What is the appropriate dosing of Plavix (clopidogrel) for a patient with facial droop, negative computed tomography (CT) scan without contrast, and negative computed tomography angiography (CTA) of the head and neck, with no known contraindications, being admitted to the floor?

Clopidogrel Dosing for Acute Ischemic Stroke

For a patient with acute ischemic stroke (facial droop) and negative CT/CTA, initiate clopidogrel 300 mg loading dose immediately, followed by 75 mg daily maintenance therapy. 1, 2

Rationale for Loading Dose Strategy

The 300 mg loading dose is specifically recommended for acute ischemic stroke patients within 24-48 hours of symptom onset, ideally within 12 hours. 2 This differs from the 600 mg loading dose used in acute coronary syndrome because:

• Stroke patients require rapid platelet inhibition without excessive bleeding risk - the 300 mg dose achieves therapeutic effect while minimizing intracranial hemorrhage risk in the setting of acute cerebral ischemia. 1, 2

• Your patient has confirmed no hemorrhage on CT - this is critical, as clopidogrel is absolutely contraindicated in active intracranial hemorrhage. 3

• The negative CTA indicates no large vessel occlusion requiring mechanical thrombectomy - if thrombectomy were needed, antiplatelet therapy timing would be adjusted accordingly. 4

Specific Dosing Protocol

Initial Management:

• Administer clopidogrel 300 mg orally immediately upon admission to the floor. 1, 2
• Begin aspirin 160-300 mg within 24-48 hours if not already given (dual antiplatelet therapy for high-risk TIA/minor stroke). 4
• Continue clopidogrel 75 mg daily starting 24 hours after the loading dose. 1, 3

Duration of Therapy:

• Maintain dual antiplatelet therapy (clopidogrel + aspirin) for 21-90 days depending on stroke severity and bleeding risk. 1
• After the initial dual therapy period, continue clopidogrel 75 mg daily as monotherapy indefinitely for secondary stroke prevention. 1

Critical Safety Considerations

Contraindications to verify before dosing:

• Active pathological bleeding (already ruled out by negative CT). 3
• Known hypersensitivity to clopidogrel. 3
• Do NOT delay clopidogrel for concern about future procedures - the mortality/morbidity benefit of immediate antiplatelet therapy outweighs procedural bleeding risk in acute stroke. 1, 2

Bleeding Risk Monitoring:

• Clopidogrel increases bleeding risk, but this is acceptable given the high risk of recurrent stroke without treatment. 3
• Thrombotic thrombocytopenic purpura (TTP) can occur within the first 2 weeks - monitor for fever, thrombocytopenia, neurologic changes. 1, 3
• If urgent surgery becomes necessary, clopidogrel should be discontinued 5 days prior, but this decision must weigh stroke recurrence risk. 3

Common Pitfalls to Avoid

Do NOT use the 600 mg loading dose - this is for acute coronary syndrome/PCI patients, not stroke patients. 5, 1 The higher dose increases bleeding risk without additional benefit in cerebrovascular disease. 1, 2

Do NOT wait for MRI results - initiate clopidogrel immediately based on clinical presentation and negative CT. 2 Delaying antiplatelet therapy by even hours increases risk of stroke progression and recurrence. 1, 2

Do NOT omit the loading dose - starting with 75 mg daily maintenance therapy delays therapeutic platelet inhibition by several days, leaving the patient vulnerable to early recurrent stroke. 3

Do NOT combine with proton pump inhibitors (PPIs) omeprazole or esomeprazole - these are strong CYP2C19 inhibitors that reduce clopidogrel's antiplatelet effect. 3 If gastroprotection is needed, use pantoprazole or an H2-blocker instead. 3

Drug Metabolism Considerations

Clopidogrel requires conversion by CYP2C19 to its active metabolite. 3 Approximately 2-15% of patients are CYP2C19 poor metabolizers with reduced drug efficacy. 3 However:

• Do NOT delay treatment for genetic testing - initiate standard dosing immediately. 3
• If the patient has known CYP2C19 poor metabolizer status or experiences recurrent events despite clopidogrel, consider alternative P2Y12 inhibitors (ticagrelor or prasugrel), though these have limited data in stroke. 3

Concomitant Medications

Safe to continue:

• Antihypertensives, statins, and most cardiovascular medications have no clinically significant interactions with clopidogrel. 6
• Digoxin, beta-blockers, calcium channel blockers can be continued without dose adjustment. 6, 7

Use with caution:

• NSAIDs increase bleeding risk - avoid if possible or use lowest effective dose. 3, 6
• SSRIs/SNRIs increase bleeding risk - continue if benefits outweigh risks but monitor closely. 3