For an adult patient with episodic or chronic migraine who has no severe hepatic impairment, no known hypersensitivity to atogepant, and is not taking strong CYP3A4 inhibitors, what are the recommended starting doses of Qulipta (atogepant), necessary safety precautions, and monitoring plan?

Qulipta (Atogepant) Dosing, Safety, and Monitoring for Migraine Prevention

Recommended Starting Doses

For episodic migraine (1–14 headache days/month), start atogepant 60 mg once daily; for chronic migraine (≥15 headache days/month), start atogepant 60 mg once daily. 1

Episodic Migraine Dosing Options

• 60 mg once daily is the FDA-approved standard dose, demonstrating the greatest reduction in monthly migraine days (mean difference -1.48 days vs. placebo, p<0.001) 2
• 30 mg once daily is an alternative dose that showed significant efficacy (mean difference -1.15 days vs. placebo) with a potentially lower side-effect burden 3
• 10 mg once daily is the lowest effective dose (mean difference -1.16 days vs. placebo) and may be preferred when tolerability is a primary concern 3

Chronic Migraine Dosing

• 60 mg once daily reduced mean monthly migraine days by -6.9 days (vs. -5.1 with placebo; adjusted p=0.0009) 4
• 30 mg twice daily (total 60 mg/day in divided doses) showed superior efficacy in chronic migraine, reducing mean monthly migraine days by -7.5 days (vs. -5.1 with placebo; adjusted p<0.0001) 4

Critical Dose Adjustments for Drug Interactions

With Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, ritonavir)

• Episodic migraine: Reduce dose to 10 mg once daily 1
• Chronic migraine: Avoid concomitant use entirely 1

With CYP3A4 Inducers (strong, moderate, or weak—including topiramate)

• Episodic migraine: Increase dose to 30 mg or 60 mg once daily 1
• Chronic migraine: Avoid concomitant use entirely 1

With OATP Inhibitors (e.g., single-dose rifampin, cyclosporine)

• Episodic migraine: Reduce dose to 10 mg or 30 mg once daily 1
• Chronic migraine: Reduce dose to 30 mg once daily 1

Absolute Contraindications

• Known hypersensitivity to atogepant (including anaphylaxis, dyspnea, rash, pruritus, urticaria, facial edema) 1
• Severe hepatic impairment (Child-Pugh C) 1

Most Common Adverse Events and Management

Expected Side Effects (Incidence ≥4% and Greater Than Placebo)

• Nausea: 6–9% (vs. 3% placebo) 1
• Constipation: 6–8% (vs. 2% placebo) 1
• Fatigue/somnolence: 4–5% (vs. 4% placebo) 1

Dose-Dependent Adverse Events

• Constipation is significantly more common with 30 mg (RR 5.19, p=0.001) and 60 mg (RR 4.92, p=0.001) compared to placebo 3
• Nausea is significantly more common with 60 mg (RR 2.73, p=0.001) compared to placebo 3

Serious but Rare Adverse Events

• Hypersensitivity reactions (including anaphylaxis) have been reported post-marketing; discontinue immediately if suspected 1
• Transaminase elevations >3× upper limit of normal occurred in 0.9% of atogepant-treated patients (vs. 1.2% placebo), were asymptomatic, and resolved within 8 weeks of discontinuation 1

Monitoring Plan

Baseline Assessment

• Liver function tests (ALT, AST, bilirubin) to establish baseline hepatic function 1
• Body weight to monitor for clinically significant weight loss 1
• Pregnancy status in women of childbearing potential (no adequate human data; animal studies showed decreased fetal weight and skeletal variations at exposures ≥3–4× human exposure) 1

Ongoing Monitoring

• Liver enzymes should be checked if symptoms of hepatotoxicity develop (jaundice, right upper quadrant pain, unexplained fatigue), though routine monitoring is not required based on clinical trial data 1
• Body weight at follow-up visits; 5.3% of patients on 60 mg experienced ≥7% weight decrease at any point during 12 weeks 1
• Efficacy assessment at 12 weeks: evaluate reduction in monthly migraine days using a prospective headache diary 5, 2

When to Discontinue

• Hypersensitivity reaction (immediate discontinuation required) 1
• Symptomatic liver injury (though none occurred in clinical trials) 1
• Inadequate response after 12 weeks (consider alternative preventive therapy) 5

Position in Treatment Algorithm

When to Initiate Atogepant as First-Line

• Significant migraine-related disability affecting quality of life 6
• Contraindications to traditional preventives (e.g., topiramate in women of childbearing potential, beta-blockers in asthma, valproate due to teratogenicity) 6

When to Consider After Other Preventives

• Intolerance or inadequate response to beta-blockers (propranolol, metoprolol), antiseizure medications (topiramate, valproate), angiotensin II-receptor blockers (candesartan), or tricyclic antidepressants (amitriptyline) 5, 6
• Chronic migraine when topiramate (the only oral medication with proven efficacy in chronic migraine) has failed or when onabotulinumtoxinA is not tolerated 6

Critical Pitfalls to Avoid

• Do not use atogepant with strong CYP3A4 inhibitors in chronic migraine patients—the drug interaction significantly increases atogepant exposure, and no safe dose has been established in this population 1
• Do not use atogepant with any CYP3A4 inducer in chronic migraine patients—efficacy will be substantially reduced 1
• Do not overlook medication-overuse headache—atogepant remains effective in patients with medication-overuse headache (80.6% reduction in monthly migraine days at 6 months), but acute medication use must still be limited to ≤2 days/week to prevent perpetuating the cycle 6, 5
• Do not prescribe atogepant in severe hepatic impairment—it is absolutely contraindicated 1

Expected Timeline for Efficacy

• Primary efficacy endpoint is change in mean monthly migraine days across 12 weeks of treatment 1, 2
• Sustained benefit was demonstrated throughout the 12-week treatment period in all pivotal trials 7, 4
• Reassess at 12 weeks; if inadequate response, consider dose adjustment (if not already on 60 mg) or alternative preventive therapy 5