Introduction
Qulipta (atogepant) is an oral calcitonin gene-related peptide (CGRP) receptor antagonist approved by the FDA in September 2021 for the preventive treatment of episodic migraine in adults. It represents a novel class of migraine prevention medications that specifically target the CGRP pathway, which plays a crucial role in migraine pathophysiology.
Mechanism of Action
Atogepant is a potent, selective, and competitive antagonist of the human calcitonin gene-related peptide (CGRP) receptor. CGRP is a neuropeptide released during migraine attacks that causes vasodilation and promotes neurogenic inflammation. By blocking CGRP binding to its receptor, atogepant inhibits the CGRP-mediated pathophysiology of migraine, including vasodilation of cerebral and dural blood vessels, neurogenic inflammation, and pain signal transmission.
Indications
Qulipta is indicated for the preventive treatment of episodic migraine in adults. Episodic migraine is defined as headaches occurring on fewer than 15 days per month. The medication is not indicated for the acute treatment of migraine attacks.
Dosage and Administration
The recommended dosage is 10 mg, 30 mg, or 60 mg taken orally once daily with or without food. The appropriate dosage should be individualized based on patient response and tolerability.
Special Populations:- Renal impairment: Not recommended in severe renal impairment (CrCl <30 mL/min)
- Hepatic impairment: Not recommended in patients with severe hepatic impairment (Child-Pugh C)
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of 1-2 hours. Bioavailability is approximately 60% without food effect. Distribution: Mean apparent volume of distribution is approximately 292 L. Protein binding is approximately 93-95%. Metabolism: Primarily metabolized by CYP3A4 with minor contributions from CYP2D6. The major circulating component is unchanged atogepant. Elimination: Mean elimination half-life is approximately 11 hours. Approximately 42% of the dose is excreted in urine and 5% in feces as metabolites.Contraindications
- History of hypersensitivity to atogepant or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors
Warnings and Precautions
Hepatotoxicity: Monitor liver enzymes before starting treatment and periodically during treatment. Discontinue if clinical signs or symptoms of liver injury develop. Constipation: May cause constipation with complications including hospitalization. Monitor patients, especially those with underlying constipation. Hypersensitivity Reactions: Angioedema and urticaria have been reported. Discontinue if hypersensitivity reactions occur. Pregnancy: Based on animal data, may cause fetal harm. Advise women of reproductive potential of potential risk.Drug Interactions
Strong CYP3A4 Inhibitors: Contraindicated (e.g., clarithromycin, itraconazole, ritonavir) Moderate CYP3A4 Inhibitors: Reduce Qulipta dose to 10 mg once daily (e.g., erythromycin, verapamil) Strong CYP3A4 Inducers: Avoid concomitant use (e.g., rifampin, carbamazepine, St. John's wort) OATP Inhibitors: Use with caution with drugs that inhibit OATP (e.g., cyclosporine)Adverse Effects
Most common adverse reactions (≥4% and greater than placebo):- Nausea (6% vs 3% placebo)
- Constipation (6% vs 1% placebo)
- Fatigue (4% vs 2% placebo)
- Somnolence (4% vs 2% placebo)
- Hepatotoxicity
- Severe constipation
- Hypersensitivity reactions
Monitoring Parameters
- Migraine frequency and severity
- Liver function tests (baseline and periodically)
- Bowel function and signs of constipation
- Signs of hypersensitivity reactions
- Renal function in patients with renal impairment
- Pregnancy status in women of reproductive potential
Patient Education
- Take Qulipta exactly as prescribed, once daily
- May take with or without food
- Report any signs of liver problems (yellowing skin/eyes, dark urine, abdominal pain)
- Report severe constipation or changes in bowel habits
- Inform healthcare provider of all medications being taken
- Use effective contraception during treatment
- Not for acute migraine treatment
- May cause drowsiness or fatigue; use caution when driving or operating machinery
References
1. Goadsby PJ, et al. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol. 2020;19(9):727-737. 2. Ailani J, et al. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021;385(8):695-706. 3. Qulipta [package insert]. AbbVie Inc.; 2021. 4. Dodick DW. CGRP ligand and receptor monoclonal antibodies for migraine prevention: Evidence review and clinical implications. Cephalalgia. 2019;39(3):445-458. 5. FDA Approval: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215206s000lbl.pdf
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.