What is the role of Qlipta (atogepant) in treating headaches, specifically migraines?

Qlipta (Atogepant) for Migraine Prevention

Qlipta (atogepant) is an effective oral medication specifically approved for the preventive treatment of episodic migraine in adults, with current guidelines providing a weak recommendation for its use. 1

FDA-Approved Indication

• Atogepant is FDA-approved specifically for the preventive treatment of migraine in adults 2
• It is an oral, small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist taken once daily 2

Guideline Recommendations

• The 2023 VA/DoD Clinical Practice Guideline suggests atogepant for the prevention of episodic migraine (weak recommendation) 1
• This recommendation is specifically for episodic migraine (fewer than 15 headache days per month), not chronic migraine 1
• The American College of Physicians 2025 guideline includes atogepant among pharmacologic treatments for episodic migraine prevention 1

Efficacy Data

Migraine Day Reduction

• Atogepant 60 mg once daily produces the greatest reduction in monthly migraine days, with a mean difference of -1.48 days compared to placebo (p < 0.001) 3
• All doses (10 mg, 30 mg, 60 mg) significantly reduce mean monthly migraine days and monthly headache days compared to placebo over 12 weeks 2, 3, 4
• The 60 mg dose showed mean reductions of -3.6 to -4.1 monthly migraine days versus -2.9 days for placebo 4

Response Rates

• 50% responder rates (patients achieving ≥50% reduction in migraine days) are significantly improved with atogepant across all doses 2, 3
• Long-term data shows increasing efficacy over time: 60.4% achieved ≥50% reduction at weeks 1-4, increasing to 84.2% at weeks 49-52 5
• At one year, 69.9% achieved ≥75% reduction and 48.4% achieved 100% reduction in monthly migraine days 5

Additional Benefits

• Significant reductions in acute medication use across all doses 2, 3
• Improvements in quality of life measures, including the Migraine Specific Quality of Life Questionnaire Role Function-Restrictive domain 2
• Reductions in activity impairment and physical impairment related to migraine 2

Safety Profile

Common Adverse Events

• The most common side effects are nausea (5-12%), constipation (7.2%), and fatigue/sleepiness 2, 4
• Upper respiratory tract infection (10.3%) and urinary tract infection (5.2%) were reported in long-term studies 5
• Most adverse events are mild to moderate in severity 3, 4

Serious Adverse Events

• Serious treatment-emergent adverse events occurred in 4.4% of participants in the 52-week trial, with no significant difference from placebo 5, 4
• Treatment discontinuation due to adverse events occurred in approximately 5% of atogepant participants versus 3% for placebo 4
• Hypersensitivity reactions, including anaphylaxis, can occur and require immediate discontinuation 2

Dosing and Administration

• Available doses: 10 mg, 30 mg, and 60 mg tablets 2
• Taken once daily with or without food 2
• Dose adjustments required with certain drug interactions, particularly strong CYP3A4 inhibitors or inducers 2
• Contraindicated in patients with previous allergic reactions to atogepant 2

Clinical Context and Positioning

When to Consider Atogepant

• For adults with episodic migraine (4-14 migraine days per month) requiring preventive therapy 1, 4
• When patients prefer oral daily medication over injectable options 1
• As an alternative when other preventive medications have failed or are contraindicated 1

Hierarchy in Treatment Guidelines

• The VA/DoD guidelines give strong recommendations to CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and certain ARBs (candesartan, telmisartan) for episodic migraine prevention 1
• Atogepant receives a weak recommendation, placing it on similar footing with topiramate, propranolol, valproate, and memantine 1
• This weaker recommendation reflects the newer evidence base compared to more established therapies, not necessarily inferior efficacy 1

Important Limitations

• Atogepant is NOT indicated for chronic migraine (≥15 headache days per month) 1
• For chronic migraine, onabotulinumtoxinA injections are specifically recommended instead 1, 6
• Insufficient evidence exists for atogepant in tension-type headache or cluster headache, though case reports suggest possible benefit in refractory cluster headache 7

Common Pitfalls to Avoid

• Do not prescribe atogepant for chronic migraine—it is only studied and approved for episodic migraine 1, 4
• Monitor for constipation, which occurs in 7.2% of patients and may require management 2, 5
• Check for drug interactions, particularly with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) or inducers, which require dose adjustments 2
• Counsel patients that efficacy may improve over time, with maximal benefit often seen after several months of treatment 5
• Educate patients to discontinue immediately and seek medical attention if signs of hypersensitivity reaction occur (swelling, itching, trouble breathing, hives, rash) 2