vorapaxar

Vorapaxar is a medication used to reduce the risk of blood clot formation and consequent blood vessel blocks in adult patients with a history of heart attack (myocardial infarction) or peripheral artery disease (PAD). Vorapaxar reduces the rate of a combined endpoint of cardiovascular death, myocardial infarction (MI), stroke, and need for emergency coronary artery bypass grafting (CABG) surgery (urgent coronary revascularization [UCR]). Vorapaxar is usually administered with other anticoagulants such as acetylsalicylic acid and/or clopidogrel.

When a blood vessel is injured, the first activity in blood clotting (coagulation) process is the aggregation of platelets which form a plug to arrest bleeding (hemostasis). Other specialized insoluble proteins known as coagulation factors in the blood continue the process. Coagulation is an important process for achieving hemostasis, however, people with a history of MI or PAD have a high risk of developing clots that can block blood vessels. Vorapaxar hinders clot formation by inhibiting the aggregation of platelets.

Vorapaxar belongs to a class of drugs known as protease activated receptor-1 (PAR-1) inhibitors. Vorapaxar binds to PAR-1, a protein molecule expressed on platelets, and inhibits platelet aggregation induced by thrombin and thrombin receptor agonist peptide (TRAP). Thrombin is a unique molecule that plays an important role in both coagulation and anticoagulation processes. PAR-1 is found in many types of cells, including smooth muscle, nerve and endothelial cells, but vorapaxar’s effect on these cells has not been assessed.

• Do not use vorapaxar in patients with a history of stroke, transient ischemic attack (TIA) or intracranial hemorrhage (ICH), vorapaxar increases the risk for ICH and fatal bleeding in these patients. Discontinue vorapaxar if a patient develops stroke, TIA or ICH.
• Do not use vorapaxar in patients with pathological bleeding such as ICH or peptic ulcers.
• Antiplatelet agents, including vorapaxar increase the risk for bleeding, including ICH and fatal bleeding.
  • Consider the patient's underlying risks for bleeding before prescribing vorapaxar. General risk factors for bleeding include:
    • Advanced age
    • Low body weight
    • History of bleeding disorders
    • Impaired liver or kidney function
    • Concurrent use of certain medications such as anticoagulants, fibrinolytic therapy, chronic nonsteroidal anti-inflammatory drugs [NSAIDS], selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors
  • Avoid concomitant use of other anticoagulants such as warfarin
  • Evaluate for bleeding in any patient who has low blood pressure and has recently undergone coronary angiography, percutaneous coronary intervention, coronary artery bypass graft surgery, or other surgical procedures.
  • Withholding vorapaxar for a short period to manage an acute bleeding episode is not useful, because significant antiplatelet effects last for 4 weeks after discontinuation of the drug.
• Vorapaxar is metabolized by the liver enzyme CYP3A. Avoid concomitant use with other drugs that are strong inducers or inhibitors of CYP3A. Strong CYP3A inhibitors increase and inducers decrease vorapaxar exposure.

Common side effects of vorapaxar include:

• Bleeding events, including:
  • Clinically significant bleeding
  • Any organ bleeding
  • Gastrointestinal bleeding
  • Moderate or severe bleeding
  • Severe bleeding
  • Intracranial hemorrhage
  • Fatal bleeding
• Low red blood cell count (anemia)
• Depression
• Skin reactions including:
  • Rashes
  • Eruptions
  • Wide-spread rashes (exanthemas)
• Double vision (diplopia)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 2.08 mg

Adult:

Thromboembolism

• Indicated to reduce thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease
• 2.08 mg orally once daily in combination with either aspirin and/or clopidogrel (according to their indications or standard of care); there is limited clinical experience with other antiplatelet drugs and none with vorapaxar as the only antiplatelet agent

Dosage Modifications

• Renal impairment: No dose adjustment required
• Mild-to-moderate hepatic impairment: No dose adjustment required
• Severe hepatic impairment: Not recommended; based on the increased inherent risk of bleeding in patients with severe hepatic impairment

Dosing Considerations

• Results from clinical trials have shown vorapaxar reduces the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization (UCR)

Administration

• May take with or without food

Pediatric:

• Safety and accuracy not established

Overdose

Vorapaxar prevents platelet aggregation and overdose can further increase the risk of bleeding. The antiplatelet effects can last for weeks after discontinuation of vorapaxar. There is no known treatment to reverse the effect of vorapaxar. Neither dialysis nor platelet transfusion is expected to be beneficial if bleeding occurs after overdose.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of vorapaxar include:
  • abrocitinib
  • apixaban
  • defibrotide
  • rivaroxaban
• Vorapaxar has serious interactions with at least 57 different drugs.
• Vorapaxar has moderate interactions with at least 74 different drugs.
• Mild interactions of vorapaxar include:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Animal reproductive studies did not show fetal harm, and available data on the use of vorapaxar in pregnant women are insufficient to determine a drug-associated risk for major birth defects or adverse maternal or fetal outcomes.
• If a patient becomes pregnant, discontinue vorapaxar because of its long half-life and potential for serious hemorrhage in the mother, and initiate alternate treatment with a drug that has a shorter duration of action.
• There are no data on the presence of vorapaxar or its metabolites in breastmilk. The drug is excreted in rat’s milk, and likely will be present in human milk as well. Nursing mothers should avoid breastfeeding while on treatment with vorapaxar, because of the potential for serious bleeding in the breastfed infant.

• Take vorapaxar exactly as prescribed. Do not discontinue on your own without checking with your prescribing physician.
• You may bleed and bruise easily. Exercise care to avoid injury. Report to your physician if you experience any unexpected, prolonged or excessive bleeding, or find blood in your stool or urine.
• Inform other physicians and dentists that you are taking vorapaxar, if you require any surgical or dental procedure and ask them to consult with your prescribing physician before stopping vorapaxar.
• Store vorapaxar safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.