What are the recommendations for managing atogepant (oral calcitonin gene-related peptide receptor antagonist) in a patient with a history of migraines undergoing surgery in the perioperative period?

Perioperative Management of Atogepant

Continue atogepant through the perioperative period, including the day of surgery, as there are no specific contraindications or documented anesthetic interactions with this oral CGRP receptor antagonist.

Rationale for Continuation

The 2021 Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement specifically addresses CGRP receptor antagonists in the perioperative setting 1. While the guideline discusses monoclonal antibody CGRP antagonists (erenumab, fremanezumab, galcanezumab), it notes these agents are "free of cardiovascular adverse effects" and mentions only "theoretical concerns regarding vasoconstriction" without providing definitive recommendations to hold them 1.

Atogepant has a distinct safety profile compared to older migraine medications:

• Unlike ergotamine (which must be held at least 2 days preoperatively due to prolonged vasoconstriction and risk of myocardial ischemia), atogepant does not cause significant vasoconstrictive effects 1
• Unlike triptans (which should be held on the day of surgery due to serotonin syndrome risk and multiple metabolic pathways), atogepant has no documented serotonergic interactions 1
• Unlike butalbital (which requires holding on surgery day due to respiratory depression risk with anesthetics), atogepant does not potentiate anesthetic effects 1

Pharmacokinetic Considerations

Atogepant's pharmacokinetic profile supports perioperative continuation:

• Rapid absorption with median time to maximum concentration of approximately 2 hours 2
• Terminal half-life of approximately 11 hours with no evidence of accumulation 2
• No clinically meaningful drug interactions with common anesthetic agents documented 3

The FDA-approved dosing for atogepant is 10 mg, 30 mg, or 60 mg once daily for episodic migraine, and 60 mg once daily for chronic migraine, taken with or without food 3.

Safety Profile Relevant to Surgery

Atogepant demonstrates favorable perioperative safety characteristics:

• No clinically meaningful elevations in liver enzymes (ALT) even at supratherapeutic doses (170 mg daily for 28 days) 2
• Most common adverse events are constipation (7-11%) and nausea (4-10%), which are manageable perioperatively 4, 5
• No cardiovascular adverse effects documented, unlike some other migraine preventive agents 1
• No respiratory depression or interaction with opioids or benzodiazepines 3

Clinical Evidence Supporting Use

The VA/DoD 2024 guidelines provide a "weak for" recommendation for atogepant in episodic migraine prevention, demonstrating its established role in migraine management 1. Atogepant reduces mean monthly migraine days by 1.2-1.7 days compared to placebo, with efficacy beginning as early as the first day after treatment initiation 5, 6.

Important Caveats

Consider dose adjustments only in specific circumstances unrelated to surgery itself:

• Severe renal impairment or end-stage renal disease: reduce to 10 mg once daily for episodic migraine; avoid in chronic migraine 3
• Concomitant strong CYP3A4 inhibitors: reduce to 10 mg once daily for episodic migraine; avoid in chronic migraine 3
• Concomitant OATP inhibitors: reduce to 10 mg or 30 mg once daily for episodic migraine; 30 mg once daily for chronic migraine 3

Discontinue immediately if hypersensitivity reaction occurs (including anaphylaxis or dyspnea, which can occur days after administration) 3.

Practical Implementation

• Administer atogepant on the morning of surgery with a sip of water as part of the patient's regular medication regimen
• No need to adjust timing relative to anesthetic administration
• Continue postoperatively without interruption to maintain migraine prophylaxis
• Monitor for constipation and nausea, which may be additive with postoperative symptoms but are not contraindications to use 4