MIGRANAL: Migraine Treatment That Works Differently

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migraine patients do not achieve adequate pain relief with certain treatments1
References:
  1. Baron EP, Tepper SJ. Revisiting the role of ergots in the treatment of migraine and headache. Headache. 2010;50(8):1353-1361.
  2. Burstein R, Cutrer MF, Yarnitsky D. The development of cutaneous allodynia during a migraine attack: clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain. 2000;123(Pt 8):1703-1709.
  3. MIGRANAL [package insert]. Bridgewater, NJ: Bausch Health Companies Inc.
  4. Gallagher RM; Dihydroergotamine Working Group. Acute treatment of migraine with dihydroergotamine nasal spray. Arch Neurol. 1996;53(12):1285-1291.
  5. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55(6):754-762.
  6. Masterson CG, Durham PL. DHE repression of ATP-mediated sensitization of trigeminal ganglion neurons. Headache. 2010;50(9):1424-1439.
  7. Burstein R, Jakubowski M, Rauch SD. The science of migraine. J Vestib Res. 2011;21(6):305-314.
  8. Levy D, Jakubowski M, Burstein R. Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT1B/1D receptor agonists. Proc Natl Acad Sci U S A. 2004;101(12):4274-4279.
  9. Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain. Pain. 2013;154(suppl 1):S44-S53.
  10. Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium. Headache. 2012;52(1):114-128.
  11. Pini LA, Brovia D. Different characteristics of triptans. J Headache Pain. 2004;5:S109-S111.
  12. National Center for Biotechnology Information. PubChem Database. Dihydroergotamine, CID=10531. https://pubchem.ncbi.nlm.nih.gov/compound/10531. Accessed June 20, 2019.
  13. National Center for Biotechnology Information. PubChem Database. Ergotamine, CID=8223. https://pubchem.ncbi.nlm.nih.gov/compound/8223. Accessed June 20, 2019.
  14. Silberstein SD, McCrory DC. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache. 2003;43(2):144-166.
  15. Winner P, Dalessio D, Mathew N, et al. Concomitant administration of antiemetics is not necessary with intramuscular dihydroergotamine. Am J Emerg Med. 1994;12(2):138-141.
  16. Lipton RB. Ergotamine tartrate and dihydroergotamine mesylate: safety profiles. Headache. 1997;37(suppl 1):S33-S41.
  17. Andersen AR, Tfelt-Hansen P, Lassen NA. The effect of ergotamine and dihydroergotamine on cerebral blood flow in man. Stroke. 1987;18(1):120-123.
  18. Silberstein SD, Young WB. Safety and efficacy of ergotamine tartrate and dihydroergotamine in the treatment of migraine and status migrainosus. Working Panel of the Headache and Facial Pain Section of the American Academy of Neurology. Neurology. 1995;45(3 Pt 1):577-584.
  19. Willems EW, Valdivia LF, Villalón CM, Saxena PR. Possible role of alpha-adrenoceptor subtypes in acute migraine therapy. Cephalalgia. 2003;23(4):245-257.
INDICATIONS AND USAGE

MIGRANAL® (dihydroergotamine mesylate) Nasal Spray is indicated for the acute treatment of migraine headaches with or without aura. MIGRANAL Nasal Spray is not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine.

IMPORTANT SAFETY INFORMATION

WARNING

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of DIHYDROERGOTAMINE with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP3A4 inhibition elevates the serum levels of DIHYDROERGOTAMINE, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.

  • MIGRANAL Nasal Spray should not be given to patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina.
  • MIGRANAL Nasal Spray also should not be given to patients with uncontrolled hypertension, or patients who have used 5-HT1 agonists, ergotamine-containing or ergot-type medications, or methysergide within the last 24 hours.
  • MIGRANAL Nasal Spray should not be administered to patients with hemiplegic or basilar migraine.
  • MIGRANAL Nasal Spray is also contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery, and severely impaired hepatic or renal function.
  • MIGRANAL Nasal Spray may cause fetal harm and possesses oxytocic properties and therefore, should not be administered to pregnant women and should not be used by nursing mothers.
  • MIGRANAL Nasal Spray is contraindicated in patients who have previously shown hypersensitivity to ergot alkaloids.
  • MIGRANAL Nasal Spray should not be used with peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure.
  • MIGRANAL Nasal Spray should be used only where a clear diagnosis of migraine headache has been established.
  • MIGRANAL should not be used by patients with documented ischemic or vasospastic coronary artery disease. MIGRANAL should not be administered unless a cardiovascular evaluation provides satisfactory clinical evidence that a patient with risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) is reasonably free of unrecognized coronary artery disease (CAD). Even for patients with a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of MIGRANAL take place in the setting of a medically staffed facility.
  • During clinical studies and the foreign post-marketing experience with MIGRANAL Nasal Spray, there have been no fatalities due to cardiac events. Serious cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine mesylate injection, but are extremely rare.
  • The most commonly reported adverse events in clinical trials for MIGRANAL Nasal Spray were rhinitis, altered sense of taste, application site reactions, dizziness, nausea, and vomiting. Adverse events associated with discontinuation were rhinitis, dizziness, facial edema, cold sweats, accidental trauma, depression, elective surgery, somnolence, allergy, vomiting, hypotension, and paresthesia.

To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here for full Prescribing Information for MIGRANAL Nasal Spray, including Boxed Warning and Patient Information.