Aspirin vs. Xarelto: Dosage & Side Effects for Anti-clotting Drugs

Aspirin vs. Xarelto: What’s the difference?

What is aspirin? What is Xarelto?

Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) used for treating fever, pain, and inflammation. Aspirin is also used to prevent blood clots (antithrombotic). Other NSAIDs include ibuprofen (Motrin), nabumetone (Relafen), and indomethacin (Indocin). NSAIDs work by reducing levels of prostaglandins, chemicals that are released when there is inflammation that cause pain and fever. NSAIDs block cyclooxygenase, the enzyme that makes prostaglandins, causing lower concentrations of prostaglandins, and resulting in reduced levels of inflammation, pain, and fever. Reduction of prostaglandins also diminishes the function of platelets and the ability of the blood to clot. Aspirin inhibits the function of platelets for prolonged periods of time so it is used to reduce the risk of another stroke or heart attack in patients who have had a previous stroke or heart attack.

Xarelto (rivaroxaban) is an oral anticoagulant (blood thinner) used to prevent and treat blood clots. Xarelto is a selective inhibitor of factor Xa, an enzyme necessary to form blood clots. Xarelto is used to reduce the risk of stroke and blood clots in patients with atrial fibrillation not due to a heart valve problem; to treat and reduce the risk of deep vein thrombosis (DVT, blood clots in the veins of the legs) and pulmonary embolism (PE, blood clots in the lungs); and reduce the risk of blood clots in the legs and lungs of patients who have just had hip or knee replacement surgery. Xarelto, in combination with aspirin, is indicated to reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in patients with chronic coronary artery disease or peripheral artery disease.

What are the side effects of aspirin and Xarelto?


Most patients benefit from aspirin and other NSAIDs with few side effects. However, serious side effects can occur and generally tend to be dose-related. Therefore, it is advisable to use the lowest effective dose to minimize side effects.

The most common side effects of aspirin involve the gastrointestinal system and ringing in the ears.

Gastrointestinal side effects are

  • ulcerations,
  • abdominal burning,
  • pain,
  • cramping,
  • nausea,
  • gastritis, and
  • even serious gastrointestinal bleeding and
  • liver toxicity.

Sometimes, ulceration and bleeding can occur without any abdominal pain. Black tarry stools, weakness, and dizziness upon standing may be the only signs of internal bleeding.

Ringing in the ears

  • Should ringing in the ears occur, the daily dose should be reduced.

Other side effects include:

Other side effects and adverse reactions

  • Aspirin should be avoided by patients with peptic ulcer disease or poor kidney function, since this medication can aggravate both conditions.
  • Aspirin may exacerbate asthma.
  • Aspirin can raise the blood uric acid level and is avoided in patients with hyperuricemia and gout.
  • Children and teenagers should avoid aspirin for symptoms of the flu or chickenpox because of the associated risk of Reye's Syndrome, a serious disease of the liver and nervous system that can lead to coma and death.
  • Aspirin can increase the effect of medicines used to treat diabetes mellitus, resulting in abnormally low blood sugars if blood sugar levels are not monitored.
  • NSAIDs should be discontinued prior to elective surgery because of a mild tendency to interfere with blood clotting. Aspirin, because of its prolonged effect on platelets, is best discontinued at least ten to fourteen days in advance of the procedure.


The most common side effect of Xarelto is bleeding. The risk of bleeding is higher when Xarelto is taken with medicines such as aspirin or aspirin-containing products, nonsteroidal anti-inflammatory drugs (NSAIDS), warfarin (Coumadin, Jantoven), heparin, clopidogrel (Plavix), and other medicines used to prevent or treat blood clots.

Some rare but serious cases of bleeding and paralysis have been reported with the use of Xarelto in patients undergoing spinal or epidural procedures. The risk is highest in patients who have problems with their spine, use indwelling epidural catheters, have had spinal surgery, or use other medicines that prevent clotting or make them more likely to bleed.

Other common side effects of Xarelto include:

  • Back pain
  • Pruritus
  • Elevated levels of liver enzymes

Serious side effects of Xarelto include:

  • Severe bleeding
  • Hepatitis
  • Decreased platelets
  • Allergic reactions
  • Stevens-Johnson syndrome

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What is the dosage for aspirin vs. Xarelto?


  • Aspirin should be taken with food. Doses range from 50 mg to 6000 mg daily depending on the use.
  • Usual doses for mild to moderate pain are 350 or 650 mg every 4 hours or 500 mg every 6 hours.
  • Doses for rheumatoid arthritis include 500 mg every 4-6 hours; 650 mg every 4 hours; 1000 mg every 4-6 hours; 1950 mg twice daily.
  • Heart attacks are prevented with 75, 81, 162 or 325 mg daily.
  • 160 to 325 mg of non-enteric coated aspirin should be chewed immediately when experiencing symptoms of a heart attack.
  • The dose for preventing another stroke is 75 to 100 mg daily.


  • To reduce the risk of stroke in nonvalvular atrial fibrillation, patients with creatinine clearance (a measure of kidney function) >50 ml/min should be given 20 mg once a day with the evening meal. (Xarelto is better absorbed if it is given with food.) Patients with creatinine clearance between 15 to 50 ml/min should be given 15 mg once a day with the evening meal.
  • To treat blood DVT or pulmonary embolism, 15 mg is administered by mouth twice daily with food for the first 21 days, followed by 20 mg once daily with food for 6 months.
  • To reduce the risk of recurrence of DVT or pulmonary embolism, 20 mg should be administered by mouth once daily with food.
  • To prevent DVT following hip replacement surgery, 10 mg is administered by mouth once daily for 35 days.
  • To prevent DVT following knee replacement surgery, 10 mg is administered by mouth once daily for 12 days.
  • When switching from warfarin (Coumadin) to rivaroxaban, warfarin should be stopped and then rivaroxaban started as soon as the international normalized ratio (a measure of the effects of warfarin) is < 3.0.
  • When switching from blood thinning medicines other than warfarin to rivaroxaban, rivaroxaban should be started up to 2 hours before or at the time of the next scheduled evening dose.
  • Use of rivaroxaban is not recommended in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) liver disease or another type of liver disease associated with blood disorders.
  • To avoid serious side effects rivaroxaban should not be used in patients with significantly reduced kidney function defined as creatinine clearance <30 ml/min.
  • Patients who are having difficulty swallowing whole tablets can crush the 10 mg, 15 mg, and 20 mg tablets and mix with applesauce immediately before use.
  • • Note: While the 15 and 20 mg tablets should be taken with food, the 10 mg tablets can be taken with or without food.


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What drugs interact with aspirin and Xarelto?


Aspirin is associated with several suspected or probable interactions that affect the action of other drugs. The following examples are the most common of the suspected interactions.

NSAIDs may increase the blood levels of lithium (Eskalith, Lithobid) by reducing the excretion of lithium by the kidneys. Increased levels of lithium may lead to lithium toxicity.

Aspirin may reduce the blood pressure lowering effects of blood pressure medications. This may occur because prostaglandins have a role in the regulation of blood pressure.

When aspirin is used in combination with methotrexate (Rheumatrex, Trexall) or aminoglycoside antibiotics (for example, gentamicin) the blood levels of the methotrexate or aminoglycoside may increase, presumably because their elimination from the body is reduced. This may lead to more methotrexate or aminoglycoside-related side effects.

Individuals taking oral blood thinners or anticoagulants, for example, warfarin, (Coumadin) should avoid aspirin because aspirin also thins the blood, and excessive blood thinning may lead to serious bleeding.


The CYP3A4 liver enzymes and P-glycoprotein (P-gp) drug transporter systems are primarily responsible for metabolizing and removing Xarelto from the body. Taking Xarelto with medicines that alter the activity of both the CYP3A4 enzymes and P-gp drug transporters may affect blood levels of Xarelto. Xarelto should not be taken with:

Xarelto should not be used with other blood thinners due to the increased risk of bleeding.

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Are aspirin and Xarelto safe to use when pregnant or breastfeeding?


  • Aspirin is generally avoided during pregnancy because it may adversely affect the fetus. However, low aspirin doses have been safely used for the prevention of complications of pregnancy.
  • Aspirin is excreted into breast milk and may cause adverse effects in the infant.


  • Due to the lack of conclusive safety data, Xarelto should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Xarelto is classified as FDA pregnancy risk category C (animal studies show harm but there are no adequate studies in humans).
  • It is not known if Xarelto is excreted in breast milk. Because many drugs enter human milk and have the potential of causing harm to the nursing baby, Xarelto should be used cautiously in nursing mothers.

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