Can Brillinta (ticagrelor) be administered rectally?

Rectal Administration of Ticagrelor (Brilinta)

Ticagrelor (Brilinta) should not be administered rectally as there is no evidence supporting this route of administration and it may result in unpredictable absorption, potentially compromising its efficacy in preventing thrombotic events.

Approved Administration Routes for Ticagrelor

Based on available evidence and guidelines, ticagrelor has only been validated for the following administration routes:

• Oral administration: The standard and FDA-approved method of administration 1
• Crushed oral administration: For patients with swallowing difficulties, tablets can be crushed and administered orally with water 2
• Nasogastric tube administration: For patients unable to take oral medications, crushed tablets can be administered via nasogastric tube 2

Evidence for Alternative Routes

The 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for management of acute coronary syndromes specifically addresses alternative routes for aspirin but not for ticagrelor, stating: "In patients who cannot take oral medication, rectal or intravenous (where available) administration are options for administration [of aspirin]" 3. However, no similar recommendation exists for ticagrelor.

Pharmacological Considerations

Several factors make rectal administration of ticagrelor problematic:

• Absorption concerns: Ticagrelor is designed for oral absorption with specific bioavailability characteristics that may not translate to rectal administration
• Unpredictable pharmacokinetics: Rectal administration could lead to variable drug levels, potentially compromising the critical antiplatelet effect needed in acute coronary syndrome patients
• Lack of clinical validation: No studies have evaluated the safety or efficacy of rectally administered ticagrelor 2

Alternative Options for Patients Unable to Take Oral Ticagrelor

For patients who cannot take oral medications but require P2Y12 inhibition:

1. Crushed ticagrelor via nasogastric tube: Research shows that "one or two crushed 90-mg ticagrelor tablets, prepared for either oral or NG tube administration, delivers a mean dose of ≥97% of the original tablet" 2

2. Intravenous antiplatelet alternatives: For patients with very high risk of stent thrombosis who cannot take oral medications, the 2017 ESC DAPT Focused Update states that "bridging therapy with IV reversible glycoprotein inhibitors, such as tirofiban or eptifibatide, may be considered" 3

3. Cangrelor (if available): "The reversible IV P2Y12 inhibitor cangrelor is an appealing alternative, given the role of P2Y12 inhibition in preventing ST and the quicker offset of action as compared with tirofiban or eptifibatide" 3

Potential Pitfalls

• Attempting rectal administration of ticagrelor could result in:
  • Subtherapeutic antiplatelet effect, increasing thrombotic risk
  • Unpredictable drug levels
  • Potential local irritation or damage to rectal mucosa
  • Compromised patient outcomes in critical situations requiring reliable P2Y12 inhibition

Conclusion

When oral administration is not possible, clinicians should use established alternative routes such as nasogastric administration of crushed ticagrelor or consider IV glycoprotein IIb/IIIa inhibitors or cangrelor rather than attempting rectal administration, which lacks evidence for safety and efficacy.