Atogepant (Monograph)

Brand name: Qulipta
Drug class: Calcitonin Gene-related Peptide (CGRP) Antagonists

Medically reviewed by Drugs.com on Feb 10, 2024. Written by ASHP.

Introduction

Antimigraine agent; a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist.

Uses for Atogepant

Preventive Treatment of Episodic Migraine

Preventive treatment of episodic migraine in adults.

Current consensus statement from the American Headache Society (AHS) discusses the evidence for atogepant in the preventive treatment of episodic migraines. AHS states that treatment plans involving the preventive use of "gepants" should be based on regimens used in clinical trials and individualized according to the needs of each patient. Repeated treatment with these drugs does not appear to be associated with medication overuse headache or liver toxicity.

Preventive Treatment of Chronic Migraine

Preventive treatment of chronic migraine in adults.

Although the current consensus statement from the AHS does not discuss the specific evidence for use of atogepant in the preventive treatment of chronic migraines, AHS states that treatment plans involving the preventive use of the "gepant" class of medications should be based on regimens used in clinical trials and individualized according to the needs of each patient.

Atogepant Dosage and Administration

Administration

Oral Administration

Administer orally without regard to food.

Dosage

Adults

Preventive Treatment of Episodic Migraine

Oral

10, 30, or 60 mg once daily. Use lowest effective dosage.

If concomitant use with a strong CYP3A4 inhibitor (e.g., itraconazole) is necessary, the manufacturer recommends an atogepant dosage of 10 mg once daily.

If concomitant use with a CYP3A4 inducer (e.g., rifampin) is necessary, the manufacturer recommends an atogepant dosage of 30 or 60 mg once daily.

If concomitant use with an OATP inhibitor is necessary, the manufacturer recommends an atogepant dosage of 10 or 30 mg once daily.

Preventive Treatment of Chronic MIgraine

Oral

60 mg once daily.

Avoid concomitant use with a strong CYP3A4 inhibitor (e.g., itraconazole).

Avoid concomitant use with a CYP3A4 inducer (e.g., rifampin).

If concomitant use with an OATP inhibitor is necessary, the manufacturer recommends an atogepant dosage of 30 mg once daily.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe hepatic impairment (Child-Pugh class C): Avoid use.

Renal Impairment

Mild or moderate renal impairment (Cl_cr 30–89 mL/minute): No dosage adjustment necessary.

Severe renal impairment (Cl_cr 15–29 mL/minute) or end-stage renal disease (Cl_cr <15 mL/minute): For prevention of episodic migraine, recommended dosage is 10 mg once daily. For patients with end-stage renal disease undergoing intermittent dialysis, manufacturer states that it is preferable to administer atogepant after dialysis. Avoid use of atogepant for prevention of chronic migraine.

Geriatric Patients

Select dosage with caution, usually starting at the low end of the dosage range.

Cautions for Atogepant

Contraindications

Hypersensitivity to atogepant or any of the inactive ingredients in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, dyspnea, rash, pruritus, urticaria, and facial edema, reported. Can occur days after administration.

Discontinue atogepant and institute appropriate therapy if a hypersensitivity reaction occurs.

Specific Populations

Pregnancy

No adequate data on developmental risk associated with use of atogepant in pregnant women. Based on animal studies, may cause fetal harm. Adverse effects on embryofetal development (e.g., decreased fetal and offspring body weight, increased fetal structural variations) observed in animals at dosages higher than those used clinically.

Possible increased risk of preeclampsia and gestational hypertension during pregnancy in women with migraine.

Lactation

Not known whether distributed into human milk; distributed into milk in rats. Effects on the breast-fed infant and on milk production not known. Consider known benefits of breast-feeding along with mother's clinical need for atogepant and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Clinically important pharmacokinetic differences not observed between geriatric and younger individuals.

Select dosage with caution, usually starting at the low end of the dosage range.

Hepatic Impairment

Exposure is increased in patients with hepatic impairment.

Dosage adjustment not necessary in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Avoid use in patients with severe (Child-Pugh class C) hepatic impairment.

Renal Impairment

Pharmacokinetics not substantially altered in patients with mild or moderate renal impairment (Cl_cr 30–89 mL/minute); dosage adjustment not necessary.

Not studied in patients with severe renal impairment (Cl_cr 15–29 mL/minute) or end-stage renal disease (Cl_cr <15 mL/minute). Recommended dosage is 10 mg once daily for prevention of episodic migraine in patients with severe renal impairment or end-stage renal disease. Avoid use in patients with severe renal impairment or end-stage renal disease for prevention of chronic migraine.

Common Adverse Effects

Common adverse reactions (≥4%) include nausea, constipation, fatigue/somnolence.

Drug Interactions

Metabolized principally by CYP3A4.

In vitro, does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4; monoamine oxidase-A (MAO-A); or uridine diphosphate-glucuronosyltransferase (UGT) 1A1 at clinically relevant concentrations. Does not induce CYP1A2, 2B6, or 3A4 at clinically relevant concentrations.

In vitro, substrate of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1 and 1B3, and organic anion transporter (OAT) 1; not a substrate of OAT3, organic cation transporter (OCT) 2, or multidrug and toxic compound extrusion (MATE) 1. In vitro, weak inhibitor of OATP1B1, OATP1B3, OCT2, and MATE1; not expected to be clinically important. In vitro, does not inhibit P-gp, BCRP, bile salt export pump (BSEP), multidrug resistance protein (MRP) 3, MRP4, OAT1, OAT3, or sodium taurocholate cotransporting polypeptide (NTCP).

Drugs and Foods Affecting Hepatic Microsomal Enzymes

Strong CYP3A4 inhibitors: Potential increased exposure to atogepant. Recommended atogepant dosage is 10 mg once daily during concomitant use for the prevention of episodic migraine. Avoid concomitant use of strong CYP3A4 inhibitors in patients recieving atogepant for prevention of chronic migraine.

Moderate CYP3A4 inhibitors or weak CYP3A4 inhibitors : No dosage adjustment is necessary.

Strong, moderate, or weak CYP3A4 inducers: Possible decreased exposure to atogepant. Recommended atogepant dosage is 30 or 60 mg once daily during concomitant use for prevention of episodic migraine. Avoid concomitant use of strong, moderate, or weak CYP3A4 inducers in patients receiving atogepant for prevention of chronic migraine.

OATP Inhibitors

Potential pharmacokinetic interaction (increased serum atogepant concentrations). Recommended atogepant dosage is 10 or 30 mg once daily during concomitant use for prevention of episodic migraine. Recommended atogepant dosage is 30 mg once daily for the prevention of chronic migraine.

Specific Drugs

Drug	Interaction	Comments
Itraconazole	Possible increased systemic exposure to atogepant Increased peak plasma concentration and exposure to atopegant by 2.15- and 5.5-fold, respectively	Itraconazole: Recommended atogepant dosage to prevent episodic migraine is 10 mg once daily Avoid use with atogepant to prevent episodic migraine
Quinidine	Increased peak plasma concentration and exposure to atogepant by 4 and 26%, respectively, in healthy individuals	Interaction not expected to be clinically important; dosage adjustment of atogepant not necessary
Rifampin	Steady-state rifampin: Decreased peak plasma concentration and exposure to atopegant by approximately 30 and 60%, respectively Single-dose rifampin: Increased peak plasma concentration and exposure to atogepant by 2.23- and 2.85-fold, respectively	Recommended atogepant dosage is 30 or 60 mg once daily Avoid use with atogepant to prevent chronic migraine
Topiramate	Decreased peak plasma concentrations and exposure of atogepant by 24 and 25%, respectively; no clinically significant changes in the pharmacokinetics of topiramate

Atogepant Pharmacokinetics

Absorption

Bioavailability

Exhibits dose-proportional pharmacokinetics within the recommended dosage range.

Rapidly absorbed; peak plasma concentrations occur approximately 1–2 hours following oral administration.

Food

High-fat meal decreased peak plasma concentration and AUC by 22 and 18%, respectively, but did not affect the median time to peak concentration.

Special Populations

Mild hepatic impairment (Child-Pugh class A): Exposure increased by 24%.

Moderate hepatic impairment (Child-Pugh class B): Exposure increased by 15%.

Severe hepatic impairment (Child-Pugh class C): Exposure increased by 38%.

Mild or moderate renal impairment (Cl_cr 30–89 mL/minute): Pharmacokinetics not substantially affected.

Severe renal impairment (Cl_cr 15–29 mL/minute) or end-stage renal disease (Cl_cr <15 mL/minute): Not studied.

Age, sex, race, and body weight do not substantially affect pharmacokinetics.

Distribution

Extent

Not known whether distributed into human milk.

Plasma Protein Binding

95%.

Elimination

Metabolism

Eliminated mainly through metabolism, primarily by CYP3A4. Parent compound and a glucuronide conjugate metabolite are most prevalent circulating components in human plasma.

Elimination Route

Excreted mainly by the biliary/fecal route; renal route is a minor route of elimination. Following a single oral dose, eliminated in feces (42%) and urine (5%) as unchanged drug.

Half-life

Approximately 11 hours.

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15–30°C).

Actions

Small molecule calcitonin gene-related peptide (CGRP) receptor antagonist (sometimes referred to as a gepant); binds to CGRP receptors with high affinity, blocking the binding of CGRP to the receptor and preventing subsequent receptor activation.
CGRP is a potent vasodilator and pain-signaling neuropeptide that has been associated with migraine pathophysiology. CGRP and its receptors are located at sites that are relevant to migraine development such as the trigeminal neurons and are also widely distributed throughout the central and peripheral nervous systems as well as in nonneuronal tissues throughout the body.
Increased serum CGRP concentrations observed in individuals during acute migraine attacks; serum CGRP concentrations return to normal after resolution of the migraine. IV infusion of CGRP induces migraines in patients with a history of migraine.
Unlike 5-HT₁ receptor agonists (triptans), CGRP receptor antagonists do not appear to cause vasoconstriction. Atogepant does not appear to prolong the QT interval in dosages up to 5 times the maximum recommended daily dosage.

Advice to Patients

Inform patients about the risk of hypersensitivity reactions and possible signs and symptoms of such reactions. Advise patients to discontinue atogepant and seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction.
Inform patients that atogepant may interact with certain other drugs. Advise patients to inform their clinician about concomitant use of any prescription and OTC drugs and dietary or herbal supplements (e.g., St. John's wort) as well as any concomitant illnesses (e.g., hepatic or renal disease).
Importance of women informing clinicians if they are or plan to become pregnant or are breast-feeding or plan to breast-feed.
Importance of informing patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.