clopidogrel, Plavix

 Indications

Acute coronary syndrome (ST-segment elevation MI,

non-ST-segment elevation MI, or unstable angina). Patients

with established peripheral arterial disease, recent

MI, or recent stroke.

Action

Inhibits platelet aggregation by irreversibly inhibiting

the binding of ATP to platelet receptors. Therapeutic

Effects: Reduction in risk of MI and stroke.

Pharmacokinetics

Absorption: Well absorbed following oral administration;

rapidly metabolized to an active antiplatelet

compound. Parent drug has no antiplatelet activity.

Distribution: Unknown.

Protein Binding: Clopidogrel—98%; active metabolite—

94%.

Metabolism and Excretion: Rapidly and extensively

converted by the liver (CYP2C19) to its active metabolite,

which is then eliminated 50% in urine and

45% in feces; 2% of Whites, 4% of Blacks, and 14%

of Asians have CYP2C19 genotype that results in reduced

metabolism of clopidogrel (poor metabolizers)

into its active metabolite (may result inpantiplatelet effects).

Half-life: 6 hr (active metabolite 30 min).

TIME/ACTION PROFILE (effects on platelet

function)

ROUTE ONSET PEAK DURATION

PO within 24 hr 3–7 days 5 days†

†Following discontinuation.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to clopidogrel

or prasugrel; Pathologic bleeding (peptic ulcer, intracranial

hemorrhage); Concurrent use of omeprazole or

esomeprazole; CYP2C19 poor metabolizers; Lactation:

Lactation.

Use Cautiously in: Patients at risk for bleeding

(trauma, surgery, or other pathologic conditions); History

of GI bleeding/ulcer disease; Severe hepatic impairment;

Hypersensitivity to another thienopyridine

(prasugrel); OB: Use only if clearly indicated; Pedi:

Safety and effectiveness not established.

Adverse Reactions/Side Effects

Incidence of adverse reactions similar to that of aspirin.

CNS: depression, dizziness, fatigue, headache. EENT:

epistaxis. Resp: cough, dyspnea, eosinophilic pneumonia.

CV: chest pain, edema, hypertension. GI: GI

BLEEDING, abdominal pain, diarrhea, dyspepsia, gastritis.

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS,

DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS,

STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL

NECROLYSIS, pruritus, purpura, rash. Hemat: BLEEDING,

NEUTROPENIA, THROMBOTIC THROMBOCYTOPENIC

PURPURA.Metab: hypercholesterolemia. MS: arthralgia,

back pain. Misc: fever, hypersensitivity reactions.

Interactions

Drug-Drug: Concurrent abciximab, eptifibatide,

tirofiban, aspirin, NSAIDs, heparin, LMWHs,

thrombolytic agents, SSRIs, SNRIs, prasugrel, or

warfarin mayqrisk of bleeding. Maypmetabolism

andqeffects of phenytoin, tolbutamide, tamoxifen,

torsemide, fluvastatin, and many NSAIDs. Concurrent

use with the CYP2C19 inhibitors, omeprazole, or

esomeprazole maypantiplatelet effects; avoid concurrent

use; may consider using H2 antagonist or another

proton pump inhibitor (e.g., dexlansoprazole,

lansoprazole, or pantoprazole).

Drug-Natural Products:qbleeding risk with anise,

arnica, chamomile, clove, fenugreek, feverfew,

garlic, ginger, ginkgo, Panax ginseng, and

others.

Route/Dosage

Recent MI, Stroke, or Peripheral Arterial

Disease

PO (Adults): 75 mg once daily.

Acute Coronary Syndrome

PO (Adults): 300 mg initially, then 75 mg once daily;

aspirin 75–325 mg once daily should be given concurrently.

Availability (generic available)

Tablets: 75 mg, 300 mg. Cost: Generic—75 mg

$23.46/90.