Plavix (clopidogrel) vs. Xarelto (rivaroxaban)

• Clopidogrel and Xarelto (rivaroxaban) are blood thinners used for preventing strokes, heart attacks, and death in individuals who have had a previous stroke, unstable angina, heart attack, or have peripheral arterial disease (PAD).
• Xarelto is also used to treat and reduce the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) and reduce the risk of blood clots in the legs and lungs of patients who have just had hip or knee replacement surgery.
• A brand name for clopidogrel is Plavix.
• Side effects of clopidogrel and Xarelto that are similar include itching and increased bleeding.
• Side effects of clopidogrel that are different from Xarelto include diarrhea, rash, abdominal pain, headache, chest pain, muscle aches, dizziness, allergic reactions, pancreatitis, and liver failure.
• Side effects of Xarelto that are different from clopidogrel include back pain and elevated levels of liver enzymes.

Clopidogrel is an anti-platelet drug used for preventing strokes, heart attacks, and death in high-risk individuals who have had a heart attack, unstable angina, previous stroke, or have peripheral arterial disease (PAD). It prevents blood clots by binding to the P2Y12 receptor on platelets, preventing adenosine diphosphate (ADP) from activating platelets. Clopidogrel is a P2Y12 inhibitor, a drug class that also includes ticagrelor (Brilinta) and prasugrel (Effient). Clopidogrel is similar to ticlopidine (Ticlid) in chemical structure and in the way it works.

Xarelto (rivaroxaban) is an anticoagulant (blood thinner) used to prevent and treat blood clots. Blood clots formed in the heart are dangerous since they can travel to the brain and cause a stroke. Blood clots formed in the legs or lungs can also be life threatening if not treated. Xarelto is a selective inhibitor of factor Xa, an enzyme necessary to form blood clots. It reduces the ability of blood to clot. 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. In combination with aspirin, Xarelto is used to reduce the risk of major cardiovascular events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).

Clopidogrel

The tolerability of clopidogrel is similar to that of aspirin. The more common side effects of clopidogrel are:

• diarrhea,
• rash,
• itching,
• Abdominal pain
• headache,
• chest pain,
• muscle aches,
• dizziness.
• severe bleeding,
• allergic reactions,
• pancreatitis, and
• liver failure.

Ticlopidine (Ticlid) is an antiplatelet medication quite similar to clopidogrel. It has been associated with a severe reduction in white blood cell count in between 0.8% and 1% of persons. The risk of this dangerous side effect with clopidogrel is about 0.04%, much less than with ticlopidine but twice that of aspirin.
Clopidogrel rarely causes a condition called thrombotic thrombocytopenic purpura (TTP) in one out of every 250,000 people. TTP is a serious condition in which blood clots form throughout the body. Blood platelets, which participate in clotting, are consumed, and the result can be bleeding because enough platelets are no longer left to allow blood to clot normally. For comparison, the related drug, ticlodipine (Ticlid), causes TTP 17-50 times more frequently than clopidogrel.

Xarelto

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. 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 (itching)
• Elevated levels of liver enzymes

Serious side effects of Xarelto include:

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

Clopidogrel

Clopidogrel bisulfate usually is taken once daily. It can be taken with or without food. Clopidogrel is activated by enzymes in the liver to its active form. Individuals who have reduced activity of liver enzymes that activate clopidogrel due to liver disease may not adequately respond to clopidogrel. Alternative treatments should be used for these patients. The recommended dose for treating unstable angina or heart attack is 300 mg initially followed by 75 mg daily in combination with 75-325 mg of aspirin. Peripheral arterial disease or recent stroke is treated with 75 mg daily.

Xarelto

• 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.

Clopidogrel

The combination of clopidogrel with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil, Nuprin), naproxen (Naprosyn, Aleve), diclofenac (Voltaren), etodolac (Lodine), nabumetone (Relafen), fenoprofen (Nalfon), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis; Oruvail), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), tolmetin (Tolectin), and mefenamic acid (Ponstel) may increase the risk of stomach and intestinal bleeding.

Combining clopidogrel with warfarin (Coumadin) or other drugs that cause bleeding increases the risk of bleeding.

Clopidogrel is converted to its active form by enzymes in the liver. Drugs that reduce the activity of these enzymes, for example, omeprazole (Prilosec, Zegerid) or esomeprazole (Nexium) may reduce the activity of clopidogrel and should not be used with clopidogrel. Other drugs that also may react with clopidogrel in a similar fashion include fluoxetine (Prozac, Sarafem), cimetidine (Tagamet), fluconazole (Diflucan), ketoconazole (Nizoral, Extina, Xolegel, Kuric), voriconazole (Vfend), ethaverine (Ethatab, Ethavex), felbamate (Felbatol), and fluvoxamine (Luvox).

Xarelto

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:

• ketoconazole (Nizoral),
• ritonavir (Norvir),
• clarithromycin (Biaxin),
• erythromycin (Ery-Tabs),
• fluconazole (Diflucan),
• carbamazepine (Tegretol),
• phenytoin (Dilantin),
• rifampin (Rimactane), or,
• St. John's Wort.

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

Clopidogrel

There are no adequate studies of clopidogrel in pregnant women.

Studies in rats have shown that clopidogrel appears in breast milk; however, it is not known whether it also appears in human breast milk. Because of a potential for side effects in the nursing infant, the physician must weigh the potential benefits and possible risks before prescribing clopidogrel to nursing mothers.

Xarelto

• 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.