Qulipta Drug Information
Generic name: ATOGEPANT
Calcitonin Gene-related Peptide Receptor Antagonist [EPC]
Uses of Qulipta
QULIPTA is indicated for the preventive treatment of migraine in adults.
Dosage & Administration of Qulipta
Recommended Dosage QULIPTA is taken orally with or without food. Episodic Migraine The recommended dosage of QULIPTA for episodic migraine is 10 mg, 30 mg, or 60 mg taken once daily.
Dosage
Modification s Dosage modifications and usage recommendations for episodic and chronic migraine with concomitant use of specific drugs and for patients with renal impairment are provided in Table 1. Table 1: Dos age Modifications for Drug Interactions and for Specific Populations Dosage Modifications Recommended Once Daily Dosage for Episodic Migraine Usage and Recommended Once Daily Dosage for Chronic Migraine Concomitant Drug Strong CYP3A4 Inhibitors Renal Impairment Severe Renal Impairment and End-Stage Renal Disease (CLcr <30 mL/min) 10 mg Not recommended a Coadministration decreases atogepant exposure. Monitor for reduced efficacy.
| Dosage Modifications | Recommended Once Daily Dosage for Episodic Migraine | Usage and Recommended Once Daily Dosage for Chronic Migraine |
|---|---|---|
| Concomitant Drug [see Drug Interactions ( 7 )] | ||
| Strong CYP3A4 Inhibitors ( 7.1 ) | 10 mg | 10 mg |
| Strong CYP3A4 Inducers ( 7.2 ) | 60 mg a | Not recommended |
| Moderate CYP3A4 Inducers ( 7.2 ) | 60 mg | Not recommended |
| Weak CYP3A4 Inducers ( 7.2 ) | 30 mg or 60 mg | 60 mg a |
| OATP Inhibitors ( 7.3 ) | 10 mg or 30 mg | 30 mg |
| Renal Impairment [see Use in Specific Populations ( 8 )] | ||
| Severe Renal Impairment and End-Stage Renal Disease (CLcr <30 mL/min) ( 8.6 ) | 10 mg | Not recommended |
Side Effects of Qulipta
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of QULIPTA was evaluated in 2657 patients with migraine who received at least one dose of QULIPTA. In the 12-week, placebo-controlled clinical studies Studies patients received at least one dose of QULIPTA 10 mg once daily, 411 patients received at least one dose of QULIPTA 30 mg once daily, 678 patients received at least one dose of QULIPTA 60 mg once daily, and 663 patients received placebo.
The mean age at study entry was 41 years (range 18 to 74 years). The most common adverse reactions (incidence at least 4% and greater than placebo) are nausea, constipation, and fatigue/somnolence. The adverse reactions that most commonly led to discontinuation of QULIPTA in these studies were nausea (0.6%), constipation (0.5%), and fatigue/somnolence (0.2%).
However, there were cases with transaminase elevations over 3 times the upper limit of normal that were temporally associated with QULIPTA treatment; these were asymptomatic and resolved within 8 weeks of discontinuation. There were no cases of severe liver injury or jaundice. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders: Hypersensitivity (e.g., anaphylaxis, dyspnea, rash, pruritus, urticaria, facial edema) Vascular Disorders: Hypertension, Raynaud’s phenomenon
| Placebo (N= 663 ) % | QULIPTA 10 mg (N=314) % | QULIPTA 30 mg (N=411) % | QULIPTA 60 mg (N= 678 ) % | |
|---|---|---|---|---|
| Nausea | 3 | 5 | 6 | 9 |
| Constipation | 2 | 6 | 6 | 8 |
| Fatigue/Somnolence | 4 | 4 | 4 | 5 |
| Decreased Appetite | <1 | 2 | 1 | 3 |
| Dizziness | 2 | 2 | 2 | 3 |
Warnings & Cautions for Qulipta
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, dyspnea, rash, pruritus, urticaria, and facial edema, have been reported with use of QULIPTA. Hypersensitivity reactions can occur days after administration. If a hypersensitivity reaction occurs, discontinue QULIPTA and institute appropriate therapy. 5. 2 Hyper tension Development of hypertension and worsening of pre-existing hypertension have been reported following the use of CGRP antagonists, including QULIPTA, in the postmarketing setting.
Some of the patients who developed new-onset hypertension had risk factors for hypertension. There were cases requiring initiation of pharmacological treatment for hypertension and, in some cases, hospitalization. Hypertension may occur at any time during treatment, but was most frequently reported within 7 days of therapy initiation.
QULIPTA was discontinued in many of the reported cases. Monitor patients treated with QULIPTA for new-onset hypertension, or worsening of pre-existing hypertension, and consider whether discontinuation of QULIPTA is warranted if evaluation fails to establish an alternative etiology or blood pressure is inadequately controlled. 5. 3 Raynaud’s Phenomenon Development of Raynaud’s phenomenon and recurrence or worsening of pre-existing Raynaud’s phenomenon have been reported in the postmarketing setting following the use of CGRP antagonists, including QULIPTA. In reported cases with small molecule CGRP antagonists, symptom onset occurred a median of 1.5 days following dosing.
Many of the cases reported serious outcomes, including hospitalizations and disability, generally related to debilitating pain. In most reported cases, discontinuation of the CGRP antagonist resulted in resolution of symptoms. QULIPTA should be discontinued if signs or symptoms of Raynaud’s phenomenon develop, and patients should be evaluated by a healthcare provider if symptoms do not resolve.
Patients with a history of Raynaud’s phenomenon should be monitored for, and informed about the possibility of, worsening or recurrence of signs and symptoms.
Drug Interactions with Qulipta
CYP3A4 Inhibitors Coadministration of QULIPTA with itraconazole, a strong CYP3A4 inhibitor, resulted in a significant increase in exposure of atogepant in healthy subjects. The recommended dosage of QULIPTA with concomitant use of strong CYP3A4 inhibitors is 10 mg once daily. No dosage adjustment of QULIPTA is needed with concomitant use of moderate or weak CYP3A4 inhibitors.
CYP3A4 Inducers Coadministration of QULIPTA with steady-state rifampin, a strong CYP3A4 inducer and OATP1B1 and OATP1B3 inhibitor, resulted in a significant decrease in exposure of atogepant in healthy subjects. Concomitant administration of QULIPTA with moderate inducers of CYP3A4 can also result in decreased exposure of atogepant. Coadministration of QULIPTA with steady-state topiramate, a weak CYP3A4 inducer, resulted in decreased exposure of atogepant in healthy subjects.
For episodic migraine, the recommended dosage of QULIPTA with concomitant use of strong or moderate CYP3A4 inducers is 60 mg once daily. During concomitant use of QULIPTA with strong CYP3A4 inducers, monitor monthly for signs of reduced efficacy, and consider alternative therapies if a reduction in efficacy is observed. The recommended dosage of QULIPTA with concomitant use of weak CYP3A4 inducers is 30 mg or 60 mg once daily.
For chronic migraine, concomitant use of strong or moderate CYP3A4 inducers with QULIPTA is not recommended. Monitor monthly for signs of reduced efficacy, and consider alternative therapies if a reduction in efficacy is observed. 7.3 OATP Inhibitors Coadministration of QULIPTA with single dose rifampin, an OATP inhibitor, resulted in a significant increase in exposure of atogepant in healthy subjects. For episodic migraine, the recommended dosage of QULIPTA with concomitant use of OATP inhibitors is 10 mg or 30 mg once daily.
Pregnancy Safety for Qulipta
Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while taking QULIPTA. Patients should be encouraged to enroll by calling 1-833-277-0206 or visiting http://empresspregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of QULIPTA in pregnant women.
In animal studies, oral administration of atogepant during the period of organogenesis (rats and rabbits) or throughout pregnancy and lactation (rats) resulted in adverse developmental effects (decreased fetal and offspring body weight in rats; increased incidence of fetal structural variations in rabbits) at exposures greater than those used clinically. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The estimated rate of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy. Data Animal Data Oral administration of atogepant mg/kg/day to pregnant rats during the period of organogenesis resulted in decreases in fetal body weight and in skeletal ossification at the two highest doses tested (125 and 750 mg/kg), which were not associated with maternal toxicity. At the no-effect dose (15 mg/kg/day) for adverse effects on embryofetal development, plasma exposure (AUC) was approximately 4 times that in humans at the maximum recommended human dose (MRHD) of 60 mg/day.
Oral administration of atogepant mg/kg/day to pregnant rabbits during the period of organogenesis resulted in an increase in fetal visceral and skeletal variations at the highest dose tested (130 mg/kg/day), which was associated with minimal maternal toxicity. Oral administration of atogepant mg/kg/day to rats throughout gestation and lactation resulted in decreased pup body weight at the highest dose tested (125 mg/kg/day), which persisted into adulthood. At the no-effect dose (45 mg/kg/day) for adverse effects on pre- and postnatal development, plasma exposure (AUC) was approximately 5 times that in humans at the MRHD.
Pediatric Use of Qulipta
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for Qulipta
QULIPTA is contraindicated in patients with a history of hypersensitivity to atogepant or any of the components of QULIPTA. Reactions have included anaphylaxis and dyspnea.
Clinical Studies of Qulipta
Episodic Migraine
The efficacy of QULIPTA for the preventive treatment of episodic migraine in adults was demonstrated in two randomized, multicenter, double-blind, placebo-controlled studies (Study 1 and Study 2). The studies enrolled patients with at least a 1-year history of migraine with or without aura, according to the International Classification of Headache Disorders (ICHD-3) diagnostic criteria. In both studies, patients were allowed to use acute headache treatments (i.e., triptans, ergotamine derivatives, NSAIDs, acetaminophen, and opioids) as needed.
The use of a concomitant medication that acts on the CGRP pathway was not permitted for either acute or preventive treatment of migraine. The studies excluded patients with myocardial infarction, stroke, or transient ischemic attacks within six months prior to screening. Study 1 The primary efficacy endpoint was the change from baseline in mean monthly migraine days (MMD) across the 12-week treatment period.
Secondary endpoints included the change from baseline in mean monthly headache days, the change from baseline in mean monthly acute medication use days, the proportion of patients achieving at least a 50% reduction from baseline in mean MMD (3-month average), the change from baseline in mean monthly Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities (PDA) domain scores, the change from baseline in mean monthly AIM-D Physical Impairment (PI) domain scores, across the 12-week treatment period, and the change from baseline at Week 12 for Migraine Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR) domain scores. The AIM-D evaluates difficulty with performance of daily activities (PDA domain) and physical impairment (PI domain) due to migraine, with scores ranging from 0 to 100. Higher scores indicate greater impact of migraine, and reductions from baseline indicate improvement.
The MSQ v2.1 Role Function-Restrictive (RFR) domain score assesses how often migraine impacts function related to daily social and work-related activities over the past 4 weeks, with scores ranging from 0 to 100. Higher scores indicate lesser impact of migraine on daily activities, and increases from baseline indicate improvement. The mean migraine frequency at baseline was approximately 8 migraine days per month and was similar across treatment groups.
A total of 805 (88%) patients completed the 12-week double-blind study period. Key efficacy results of Study 1 are summarized in Table 3. Patients treated with QULIPTA had greater mean decreases from baseline in MMD across the 12-week treatment period compared to patients who received placebo.
Figure 1: Change from Baseline in Monthly Migraine Days in Study 1 Figure 2 shows the distribution of change from baseline in mean MMD across the 12-week treatment period, in 2-day increments, by treatment group. A treatment benefit over placebo for all doses of QULIPTA is seen across a range of mean changes from baseline in MMD. A total of 541 (83%) patients completed the 12-week double-blind study period.
In Study 2, there was a significantly greater reduction in mean monthly migraine days across the 12-week treatment period in all three QULIPTA treatment groups, compared with placebo, as summarized in Table 4.
Chronic Migraine Study 3
The efficacy of QULIPTA for the preventive treatment of chronic migraine in adults was demonstrated in a randomized, multicenter, double-blind, placebo-controlled study (Study 3). A subset of patients (11%) was allowed to use one concomitant migraine preventive medication. Patients with medication overuse headache also were enrolled.
A total of 463 (89%) of these patients completed the 12-week double-blind study period. Table 5: Efficacy Endpoints in Study 3 Migraine Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive domain score Activity Impairment in Migraine-Diary Performance of Daily Activities domain score Activity Impairment in Migraine-Diary Physical Impairment domain score Figure 5 shows the mean change from baseline in MMD in Study 3. Figure 6: Distribution of Change from Baseline in Mean Monthly Migraine Days by Treatment Group in Study 3
| QULIPTA 10 mg N= 214 | QULIPTA 30 mg N= 223 | QULIPTA 60 mg N= 222 | Placebo N= 214 | |
|---|---|---|---|---|
| Monthly Migraine Days (MMD) across 12 weeks | ||||
| Baseline | 7.5 | 7.9 | 7.8 | 7.5 |
| Mean change from baseline | -3.7 | -3.9 | -4.2 | -2.5 |
| Difference from placebo | -1.2 | -1.4 | -1.7 | |
| p -value | <0.001 | <0.001 | <0.001 | |
| Monthly Headache Days across 12 weeks | ||||
| Baseline | 8.4 | 8.8 | 9.0 | 8.4 |
| Mean change from baseline | -3.9 | -4.0 | -4.2 | -2.5 |
| Difference from placebo | -1.4 | -1.5 | -1.7 | |
| p -value | <0.001 | <0.001 | <0.001 | |
| Monthly Acute Medication Use Days across 12 weeks | ||||
| Baseline | 6.6 | 6.7 | 6.9 | 6.5 |
| Mean change from baseline | -3.7 | -3.7 | -3.9 | -2.4 |
| Difference from placebo | -1.3 | -1.3 | -1.5 | |
| p -value | <0.001 | <0.001 | <0.001 | |
| ≥ 50% MMD Responders across 12 weeks | ||||
| % Responders | 56 | 59 | 61 | 29 |
| Difference from placebo (%) | 27 | 30 | 32 | |
| p -value | <0.001 | <0.001 | <0.001 | |
| MSQ v2.1 RFR Domain* at week 12 | ||||
| Baseline | 44.9 | 44.0 | 46.8 | 46.8 |
| Mean change from baseline | 30.4 | 30.5 | 31.3 | 20.5 |
| Difference from placebo | 9.9 | 10.1 | 10.8 | |
| p -value | <0.001 | <0.001 | <0.001 | |
| AIM-D PDA Domain* across 12 weeks | ||||
| Baseline | 15.5 | 16.9 | 15.9 | 15.2 |
| Mean change from baseline | -7.3 | -8.6 | -9.4 | -6.1 |
| Difference from placebo | -1.2 | -2.5 | -3.3 | |
| p -value | NS | <0.001 | <0.001 | |
| AIM-D P I Domain* across 12 weeks | ||||
| Baseline | 11.7 | 13.0 | 11.6 | 11.2 |
| Mean change from baseline | -5.1 | -6.0 | -6.5 | -4.0 |
| Difference from placebo | -1.1 | -2.0 | -2.5 | |
| p -value | NS | 0.002 | <0.001 | |
| Migraine Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive domain score Activity Impairment in Migraine-Diary Performance of Daily Activities domain score Activity Impairment in Migraine-Diary Physical Impairment domain score Not statistically significant (NS) | ||||
| QULIPTA 10 mg N=92 | QULIPTA 30 mg N=182 | QULIPTA 60 mg N=177 | Placebo N=178 | |
|---|---|---|---|---|
| Monthly Migraine Days (MMD) across 12 weeks | ||||
| Baseline | 7.6 | 7.6 | 7.7 | 7.8 |
| Mean change from baseline | -4.0 | -3.8 | -3.6 | -2.8 |
| Difference from placebo | -1.1 | -0.9 | -0.7 | |
| p -value | 0.024 | 0.039 | 0.039 | |
| Monthly Headache Days across 12 weeks | ||||
| Baseline | 8.9 | 8.7 | 8.9 | 9.1 |
| Mean change from baseline | -4.3 | -4.2 | -3.9 | -2.9 |
| Difference from placebo | -1.4 | -1.2 | -0.9 | |
| p -value | 0.024 | 0.039 | 0.039 | |
| QULIPTA 60 mg QD N= 256 | Placebo N= 246 | |
|---|---|---|
| Monthly Migraine Days (MMD) across 12 weeks | ||
| Baseline | 19.2 | 18.9 |
| Mean change from baseline | -6.9 | -5.1 |
| Difference from placebo | -1.8 | |
| p -value | <0.001 | |
| Monthly Headache Days across 12 weeks | ||
| Baseline | 21.5 | 21.4 |
| Mean change from baseline | -7.0 | -5.1 |
| Difference from placebo | -1.9 | |
| p -value | <0.001 | |
| Monthly Acute Medication Use Days across 12 weeks | ||
| Baseline | 15.5 | 15.4 |
| Mean change from baseline | -6.2 | -4.1 |
| Difference from placebo | -2.1 | |
| p -value | <0.001 | |
| ≥ 50% MMD Responders across 12 weeks | ||
| % Responders | 41 | 26 |
| Difference from placebo (%) | 15 | |
| p -value | <0.001 | |
| MSQ v2.1 RFR Domain* at week 12 | ||
| Baseline | 43.4 | 43.9 |
| Mean change from baseline | 23.3 | 17.2 |
| Difference from placebo | 6.2 | |
| p -value | <0.001 | |
| AIM-D PDA Domain* across 12 weeks | ||
| Baseline | 31.2 | 29.5 |
| Mean change from baseline | -12.8 | -9.4 |
| Difference from placebo | -3.4 | |
| p -value | <0.001 | |
| AIM-D P I Domain* across 12 weeks | ||
| Baseline | 27.1 | 25.2 |
| Mean change from baseline | -10.6 | -7.9 |
| Difference from placebo | -2.7 | |
| p -value | 0.003 | |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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