Xarelto (rivaroxaban) is generally well tolerated over months and years of use, but it does carry real long-term risks. The most significant is bleeding, which occurs in roughly 7% of patients over extended treatment. Beyond bleeding, long-term use can affect the liver, kidneys, skin, and hair, though most of these effects are uncommon or rare.
Bleeding: The Primary Long-Term Risk
Bleeding is the side effect that matters most with any blood thinner, and Xarelto is no exception. In a real-world study of 450 patients followed for an average of 22 months, 2.9% experienced major bleeding and another 2.7% had clinically relevant non-major bleeding. No fatal bleeding events occurred. Most bleeding episodes happened within the first two years of treatment, with the highest concentration in the first three months.
Your individual risk depends heavily on your baseline health. Patients with more bleeding risk factors (older age, kidney problems, history of bleeding, use of certain other medications) had dramatically higher rates. Those with the most risk factors experienced bleeding at roughly six times the rate of lower-risk patients. In people with severe chronic kidney disease specifically, Xarelto was associated with a major bleeding rate of 4.9 per 100 person-years, which was notably higher than the 2.9 per 100 person-years seen with warfarin in the same population. For people with healthy kidneys, the risk profile is more favorable.
The types of major bleeding include gastrointestinal bleeds (the most common), intracranial bleeding, and bleeding into joints, the space around the spine, or behind the abdominal organs. Gastrointestinal bleeding tends to be more frequent with Xarelto than with some other blood thinners, particularly at the full 20 mg dose.
Effects on Kidney Function
Rather than harming the kidneys, long-term Xarelto use appears to be easier on them than warfarin. In a large analysis of over 72,000 patients with atrial fibrillation, Xarelto was linked to a 19% lower risk of acute kidney injury compared to warfarin (absolute risk of 2.1%) and an 18% lower risk of progressing to kidney failure or needing dialysis (absolute risk of 0.9%). Over 21 months of follow-up, kidney function declined in both groups, but the decline was slower with Xarelto.
That said, kidney function naturally changes over time, especially in older adults, and Xarelto is cleared partly through the kidneys. The FDA recommends periodic kidney function checks during long-term use, particularly if you have conditions that could worsen kidney health, like diabetes or high blood pressure. If kidney function drops significantly, your dose may need to be adjusted or the medication reconsidered.
Liver Enzyme Elevations
Between 1.5% and 3% of people on long-term Xarelto develop moderate elevations in liver enzymes, a sign the liver is under some stress. This rate is similar to warfarin and slightly lower than some injectable blood thinners. In clinical trials, the rate of combined liver enzyme and bilirubin elevations (a more concerning pattern suggesting actual liver damage) was just 0.1% to 0.2%, identical to comparison drugs.
Hospitalization for acute liver injury occurs in roughly 1 in 2,200 Xarelto users based on large healthcare databases, though not all of those cases are necessarily caused by the drug itself. Clinically significant liver damage from Xarelto is rare, but it’s one reason routine blood work during long-term use can be valuable even though the FDA doesn’t require specific monitoring schedules.
Hair Loss
Hair thinning is an underappreciated side effect of Xarelto. In one study, about 1.2% of patients (9 out of 730) reported hair loss, typically appearing two to four months after starting the medication. The mechanism involves hair follicles prematurely shifting from their growth phase into their resting phase, a process called telogen effluvium. This type of hair loss is usually diffuse rather than patchy and is often reversible if the medication is stopped or the body adjusts. It’s not dangerous, but it can be distressing, especially since many patients aren’t warned about it beforehand.
Skin and Allergic Reactions
Allergic and hypersensitivity reactions occur in an estimated 0.1% to 1% of Xarelto users. Most are mild, but a range of skin reactions has been documented since the drug came to market. In the large ROCKET-AF trial of over 7,000 patients, reported reactions included toxic skin eruptions (0.03%), skin-related vasculitis (0.01%), and anaphylaxis (0.01%).
Rarer but more serious skin reactions have been reported in individual cases. These include leukocytoclastic vasculitis, which appears as a non-blanching purplish rash typically within the first two weeks of starting the drug, and DRESS syndrome, a severe reaction involving fever, widespread rash, and internal organ inflammation that usually develops three to eight weeks after starting treatment. Both are very rare but require immediate medical attention. Some patients have also developed blistering rashes or widespread redness after even a single dose, suggesting a true drug allergy.
Bone Health Compared to Warfarin
If you’re choosing between Xarelto and warfarin for long-term use, bone health is one area where Xarelto has a clear advantage. Warfarin interferes with vitamin K, which plays a role in bone metabolism, and long-term warfarin use is associated with higher rates of osteoporosis and fractures. In one study comparing the two drug classes, 11 cases of osteoporosis were recorded among warfarin users versus zero among patients on newer blood thinners like Xarelto.
When patients with atrial fibrillation were switched from warfarin to Xarelto, researchers found that markers of bone formation increased while markers of bone breakdown decreased. This suggests Xarelto is essentially neutral for bone health, making it a better option for people already at risk of osteoporosis, including older women and anyone with a history of fractures.
What Long-Term Monitoring Looks Like
One practical advantage of Xarelto over warfarin is that it doesn’t require regular blood clotting tests. There’s no equivalent of the INR checks that warfarin users need every few weeks. The FDA specifically states that monitoring clotting times is not recommended for Xarelto because the results don’t reliably guide dosing decisions.
What is recommended is periodic kidney function testing, especially if you’re older, have diabetes, take medications that affect the kidneys, or have any condition where kidney function might change. Your doctor may also check liver enzymes periodically, though there’s no mandated schedule. The simplicity of monitoring is one reason many patients and doctors prefer Xarelto for indefinite anticoagulation, but it also means you should pay attention to symptoms like unusual bruising, dark or bloody stools, blood in urine, prolonged bleeding from cuts, or unexplained fatigue, which could signal a problem between visits.