Safety and Efficacy of Calcitonin Gene-related Peptide Receptor Antagonists and Selective Serotonin Receptor Agonist in the Management of Migraine: A Systematic Review and Meta-analysis.

BACKGROUND: Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far. METHODS: The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia). RESULTS: The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan. CONCLUSION: The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.

LC-HRMS and NMR studies for the characterization of degradation impurities of ubrogepant along with the in silico approaches for the prediction of degradation and toxicity.

Ubrogepant is the first oral calcitonin gene-related peptide (CGRP) receptor antagonist which is used for the acute treatment of migraine in adults. The present study employs liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance spectroscopy (NMR) techniques for the identification and characterization of degradation impurities of ubrogepant. The forced degradation study of ubrogepant was performed as per the International Council for Harmonisation (ICH) Q1A and Q1B guidelines. The in silico degradation profile of ubrogepant was predicted by Zeneth. It was observed that ubrogepant was labile to acidic hydrolysis, basic hydrolysis, and oxidative degradation conditions (H2O2), although it was stable in neutral hydrolysis and photolytic (UV light and visible light) conditions. Eight degradation impurities were formed, which were separated on reversed-phase HPLC with a gradient program on an InertSustain C8 column (4.6 × 250 mm, 5 µm) using 10 mM ammonium formate (pH unadjusted) and acetonitrile as the mobile phase. The structures of all the degradation impurities were characterized using the exact masses obtained from the HRMS/MS. Further, NMR studies were conducted on two major degradation impurities (UB-4 and UB-7). A plausible mechanism was proposed to support the structures of all the degradation impurities of UBR. In silico toxicity and mutagenicity assessment were done by DEREK Nexus, SARAH Nexus, and ProTox-II.

CGRP receptor antagonists (gepants).

Small molecule calcitonin gene-related peptide (CGRP) receptor antagonists are commonly referred to as gepants. The first generation of gepants provided the first line of evidence of CGRP-mediated antimigraine medication in 2004-2011. However, further development was halted due to either lack of oral availability or concerns of hepatotoxicity. More than 15 years later, the first second generation of gepants, ubrogepant and rimegepant, are now approved for the acute treatment of migraine with or without aura. Furthermore, a novel and promising third-generation gepant, zavegepant, has recently been approved as well. In this chapter, we review the evidence supporting the effectiveness, safety, and tolerability of gepants for the acute treatment of migraine. Furthermore, we discuss the potential limitations and future directions of this class of migraine-specific medication.

Pharmacokinetics of Ubrogepant in Healthy Japanese and White Adults.

Ubrogepant is a calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults. The objectives of this study were to evaluate (1) single-dose pharmacokinetics (PK) and dose proportionality of ubrogepant in Japanese participants, (2) the safety and tolerability of ubrogepant in healthy Japanese and White participants, and (3) to compare the PK of ubrogepant in Japanese versus White participants. A total of 48 participants were enrolled into 4 cohorts (N = 12 [9 active + 3 placebo] per cohort). A single dose was administered on Day 1 following an overnight fast to assess the PK of ubrogepant at 3 dose levels and test dose proportionality between 25 and 100 mg in Japanese participants. White participants were randomly assigned to ubrogepant (100 mg) or placebo. Dose proportionality was observed in the dose range of 25-100 mg in Japanese participants. Systemic exposure was 20% lower in Japanese participants as compared with White participants, but this difference is unlikely to be clinically relevant. Single doses of ubrogepant (25-100 mg) had a safety profile similar to placebo, and no differences in the safety profile of ubrogepant 100 mg were observed between Japanese versus White participants.

Nueva era terapéutica para el ataque de migraña con los recientemente aprobados anticuerpos monoclonales, ditanes y gepantes / New therapeutic era for migraine attacks with recently approved monoclonal antibodies, ditans and gepants

El tratamiento de los ataques de migraña se aconseja en todos los pacientes, utilizando antiinflamatorios no esteroideos cuando el dolor es leve y triptanes cuando la intensidad del dolor es moderada-grave. Sin embargo, la efectividad de estos fármacos es modesta, un porcentaje elevado de pacientes presenta efectos secundarios y los triptanes están contraindicados en las personas con antecedentes de ictus, cardiopatía isquémica o hipertensión mal controlada. Por tanto, es imprescindible disponer de nuevas alternativas terapéuticas. En los últimos años han ido apareciendo nuevos fármacos para los ataques de migraña, entre los que destacan los ditanes (lasmiditán) y los gepantes (ubrogepant y rimegepant). Por otro lado, el eptinezumab, que ha sido aprobado para el tratamiento preventivo de la migraña en adultos, se ha utilizado también para los ataques de migraña. En este manuscrito se revisan los resultados de eficacia y seguridad de los nuevos fármacos para los ataques de migraña que se comercializarán próximamente. (AU)

Treatment of migraine attacks is advised in all patients, using non-steroidal anti-inflammatory drugs when the pain is mild and triptans when the pain intensity is moderate-severe. However, the effectiveness of these drugs is moderate, a high percentage of patients have side effects, and triptans are contraindicated in people with a history of stroke, ischaemic heart disease or poorly controlled hypertension. Hence, there is an urgent need for new therapeutic alternatives. In recent years, new drugs for migraine attacks have become available, most notably ditans (lasmiditan) and gepants (ubrogepant and rimegepant). Furthermore, eptinezumab, which has been approved for the preventive treatment of migraine in adults, has also been used for migraine attacks. This manuscript reviews the efficacy and safety results of the new drugs for migraines that will soon be on the market. (AU)

Evaluating Ubrogepant-related adverse events using the FDA adverse event reporting system.

BACKGROUND: Migraine has a high prevalence in the population and accounts for 12% of primary headaches. Ubrogepant is used for the treatment of acute migraine, and although some clinical trials have demonstrated the safety of Ubrogepant, its long-term safety in a large sample of the population remains to be investigated. METHODS: We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC) and the empirical Bayes geometric mean (EBGM) to evaluate Ubrogepant-induced adverse events (AEs). RESULTS: We screened out 2,067 reports of Ubrogepant as primary suspected (PS) and 6,190 reports of Ubrogepant-induced AEs as PS. Our results showed that Ubrogepant-induced AEs targeted 4 system organ classes (SOCs), detected 32 Preferred terms (PTs) signals in 9 SOCs, including common Ubrogepant label consistent with Migraine, Nausea, Somnolence, Paraesthesia oral and Dizziness, It also includes the AEs of Hemiparesis, Mental impairment, Dysstasia, Tinnitus, Chest pain, Cold sweat, Neck pain, etc. that have not been demonstrated in previous studies. CONCLUSIONS: Our study identified new AEs that have not been reported, which provides a new guidance to deepen the comprehension of the safety of Ubrogepant.

Real-World Use of Ubrogepant as Acute Treatment for Migraine with an Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody: Results from COURAGE.

INTRODUCTION: Although acute and preventive treatments for migraine are commonly given in combination, data on the real-world effectiveness of ubrogepant as an acute treatment when used with an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (with or without onabotulinumtoxinA) are limited. This analysis sought to evaluate the real-world effectiveness, treatment satisfaction, and optimization of ubrogepant for the acute treatment of migraine when used in combination with an anti-CGRP monoclonal antibody, with or without concomitant onabotulinumtoxinA. METHODS: This prospective, multiple-attack, open-label, observational study (COURAGE) assessed meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization of ubrogepant (50 or 100 mg) when combined with an anti-CGRP monoclonal antibody, onabotulinumtoxinA, or both in adult users of Migraine Buddy, a migraine tracking application. RESULTS: In the ubrogepant and anti-CGRP monoclonal antibody arm (n = 245), following the first ubrogepant-treated attack, 61.6% (151/245) and 80.4% (197/245) of ubrogepant-treated participants achieved MPR at 2 and 4 h post-dose, respectively, and 34.7% (85/245) and 55.5% (136/245) achieved RNF at 2 and 4 h post-dose, respectively. Across up to 10 ubrogepant-treated attacks (N = 1153), MPR was achieved in 51.3% (592/1153) and 73.5% (847/1153) at 2 and 4 h post-dose, respectively. RNF was achieved by 32.2% (371/1153) and 53.2% (613/1153) at 2 and 4 h post-dose. After 30 days, 72.7% (168/231) of participants reported satisfaction (using a 7-point scale) with ubrogepant when used in combination with an anti-CGRP monoclonal antibody, and 79.7% (184/231) of participants achieved acute treatment optimization (defined as moderate-maximum treatment efficacy using the Migraine Treatment Optimization Questionnaire-4). CONCLUSION: Real-world ubrogepant use with an anti-CGRP monoclonal antibody was associated with MPR, RNF, satisfaction, and acute treatment optimization.

A Comprehensive Review of the Mechanism, Efficacy, Safety, and Tolerability of Ubrogepant in the Treatment of Migraine.

Ubrogepant is an innovative medication designed for the acute treatment of migraine, a debilitating neurological condition that profoundly impairs quality of life, productivity, and social interactions. This comprehensive review assesses the efficacy, safety, tolerability, and mechanism of action of ubrogepant through a rigorous methodology, including an in-depth literature review from reputable databases like PubMed, Web of Science, Embase, Scopus, and Cochrane. Classified as a calcitonin gene-related peptide (CGRP) receptor antagonist, ubrogepant has emerged as a potential revolutionary medication for migraine treatment. CGRP is a peptide integral to migraine pathophysiology, and its blockade has demonstrated great therapeutic potential. Unlike triptans, known for their cardiovascular risks, ubrogepant lacks vasoconstrictive properties, making it a safer alternative for a broader patient population. Ubrogepant offers significant potential for pain relief, symptom reduction, and restoration of normal function during a migraine attack, and it outperforms placebo in terms of efficacy. It also presents favorable safety, with generally mild adverse drug events (ADEs), such as nausea, dizziness, and somnolence, similar to placebo effects. Consistent results from clinical trials confirm its tolerability, with minor ADEs and no safety alerts for the tested doses, indicating that ubrogepant is a safe and well-tolerated option for migraine treatment. As an effective oral medication, ubrogepant could be an alternative to traditional acute migraine treatments. Its benefits include a unique mechanism of action, rapid onset, and favorable safety profile. However, specific contraindications, such as hypersensitivity, severe hepatic impairment, concurrent use of CYP3A4 inhibitors, pregnancy or breastfeeding, and uncontrolled hypertension, require caution or avoidance of ubrogepant. Despite these limitations, ubrogepant signals a promising new direction in migraine therapeutics.

Safety and efficacy of ubrogepant for the acute treatment of perimenstrual migraine attacks: A post hoc analysis.

OBJECTIVE: To evaluate the efficacy and safety of ubrogepant for the acute treatment of perimenstrual migraine (pmM) attacks. BACKGROUND: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine in adults. METHODS: After completing one of two phase 3 trials, participants could enroll in a phase 3, 52-week, open-label, long-term safety extension trial and were re-randomized 1:1:1 to usual care, ubrogepant 50 mg, or ubrogepant 100 mg. This post hoc analysis evaluated the efficacy of ubrogepant in a subset of women who treated ≥1 pmM or non-pmM attack with ubrogepant. A pmM attack started on or between 2 days before and the first 3 days of menstrual bleeding. Mean (standard deviation [SD]) percentages of ubrogepant-treated attacks achieving 2-h pain freedom and pain relief were reported, with outcomes weighted equally by participant. RESULTS: Of 734 women in the modified intent-to-treat population, 354 reported ≥1 menstrual cycle start date and a ubrogepant-treated headache day in the same month. A qualifying pmM and non-pmM attack was reported by 278 and 716 women, respectively. Pain freedom at 2 h was achieved in a mean (SD) of 28.7% (37.4) of pmM attacks and 22.1% (26.9) of non-pmM attacks treated with ubrogepant 50 mg (p = 0.054) and 29.7% (35.2) versus 25.3% (26.3) of attacks treated with ubrogepant 100 mg (p = 0.757). No difference was found in the mean percentage of ubrogepant-treated pmM and non-pmM attacks that achieved 2-h pain relief with ubrogepant 50 mg (64.8% [39.9] vs. 65.2% [32.4]; p = 0.683) and with 100 mg (67.1% [37.4] vs. 68.4% [30.2]; p = 0.273). Treatment-related treatment-emergent adverse events were reported by 8.8% (12/137) and 12.8% (18/141) in the ubrogepant 50 and 100 mg pmM subgroups, respectively. CONCLUSIONS: Ubrogepant demonstrated similar efficacy for the treatment of pmM and non-pmM attacks. No new safety signals were identified.

Real-world effectiveness, satisfaction, and optimization of ubrogepant for the acute treatment of migraine in combination with onabotulinumtoxinA: results from the COURAGE Study.

BACKGROUND: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited. METHODS: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4). RESULTS: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%. CONCLUSIONS: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments.

A Brief Review of Gepants.

PURPOSE OF REVIEW: Gepants are small molecules that antagonize calcitonin gene-related peptide (CGRP) receptors. Due to their favorable side effect profile and versatility in treating headaches acutely and preventively, gepants are preferred over triptans. We will cover the indications for the four FDA-approved gepants in adults: rimegepant, atogepant, ubrogepant, and zavegepant. This review will illustrate how gepants will continue to revolutionize the acute and preventive treatment of headaches. RECENT FINDINGS: Gepants are now available in oral tablet, dissolving tablet, and intra-nasal spray formulations. Recent studies have shown promising utility in treating the pre-headache or prodromal phase. They have favorable tolerability, no evidence for association with medication overuse, and remain a safer alternative in those who have cerebrovascular risk factors. Additional research is needed to explore occurrence of Raynaud's phenomenon in participants treated with gepants, as it has been associated with CGRP monoclonal antibodies, but are not extensively studied in gepants. Gepants are expected to play a significant role in the next generation of migraine treatments.

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: In this study, we fill this gap in knowledge by updating the safety profile of ubrogepant and rimegepant via disproportionality analysis in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a US-based database registering spontaneous reports. RESEARCH DESIGN AND METHODS: ASCII files of quarterly extraction of FAERS data were downloaded from the FDA website up to the 3rd quarter (Q3) of 2021 (last accessed 03/02/2022). Disproportionality analysis was done using the Reporting Odds Ratio (ROR) as a disproportionality measure. RORs of all AEs related to ubrogepant and rimegepant in FAERS were calculated in comparison with those related to erenumab. Drug-event pairs with a frequency ≤ 2, were removed according to European Medicine Agency (EMA)'s procedures. RESULTS: In total, 2010 and 3691 individual case safety reports (ICSRs) recorded in FAERS reported ubrogepant and rimegepant, respectively, as suspect drugs. Ten disproportionality signals for ubrogepant and 25 disproportionality signals for rimegepant were identified; these were mostly related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious type of adverse events. CONCLUSIONS: New safety aspects related to the treatment of ubrogepant and rimegepant using disproportionality analysis from spontaneous reporting databases were identified. Further studies are needed to confirm these findings.

Ubrogepant and rimegepant: systematic review, meta-analysis, and meta-regression of clinical studies.

OBJECTIVES: This study aimed at providing pooled estimates of the incidence of adverse drug reactions (ADRs) of ubrogepant and rimegepant and to use meta-regression to identify correlations between the occurrence of selected ADRs, socio-demographic, and clinical characteristics from data published in clinical studies. METHODS: Ovid MEDLINE (up to 03/02/2022) was searched along with the references listed in the reviews identified with the research query. Random intercept and slope logistic regression models were used to estimate the logit transformation of the pooled incidence. To examine how selected clinical and socio-demographic characteristics correlated with the pooled incidence rates, we performed random-effects meta-regression. RESULTS: Significant heterogeneity of incidence estimates was observed in clinical studies along with correlations between ADRs and the sociodemographic and clinical characteristics of patients exposed to ubrogepant. In particular, we observed a correlation between ubrogepant dosage and muscle strain and between Body Mass Index (BMI) and liver function values. For rimegepant, significant correlations were observed between age and infections and having aura symptoms at baseline and nausea/dizziness/diarrhea/muscle strain. CONCLUSION: This study provided pooled incidence estimates of ubrogepant and rimegepant's ADRs and highlighted new safety aspects of the pharmacological treatment with ubrogepants and rimigepants from correlations obtained from the meta-regression.

Place of next generation acute migraine specific treatments among triptans, non-responders and contraindications to triptans and possible combination therapies.

Background: For many years triptans have been the cornerstone of acute migraine treatment. Nevertheless, treatment with triptans may not always be initiated due to contraindications (seen in approximately one fifth of patients) or inadequate response (seen in approximately one third of patients). New acute therapies, including 5-hydroxytryptamine (5-HT)1F receptor agonists, also known as ditans (lasmiditan) and small molecule antagonists of the calcitonin gene-related peptide receptor, also known as gepants (rimegepant and ubrogepant), may be an effective alternative. Methods: We searched Pubmed for keywords, summarized the literature and provided a comprehensive review on the place of next generation acute migraine specific treatments among triptans. Results and conclusion: Post-hoc analyses reported no differences in efficacy of gepants/ditans between responders and non-responders to triptans, but research is hampered by lack of consensus on the definition of non-responder. Due to (partially) overlapping mechanisms of action, it remains unknown whether combination therapy with lasmiditan, gepants and triptans will have added value over monotherapy. Preclinical studies and post-hoc analyses cautiously indicate that these new drugs are safe for patients with cardiovascular risk factors. However, long-term studies are needed to prove cardiovascular safety. The risk of developing medication overuse headache may differ between triptans, ditans and gepants, but further studies are needed to confirm this difference. Head-to-head randomized controlled trials of acute therapies and combinations of therapies are needed to determine their place in migraine treatment among established therapies.

Phase Ib, open-label, fixed-sequence, drug-drug interaction, safety, and tolerability study between atogepant and ubrogepant in participants with a history of migraine.

OBJECTIVE: To evaluate potential drug-drug interactions of ubrogepant and atogepant. BACKGROUND: Ubrogepant and atogepant, calcitonin gene-related peptide (CGRP) receptor antagonists, are recently approved drugs for acute and preventive treatment of migraine, respectively. For patients with migraine who are prescribed atogepant for the preventive treatment of migraine, health care providers could prescribe ubrogepant for the acute treatment of breakthrough migraine attacks. METHODS: A phase Ib, multi-center, open-label, fixed-sequence study was conducted in participants diagnosed with migraine for at least 1 year. To assess the primary objective of pharmacokinetic interactions in this phase I trial, the highest United States Food and Drug Administration-approved individual dose strengths of atogepant (60 mg once daily) and ubrogepant (100 mg) were utilized, with ubrogepant being administered on a fixed-dose schedule every 3 days, regardless of whether a participant was experiencing a migraine attack. Secondary endpoints included safety and tolerability. Clinical safety measurements were monitored throughout the study. RESULTS: Of the 31 participants enrolled, 26 completed the study. A single dose of ubrogepant had no statistically significant effect on atogepant pharmacokinetics. Co-administration of ubrogepant with atogepant resulted in a 19% increase (geometric mean ratio 118.80, 90% confidence interval [CI] 108.69-129.84) in the ubrogepant area under the plasma concentration-time curve and a 26% increase (geometric mean ratio 125.63, 90% CI 105.58-149.48) in the ubrogepant maximum plasma concentration. These statistically significant changes in ubrogepant exposure were not clinically meaningful, and no new safety concerns were identified for the combination. CONCLUSION: The combination use of atogepant and ubrogepant was safe and well tolerated in adult participants with a history of migraine enrolled in the study. Pharmacokinetic changes during co-administration were not clinically meaningful.

Gepants for Acute and Preventive Migraine Treatment: A Narrative Review.

Calcitonin gene-related peptide (CGRP) antagonists are a class of medications that act as antagonists of the CGRP receptor or ligand. They can be divided into monoclonal antibodies and non-peptide small molecules, also known as gepants. CGRP antagonists were the first oral agents specifically designed to prevent migraines. The second generation of gepants includes rimegepant (BHV-3000, BMS-927711), ubrogepant (MK-1602), and atogepant (AGN-241689, MK-8031). Zavegepant (BHV-3500, BMS-742413) belongs to the third generation of gepants characterized by different administration routes. The chemical and pharmacological properties of this new generation of gepants were calculated. The clinical trials showed that the new generation of CGRP antagonists is effective for the acute and/or preventive treatment of migraines. No increased mortality risks were observed to be associated with the second- and third-generation gepants. Moreover, the majority of the serious adverse events reported probably occurred unrelated to the medications. Interesting facts about gepants were highlighted, such as potency, hepatotoxicity, concomitant use with monoclonal antibodies targeting the CGRP, comparative analysis with triptans, and the "acute and preventive" treatment of migraine. Further studies should include an elderly population and compare the medications inside this class and with triptans. There are still concerns regarding the long-term side effects of these medications, such as chronic vascular hemodynamic impairment. Meanwhile, careful pharmacovigilance and safety monitoring should be performed in the clinical practice use of gepants.

Calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraines in adults.

Migraine headaches are widespread, debilitating and considered a main cause of disability worldwide. Symptoms of migraines include unilateral, pulsating pain that can last for hours to days, frequently associated with photophobia and phonophobia, nausea, or vomiting, and often aggravated by physical activity. The Canadian Headache Society and American Headache Society guidelines suggest strong evidence of the efficacy of triptans, acetaminophen, aspirin, diclofenac sodium, naproxen and ibuprofen for the acute treatment of migraines. The use of calcitonin gene-related peptide (CGRP) antagonists for the treatment and prevention of migraines has been gaining utilization since the approval of the first agent in this class in 2018. There are increasing available options for the acute treatment of migraines. The purpose of this article is to provide a narrative review of the pharmacological and clinical characteristics of ubrogepant and rimegepant and to discuss their implications for use.