What is the recommended usage of Qulipta (atogepant) for preventive treatment of episodic migraine in adults?

Qulipta (Atogepant) for Episodic Migraine Prevention

Atogepant (Qulipta) is recommended at 10 mg, 30 mg, or 60 mg once daily for the preventive treatment of episodic migraine in adults, taken orally with or without food. 1

FDA-Approved Indications and Dosing

• Atogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist FDA-approved for the preventive treatment of migraine in adults. 1
• For episodic migraine (defined as 1-14 headache days per month), the recommended dosage is 10 mg, 30 mg, or 60 mg taken once daily. 2, 1
• For chronic migraine (≥15 headache days per month), the recommended dosage is 60 mg once daily. 1
• The medication can be taken with or without food. 1

Guideline Recommendations

The 2024 VA/DoD guidelines provide a weak recommendation for atogepant in episodic migraine prevention, while the 2025 American College of Physicians guidelines evaluated atogepant as part of their systematic review of preventive treatments. 2

• The VA/DoD guidelines suggest atogepant for the prevention of episodic migraine (weak for recommendation). 2
• This places atogepant among other preventive options including CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab - which have strong recommendations), ARBs (candesartan, telmisartan - strong recommendations), and traditional agents like topiramate, propranolol, and valproate (all weak recommendations). 2

Dose Modifications for Special Populations

Dose adjustments are required for patients with renal impairment or those taking interacting medications: 1

• Severe renal impairment or end-stage renal disease: Use 10 mg once daily for episodic migraine; avoid use in chronic migraine. 1
• Strong CYP3A4 inhibitors: Use 10 mg once daily for episodic migraine; avoid use in chronic migraine. 1
• Strong, moderate, or weak CYP3A4 inducers: Use 30 mg or 60 mg once daily for episodic migraine; avoid use in chronic migraine. 1
• OATP inhibitors: Use 10 mg or 30 mg once daily for episodic migraine; use 30 mg once daily for chronic migraine. 1
• Severe hepatic impairment: Avoid use. 1

Efficacy Data

Clinical trials demonstrate statistically significant and clinically meaningful reductions in monthly migraine days across all doses: 3, 4

• In the ADVANCE trial, atogepant reduced mean monthly migraine days by 1.57 days (10 mg), 1.90 days (30 mg), and 2.10 days (60 mg) compared to placebo over 12 weeks (all p < 0.0001). 3
• Response rates at 12 weeks showed 60.4% of participants achieved ≥50% reduction in monthly migraine days, 37.2% achieved ≥75% reduction, and 20.7% achieved 100% reduction. 5
• Long-term data from the 52-week open-label trial showed sustained efficacy, with mean reduction in monthly migraine days increasing from -3.8 at weeks 1-4 to -5.2 at weeks 49-52. 5
• By weeks 49-52, response rates improved to 84.2% (≥50% reduction), 69.9% (≥75% reduction), and 48.4% (100% reduction). 5
• Over 70% of participants who experienced an initial response maintained sustained response with continued treatment. 4

Safety and Tolerability Profile

Atogepant is generally well tolerated with a favorable safety profile: 1, 5, 3

• The most common adverse reactions (≥4% and greater than placebo) are nausea, constipation, and fatigue/somnolence. 1
• In the 52-week long-term safety trial, treatment-emergent adverse events occurred in 67.0% of participants, with the most common being upper respiratory tract infection (10.3%), constipation (7.2%), nausea (6.3%), and urinary tract infection (5.2%). 5
• Serious adverse events were reported in only 4.4% of participants over 52 weeks. 5
• Treatment discontinuation due to adverse events was infrequent across all doses. 3

Critical Safety Warnings

Hypersensitivity reactions, including severe reactions, can occur: 1

• Atogepant is contraindicated in patients with a history of hypersensitivity to atogepant or any component of Qulipta. 1
• Severe hypersensitivity reactions have included anaphylaxis and dyspnea, which can occur days after administration. 1
• If a hypersensitivity reaction occurs, discontinue Qulipta immediately and initiate appropriate therapy. 1

Pregnancy Considerations

Based on animal data, atogepant may cause fetal harm and should be avoided in pregnancy. 1

Concomitant Use with Acute Migraine Treatments

Atogepant can be safely used concurrently with ubrogepant (another CGRP antagonist) for acute migraine treatment: 6

• The TANDEM study demonstrated that concomitant use of atogepant 60 mg daily for prevention and ubrogepant 100 mg as needed for acute treatment was safe and well tolerated over 12 weeks. 6
• No increase in adverse events was observed with increased frequency of ubrogepant use. 6
• This combination provides both preventive and acute treatment options within the same drug class. 6

Clinical Context and Positioning

Atogepant represents a newer preventive option that may be particularly useful for patients who have failed or cannot tolerate traditional preventive medications: 2, 7

• Traditional first-line preventive agents include ARBs (candesartan, telmisartan), beta-blockers (propranolol), and antiseizure medications (topiramate, valproate). 2
• CGRP-targeted therapies (including atogepant and monoclonal antibodies) offer mechanism-specific prevention with generally favorable tolerability profiles compared to traditional agents. 2, 7
• The oral formulation of atogepant provides convenience compared to injectable CGRP monoclonal antibodies. 7