Xarelto dosing for AFib: How to take it safely and effectively

In this article:

• What is Xarelto?
• Xarelto dose for atrial fibrillation (AFib)
• Xarelto safety
• Is Xarelto right for you?

In this article

• What is Xarelto?
• Xarelto dose for atrial fibrillation (AFib)
• Xarelto safety
• Is Xarelto right for you?

As a blood thinner or anticoagulant, Xarelto plays a pivotal role in preventing stroke in atrial fibrillation. Known as AFib, this condition is the most prevalent heart rhythm problem requiring treatment. The atria or top chambers of the heart beat erratically rather than rhythmically, and as a result, the ventricles or bottom pumping chambers beat erratically too. Pulse rates can be high and irregular. Within the quivering left atrium during AFib, blood clots can form and flow out of the heart to other areas of the body, including the brain, where strokes can ensue. The stakes are high when trying to avoid stroke while also limiting the risk of bleeding with anticoagulants, so knowing the details of proper Xarelto dosing is a must.

What is Xarelto?

Anticoagulants are a broad category of drugs with very different subclasses. Xarelto is a member of the direct oral anticoagulant (DOAC) subcategory, and this group truly revolutionized the care of patients with AFib. Within blood clots and circulating blood, Xarelto directly inhibits factor Xa, an enzyme responsible for generating thrombin. Without thrombin, the meshwork of fibrin within a clot cannot form.

Clots have a tendency to form within the left atrium of the heart in AFib because blood flow is relatively stagnant without rhythmic beating. The risk of clots forming and causing a stroke by being jettisoned to the brain varies significantly between patients. Stroke risk averages about 6% annually with AFib, but an individual’s risk may be higher or lower. Primary care providers and cardiologists use scoring systems like the CHA2DS2-VASc score to estimate a person’s stroke risk, thereby identifying who is most likely to benefit from an anticoagulant like Xarelto. Anticoagulation can reduce stroke risk by about 60%.

Rivaroxaban, the active ingredient in Xarelto, demonstrated its efficacy and safety for preventing stroke in Afib in the landmark 2011 ROCKET AF study. By showing itself to be at least as effective and safe as the existing option, warfarin, Xarelto presented a new therapeutic option for this critical and all too common need. The Food and Drug Administration’s approval notes the utility of Xarelto and other DOACs specifically for non-valvular AFib, when a serious heart valve issue is not precipitating the condition.

According to the Centers for Disease Control, over twelve million people in the U.S. alone suffer from AFib, so the ROCKET AF trial and subsequent reviews favoring rivaroxaban use in AFib were big news. DOACs like Xarelto achieve a predictable level of blood thinning from one person to another and do not require blood monitoring for levels. This presents a major benefit over warfarin, which requires frequent blood tests to ensure the proper amount of anticoagulation.

The trade-off for the convenience and predictable response is cost. Generic rivaroxaban is only available as a 2.5 mg dose, one that is used in the secondary prevention of heart disease and not in AFib. At that dose, generic rivaroxaban costs about $190 for a one-month supply of 60, 2.5 mg tablets when using a SingleCare discount card. In comparison, a one-month supply of 30, 20 mg tablets of brand-name Xarelto for use in AFib may cost $820 without a SingleCare coupon.

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Xarelto dose for atrial fibrillation (AFib)

The dosing of Xarelto for AFib is straightforward. It is taken as a 20 mg oral tablet once daily with food in the evening. Evening dosing is recommended because that is what was done in the ROCKET AF trial, and taking it with food improves its absorption and bloodstream availability. In the setting of reduced renal function, if the creatinine clearance (CrCl, a marker of kidney function) is less than 50 mL/minute but still greater than 15 mL/minute, the dose of Xarelto for AFib is reduced to 15 mg daily. Below a CrCl of 15 mL/minute, Xarelto is not recommended for AFib. Hence, the dose of the drug in AFib specifically can be summarized as follows:

• CrCl >50 mL/min: 20 mg orally once daily with evening meal
• CrCl 15-50 mL/min: 15 mg orally once daily with evening meal
• CrCl <15 mL/min: avoid use

While the dosing seems simple, confusion often arises based on all the other approved uses for Xarelto. The drug’s indications include the treatment of coronary artery disease, peripheral artery disease, and venous thromboembolism, such as deep vein thrombosis or pulmonary embolism. It also prevents blood clots in the acutely ill, patients at high risk of recurrent clots, and those after hip or knee replacement surgery. Dosing parameters can be different among these indications.

Once Xarelto is begun for AFib, the blood is effectively thinned within just a few hours. The same dose can be continued indefinitely as long as the benefits for stroke prevention outweigh the risks of bleeding, which are inherent in anticoagulation. Patients and healthcare providers should regularly analyze the benefit-to-risk ratio during Xarelto therapy.

Xarelto safety

Besides the convenience of avoiding frequent blood tests, Xarelto offers a safety benefit too. Providing a consistent degree of anticoagulation day-to-day, without fluctuations based on diet that plague warfarin users, Xarelto might be safer. Deviations from the therapeutic range may increase the risk of bleeding with warfarin. Xarelto’s advantage was shown in a study of AFib patients with diabetes, but in a study of those with kidney disease, safety was similar between Xarelto and warfarin.

In general, Xarelto is well tolerated, but by far, the biggest side effect concern with any anticoagulant is bleeding. Brain and intestinal bleeding are the most feared adverse effects. The FDA label for Xarelto specifically highlights the risk of bleeding and warns of dangerous spinal hematoma development after spinal anesthesia or puncture. The ROCKET AF trial showed a 3.6% per year risk of major bleeding with Xarelto, similar to those taking warfarin. Side effects of Xarelto include the following:

• Bleeding, both minor and major
• Abdominal pain
• Fatigue
• Back or muscle pain
• Dizziness
• Low blood cell counts
• Itching
• Hepatitis

The risks of Xarelto are not uniform among all users. An individual’s other medications and health conditions could influence the chance of an adverse event. In addition to those with renal impairment, seniors are another group that may be at higher risk of bleeding, enough so that those over 65 years are often advised to seek an alternative to Xarelto. Use may be avoided in pregnancy, too, based on limited clinical trial data to confirm dosing needs and safety.

Concurrent medications that interact with rivaroxaban can raise the chance of an adverse event. Drugs that strongly induce or inhibit the CYP3A enzyme or P-gp transport protein can dangerously alter Xarelto effects, leading to insufficient benefits or excessive bleeding. Examples of these drug interactions include the antifungal ketoconazole, antiviral Paxlovid (nirmetravir/ritonavir), and anticonvulsants Dilantin (phenytoin) and Tegretol (carbamazepine). Otherwise, any med that also thins the blood, such as aspirin, NSAIDs, Plavix (clopidogrel), and Brilinta (ticagrelor), can heighten bleeding risk too.

A unique hazard with DOACs like Xarelto is related to their quick onset of action. When stopped, their anticoagulant effect declines rapidly, which is advantageous if one is bleeding or needs to have the drug temporarily discontinued before surgery. However, the disappearance of anticoagulation when Xarelto is stopped leads to a temporarily heightened risk of blood clots in the days that follow. This characteristic highlights the importance of taking the medication regularly without missing doses and only discontinuing it when directed by a healthcare professional. The FDA calls attention to the hazards of prematurely discontinuing Xarelto in the drug label’s black box warning.

Is Xarelto right for you?

Xarelto is an effective and safe blood thinner for the prevention of strokes in patients with AFib. It pairs the conveniences of once-daily dosing with the lack of need for frequent blood work. For these reasons, it may be preferable to competitors like Eliquis (apixaban), which requires twice-daily dosing, and warfarin, which requires frequent lab monitoring.

Warfarin does present a cost savings opportunity in comparison to Xarelto. For 30, 5 mg tablets, which could be a one-month supply depending on one’s dose, generic warfarin may cost only $4 with a SingleCare discount. There is a big price gap between that $4 and the cost of 30, 20 mg Xarelto tablets that can amount to $370 with a SingleCare discount. In comparing Xarelto vs. warfarin, the time and expense of blood test monitoring with warfarin should be considered, too. Aside from cost, warfarin may be preferred for AFib in seniors, those with advanced kidney disease, or those with valvular disease.

As a fellow DOAC, Eliquis is often compared to Xarelto. The inconvenience of twice-daily dosing with Eliquis is coupled with a higher monthly price, $810 for 60, 5 mg tablets at retail price ($487 with a SingleCare coupon). The expense may be worth it though. Eliquis may be safer for seniors and those with significant kidney disease. Studies and meta-analysis of data have shown a lower risk of bleeding with Eliquis vs. Xarelto.

Deciding whether to take an anticoagulant in AFib, when to stop one, and whether to seek out an alternative are among the tougher calls in medicine. The opportunity to prevent a stroke is obviously appealing, but the chance of a major bleeding event is scary. Cost, conveniences, and coinciding medications and health conditions must be considered. With such a complex decision, be sure to discuss all of your questions and concerns with your healthcare provider and pharmacist.