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Drug Safety in Episodic Migraine Management in Adults Part 1: Acute Treatments

  • Episodic Migraine (S Nahas, Section Editor)
  • Published:
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Abstract

Purpose of Review

The aim of this review is to aid in choosing safe options when assessing potential risks of acute migraine treatments based on known mechanisms of action and anticipated safety concerns.

Recent Findings

Part 1 highlights safety issues associated with commonly used medications to treat acute migraine attacks. Strategies to mitigate cardiovascular and gastrointestinal risks of nonsteroidal anti-inflammatory drugs, evaluation of cardiovascular risks of triptan and ergot alkaloids, and precautions with use of antiemetics and the novel drugs gepants and ditans are discussed to help practitioners in clinical decision-making. When available, we included recommendations from professional societies and data from pharmacovigilance systems.

Summary

While guidelines on efficacy are available, one must also consider the possible risks and adverse effects of a drug when creating treatment plans.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Curtin F, Schulz P. Assessing the benefit: risk ratio of a drug–randomized and naturalistic evidence. Dialogues Clin Neurosci. 2011;13:183–90.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ferrari A, Baraldi C, Licata M, Rustichelli C. Polypharmacy Among Headache Patients: A Cross-Sectional Study. CNS Drugs. 2018;32:567–78.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Pomes LM, Guglielmetti M, Bertamino E, Simmaco M, Borro M, Martelletti P. Optimising migraine treatment: from drug-drug interactions to personalized medicine. J Headache Pain. 2019;20:56.

    Article  PubMed  PubMed Central  Google Scholar 

  4. •• Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache. 2015;55:3–20. AHS guidelines for an acute treatment of migraine.

    Article  PubMed  Google Scholar 

  5. •• American Headache Society. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache. 2019;59:1–18. Position statement with recommendations for acute and preventive treatment, including novel drugs.

    Google Scholar 

  6. Burch R. Epidemiology and Treatment of Menstrual Migraine and Migraine During Pregnancy and Lactation: A Narrative Review. Headache. 2020;60:200–16.

    Article  PubMed  Google Scholar 

  7. Oskoui M, Pringsheim T, Holler-Managan Y, Potrebic S, Billinghurst L, Gloss D, et al. Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2019;93:487–99.

    Article  PubMed  Google Scholar 

  8. Antman EM, Bennett JS. Daugherty Alan, Furberg Curt, Roberts Harold, Taubert Kathryn A. Use of Nonsteroidal Antiinflammatory Drugs Circulation. 2007;115:1634–42.

    PubMed  Google Scholar 

  9. Meek IL, Van de Laar MAFJ, E Vonkeman H. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks. Pharmaceuticals. 2010;3:2146–2162.

  10. Lange R, Schwarz JA, Hohn M. Acetylsalicylic acid effervescent 1000 mg (Aspirin) in acute migraine attacks; a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study. Cephalalgia. 2000;20:663–7.

    CAS  PubMed  Google Scholar 

  11. Diener HC, Bussone G, de Liano H, Eikermann A, Englert R, Floeter T, et al. Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks. Cephalalgia. 2004;24:947–54.

    Article  CAS  PubMed  Google Scholar 

  12. Sheppard A, Hayes SH, Chen G-D, Ralli M, Salvi R. Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology. Acta Otorhinolaryngol Ital. 2014;34:79–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Xie W, Luo Y, Liang X, Lin Z, Wang Z, Liu M. The Efficacy And Safety Of Aspirin As The Primary Prevention Of Cardiovascular Disease: An Updated Meta-Analysis. Ther Clin Risk Manag. 2019;15:1129–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lipton RB, Munjal S, Brand-Schieber E, Tepper SJ, Dodick DW. Efficacy, tolerability, and safety of DFN-15 (celecoxib oral solution, 25 mg/mL) in the acute treatment of episodic migraine: A randomized, double-blind, placebo-controlled study. Headache. 2020;60:58–70.

    Article  PubMed  Google Scholar 

  15. BRIEF-FDA Approves Dr. Reddy’s Laboratories’ Elyxyb Oral Solution For Acute Treatment Of Migraine With Or Without Aura In Adults. 5 May 2020 [cited 20 Apr 2021]. Available: https://www.reuters.com/article/brief-fda-approves-dr-reddys-laboratorie-idUSFWN2CN10I.

  16. Center for Drug Evaluation, Research. COX-2 Selective (includes Bextra, Celebrex, and Vioxx). In: U.S. Food & Drug Administration [Internet]. 2 Jan 2021 [cited 19 May 2021]. Available: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/cox-2-selective-includes-bextra-celebrex-and-vioxx-and-non-selective-non-steroidal-anti-inflammatory.

  17. Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Bhala N, Emberson J, Merhi A, Abramson S, Arber N, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382: 769–779.

  18. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018;362: k3426.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Arfè A, Scotti L, Varas-Lorenzo C, Nicotra F, Zambon A, Kollhorst B, et al. Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ. 2016;354: i4857.

    Article  PubMed  Google Scholar 

  20. Antman EM. The Aspirin-NSAID Interaction. J Am Coll Cardiol. 2018;71:1752–4.

    Article  PubMed  Google Scholar 

  21. David Waterbury L, Silliman D, Jolas T. Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006;22:1133–40.

    Article  PubMed  CAS  Google Scholar 

  22. Scally B, Emberson JR, Spata E, Reith C, Davies K, Halls H, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018;3:231–41.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gwee KA, Goh V, Lima G, Setia S. Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits. J Pain Res. 2018;11:361–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lué A, Lanas A. Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits. World J Gastroenterol. 2016;22:10477–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Dreischulte T, Morales DR, Bell S, Guthrie B. Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury. Kidney Int. 2015;88:396–403.

    Article  CAS  PubMed  Google Scholar 

  26. Novick TK, Surapaneni A, Shin J-I, Alexander GC, Inker LA, Wright EA, et al. Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR. Clin J Am Soc Nephrol. 2019;14:1581–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zand L, McKian KP, Qian Q. Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity. Am J Med. 2010;123:367–73.

    Article  CAS  PubMed  Google Scholar 

  28. Kanchanasurakit S, Arsu A, Siriplabpla W, Duangjai A, Saokaew S. Acetaminophen use and risk of renal impairment: A systematic review and meta-analysis. Kidney Res Clin Pract. 2020;39:81–92.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Nonsteroidal Antiinflammatory Drugs (NSAIDs). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases 2020.

  30. Sriuttha P, Sirichanchuen B, Permsuwan U. Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials. Int J Hepatol. 2018;2018:5253623.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Zoubek ME, González-Jimenez A, Medina-Cáliz I, Robles-Díaz M, Hernandez N, Romero-Gómez M, et al. High Prevalence of Ibuprofen Drug-Induced Liver Injury in Spanish and Latin-American Registries. Clin Gastroenterol Hepatol. 2018;16:292–4.

    Article  PubMed  Google Scholar 

  32. Bihan K, Weiss N, Théophile H, Funck-Brentano C, Lebrun-Vignes B. Drug-induced aseptic meningitis: 329 cases from the French pharmacovigilance database analysis. Br J Clin Pharmacol. 2019;85:2540–6.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Yelehe-Okouma M, Czmil-Garon J, Pape E, Petitpain N, Gillet P. Drug-induced aseptic meningitis: a mini-review. Fundam Clin Pharmacol. 2018;32:252–60.

    Article  CAS  PubMed  Google Scholar 

  34. Marinac JS. Drug- and chemical-induced aseptic meningitis: a review of the literature. Ann Pharmacother. 1992;26:813–22.

    Article  CAS  PubMed  Google Scholar 

  35. Schwartz N, Stock AD, Putterman C. Neuropsychiatric lupus: new mechanistic insights and future treatment directions. Nat Rev Rheumatol. 2019;15:137–52.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Morgan A, Clark D. CNS Adverse Effects of Nonsteroidal Anti-Inflammatory Drugs : Therapeutic Implications. CNS Drugs. 1998;9:281–90.

    Article  CAS  PubMed  Google Scholar 

  37. Barreto EF, Feely MA. Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: PRO. Kidney360. 2020;1: 1184–1188.

  38. Schjerning A-M, McGettigan P, Gislason G. Cardiovascular effects and safety of (non-aspirin) NSAIDs. Nat Rev Cardiol. 2020;17:574–84.

    Article  CAS  PubMed  Google Scholar 

  39. • Ho KY, Cardosa MS, Chaiamnuay S, Hidayat R, Ho HQT, Kamil O, et al. Practice Advisory on the Appropriate Use of NSAIDs in Primary Care. J Pain Res. 2020;13:1925–39. Practical guidance for the use of NSAIDs in cardiovascular and GI risk patients.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Asghar MS, Hansen AE, Kapijimpanga T, van der Geest RJ, van der Koning P, Larsson HBW, et al. Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers. Neurology. 2010;75:1520–6.

    Article  CAS  PubMed  Google Scholar 

  41. Amin FM, Asghar MS, Ravneberg JW, de Koning PJH, Larsson HBW, Olesen J, et al. The effect of sumatriptan on cephalic arteries: A 3T MR-angiography study in healthy volunteers. Cephalalgia. 2013;33:1009–16.

    Article  PubMed  Google Scholar 

  42. Khan S, Amin FM, Christensen CE, Ghanizada H, Younis S, Olinger ACR, et al. Meningeal contribution to migraine pain: a magnetic resonance angiography study. Brain. 2019;142:93–102.

    Article  PubMed  Google Scholar 

  43. Velentgas P, Cole JA, Mo J, Sikes CR, Walker AM. Severe vascular events in migraine patients. Headache. 2004;44:642–51.

    Article  PubMed  Google Scholar 

  44. Hall GC, Brown MM, Mo J, MacRae KD. Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice. Neurology. 2004;62:563–8.

    Article  CAS  PubMed  Google Scholar 

  45. Bigal ME, Golden W, Buse D, Chen Y-T, Lipton RB. Triptan use as a function of cardiovascular risk. A population-based study Headache. 2010;50:256–63.

    PubMed  Google Scholar 

  46. Razzaque Z, Pickard JD, Ma Q-P, Shaw D, Morrison K, Wang T, et al. 5-HT1B-receptors and vascular reactivity in human isolated blood vessels: assessment of the potential craniovascular selectivity of sumatriptan. Br J Clin Pharmacol. 2002;53:266–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Maassen Van Den Brink A, Saxena PR. Coronary vasoconstrictor potential of triptans: a review of in vitro pharmacologic data. Headache. 2004;44 Suppl 1: S13–9.

  48. Ghanshani S, Chen C, Lin B, Duan L, Shen Y-JA, Lee M-S. Risk of Acute Myocardial Infarction, Heart Failure, and Death in Migraine Patients Treated with Triptans. Headache. 2020;60: 2166–2175.

  49. •• Dodick D, Lipton RB, Martin V, Papademetriou V, Rosamond W, MaassenVanDenBrink A, et al. Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine. Headache. 2004;44:414–25. Comprehensive review of cardiovascular effects and safety of triptans.

    Article  PubMed  Google Scholar 

  50. • Diener H-C. The Risks or Lack Thereof of Migraine Treatments in Vascular Disease. Headache. 2020;60:649–53. Thought-provoking opinion statement about use of triptans in patients with cardiovascular disorders.

    Article  PubMed  Google Scholar 

  51. Leroux E, Rothrock J. Triptans for migraine patients with vascular risks: New insights, new options. Headache. 2019;59:1589–96.

    Article  PubMed  Google Scholar 

  52. Loder E, Burch R. What can data mining teach us about triptan safety that we don’t already know? Cephalalgia: an international journal of headache. 2014. pp. 3–4.

  53. Evans RW, Martin V. Assessing cardiac risk prior to use of triptans. J Headache Pain. 2000. Available: https://headachejournal.onlinelibrary.wiley.com/doi/abs/; https://doi.org/10.1046/j.1526-4610.2000.00094.x?casa_token=0mMV-5fbIKwAAAAA:SpYV7ROJxWNxoX8CBP7ml7lFL06LvDVdtwEAGPYTezFY48CKv3fRkhLoV6LBt7Ll-6Pbce2ygJxAjQM.

  54. ASCVD Risk Estimator +. In: American College of Cardiology [Internet]. [cited 31 May 2021]. Available: https://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/.

  55. ACC/AHA CV Risk Calculator (2013). In: Medscape [Internet]. [cited 31 May 2021]. Available: https://reference.medscape.com/calculator/37/acc-aha-cv-risk-calculator-2013.

  56. Bickerstaff E. BASILAR ARTERY MIGRAINE. Lancet. 1961;277:15–7.

    Article  Google Scholar 

  57. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38: 1–211.

  58. Klapper J, Mathew N, Nett R. Triptans in the treatment of basilar migraine and migraine with prolonged aura. Headache. 2001;41:981–4.

    Article  CAS  PubMed  Google Scholar 

  59. Di Stefano V, Rispoli MG, Pellegrino N, Graziosi A, Rotondo E, Napoli C, et al. Diagnostic and therapeutic aspects of hemiplegic migraine. J Neurol Neurosurg Psychiatry. 2020;91:764–71.

    Article  PubMed  Google Scholar 

  60. Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. 2012;11:906–17.

    Article  PubMed  Google Scholar 

  61. Kato Y, Hayashi T, Mizuno S, Horiuchi Y, Ohira M, Tanahashi N, et al. Triptan-induced Reversible Cerebral Vasoconstriction Syndrome: Two Case Reports with a Literature Review. Intern Med. 2016;55:3525–8.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Nguyen TQ, Lewis JH. Sumatriptan-associated ischemic colitis: case report and review of the literature and FAERS. Drug Saf. 2014;37:109–21.

    Article  PubMed  Google Scholar 

  63. Baron EP. Headache, cerebral aneurysms, and the use of triptans and ergot derivatives. Headache. 2015;55:739–47.

    Article  PubMed  Google Scholar 

  64. Evans RW. The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and Triptans: an analysis of the 29 case reports. MedGenMed. 2007;9:48.

    PubMed  PubMed Central  Google Scholar 

  65. Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. Medical Journal of Australia. 2007. pp. 361–365. https://doi.org/10.5694/j.1326-5377.2007.tb01282.x.

  66. • Gillman PK. Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache. 2010;50:264–72. Review of mechanisms of serotonin toxicity that addresses common misconceptions.

    Article  PubMed  Google Scholar 

  67. Pilgrim JL, Gerostamoulos D, Drummer OH. Deaths involving serotonergic drugs. Forensic Sci Int. 2010;198:110–7.

    Article  CAS  PubMed  Google Scholar 

  68. Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28:205–14.

    Article  CAS  PubMed  Google Scholar 

  69. Orlova Y, Rizzoli P, Loder E. Association of Coprescription of Triptan Antimigraine Drugs and Selective Serotonin Reuptake Inhibitor or Selective Norepinephrine Reuptake Inhibitor Antidepressants With Serotonin Syndrome. JAMA Neurol. 2018;75:566–72.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Robblee JV, Butterfield RJ, Kang AM, Smith JH. Triptan and ergotamine overdoses in the United States: Analysis of the National Poison Data System. Neurology. 2020;94:e1460–9.

    Article  PubMed  Google Scholar 

  71. Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50:1089–99.

    Article  PubMed  Google Scholar 

  72. Ansari H, Ziad S. Drug-Drug Interactions in Headache Medicine. Headache. 2016;56:1241–8.

    Article  PubMed  Google Scholar 

  73. Ferrari MD, Färkkilä M, Reuter U, Pilgrim A, Davis C, Krauss M, et al. Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan – A randomised proof-of-concept trial. Cephalalgia. 2010;30:1170–8.

    Article  PubMed  Google Scholar 

  74. Vila-Pueyo M. Targeted 5-HT1F Therapies for Migraine. Neurotherapeutics. 2018;15:291–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Pearlman EM, Wilbraham D, Dennehy EB, Berg PH, Tsai M, Doty EG, et al. Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls. Hum Psychopharmacol. 2020;35: e2732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Drugs for migraine. The Medical Letter. The Medical Letter: Inc; 2020. p. 61.

    Google Scholar 

  77. Krege JH, Rizzoli PB, Liffick E, Doty EG, Dowsett SA, Wang J, et al. Safety findings from Phase 3 lasmiditan studies for acute treatment of migraine: Results from SAMURAI and SPARTAN. Cephalalgia. 2019;39:957–66.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Finch A, Pillans P. P-glycoprotein and its role in drug-drug interactions. Aust Prescr. 2014;37:137–9.

    Article  Google Scholar 

  79. Szkutnik-Fiedler D. Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of New Anti-Migraine Drugs-Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies. Pharmaceutics. 2020;12. https://doi.org/10.3390/pharmaceutics12121180.

  80. de Vries T, Villalón CM, MaassenVanDenBrink A. Pharmacological treatment of migraine: CGRP and 5-HT beyond the triptans. Pharmacol Ther. 2020;211: 107528.

    Article  PubMed  CAS  Google Scholar 

  81. Lasmiditan. 11 Oct 2019 [cited 31 May 2021]. Available: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf.

  82. Tsai M, Case M, Ardayfio P, Hochstetler H, Wilbraham D. Effects of Lasmiditan on Cardiovascular Parameters and Pharmacokinetics in Healthy Subjects Receiving Oral Doses of Propranolol. Clin Pharmacol Drug Dev. 2020;9:629–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. van Hoogstraten WS, MaassenVanDenBrink A. The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse. J Headache Pain. 2019;20:54.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Rau JC, Navratilova E, Oyarzo J, Johnson KW, Aurora SK, Schwedt TJ, et al. Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache. Cephalalgia. 2020;40:903–12.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Schiff PL. Ergot and its alkaloids. Am J Pharm Educ. 2006;70:98.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Tfelt-Hansen P, Saxena PR, Dahlöf C, Pascual J, Láinez M, Henry P, et al. Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000;123(Pt 1):9–18.

    Article  PubMed  Google Scholar 

  87. Silberstein SD, Shrewsbury SB, Hoekman J. Dihydroergotamine (DHE) - Then and Now: A Narrative Review. Headache. 2020;60:40–57.

    Article  PubMed  Google Scholar 

  88. Dahlöf C, Maassen Van Den Brink A. Dihydroergotamine, ergotamine, methysergide and sumatriptan - basic science in relation to migraine treatment. Headache. 2012;52: 707–714.

  89. D.H.E. 45 (dihydroergotamine mesylate). 31 Jul 2002 [cited 31 May 2021]. Available: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/005929s044lbl.pdf.

  90. Tfelt-Hansen P, Saxena PR. Ergot alkaloids in the acute treatment of migraines. 3rd ed. In: Jes Olesen, Peter J. Goadsby, Nabih M. Ramadan, Peer Tfelt-Hansen, K. Michael A. Welch, editor. The Headaches. 3rd ed. Lippincott Williams & Wilkinz 2006;459–467.

  91. Srisuma S, Lavonas EJ, Wananukul W. Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors. Clin Toxicol. 2014;52:674–7.

    Article  CAS  Google Scholar 

  92. Cytochrome P450 3A (including 3A4) inhibitors and inducers. 2021 [cited 29 May 2021]. Available: https://www.uptodate.com/contents/image?imageKey=CARD%2F76992&topicKey=ONC%2F4621&source=see_link.

  93. Silberstein SD, Young WB. Safety and efficacy of ergotamine tartrate and dihydroergo t amine in the treatment of migraine and status migrainosus. special article Neurology. 1995;45:577–584.

  94. Saper JR, Silberstein S. Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine. Headache. 2006;46(Suppl 4):S171–81.

    Article  PubMed  Google Scholar 

  95. Impel NeuroPharma Announces U.S. FDA Approval of TRUDHESATM (Dihydroergotamine Mesylate) Nasal Spray for the Acute Treatment of Migraine. 3 Sep 2021 [cited 13 Dec 2021]. Available: https://impelnp.com/2021/09/03/impel-neuropharma-announces-u-s-fda-approval-of-trudhesa-dihydroergotamine-mesylate-nasal-spray-for-the-acute-treatment-of-migraine/.

  96. Aurora S, Jeleva M, Hocevar-Trnka J, Hoekman J, Shrewsbury S. A long-term, open-label study of safety and tolerability of precision olfactory delivery (POD®) of DHE in acute migraine (STOP 301): Clinical results. [cited 24 May 2021]. Available: https://impelnp.com/wp-content/uploads/2020/10/PAINWeek_2020_STOP-301-Clinical-Results-Poster_Final_8-25-20_FINAL.pdf.

  97. Clinical Trials. [cited 14 Dec 2021]. Available: https://www.satsumarx.com/our-research/clinical-trials/.

  98. Hauser JM, Azzam JS, Kasi A. Antiemetic Medications. StatPearls. Treasure Island (FL): StatPearls Publishing. 2020.

  99. Marmura MJ. Use of dopamine antagonists in treatment of migraine. Curr Treat Options Neurol. 2012;14:27–35.

    Article  PubMed  Google Scholar 

  100. Friedman BW. Managing Migraine. Ann Emerg Med. 2017;69:202–7.

    Article  PubMed  Google Scholar 

  101. Wijemanne S, Jankovic J, Evans RW. Movement Disorders From the Use of Metoclopramide and Other Antiemetics in the Treatment of Migraine. Headache. 2016;56:153–61.

    Article  PubMed  Google Scholar 

  102. Savitt D, Jankovic J. Tardive syndromes. J Neurol Sci. 2018;389:35–42.

    Article  PubMed  Google Scholar 

  103. Rao AS, Camilleri M. Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther. 2010;31:11–9.

    Article  CAS  PubMed  Google Scholar 

  104. Al-Saffar A, Lennernäs H, Hellström PM. Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited. Neurogastroenterol Motil. 2019;31: e13617.

    Article  PubMed  Google Scholar 

  105. McGeeney BE. Dopamine antagonists and migraine. Drug Dev Res. 2007;68:341–5.

    Article  CAS  Google Scholar 

  106. Isbister GK, Dawson A, Whyte IM. Citalopram overdose, serotonin toxicity, or neuroleptic malignant syndrome? Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2001;657–659.

  107. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999;13:100–9.

    Article  CAS  PubMed  Google Scholar 

  108. Freedman SB, Uleryk E, Rumantir M, Finkelstein Y. Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis. Ann Emerg Med. 2014;64:19-25.e6.

    Article  PubMed  Google Scholar 

  109. Lee DY, Trinh T, Roy SK. Torsades de Pointes after Ondansetron Infusion in 2 Patients. Tex Heart Inst J. 2017;44:366–9.

    Article  PubMed  PubMed Central  Google Scholar 

  110. QTDrugs Lists (registration required) :: Crediblemeds. [cited 13 Dec 2021]. Available: https://crediblemeds.org/druglist.

  111. Hargreaves R, Olesen J. Calcitonin Gene-Related Peptide Modulators - The History and Renaissance of a New Migraine Drug Class. Headache. 2019;59:951–70.

    Article  PubMed  Google Scholar 

  112. Edvinsson L, Warfvinge K. Recognizing the role of CGRP and CGRP receptors in migraine and its treatment. Cephalalgia. 2019;39:366–73.

    Article  PubMed  Google Scholar 

  113. Russell FA, King R, Smillie S-J, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94:1099–142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Biohaven Pharmaceutical Holding Company Ltd. Biohaven to Advance Vazegepant into Phase 3 for the Acute Treatment of Migraine Following Successful End of Phase 2 Meeting with FDA. 23 Mar 2020 [cited 23 May 2021]. Available: https://www.prnewswire.com/news-releases/biohaven-to-advance-vazegepant-into-phase-3-for-the-acute-treatment-of-migraine-following-successful-end-of-phase-2-meeting-with-fda-301027933.html.

  115. FDA approves QULIPTATM (atogepant), the first and only oral CGRP receptor antagonist specifically developed for the preventive treatment of migraine. [cited 14 Dec 2021]. Available: https://news.abbvie.com/news/press-releases/fda-approves-qulipta-atogepant-first-and-only-oral-cgrp-receptor-antagonist-specifically-developed-for-preventive-treatment-migraine.htm.

  116. FDA Approves Biohaven’s NURTEC® ODT (rimegepant) for Prevention: Now the First and Only Migraine Medication for both Acute and Preventive Treatment. [cited 29 May 2021]. Available: https://www.biohavenpharma.com/investors/news-events/press-releases/05-27-2021.

  117. Ankrom W, Bondiskey P, Li C-C, Palcza J, Liu W, Dockendorf MF, et al. Ubrogepant Is Not Associated With Clinically Meaningful Elevations of Alanine Aminotransferase in Healthy Adult Males. Clin Transl Sci. 2020;13:462–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Goadsby PJ, Tepper SJ, Watkins PB, Ayele G, Miceli R, Butler M, et al. Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: Randomized, placebo-controlled trial in healthy adults. Cephalalgia. 2019;39:1753–61.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Ivans A, Stringfellow J, Coric V, Croop R. Results of a Phase 1, Open-label, Single-dose, Parallel-group Study of Rimegepant 75 mg in Subjects with Hepatic Impairment (2126). Neurology. 2020;94. Available: https://n.neurology.org/content/94/15_Supplement/2126.

  120. Ailani J, Lipton RB, Hutchinson S, Knievel K, Lu K, Butler M, et al. Long-Term Safety Evaluation of Ubrogepant for the Acute Treatment of Migraine: Phase 3, Randomized, 52-Week Extension Trial. Headache. 2020;60:141–52.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Croop R, Lipton RB, Kudrow D, Stock DA, Kamen L, Conway CM, et al. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet. 2021;397:51–60.

    Article  CAS  PubMed  Google Scholar 

  122. Hutchinson S, Silberstein SD, Blumenfeld AM, Lipton RB, Lu K, Yu SY, et al. Safety and efficacy of ubrogepant in participants with major cardiovascular risk factors in two single-attack phase 3 randomized trials: ACHIEVE I and II. Cephalalgia. 2021; 3331024211000311.

  123. Hutchinson S, Schim J, Lipton R, Croop R, Jensen C, Thiry A, Stock E, Conway C, Lovegren M, Coric V, Hanna M. Oral rimegepant 75 mg is safe and well tolerated in adults with migraine and cardiovascular risk factors: results of a multicenter, long-term, open-label safety study. Presented at: American Academy of Neurology 2021 Virtual Annual Meeting; April 17–21, 2021. Available: https://index.mirasmart.com/AAN2021/PDFfiles/AAN2021-001995.html.

  124. Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, et al. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N Engl J Med. 2019;381:142–9.

    Article  CAS  PubMed  Google Scholar 

  125. Mulder IA, Li M, de Vries T, Qin T, Yanagisawa T, Sugimoto K, et al. Anti-migraine Calcitonin Gene-Related Peptide Receptor Antagonists Worsen Cerebral Ischemic Outcome in Mice. Ann Neurol. 2020;88:771–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Ubrelvy (ubrogepant) package insert. Madison, NJ: Allergan USA, Inc. Dec 2019 [cited 31 May 2020]. Available: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211765s000lbl.pdf.

  127. Nurtec (rimegepant) package insert. New Haven, CT: Biohaven Pharmaceuticals, Inc. Feb 2020 [cited 31 May 2021]. Available: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212728s000lbl.pdf.

  128. Qulipta (atogepant) package insert. North Chicago, Ill.: AbbVie Inc. Available: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215206Orig1s000lbl.pdf.

  129. Mao Q, Unadkat JD. Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport–an update. AAPS J. 2015;17:65–82.

    Article  CAS  PubMed  Google Scholar 

  130. Tamaki H, Satoh H, Hori S, Ohtani H, Sawada Y. Inhibitory effects of herbal extracts on breast cancer resistance protein (BCRP) and structure-inhibitory potency relationship of isoflavonoids. Drug Metab Pharmacokinet. 2010;25:170–9.

    Article  CAS  PubMed  Google Scholar 

  131. Inhibitors and inducers of P-glycoprotein (P-gp) drug efflux pump (P-gp multidrug resistance transporter). In: UpToDate® [Internet]. 2021 [cited 31 May 2021]. Available: https://www.uptodate.com/contents/image/print?imageKey=EM%2F73326&topicKey=RHEUM%2F1666&source=see_link.

  132. Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009;158:693–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. University of Florida, 1149 Newell Dr., L3-100, Gainesville, 32611, USA

    Yulia Y. Orlova

  2. Ayer Neurosciences Institute, Hartford Health Care Medical Group, University of Connecticut School of Medicine, Norwich, CT, USA

    Sandhya Mehla

  3. Geisinger Health Systems, 1000 E. Mountain Boulevard, Wilkes-Barre, PA, 18702, USA

    Abigail L. Chua

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Orlova, Y.Y., Mehla, S. & Chua, A.L. Drug Safety in Episodic Migraine Management in Adults Part 1: Acute Treatments. Curr Pain Headache Rep 26, 481–492 (2022). https://doi.org/10.1007/s11916-022-01057-3

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