboembolism.” Journal of Thrombosis and Haemostasis. (Jan. 2003) PMID:12871541 Accessed Dec. 16, 2014. 
  4. Dartmouth-Hitchcock Norris Cotton Cancer Center. “Rivaroxaban.” (Revised Oct. 2, 2012) Accessed Dec. 16, 2014. 
  5. National Heart, Lung, and Blood Institute. “What Are the Signs and Symptoms of Excessive Blood Clotting?” (May 20, 2012) Accessed Dec. 16, 2014. 
  6. Janssen Pharmaceuticals. “Medication Guide: Xarelto.” (Revised March 2014) Accessed Dec. 16, 2014. 
  7. Jensen CD et al, “Return to Theatre Following Total Hip and Knee Replacement, Before and After the Introduction of Rivaroxaban,” Journal of Bone & Joint Surgery, Vol. 93-B: 91-95, Jan., 2011. 
  8. Jameson SS et al, “Wound Complications Following Rivaroxaban Administration,” Journal of Bone & Joint Surgery, Vol. 94:1554-8, Sept. 5, 2012 
  9. Rath NK et al, “The Use of Rivaroxaban for Chemical Thromboprophylaxis Following Total Knee Replacement,” The Knee, Vol. 20:6, 397-400, Dec. 2013 
  10. Lotke PA, “Rivaroxaban for Thromboprophylaxis” Letter to the Editor, New England Journal of Medicine, Vol. 359:20, 2174, Nov. 13, 2008. 
  11. Brimmo, Olubusola, et al. Rivaroxaban Use for Thrombosis Prophylaxis is an Independent Risk Factor for Early Periprosthetic Joint Infections.  Paper no. 683. Annual Meeting of the American Academy of Orthopaedic Surgeons 2015. Accessed May 13, 2015. 
  12. Barrack, Robert L., Symposium on Hot Topics and Controversies in Primary Total Hip Arthroplasty: Aspirin and Mechanical Compression Sleeves are Best for Most. Annual Meeting of the American Academy of Orthopaedic Surgeons 2015. Accessed May 13, 2015
     
  13. Brimmo, Olubusola, et al. Rivaroxaban use for Thrombosis Prophylaxis is Associated with Early Periprosthetic Joint Infection http://www.arthroplastyjournal.org/article/S0883-5403(15)01108-0/abstract Journal of Arthroplasty (December 20, 2015). Accessed Dec. 31, 2015. 
  14. Dartmouth-Hitchcock Norris Cotton Cancer Center. “rivaroxaban.” (Revised Oct. 12, 2012) Accessed. Dec. 19, 2014. 

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