QULIPTA (Atogepant) Prescribing Guide
Standard Dosing
For episodic migraine (1–14 headache days per month), prescribe QULIPTA 10 mg, 30 mg, or 60 mg once daily; for chronic migraine (≥15 headache days per month), prescribe 60 mg once daily. 1
- All doses are taken orally once daily, with or without food. 1
- The 2025 American College of Physicians guideline positions atogepant as a third-line option after failure of or intolerance to first-line agents (beta-blockers, topiramate, valproate, amitriptyline, venlafaxine) and second-line triptans plus NSAIDs for acute treatment. 2
- Cost is a major consideration: CGRP antagonist-gepants like atogepant are substantially more expensive than traditional oral preventives, and economic evidence drove the ACP's recommendation to reserve them for patients who have failed multiple first-line agents. 2
Dose Adjustments for Severe Renal Impairment
In patients with severe renal impairment or end-stage renal disease (ESRD), reduce the dose to 10 mg once daily for episodic migraine and avoid use entirely for chronic migraine. 1
- Mild to moderate renal impairment does not require dose adjustment. 3
- Population pharmacokinetic modeling confirmed that mild/moderate renal impairment has no clinically relevant effect on atogepant exposure. 3
Dose Adjustments for CYP3A4 Inducer Interactions
When prescribing QULIPTA with strong, moderate, or weak CYP3A4 inducers (e.g., rifampin, topiramate), increase the dose to 30 mg or 60 mg once daily for episodic migraine; avoid concomitant use entirely for chronic migraine. 1
- Strong CYP3A4 inducers (e.g., rifampin) decrease atogepant exposure by approximately 50%, requiring dose escalation to maintain efficacy. 1, 3
- Moderate inducers also reduce atogepant exposure and necessitate the same dose adjustment. 1
- Even weak CYP3A4 inducers (e.g., topiramate) decrease atogepant exposure and require dose escalation. 1, 3
- For chronic migraine, the risk-benefit ratio does not support dose escalation in the presence of any CYP3A4 inducer; avoid the combination. 1
Dose Adjustments for CYP3A4 Inhibitor Interactions
When prescribing QULIPTA with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin), reduce the dose to 10 mg once daily for episodic migraine; avoid concomitant use for chronic migraine. 1
- Strong CYP3A4 inhibitors increase atogepant exposure by approximately 5-fold, raising the risk of dose-dependent adverse events (nausea, constipation, fatigue). 1, 3
- Moderate or weak CYP3A4 inhibitors do not require dose adjustment. 1
Dose Adjustments for OATP Inhibitor Interactions
When prescribing QULIPTA with OATP inhibitors (e.g., single-dose rifampin, cyclosporine), reduce the dose to 10 mg or 30 mg once daily for episodic migraine, or 30 mg once daily for chronic migraine. 1
- OATP inhibitors significantly increase atogepant exposure by blocking hepatic uptake transporters. 1, 3
Contraindications and Safety Monitoring
- Hypersensitivity: QULIPTA is contraindicated in patients with a history of hypersensitivity to atogepant (e.g., anaphylaxis, dyspnea, rash, pruritus, urticaria, facial edema). 1
- Liver enzyme elevations: Transaminase elevations >3× the upper limit of normal occurred in 0.9% of atogepant-treated patients (vs. 1.2% placebo); all cases were asymptomatic and resolved within 8 weeks of discontinuation. 1
- Weight loss: 5.3% of patients on 60 mg experienced ≥7% body weight decrease; monitor weight in patients at risk. 1
Common Adverse Events
- The most common adverse reactions (≥4% and greater than placebo) are nausea (6–9%), constipation (6–8%), and fatigue/somnolence (4–5%). 1
- Discontinuation due to adverse events occurred in 0.6% for nausea, 0.5% for constipation, and 0.2% for fatigue/somnolence. 1
- Long-term safety data from a 52-week open-label trial showed that 67% of patients experienced treatment-emergent adverse events, most commonly upper respiratory tract infection (10.3%), constipation (7.2%), nausea (6.3%), and urinary tract infection (5.2%). 4
Efficacy Data
- In the phase 3 ADVANCE trial, atogepant 60 mg reduced mean monthly migraine days by 4.2 days (vs. 2.5 days for placebo), a difference of −1.7 days (95% CI −2.3 to −1.2; P<0.001). 5
- At 12 weeks, 61% of patients on 60 mg achieved ≥50% reduction in monthly migraine days (vs. 29% placebo). 5
- Long-term efficacy at 52 weeks showed 84.2% of patients achieved ≥50% reduction, 69.9% achieved ≥75% reduction, and 48.4% achieved 100% reduction in monthly migraine days. 4
Clinical Positioning in Treatment Algorithm
Reserve atogepant for patients who have failed or cannot tolerate at least one trial of a beta-blocker (propranolol 80–240 mg/day or metoprolol), topiramate (50–100 mg/day), valproate (800–1500 mg/day), amitriptyline (30–150 mg/day), or venlafaxine. 2
- The 2025 ACP guideline explicitly recommends using traditional oral preventives before CGRP antagonist-gepants because of large cost differences and lack of appreciable differences in prioritized outcomes (migraine frequency, disability, quality of life). 2
- Patient preference for oral over injectable medications supports atogepant over CGRP monoclonal antibodies when cost is not a barrier. 2
Critical Pitfalls to Avoid
- Do not prescribe atogepant as first-line preventive therapy unless all traditional oral agents are contraindicated or the patient has failed multiple prior preventives; cost-effectiveness data strongly favor traditional agents first. 2
- Do not combine atogepant with strong CYP3A4 inducers in chronic migraine patients; the combination is contraindicated due to inadequate exposure. 1
- Do not use atogepant in severe renal impairment for chronic migraine; it is contraindicated in this population. 1
- Do not overlook medication-overuse headache before initiating preventive therapy; acute medication use must be limited to ≤2 days per week to avoid paradoxical worsening. 2