clopidogrel

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/Excretion: Rapidly and extensively converted by the liver via the CYP2C19 isoenzyme 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 in ↓ antiplatelet 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.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to clopidogrel or prasugrel;
Pathologic bleeding (peptic ulcer, intracranial hemorrhage);
Concurrent use of omeprazole or esomeprazole;
CYP2C19 poor metabolizers.

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 should not be withheld, if needed for emergent treatment of stroke or MI during pregnancy. Discontinue use 5 to 7 days prior to labor, delivery, or neuraxial blockade, if possible, due to risk of maternal bleeding and hemorrhage;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain, edema, hypertension

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS, pruritus, purpura, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: epistaxis

GI: abdominal pain, diarrhea, dyspepsia, gastritis, GI BLEEDING

Hemat: BLEEDING, NEUTROPENIA, THROMBOTIC THROMBOCYTOPENIC PURPURA

Metab: hypercholesterolemia

MS: arthralgia, back pain

Neuro: depression, dizziness, fatigue, headache

Resp: cough, dyspnea, eosinophilic pneumonia

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Concurrent eptifibatide, tirofiban, aspirin, dipyridamole, NSAIDs, heparin, LMWHs, thrombolytic agents, SSRIs, SNRIs, or warfarin may ↑ risk of bleeding.
Strong CYP2C19 inducers, including rifampin, may ↑ risk of bleeding; avoid concurrent use.
May ↓ metabolism and ↑ effects of phenytoin, repaglinide, tamoxifen, torsemide, fluvastatin, and many NSAIDs; avoid concurrent use with repaglinide.
Concurrent use with the CYP2C19 inhibitors, omeprazole, or esomeprazole may ↓ antiplatelet effects; avoid concurrent use; may consider using H2 antagonist or pantoprazole.
Opioids may ↓ absorption of clopidogrel and its active metabolite and ↓ antiplatelet effects; consider using parenteral antiplatelet in patients with acute coronary syndrome if concurrent use of opioids needed.

Drug-Natural Products:

↑bleeding 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

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. Neutropenia and thrombocytopenia may rarely occur.
- May cause ↑ serum bilirubin, hepatic enzymes, total cholesterol, nonprotein nitrogen, and uric acid concentrations.

Implementation ⬆ ⬇

Do not confuse Plavix with Paxil or Pradaxa.
Discontinue clopidogrel 5–7 days before planned surgical procedures. If clopidogrel must be temporarily discontinued, restart as soon as possible. Premature discontinuation of therapy may increase risk of cardiovascular events.
PO: Administer once daily without regard to food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication exactly as directed. Take missed doses as soon as possible unless almost time for next dose; do not double doses. Do not discontinue clopidogrel without consulting health care professional; may increase risk of cardiovascular events. Advise patient to read the Medication Guide before starting clopidogrel and with each Rx refill in case of changes.
Advise patient to notify health care professional promptly if signs and symptoms of bleeding (unexpected bleeding or bleeding that lasts a long time; blood in urine [pink, red, or brown urine], red or black stools [looks like tar], bruises without known cause or get larger; cough up blood or blood clots; vomit blood or vomit looks like coffee grounds); fever, weakness, chills, sore throat, rash, unusual bleeding or bruising, extreme skin paleness, purple skin patches, yellowing of skin or eyes, or neurological changes occur.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Caution patient to avoid taking omeprazole or esomeprazole during therapy. Consult health care professional for other options.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products, especially those containing aspirin or NSAIDs or proton pump inhibitors.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Therapy should not be withheld because of potential concerns regarding effects of clopidogrel on the fetus. Use during labor or delivery increases risk of maternal bleeding and hemorrhage. Avoid neuraxial blockade during clopidogrel use due to risk of spinal hematoma. When possible, discontinue clopidogrel 5 to 7 days prior to labor, delivery, or neuraxial blockade.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇