prasugrel

Prasugrel is a medication used during the treatment of patients with acute coronary syndrome (ACS), which includes two types of heart attacks (myocardial infarctions), ST-elevation myocardial infarction (STEMI) that can be traced in the ECG and non-ST elevation myocardial infarction (NSTEMI), and unstable angina, which is chest pain that occurs without any exertion and is associated with heart attack and impaired blood flow to the heart.

Heart attacks are caused when blood supply to the heart muscles is interrupted or blocked because of coronary arteries being clogged with fat and cholesterol deposits (plaques). If a plaque ruptures, blood clot forms and blocks blood flow to the heart, leading to acute coronary syndrome. Prasugrel prevents blood clot formation and reduces the risk of further cardiovascular events in patients with ACS.

Acute coronary syndrome is mostly treated with percutaneous coronary intervention (PCI), a minimally invasive procedure used to unclog the artery, place a stent and restore blood flow to the heart muscles. Prasugrel is part of the initial therapy to prevent clot formation in the coronary arteries, including in the newly placed stent.

Prasugrel is an antiplatelet drug that works by inhibiting the activation and aggregation of platelets. Platelets are blood cells that play a major role in blood clotting process, which is normally required for preventing excessive bleeding.

During a heart attack when a plaque ruptures, platelets get activated and release blood-clotting substances, and clump together to form clots. Prasugrel binds to P2Y12 receptor, a protein molecule on platelets that is responsible for platelet aggregation, and irreversibly blocks its activity.

Prasugrel is also being investigated for use in sickle cell disease, an inherited blood disorder that causes red blood cells to become sickle-shaped and break down.

Bleeding risk

Prasugrel can cause significant, sometimes fatal, bleeding.

• Do not start prasugrel in patients:
  • With active pathological bleeding such as peptic ulcer or intracranial hemorrhage
  • With a history of transient ischemic attack (TIA) or stroke
  • Who are likely to undergo urgent coronary artery bypass graft surgery (CABG)
• When possible, discontinue prasugrel at least 7 days prior to any surgery
• Suspect bleeding in any patient on prasugrel therapy who has recently undergone coronary angiography, PCI, CABG, or other surgical procedures, and becomes hypotensive
• If possible, manage bleeding without discontinuing prasugrel because, discontinuing the drug, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events
• Avoid use of prasugrel in geriatric patients older than 75 of age, except in high-risk situations, such as patients with diabetes or a history of heart attack
• Other risk factors for bleeding with the use of prasugrel include:
  • Body weight of less than 60 kg
  • Propensity to bleed, including recent trauma or surgery, recent or recurrent gastrointestinal bleeding, active peptic ulcer disease, severe liver impairment, or moderate-to-severe kidney impairment
  • Concurrent use of other drugs that can increase bleeding risk, including blood thinners or chronic use of non-steroidal anti-inflammatory drugs (NSAIDs)

Other warnings

• Do not use in patients with hypersensitivity to prasugrel or any of its components
• Prasugrel can cause thrombotic thrombocytopenic purpura (TTP), a blood disorder that causes clotting in small blood vessels all over the body, resulting in low platelet count (thrombocytopenia). TTP can be fatal and requires urgent treatment
• Discontinue prasugrel in case of active bleeding, elective surgery, TIA or stroke
• In patients with stent placement after acute coronary syndrome, premature discontinuation of prasugrel increases the risk for clot in the stent, heart attacks and death. If prasugrel is discontinued because of any adverse event, restart therapy as soon as possible

Common side effects of prasugrel include:

• High blood pressure (hypertension)
• High level of cholesterol/lipids in blood (hypercholesterolemia/hyperlipidemia)
• Headache
• Back pain
• Shortness of breath (dyspnea)
• Nausea
• Diarrhea
• Dizziness
• Cough
• Low blood pressure (hypotension)
• Fatigue
• Noncardiac chest pain
• Rapid and irregular rhythm in the atria (atrial fibrillation)
• Slow heart rate (bradycardia)
• Low blood count of leukocyte immune cells (leukopenia)
• Low red blood cell count (anemia)
• Rash
• Fever (pyrexia)
• Swelling of extremities (peripheral edema)
• Pain in extremity

Serious side effects of prasugrel include:

• Major or minor bleeding events including:
  • Nasal bleeding (epistaxis)
  • Gastrointestinal hemorrhage
  • Coughing up blood (hemoptysis)
  • Bleeding under the skin (subcutaneous hematoma)
  • Bleeding in the abdominal cavity (retroperitoneal hemorrhage)
  • Bleeding in the membrane-bound space around the heart (pericardial hemorrhage)
  • Retinal hemorrhage
• Thrombotic thrombocytopenic purpura
• Severe thrombocytopenia

Less common side effects of prasugrel include:

• Abnormal liver function tests
• Swelling under the skin and mucous membrane (angioedema)
• Severe hypersensitivity reaction (anaphylaxis)

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

• 5mg
• 10mg

Acute Coronary Syndrome

Adult:

Reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome (ACS) managed by means of PCI who have either (a) unstable angina or non-ST-elevation MI (NSTEMI) or (b) ST-elevation MI (STEMI) when managed with primary or delayed PCI

• 60 mg orally once as loading dose, then 10 mg/day orally in combination with aspirin 81-325 mg/day.
• If patient is below 60 kg, consider 5 mg/day orally because of potentially increased bleeding risk (efficacy and safety not established)

Dosing Modifications

Renal impairment

• No dosage adjustment necessary
• End-stage renal disease: Limited experience; these patients are generally at higher risk of bleeding

Hepatic impairment

• Mild-to-moderate (Child-Pugh Class A or B): No dosage adjustment necessary
• Severe (Child-Pugh Class C): Not studied

Dosing in low weight patients

• Patients (under 60 kg) had an increased exposure to active metabolite of prasugrel and an increased risk of bleeding on a 10-mg daily maintenance dose
• Consider lowering the maintenance dose to 5-mg in patients under 60 kg

Geriatric:

Below 75 years

• Same as adult dosing

75 years and above

• Generally not recommended, because of increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk patients (diabetes or prior MI), for whom effect appears to be greater and use may be considered

Pediatric:

Not recommended

• Prasugrel inhibits platelet activation rapidly and irreversibly, and can cause life-threatening bleeding.
• There is no known antidote for prasugrel.
• Platelet transfusion may restore blood clotting ability.

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 prasugrel include:
  • abrocitinib
• Serious interactions of prasugrel include:
  • apixaban
  • cangrelor
  • caplacizumab
  • codeine
  • heparin
  • hydromorphone
  • morphine
  • oxycodone
  • oxymorphone
  • protamine
• Prasugrel has moderate interactions with at least 61 different drugs.
• Mild interactions of prasugrel include:
  • devil’s claw
  • ginger
  • ginkgo biloba
  • horse chestnut seed
  • verteporfin

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 studies reveal no evidence of fetal harm with prasugrel use, however, there are no well-controlled studies in pregnant women. Prasugrel should be used during pregnancy only if the benefits to the mother outweigh potential risks to the fetus.
• It is not known if prasugrel is excreted in breast milk, its effects on milk production and on the breastfed infant. Metabolites of prasugrel present in rat milk. Use with caution in nursing women after considering benefits to the mother, the infant’s health benefits from breastfeeding, and the potential adverse effects on the breastfed infant from the drug or the underlying condition in the mother.

• Take prasugrel exactly as directed
• Prasugrel may cause you to bruise or bleed easily, take care to avoid injury
• Seek medical help if you:
  • Have excessive or prolonged bleeding
  • Notice blood in your stools or urine
  • Experience unexplained symptoms such as fever, weakness, extreme skin paleness or purple skin patches
• Store prasugrel safely out of reach of children