prasugrel

General

**BEERS Drug**

Pronunciation:
pra-soo-grel


Trade Name(s)

  • Effient

Ther. Class.

antiplatelet agents

Pharm. Class.

thienopyridines

Indications

  • Reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who will be managed with percutaneous coronary intervention (PCI) including patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI).
  • Reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with ST-elevation myocardial infarction (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 Effect(s):

Decreased thrombotic events including cardiovascular death, nonfatal 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)

ROUTEONSETPEAKDURATION
POwithin 1 hr2 hr5–9 days†
†Following discontinuation.

Contraindication/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);
  • OB:   Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  • Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
  • Pedi:  Safety and effectiveness not established in children
  • Geri:   Appears on Beers list. ↑ risk of major bleeding compared to clopidogrel, especially in patients ≥75 yrs old. Use with caution in older adults, especially in patients ≥75 yrs old. If used in patients ≥75 yrs old, consider using a lower dose (5 mg once daily).

Adverse Reactions/Side Effects

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

Derm: rash

GI: diarrhea, nausea

Hemat: BLEEDING, leukopenia, THROMBOTIC THROMBOCYTOPENIC PURPURA

Metabolic: hyperlipidemia

MS: back pain, extremity pain, non-cardiac chest pain

Neuro: dizziness, fatigue, headache

Resp: cough, dyspnea

Misc: fever, HYPERSENSITIVITY REACTIONS (including angioedema)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • ↑ risk of bleeding with  warfarin  and  NSAIDs.
  •  Opioids  may ↓ absorption of active metabolite and ↓ antiplatelet effects; consider using parenteral antiplatelet in patients with acute coronary syndrome if concurrent use of opioids needed.

Route/Dosage

Aspirin 75–325 mg/daily should be taken concurrently

PO (Adults  ≥60 kg): 60 mg initially as a loading dose, then 10 mg once daily.

PO (Adults  <60 kg): 60 mg initially as a loading dose, then consider maintenance dose of 5 mg once daily.

Availability (generic available)

Tablets: 5 mg, 10 mg

Assessment

  • Assess patient for symptoms of stroke, peripheral vascular disease, or MI periodically during therapy.
  • Monitor patient for signs of thrombotic thrombocytopenic 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.

Implementation

  • Discontinue prasugrel 7 days before planned surgical procedures.

    • Patients should take aspirin 75–325 mg daily with prasugrel.
    • In patients with UA or NSTEMI,  dose is usually administered at time of diagnosis or at time of PCI.
    • In patients with STEMI  presenting within 12 hrs of symptom onset, loading dose is usually administered at time of diagnosis or at time of PCI.
  • PO Administer once daily without regard to food. DNC:  Swallow tablets whole; do not break. 

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; in case of changes. Instruct patient to keep prasugrel in original container with dessicant, and keep tightly capped to protect from moisture.
  • Inform patient that they will bleed and bruise more easily and will take longer to stop bleeding. Notify health care professional immediately if you have unexpected bleeding or bleeding that lasts a long time, bleeding that is severe or you cannot control, pink or brown urine, red or black stool (looks like tar), bruises that happen without a known cause or get larger, cough up blood or blood clots, vomit blood or your vomit looks like "coffee grounds."
  • 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 occur.

  • Advise patient to notify health care professional and dentists 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.
  • Rep:  Advise female patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

Evaluation/Desired Outcomes

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

prasugrelis the Anesthesia Central Word of the day!