MIGRANAL Provided Rapid,
Long-Lasting Relief

Effective treatment for moderate to severe migraine pain1,2

  • In a clinical study, headache response, defined as a reduction in headache severity to mild or no pain, was reported by 27% of patients within 0.5 hours (P=NS)2
    • At 4 hours, 70% of MIGRANAL patients had headache pain relief; at 2 hours, 61% of patients experienced a reduction in headache pain (P<.001)
  • In a second study, 47% of MIGRANAL patients and 33% of placebo-treated patients had a headache response at 2 hours posttreatment. At 4 hours, headache response rates were 56% for MIGRANAL, 35% for placebo (P<.01)1
  • In Study 3, 32% of MIGRANAL patients and 20% of placebo-treated patients had a headache response at 2 hours. At 4 hours posttreatment, headache response rates were 48% for MIGRANAL, 22% for placebo (P<.01)
  • In Study 4, 30% of MIGRANAL patients and 20% of placebo-treated patients had a headache response at 2 hours posttreatment. At 4 hours, headache response rates were 47% for MIGRANAL, 30% for placebo
  • Design: Efficacy was evaluated in randomized, double-blind placebo-controlled studies. The patient population was predominantly female (87%) with a mean age of 39 years. Patients treated a single moderate to severe migraine headache with a single dose of MIGRANAL and assessed pain severity over the 24 hours following treatment. Headache response was determined 0.5, 1, 2, 3, and 4 hours after dosing and was defined as a reduction in headache severity to mild or no pain. In studies 1 and 2, a 4-point pain intensity scale was used. In Studies 3 and 4, a 5-point scale was used that included both pain response and restoration of function for “severe” or “incapacitating” pain, a less clear endpoint. Patients received a regimen consisting of 0.5 mg in each nostril, repeated in 15 minutes. 1
  • Headache response was defined as a reduction in headache severity to mild or no pain.

Low recurrence rate at 24 hours

  • In a clinical trial of more than 300 patients, 85% of those who had responded at 4 hours had no recurrence for 24 hours (compared to 67% for placebo; P<.05)2
  • Compared to placebo, MIGRANAL use was associated with reduced need for analgesics during the 24 hours following treatment1

Low incidence of nausea, photophobia, and phonophobia

  • Lower incidence of migraine-associated nausea, photophobia, and phonophobia in susceptible patients at 2 and 4 hours following administration of MIGRANAL compared with placebo (P<.05)1,2
According to US Headache Consortium Guidelines, DHE Nasal Spray is a Group 1 treatment option: "Proven, pronounced statistical and clinical benefit"3

Broad receptor coverage4

  • The clinical significance of the receptor activity is unknown
  • RECEPTOR
  • MIGRANAL
Serotonergic
  • 5-HT1A
  • 5-HT1B
  • 5-HT1E
  • 5-HT1D
  • 5-HT1F
  • 5-HT2C
  • 5-HT2A
  • 5-HT4
Adrenergic
  • alpha1
  • alpha2
  • beta
Dopaminergic
  • D1
  • D2

Active ingredient treats both peripheral and central migraine sensitization1,5

  • The clinical significance of treatment of peripheral and central sensitization is unknown

Peripheral sensitization is associated with1:

  • Nausea
  • Photophobia
  • Phonophobia
  • Throbbing pain
EARLIER

Central sensitization is associated with5:

  • Cutaneous allodynia
  • Increased pain
LATER

INDICATIONS AND USAGE

Migranal® (dihydroergotamine mesylate, USP) 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, 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 only be used 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 postmarketing 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.
Please click here for full Prescribing Information for Migranal Nasal Spray, including Boxed Warning and Patient Information.
 
 
 

REFERENCES

  • 1.MIGRANAL [package insert]. Aliso Viejo, CA: Valeant Pharmaceuticals North America; 2014.
  • 2.Gallagher RM; Dihydroergotamine Working Group. Acute treatment of migraine with dihydroergotamine nasal spray. Arch Neurol. 1996;53(12):1285-1291.
  • 3.Silberstein SD; US Headache Consortium. 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.
  • 4. Silberstein SD, McCrory DC. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache. 2003;43(2):144-166.
  • 5.Masterson CG, Durham PL. DHE repression of ATP-mediated sensitization of trigeminal ganglion neurons. Headache. 2010;50(9):1424-1439.
  • 6. 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.

MIG.0065.USA.18

INDICATION AND USAGE

Migranal® (dihydroergotamine mesylate, USP) 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, 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 only be used 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 postmarketing 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.
Please click here for full Prescribing Information for Migranal Nasal Spray, including Boxed Warning and Patient Information.