prasugrel

Effient

Pharmacologic class: Thienopyridine platelet inhibitor

Therapeutic class: Antiplatelet drug

Pregnancy risk category B

FDA Box Warning

• Drug can cause significant, sometime fatal, bleeding.

• Don't use in patients with active pathological bleeding or history of transient ischemic attack or stroke (patients age 75 and older).

• Drug is generally not recommended, because of increased risk of fatal and intracranial bleeding and uncertain benefit. In high-risk situations (such as patients with diabetes or history of prior myocardial infarction, where its effect appears to be greater), its use may be considered.

• Don't start drug in patients likely to undergo urgent coronary artery bypass graft (CABG). If possible, discontinue drug at least 7 days before any surgery.

• Additional risk factors for bleeding include body weight of less than 132 lb (60 kg), propensity for bleeding, concomitant use of medications that increase bleeding risk (such as warfarin, heparin, fibrinolytics, and nonsteroidal anti-inflammatory drugs [prolonged use]). Suspect bleeding in patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures.

• If possible, manage bleeding without discontinuing drug. Discontinuing drug, particularly in first few weeks after acute coronary syndrome, increases risk of subsequent cardiovascular events.

Action

Inhibits platelet activation and aggregation through irreversible binding of its active metabolite to the P2Y12 class of adenosine diphosphate receptors on platelets

Availability

Tablets: 5 mg, 10 mg

Indications and dosages

➣ Reduction of rate of thrombotic cardiovascular events in patients with acute coronary syndrome who are to be managed with PCI as follows: patients with unstable angina or non-ST-elevation myocardial infarction (MI) and patients with ST-elevation MI when managed with primary or delayed PCI

Adults: Initially, 60 mg P.O. as loading dose; then, 10 mg P.O. daily (with aspirin 75 to 325 mg daily)

Dosage adjustment

• Adults weighing less than 132 lb

Contraindications

• Hypersensitivity to drug or its components

• Active pathological bleeding

• History of transient ischemic attack or cerebrovascular accident

Precautions

Use cautiously in:

• CABG-related bleeding, patients at general risk for bleeding

• thrombotic thrombocytopenia purpura

• low body weight (less than 132 lb)

• elderly patients age 75 and older (use not recommended except in high-risk situations, such as diabetes and history of MI)

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Administer with or without food.

See Be aware that premature drug discontinuation increases risk of stent thrombosis, MI, and death.

Adverse reactions

CNS: headache, dizziness, fatigue, intracranial hemorrhage

CV: hypertension, hypotension, bradycardia, peripheral edema, atrial fibrillation

EENT: epistaxis

GI: nausea, diarrhea, GI hemorrhage

Hematologic: leukopenia, bleeding, life-threatening bleeding, thrombotic thrombocytopenia purpura

Metabolic: hypercholesterolemia, hyperlipidemia

Musculoskeletal: back pain, extremity pain

Respiratory: dyspnea, cough

Skin: rash

Other: chest pain, pyrexia, newly diagnosed malignancies

Interactions

Drug-drug. Nonsteroidal anti-inflammatory drugs, warfarin: increased risk of bleeding

Drug-diagnostic tests. Cholesterol, lipids: increased levels

White blood cells: decreased count

Patient monitoring

See Closely monitor coagulation studies and CBC with white cell differential and watch for evidence of bleeding.

• Monitor cholesterol and lipid levels closely.

Patient teaching

• Instruct patient to take drug with or without food.

See Instruct patient to immediately report to prescriber blood in stool or urine or unanticipated, prolonged, or excessive bleeding.

See Instruct patient to promptly report to prescriber if fever, weakness, extreme skin paleness, purple skin patches, or neurologic changes, such as dizziness or headache, occur.

• Advise patient to notify all health care professionals that he's taking prasugrel.

• Advise patient not to take other prescription or nonprescription drugs or dietary supplements without first discussing with prescriber.

• Caution patient not to discontinue drug without first discussing with prescriber.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

prasugrel

(pra-soo-grel) prasugrel,

Effient

(trade name)

Classification

Therapeutic: antiplatelet agents
Pharmacologic: thienopyridines
Pregnancy Category: B

Indications

Reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who will be managed with PCI including patients with unstable angina or non-ST-elevation myocardial infarction (NSTEMI).Reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with STEMI when managed with either primary/delayed PCI.

Action

Acts by irreversibly binding its active metabolite to the P2Y₁₂ class of ADP receptors on platelets; inhibiting platelet activation and aggregation.

Therapeutic effects

Decreased thrombotic events including cardiovascular death, nonfatal myocardial infarction (MI) and nonfatal stroke.

Pharmacokinetics

Absorption: Well absorbed following oral administration (79%), then rapidly converted to an active metabolite.Distribution: Unknown.Protein Binding: Active metabolite—98%.Metabolism and Excretion: Active metabolite is metabolized to two inactive compounds; 68% excreted in the urine and 27% in feces as inactive metabolites.Half-life: Active metabolite—7 hr (range 2–15 hr).

Time/action profile (effect on platelet function)

ROUTE	ONSET	PEAK	DURATION
PO	within 1 hr	2 hr	5–9 days†

† Following discontinuation.

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Active pathological bleeding;History of transient ischemic attack or stroke.Use Cautiously in: Patients about to undergo coronary artery bypass grafting (CABG) (↑ risk of bleeding; discontinue at least 7 days prior to surgery);Premature discontinuation (↑ risk of stent thrombosis, MI, and death);Body weight <60 kg, propensity to bleed, severe hepatic impairment, concurrent use of medications that ↑ the risk of bleeding (↑ risk of bleeding);Hypotension in the setting of recent coronary angiography, PCI, CABG, or other surgical procedure (suspect bleeding but do not discontinue prasugrel); Geriatric: Use in patients ≥75 yr of age generally not recommended (↑ risk of fatal/intracranial bleeding and questionable benefit, except in high-risk patients such as diabetes or prior MI); Obstetric: Use only if potential benefit to mother justifies potential risk to fetus; Lactation: Use only if potential benefit to the mother justifies potential risk to nursing infant; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

dizziness
fatigue
headache

Respiratory

cough
dyspnea

Cardiovascular

atrial fibrillation
bradycardia
hypertension
hypotension
peripheral edema

Gastrointestinal

diarrhea
nausea

Dermatologic

rash

Hematologic

bleeding (life-threatening)
thrombotic thrombocytopenic purpura (life-threatening)
leukopenia

Metabolic

hyperlipidemia

Musculoskeletal

back pain
extremity pain

Miscellaneous

allergic reactions including angioedema (life-threatening)
fever
non-cardiac chest pain

Interactions

Drug-Drug interaction

↑ risk of bleeding with warfarin and NSAIDs.

Route/Dosage

Aspirin 75–325 mg/daily should be taken concurrentlyOral (Adults ≥60 kg) 60 mg initially as a loading dose, then 10 mg once daily.Oral (Adults < 60 kg) Consider maintenance dose of 5 mg once daily.

Availability

Tablets: 5 mg, 10 mg

Nursing implications

Nursing assessment

Assess patient for symptoms of stroke, peripheral vascular disease, or MI periodically during therapy.
Monitor patient for signs of thrombotic thrombocytic purpura (thrombocytopenia, microangiopathic hemolytic anemia, neurologic findings, renal dysfunction, fever). May rarely occur, even after short exposure (<2 wk). Requires prompt treatment.
Lab Test Considerations: Monitor bleeding time during therapy. Prolonged bleeding time, which is time- and dose-dependent, is expected.
- Monitor CBC with differential and platelet count periodically during therapy. Thrombocytopenia and anemia may rarely occur.

Potential Nursing Diagnoses

Risk for injury (Indications, Side Effects)

Implementation

Discontinue prasugrel 7 days before planned surgical procedures.
- Patients should take aspirin 75–325 mg daily with prasugrel.
Oral: Administer once daily without regard to food.

Patient/Family Teaching

Instruct patient to take medication as directed. Take missed doses as soon as possible unless almost time for next dose; do not double doses. Do not discontinue without consulting health care professional. Advise patient to read Medication Guide before taking and with each Rx refill; new information may be available.
Advise patient to notify health care professional promptly if fever, weakness, skin paleness, purple skin patches, yellowing of skin or eyes, chills, sore throat, neurological changes, or unusual bleeding or bruising, swelling of lips, difficulty breathing, rash, or hives occurs.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially NSAIDs.

Evaluation/Desired Outcomes

Prevention of stroke, MI, and vascular death in patients at risk.