What is the recommended dosing regimen for patients taking Eliquis (apixaban) and Brilinta (ticagrelor) together?

Combining Eliquis (Apixaban) and Brilinta (Ticagrelor): Dosing and Safety Recommendations

When combining apixaban with ticagrelor, use standard-dose ticagrelor (90 mg twice daily after a 180 mg loading dose) with standard-dose apixaban (5 mg twice daily, or 2.5 mg twice daily if dose-reduction criteria are met), but recognize this combination carries significantly increased bleeding risk and should generally be avoided unless absolutely necessary for a limited duration.

Drug Interaction Mechanism

Ticagrelor is a P-gp inhibitor that increases apixaban exposure, requiring careful consideration of dosing adjustments:

• A loading dose of ticagrelor 180 mg increases dabigatran peak concentration by 65% when given together, but only 24% when staggered 2 hours apart 1
• Ticagrelor 90 mg twice daily (maintenance dose) increases dabigatran exposure by 26-29% 1
• While these studies examined dabigatran, apixaban is also a P-gp substrate and would be similarly affected 1
• The interaction is moderate in magnitude—P-gp inhibitors that only moderately inhibit CYP3A4 have less pronounced effects on apixaban than combined strong inhibitors 1

Recommended Dosing Strategy

For apixaban when combined with ticagrelor:

• No empiric dose reduction is recommended for standard apixaban doses (5 mg twice daily) when combined with moderate P-gp inhibitors like ticagrelor 1
• Dose reduction by 50% is only recommended when apixaban is combined with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin), not moderate P-gp inhibitors 1
• If the patient already meets criteria for reduced-dose apixaban (2.5 mg twice daily), concomitant use with ticagrelor is not recommended due to excessive bleeding risk 1

For ticagrelor when combined with apixaban:

• Use standard dosing: 180 mg loading dose, then 90 mg twice daily 1
• Maintain aspirin at 75-100 mg daily (not higher doses) to minimize bleeding 1

Critical Safety Considerations

This combination carries substantially elevated bleeding risk that often outweighs benefits:

• Triple therapy (DOAC + dual antiplatelet therapy) significantly increases major bleeding without consistently reducing ischemic events 2, 3
• In the APPRAISE-2 trial, apixaban 5 mg twice daily added to antiplatelet therapy increased major bleeding 2.59-fold (HR 2.59,95% CI 1.50-4.46) without reducing ischemic events 2
• Ticagrelor specifically increases bleeding risk more than clopidogrel when combined with anticoagulation (OR 1.52 for dual therapy, OR 1.7 for triple therapy) 4
• Intracranial and fatal bleeding events are increased with this combination 2

When This Combination May Be Necessary

The only scenario where combining apixaban with ticagrelor is guideline-supported:

• Acute coronary syndrome patients with atrial fibrillation requiring both anticoagulation and potent antiplatelet therapy 1
• Duration should be minimized—typically 1-6 months maximum, then transition to dual therapy (anticoagulant + single antiplatelet agent) 1, 5
• Clopidogrel is strongly preferred over ticagrelor when combining with anticoagulation due to lower bleeding risk 1

Practical Management Algorithm

If this combination is deemed absolutely necessary:

1. Verify apixaban dosing is appropriate (5 mg twice daily for most patients; avoid if already on 2.5 mg twice daily) 1
2. Use low-dose aspirin only (75-100 mg daily, never higher) 1
3. Add proton pump inhibitor for gastrointestinal protection 1
4. Plan early transition strategy (within 1-6 months) to discontinue either ticagrelor or aspirin 1, 5
5. Consider measuring apixaban levels if significant drug interaction is suspected, though this is not routinely recommended 1
6. Monitor closely for bleeding and educate patient on bleeding signs 3

Preferred Alternative Strategies

To minimize bleeding risk, strongly consider:

• Switching from ticagrelor to clopidogrel (75 mg daily) when anticoagulation is required—this is the guideline-preferred approach 1
• Using dual therapy (apixaban + single antiplatelet agent) rather than triple therapy whenever possible 5, 4
• Shortening triple therapy duration to the absolute minimum necessary 1