BREKIYA is indicated for the acute treatment of migraine with or without aura and the acute treatment of cluster headaches in adults.

{ "type": "p", "children": [], "text": "BREKIYA is indicated for the acute treatment of migraine with or without aura and the acute treatment of cluster headaches in adults." }

Limitations of Use

{ "type": "p", "children": [], "text": "\nLimitations of Use \n" }

BREKIYA is not indicated for the preventive treatment of migraine.

{ "type": "p", "children": [], "text": "BREKIYA is not indicated for the preventive treatment of migraine. " }

BREKIYA is not indicated for the management of hemiplegic migraine or migraine with brainstem aura.

{ "type": "p", "children": [], "text": "BREKIYA is not indicated for the management of hemiplegic migraine or migraine with brainstem aura." }

BREKIYA autoinjector is for subcutaneous injection only.

The recommended dose of BREKIYA is 1 mg administered subcutaneously via a single 1 mL autoinjector. The dose may be repeated, as needed, at 1-hour intervals to a total maximum of 3 mg (3 doses) in a 24-hour period.

Do not exceed 6 mg (6 doses) total in a week.

Prior to initiation of BREKIYA, a cardiovascular evaluation is recommended [see Warnings and Precautions (5.3)]. For patients with risk factors predictive of coronary artery disease who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of BREKIYA take place in the setting of an equipped healthcare facility.

See the “Instructions for Use” for detailed steps for administering the subcutaneous injection using the autoinjector.

Preparation

Injection: 1 mg/mL dihydroergotamine mesylate as a clear, colorless solution in a 1 mL single-dose autoinjector.

{ "type": "p", "children": [], "text": "Injection: 1 mg/mL dihydroergotamine mesylate as a clear, colorless solution in a 1 mL single-dose autoinjector." }

BREKIYA is contraindicated in patients:

{ "type": "p", "children": [], "text": "BREKIYA is contraindicated in patients:" }

{ "type": "ul", "children": [ "with concomitant use of strong CYP3A4 inhibitors [see Warnings and Precautions (5.1) and Drug Interactions (7.1)]\n", "with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina [see Warnings and Precautions (5.4)]\n", "with uncontrolled hypertension [see Warnings and Precautions (5.5)]\n", "with peripheral arterial disease ", "with sepsis ", "following vascular surgery ", "with severe hepatic impairment ", "with severe renal impairment", "with known hypersensitivity to dihydroergotamine, ergot alkaloids, latex, or any of the ingredients in BREKIYA [see Warnings and Precautions (5.9)]\n", "with recent use (i.e., within 24 hours) of other 5-HT1 agonists, ergotamine-containing or ergot-type medications [see Drug Interactions (7.2)]\n", "with concomitant use of peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure [see Warnings and Precautions (5.5)]\n" ], "text": "" }

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine and strong CYP3A4 inhibitors.  Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or and ischemia of the extremities is increased. Hence, concomitant use of BREKIYA with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4) and Drug Interactions (7.1)].

The potential for cardiac adverse reactions exists with BREKIYA treatment. Serious adverse cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine mesylate. These events have included acute myocardial infarction, life-threatening disturbances of cardiac rhythm (e.g., ventricular tachycardia and ventricular fibrillation), coronary artery vasospasm, and transient myocardial ischemia.

Prior to initiation of BREKIYA, a cardiovascular evaluation is recommended to determine if the patient is free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. If, during the cardiovascular evaluation, the patient’s medical history (including risk factors), or electrocardiographic investigation findings are consistent with coronary artery vasospasm or myocardial ischemia, BREKIYA should   not   be   administered [see Contraindications (4)].

For patients with risk factors predictive of coronary artery disease (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of coronary artery disease, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of BREKIYA take place in the setting of an equipped healthcare facility, unless the patient has previously received dihydroergotamine. During the interval immediately following the first use of BREKIYA, an electrocardiogram is recommended in those patients with risk factors because ischemia can occur in the absence of clinical symptoms.

The potential for adverse cerebrovascular events exists with BREKIYA treatment. Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with dihydroergotamine mesylate; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the dihydroergotamine mesylate having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack). Discontinue BREKIYA if a cerebrovascular event is suspected.

BREKIYA, like other ergot alkaloids, may cause vasospastic reactions other than coronary artery vasospasm. Myocardial, peripheral vascular, and colonic ischemia have been reported with dihydroergotamine mesylate.

Dihydroergotamine associated vasospastic phenomena may also cause muscle pains, numbness, coldness, pallor, and cyanosis of the digits. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. BREKIYA should be discontinued immediately if signs or symptoms of vasoconstriction develop.

Patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud’s syndrome following the use of any 5-HT agonist, including BREKIYA, should be evaluated by a healthcare provider.

Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension treated with dihydroergotamine mesylate. BREKIYA is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].

An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5-HT1 agonist in a study evaluating subjects undergoing cardiac catheterization.

Overuse of acute migraine drugs (e.g., ergotamines, triptans, opioids, or a combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

Based on the mechanism of action of dihydroergotamine and findings from the published literature, BREKIYA may cause preterm labor. Avoid use of BREKIYA during pregnancy [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.2)].

The potential for fibrotic complications exists with BREKIYA treatment. There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of dihydroergotamine mesylate. Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis. Rare cases have also been reported in association with the use of dihydroergotamine mesylate; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis.

Administration of BREKIYA should not exceed the dosing guidelines and should not be used for chronic daily administration [see Dosage and Administration (2.1)].

The rigid needle shield of the BREKIYA autoinjector contains a needle cover (located inside the cap) that contains dry natural rubber, which is made from latex. BREKIYA is contraindicated in patients who have previously shown hypersensitivity to ergot alkaloids or latex.

The following clinically significant adverse reactions are described elsewhere in the labeling:

{ "type": "p", "children": [], "text": "The following clinically significant adverse reactions are described elsewhere in the labeling:" }

{ "type": "ul", "children": [ "Peripheral Ischemia Following Coadministration with Strong CYP3A4 Inhibitors [see Boxed Warning and Warnings and Precautions (5.1)]\n", "Myocardial Ischemia and/or Infarction, Other Adverse Cardiac Events, and Fatalities [see Warnings and Precautions (5.2)]\n", "Cerebrovascular Adverse Reactions and Fatalities [see Warnings and Precautions (5.3)]\n", "Other Vasospasm Related Adverse Reactions [see Warnings and Precautions (5.4)]\n", "Increase in Blood Pressure [see Warnings and Precautions (5.5)]\n", "Medication Overuse Headache [see Warnings and Precautions (5.6)]\n", "Preterm Labor [see Warnings and Precautions (5.7)]\n", "Fibrotic Complications [see Warnings and Precautions (5.8)]\n", "Hypersensitivity [see Warnings and Precautions (5.9)]\n" ], "text": "" }

The following adverse reactions associated with the use of dihydroergotamine were identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions associated with the use of dihydroergotamine were identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure." }

Serious cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation [see Contraindications (4) and Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Serious cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation [see Contraindications (4) and Warnings and Precautions (5.3)].\n" }

Fibrotic complications have been reported in association with long term use of injectable dihydroergotamine mesylate [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "Fibrotic complications have been reported in association with long term use of injectable dihydroergotamine mesylate [see Warnings and Precautions (5.8)].\n" }

Vasospasm, paresthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis occurred after long-term use of dihydroergotamine.

{ "type": "p", "children": [], "text": "Vasospasm, paresthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis occurred after long-term use of dihydroergotamine." }

Cases of myocardial infarction and stroke have been reported following the use of dihydroergotamine [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Cases of myocardial infarction and stroke have been reported following the use of dihydroergotamine [see Warnings and Precautions (5.2)].\n" }

There have been rare reports of serious adverse events in connection with the coadministration of intravenous administration of dihydroergotamine and strong CYP3A4 inhibitors resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities [see Warnings and Precautions (5.1)]. The use of strong CYP3A4 inhibitors with BREKIYA is contraindicated [see Contraindications (4)]. Administer moderate CYP3A4 inhibitors with caution.

Triptans (serotonin [5-HT 1B/1D receptor agonists) have been reported to cause coronary artery vasospasm, and its effect could be additive with BREKIYA. Therefore, triptans and BREKIYA should not be taken within 24 hours of each other [see Contraindications (4)].

There have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.

BREKIYA is contraindicated for use with peripheral and central vasoconstrictors because the combination may cause synergistic elevation of blood pressure [see Warnings and Precautions (5.5)].

Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy [see Warnings and Precautions (5.2, 5.4)].

Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT1 agonists have been co-administered with selective serotonin reuptake inhibitors (SSRI’s) (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline). 

Risk Summary

Available data from published literature indicate an increased risk of preterm delivery with dihydroergotamine, the active moiety in BREKIYA, use during pregnancy. Avoid use of BREKIYA during pregnancy [see Warnings and Precautions (5.9)]. Data collected over decades have shown no increased risk of major birth defects or miscarriage with the use of dihydroergotamine mesylate during pregnancy.

In animal reproduction studies, adverse effects on development were observed following administration of dihydroergotamine mesylate during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation in rats (decreased body weight and impaired reproductive function in the offspring) at doses that were not associated with maternal toxicity (see Data).

The estimated rate of major birth defects (2.2% to 2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

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

Intranasal administration of dihydroergotamine mesylate to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weight and/or skeletal ossification at doses of 0.16 mg/day or greater. A no-effect level for adverse effects on embryofetal toxicity was not identified in rats. Intranasal administration of dihydroergotamine mesylate to pregnant rabbits throughout organogenesis resulted in decreased skeletal ossification at 3.6 mg/day. The no-effect dose for adverse effects on embryofetal toxicity in rabbits was 1.2 mg/day.

Intranasal administration of dihydroergotamine mesylate to female rats throughout pregnancy and lactation resulted in decreased body weight and impaired reproductive function (decreased mating indices) in the offspring at doses of 0.16 mg/day or greater. A no-effect dose for adverse developmental effects in rats was not established. Effects on offspring development occurred at doses below those that produced evidence of maternal toxicity in these studies.

Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.

Risk Summary

There are no data on the presence of dihydroergotamine in human milk; however, ergotamine, a related drug, is excreted in human milk. There are reports of vomiting, diarrhea, weak pulse, and unstable blood pressure in breastfed infants exposed to ergotamine. BREKIYA may reduce milk supply because it may decrease prolactin levels.

Because of the potential for reduced milk supply and serious adverse events in the breastfed infant, including diarrhea, vomiting, weak pulse, and unstable blood pressure; advise patients not to breastfeed during treatment with BREKIYA and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded.

Safety and effectiveness in pediatric patients have not been established.

Clinical studies of dihydroergotamine products did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

BREKIYA contains dihydroergotamine (as the mesylate salt), which is not a controlled substance. 

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Currently available data have not demonstrated drug abuse with dihydroergotamine. However, cases of drug abuse in patients on other forms of ergot therapy have been reported.

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Currently available data have not demonstrated physical or psychological dependence with dihydroergotamine. However, cases of psychological dependence in patients on other forms of ergot therapy have been reported.

Symptoms

{ "type": "p", "children": [], "text": "\nSymptoms\n" }

Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism.

{ "type": "p", "children": [], "text": "Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism. " }

In general, the symptoms of an acute BREKIYA overdose may be similar to those of an ergotamine overdose, although there may be less pronounced nausea and vomiting with BREKIYA. The symptoms of an ergotamine overdose include the following: numbness, tingling, pain, and cyanosis of the extremities associated with diminished or absent peripheral pulses; respiratory depression; an increase and/or decrease in blood pressure, usually in that order; confusion, delirium, convulsions, and coma; and/or some degree of nausea, vomiting, and abdominal pain.

{ "type": "p", "children": [], "text": "In general, the symptoms of an acute BREKIYA overdose may be similar to those of an ergotamine overdose, although there may be less pronounced nausea and vomiting with BREKIYA. The symptoms of an ergotamine overdose include the following: numbness, tingling, pain, and cyanosis of the extremities associated with diminished or absent peripheral pulses; respiratory depression; an increase and/or decrease in blood pressure, usually in that order; confusion, delirium, convulsions, and coma; and/or some degree of nausea, vomiting, and abdominal pain." }

In laboratory animals, dihydroergotamine was lethal when given at intravenous doses of 44 mg/kg in mice, 130 mg/kg in rats, and 37 mg/kg in rabbits.

{ "type": "p", "children": [], "text": "In laboratory animals, dihydroergotamine was lethal when given at intravenous doses of 44 mg/kg in mice, 130 mg/kg in rats, and 37 mg/kg in rabbits." }

Treatment

{ "type": "p", "children": [], "text": "\nTreatment\n" }

Treatment includes discontinuance of the drug, local application of warmth to the affected area, the administration of vasodilators, and nursing care to prevent tissue damage. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

{ "type": "p", "children": [], "text": "Treatment includes discontinuance of the drug, local application of warmth to the affected area, the administration of vasodilators, and nursing care to prevent tissue damage. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations." }

BREKIYA (dihydroergotamine mesylate) injection is an ergotamine derivative. Dihydroergotamine mesylate is a white or almost white, crystalline powder. It is slightly soluble in water and chloroform and sparingly soluble in methanol. The chemical name for dihydroergotamine mesylate is ergotaman-3´,6´,18-trione,9,10-dihydro-12´-hydroxy-2´-methyl-5´-(phenylmethyl) monomethanesulfonate (salt). Its molecular weight is 679.8g/mol and its molecular formula is C33H37N5O5∙CH4O3S.

{ "type": "p", "children": [], "text": "BREKIYA (dihydroergotamine mesylate) injection is an ergotamine derivative. Dihydroergotamine mesylate is a white or almost white, crystalline powder. It is slightly soluble in water and chloroform and sparingly soluble in methanol. The chemical name for dihydroergotamine mesylate is ergotaman-3´,6´,18-trione,9,10-dihydro-12´-hydroxy-2´-methyl-5´-(phenylmethyl) monomethanesulfonate (salt). Its molecular weight is 679.8g/mol and its molecular formula is C33H37N5O5∙CH4O3S." }

The chemical structure is

{ "type": "p", "children": [], "text": "The chemical structure is" }

BREKIYA is a clear, colorless, sterile solution supplied in 1 mL single-dose autoinjector for subcutaneous administration. Each mL contains 1 mg dihydroergotamine mesylate, USP (equivalent to 0.86 mg of dihydroergotamine). BREKIYA also contains ethanol, USP 6.1% by volume; glycerin, USP 15% by weight; water for injection, USP; may contain methanesulfonic acid and/or sodium hydroxide, NF for pH adjustment. pH range is 3.4 to 4.9.

{ "type": "p", "children": [], "text": "BREKIYA is a clear, colorless, sterile solution supplied in 1 mL single-dose autoinjector for subcutaneous administration. Each mL contains 1 mg dihydroergotamine mesylate, USP (equivalent to 0.86 mg of dihydroergotamine). BREKIYA also contains ethanol, USP 6.1% by volume; glycerin, USP 15% by weight; water for injection, USP; may contain methanesulfonic acid and/or sodium hydroxide, NF for pH adjustment. pH range is 3.4 to 4.9." }

Dihydroergotamine binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors.  The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effects at 5-HT1D receptors.

Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine with and without a history of hypertension [see Warnings and Precautions (5.5)].

Dihydroergotamine possesses oxytocic properties [see Warnings and Precautions (5.7)].

Absorption

Following BREKIYA administration, the mean maximum plasma concentration was 3.8 ng/mL, and the median time from dosing to maximum plasma concentration was approximately 0.4 hours.

Distribution

Dihydroergotamine mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.

Elimination

Metabolism

Four dihydroergotamine mesylate metabolites have been identified in human plasma following oral administration. The major metabolite, 8´-β-hydroxydihydroergotamine, exhibits affinity equivalent to its parent for adrenergic and 5-HT receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites (i.e., dihydrolysergic acid, dihydrolysergic amide, and a metabolite formed by oxidative opening of the proline ring) are of minor importance. Following nasal administration, total metabolites represent only 20% to 30% of plasma AUC. Quantitative pharmacokinetic characterization of the four metabolites has not been performed.

Excretion

The major excretory route of dihydroergotamine is via the bile in the feces. The total body clearance is 1.5 L/min which reflects mainly hepatic clearance. Only 6% to 7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection. The renal clearance (0.1 L/min) is unaffected by the route of dihydroergotamine administration. The decline of plasma dihydroergotamine after intramuscular or intravenous administration is multi-exponential with a terminal half-life of about 9 hours.

Specific Populations

No studies have been conducted on the effect of renal or hepatic impairment, gender, race, or ethnicity on dihydroergotamine pharmacokinetics [see Contraindications (4)].

Drug Interaction Studies

Pharmacokinetic interactions have been reported in patients treated orally with other ergot alkaloids (e.g., increased levels of ergotamine) and macrolide antibiotics, presumably due to inhibition of cytochrome P450 3A metabolism of the alkaloids. Dihydroergotamine has also been shown to be an inhibitor of cytochrome P450 3A catalyzed reactions and rare reports of ergotism have been obtained from patients treated with dihydroergotamine and macrolide antibiotics (e.g., clarithromycin, erythromycin), and in patients treated with dihydroergotamine and protease inhibitors (e.g., ritonavir), presumably due to inhibition of cytochrome P450 3A metabolism of ergotamine [see Contraindications (4)].

Carcinogenesis

In a 2-year mouse carcinogenicity study, subcutaneous (SC) administration of dihydroergotamine mesylate (0, 0.5, 1.5 or 5 mg/kg/day) resulted in an increased incidence of fibrosarcoma at the injection sites in males and females at the high dose. The higher dose not associated with an increase in tumors (1.5 mg/kg/day) is approximately 2 times the recommended human dose (RHD) of 3 mg/day SC on a body surface area (mg/m2) basis.

In a 2-year rat carcinogenicity study, intranasal administration of dihydroergotamine mesylate (0, 0.4, 0.8 or 1.6 mg/day for 13 weeks, followed by 0, 0.08, 0.24 or 0.8 mg/day for the remainder of the study) did not result in an increase in tumors.

Mutagenesis

Dihydroergotamine mesylate was negative in an in vitro mutagenicity (Ames) assay and positive in in vitro chromosomal aberration (V79 Chinese hamster cell assay with metabolic activation, and human peripheral blood lymphocyte) assays. Dihydroergotamine was negative in in vivo micronucleus assays in mouse and hamster.

Impairment of Fertility

Intranasal administration of dihydroergotamine to rats at doses up to 1.6 mg/day was not associated with adverse effects on fertility.

BREKIYA (dihydroergotamine mesylate) injection is a clear, colorless, sterile solution of 1 mg/mL dihydroergotamine mesylate available as:

<div class="scrollingtable"><table width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Dosage Unit</span> </td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Package Size</span> </td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">NDC #</span> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">1 mL prefilled single-dose autoinjector </td><td class="Botrule Lrule Rrule Toprule">Carton of 4 </td><td class="Botrule Lrule Rrule Toprule">NDC 64896-509-02 </td> </tr> </tbody> </table></div>

Caution: The rigid needle shield of the BREKIYA autoinjector contains a needle cover (located inside the cap) that contains dry natural rubber, which is made from latex [see Contraindications (4) and Warnings and Precautions (5.9)].

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature]. Do not refrigerate or freeze. Protect from light. Retain in original pack until time of use.

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use)." }

Serious and/or Life-Threatening Reactions with Coadministration of CYP3A4 Inhibitors

{ "type": "p", "children": [], "text": "\nSerious and/or Life-Threatening Reactions with Coadministration of CYP3A4 Inhibitors\n" }

Inform patients that serious and/or life-threatening peripheral ischemia (cerebral ischemia and/or ischemia of the extremities) has been associated with the coadministration of dihydroergotamine and strong CYP3A4 inhibitors, [see Contraindications (4), Warnings and Precautions (5.1), and Drug Interactions (7.1)].

{ "type": "p", "children": [], "text": "Inform patients that serious and/or life-threatening peripheral ischemia (cerebral ischemia and/or ischemia of the extremities) has been associated with the coadministration of dihydroergotamine and strong CYP3A4 inhibitors, [see Contraindications (4), Warnings and Precautions (5.1), and Drug Interactions (7.1)]. " }

Myocardial Ischemia and/or Infarction, Other Cardiac Events, Cerebrovascular Events, and Fatalities

{ "type": "p", "children": [], "text": "\nMyocardial Ischemia and/or Infarction, Other Cardiac Events, Cerebrovascular Events, and Fatalities\n" }

Inform patients of the risk for serious cardiac, cerebrovascular, and other vasospasm related events. Advise patients to notify their healthcare provider if they develop any risk factors or symptoms while taking BREKIYA. Inform patients that nicotine may provoke vasoconstriction predisposing to a greater ischemic response [see Warnings and Precautions (5.2, 5.3, 5.4)].

{ "type": "p", "children": [], "text": "Inform patients of the risk for serious cardiac, cerebrovascular, and other vasospasm related events. Advise patients to notify their healthcare provider if they develop any risk factors or symptoms while taking BREKIYA. Inform patients that nicotine may provoke vasoconstriction predisposing to a greater ischemic response [see Warnings and Precautions (5.2, 5.3, 5.4)].\n" }

Increase in Blood Pressure

{ "type": "p", "children": [], "text": "\nIncrease in Blood Pressure\n" }

Inform patients of the risk for significant elevation in blood pressure [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform patients of the risk for significant elevation in blood pressure [see Warnings and Precautions (5.5)]. " }

Medication Overuse Headache

{ "type": "p", "children": [], "text": "\nMedication Overuse Headache \n" }

Inform patients that use of drugs to treat migraine attacks for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Inform patients that use of drugs to treat migraine attacks for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)]." }

Hypersensitivity

{ "type": "p", "children": [], "text": "\nHypersensitivity\n" }

Inform patients that the rigid needle shield of the BREKIYA autoinjector contains a needle cover (located inside the cap) that contains dry natural rubber, which is made from latex, and can cause allergic reactions in latex-sensitive individuals [see Warnings and Precautions (5.9)].

{ "type": "p", "children": [], "text": "Inform patients that the rigid needle shield of the BREKIYA autoinjector contains a needle cover (located inside the cap) that contains dry natural rubber, which is made from latex, and can cause allergic reactions in latex-sensitive individuals [see Warnings and Precautions (5.9)].\n" }

Drug Interactions

{ "type": "p", "children": [], "text": "\nDrug Interactions\n" }

Advise patients to inform their healthcare providers if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7)].

{ "type": "p", "children": [], "text": "Advise patients to inform their healthcare providers if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7)]." }

Pregnancy

{ "type": "p", "children": [], "text": "\nPregnancy \n" }

Advise patients of the risk for preterm birth. Advise women to inform their healthcare provider if they are pregnant or intend to become pregnant [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise patients of the risk for preterm birth. Advise women to inform their healthcare provider if they are pregnant or intend to become pregnant [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)]. \n" }

Lactation

{ "type": "p", "children": [], "text": "\nLactation \n" }

Advise patients not to breastfeed during treatment with BREKIYA [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise patients not to breastfeed during treatment with BREKIYA [see Use in Specific Populations (8.2)].\n" }

Important Administration Instructions

{ "type": "p", "children": [], "text": "\nImportant Administration Instructions\n" }

Advise patients on the proper use of BREKIYA prior to the initial use and instruct them to read the Instructions for Use [see Dosage and Administration (2.3)].

{ "type": "p", "children": [], "text": "Advise patients on the proper use of BREKIYA prior to the initial use and instruct them to read the Instructions for Use [see Dosage and Administration (2.3)].\n" }

For more information, call 1-877-835-5472.

{ "type": "p", "children": [], "text": "For more information, call 1-877-835-5472." }

BREKIYA® is a registered trademark of Amneal Pharmaceuticals LLC.

{ "type": "p", "children": [], "text": "BREKIYA® is a registered trademark of Amneal Pharmaceuticals LLC." }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Amneal Specialty, a division of Amneal Pharmaceuticals LLC

{ "type": "p", "children": [], "text": "\nAmneal Specialty, a division of Amneal Pharmaceuticals LLC\n" }

Bridgewater, NJ  08807

{ "type": "p", "children": [], "text": "Bridgewater, NJ  08807" }

Manufactured by:

{ "type": "p", "children": [], "text": "Manufactured by:" }

Amneal Pharmaceuticals Pvt. Ltd.

{ "type": "p", "children": [], "text": "\nAmneal Pharmaceuticals Pvt. Ltd.\n" }

Ahmedabad 382213, INDIA

{ "type": "p", "children": [], "text": " Ahmedabad 382213, INDIA" }

Rev. 05-2025-01

{ "type": "p", "children": [], "text": "Rev. 05-2025-01" }

<div class="scrollingtable"><table width="100%"> <col width="17px"/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">BREKIYA<span class="Sup">®</span></span><span class="Bold">[breh-kee-yah]</span> </p> <p> <span class="Bold"> </span><span class="Bold">(dihydroergotamine mesylate)</span> </p> <p> <span class="Bold"> </span><span class="Bold">injection, for subcutaneous use</span> </p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">What is the most important information I should know about BREKIYA?</span> </p> <p> <span class="Bold">BREKIYA can cause serious side effects, including: </span> </p> <ul class="Disc"> <li> <span class="Bold">Serious problems with blood circulation to your legs and feet (peripheral ischemia)</span>. BREKIYA can cause peripheral ischemia when you take it with certain medicines known as CYP3A4 inhibitors. Peripheral ischemia may lead to a stroke and death. Stop taking BREKIYA and get emergency medical help right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="4"> <ul class="Circle"> <li>cramping and pain in your legs or hips</li> <li>feeling of heaviness or tightness in your leg muscles</li> <li>burning or aching pain in your feet or toes while resting</li> <li>numbness, tingling, or weakness in your legs</li> <li>cold feeling or color changes in 1 or both legs or feet</li> <li>slurred speech</li> <li>sudden weakness</li> </ul> <p class="First">Do not take medicines known as strong CYP3A4 inhibitors, such as:</p> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li> ritonavir </li> </ul> </td><td> <ul class="Circle"> <li>indinavir </li> </ul> </td><td> <ul class="Circle"> <li>clarithromycin </li> </ul> </td><td class="Rrule"> <ul class="Circle"> <li>itraconazole </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>nelfinavir </li> </ul> </td><td> <ul class="Circle"> <li>erythromycin </li> </ul> </td><td> <ul class="Circle"> <li>ketoconazole </li> </ul> </td><td class="Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4">These are not all of the medicines that could affect how BREKIYA works. Your healthcare provider can tell you if it is safe to take BREKIYA with other medicines. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">What is BREKIYA?</span> </p> <p>BREKIYA is a prescription medicine used for the acute treatment of migraine with or without aura and acute cluster headaches in adults.</p> <ul class="Disc"> <li>BREKIYA is not used to prevent migraine.</li> <li>BREKIYA is not used to treat other types of headaches such as hemiplegic migraines (that make you unable to move on one side of your body) or basilar migraines (rare form of migraine with aura).</li> </ul> It is not known if BREKIYA is safe and effective in children. </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">Who should not take BREKIYA? Do not use BREKIYA if you:</span> </p> <ul class="Disc"> <li>are taking medicines known as strong CYP3A4 inhibitors.</li> <li>have heart problems or a history of heart problems.</li> <li>have uncontrolled high blood pressure.</li> <li>have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease).</li> <li>have sepsis.</li> <li>have had vascular surgery.</li> <li>have severe liver problems.</li> <li>have severe kidney problems.</li> <li>are allergic to dihydroergotamine, ergot alkaloids, latex, or any of the ingredients in BREKIYA. See the end of this Medication Guide for a complete list of ingredients in BREKIYA.</li> <li>have taken any of the following medicines in the last 24 hours: </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>sumatriptan </li> </ul> </td><td> <ul class="Circle"> <li>almotriptan </li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Circle"> <li>eletriptan </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>frovatriptan </li> </ul> </td><td> <ul class="Circle"> <li>naratriptan </li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Circle"> <li>rizatriptan </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>ergotamine or ergotamine-type medicines </li> </ul> </td><td> <ul class="Circle"> <li>zolmitriptan </li> </ul> </td><td class="Rrule" colspan="2"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4"> <ul class="Disc"> <li>have taken any medicines that constrict your blood vessels or raise your blood pressure. </li> </ul> <p class="First">Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take BREKIYA with other medicines. </p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">Before you take BREKIYA, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <ul class="Disc"> <li>have high blood pressure.</li> <li>have liver problems.</li> <li>have kidney problems.</li> </ul> <ul class="Disc"> <li>have risk factors for heart disease. You have a higher risk for heart disease if you: <ul class="Circle"> <li>have high blood pressure</li> <li>have high cholesterol levels</li> <li>smoke</li> <li>are overweight</li> <li>have diabetes</li> <li>have a family history of heart disease</li> </ul> </li> <li>are taking medicines known as strong CYP3A4 inhibitors.</li> </ul> <ul class="Disc"> <li>are pregnant or plan to become pregnant. BREKIYA may cause preterm labor. BREKIYA should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant. </li> <li>are breastfeeding or plan to breastfeed. BREKIYA may reduce breast milk supply and pass into your breast milk. BREKIYA may be harmful to your baby. Do not breastfeed your baby while taking BREKIYA and for 3 days after you use BREKIYA. Talk with your healthcare provider about the best way to feed your baby if you take BREKIYA.</li> </ul> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider will decide if you can take BREKIYA with your other medicines.</p> <p> <span class="Bold">Especially tell your healthcare provider if you take:</span> </p> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>sumatriptan </li> </ul> </td><td> <ul class="Circle"> <li>fluconazole </li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Circle"> <li>propranolol or other medicines that can lower your heart rate </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>ergot-type medicine </li> </ul> </td><td> <ul class="Circle"> <li>grapefruit juice </li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Circle"> <li>any medicines that can increase your blood pressure </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>saquinavir </li> </ul> </td><td> <ul class="Circle"> <li>zileuton </li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Circle"> <li>selective serotonin reuptake inhibitors </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>nefazodone </li> </ul> </td><td> <ul class="Circle"> <li>nicotine </li> </ul> </td><td class="Rrule" colspan="2"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4">These are not all of the medicines that could affect how BREKIYA works. Your healthcare provider can tell you if it is safe to take BREKIYA with other medicines. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">How should I use BREKIYA? </span> </p> <ul class="Disk"> <li>Certain people should take their first dose of BREKIYA in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li> <li>BREKIYA is for injection under the skin (subcutaneous) only.</li> <li>Use BREKIYA exactly as your healthcare provider tells you to use it. </li> <li>See the detailed Instructions for Use that comes with BREKIYA for information about how to use BREKIYA. </li> <li>Each autoinjector contains 1 dose (1 mg) of BREKIYA. </li> <li>If your headache comes back after the first complete dose, you may give yourself up to 2 more doses as needed. Wait at least 1 hour between doses.</li> <li> <span class="Bold">Do not</span> inject more than 3 doses (3 mg) of BREKIYA in a 24-hour period or 6 doses (6 mg) in a 1-week (7 day) period. </li> <li>Using BREKIYA for 10 or more days in 1 month may make your headache worse. You should write down when you have headaches and when you take BREKIYA so that you can talk with your healthcare provider about how BREKIYA is working for you.</li> <li>If you use too much BREKIYA, call your healthcare provider or the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">What are the possible side effects of </span><span class="Bold">BREKIYA</span><span class="Bold">?</span> </p> <p> <span class="Bold">BREKIYA can cause serious side effects, including: </span> </p> <p>See<span class="Bold"> “What is the most important information I should know about BREKIYA?”</span> </p> <ul class="Disc"> <li> <span class="Bold">Heart attack and other heart problems. </span>Heart problems may lead to death. Stop taking BREKIYA and get emergency medical help right away if you have any of the following symptoms of a heart attack: <ul class="Circle"> <li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li> <li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li> <li>pain or discomfort in your arms, back, neck, jaw, or stomach</li> <li>shortness of breath with or without chest discomfort</li> <li>breaking out in a cold sweat</li> <li>nausea or vomiting</li> <li>feeling lightheaded</li> </ul> <p class="First"> BREKIYA is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. See <span class="Bold">“Before you take BREKIYA, tell your healthcare provider about all of your medical conditions, including if you:” </span>for the risk factors for heart disease.</p> </li> <li> <span class="Bold">Stroke. </span>Stop using BREKIYA and get emergency medical help right away if you have any of the following symptoms of a stroke:</li> </ul> <ul class="Circle"> <li>face drooping</li> <li>unusual weakness or numbness</li> <li>slurred speech</li> </ul> <ul class="Disc"> <li> <span class="Bold">Changes in color or sensation in your fingers and toes (Raynaud’s syndrome).</span> </li> </ul> <ul class="Disc"> <li> <span class="Bold">Stomach and intestinal problems</span> (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include: </li> </ul>  </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>sudden or severe stomach pain </li> </ul> </td><td> <ul class="Circle"> <li>constipation or diarrhea </li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Circle"> <li>stomach pain after meals </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>bloody diarrhea </li> </ul> </td><td> <ul class="Circle"> <li>weight loss </li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Circle"> <li>fever </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>nausea or vomiting </li> </ul> </td><td> </td><td class="Rrule" colspan="2"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">Increased blood pressure.</span> </li> <li> <span class="Bold">Medicine overuse headache. </span>Some people who use too much BREKIYA may make their headaches worse (medicine overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with BREKIYA.</li> <li> <span class="Bold">Preterm labor.</span> </li> <li> <span class="Bold">Tissue changes (fibrotic complications).</span> Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach.</li> </ul> <p class="First"> <span class="Bold">The most common but serious side effects of BREKIYA are heart problems that happen but may lead to death. These heart problems include:</span> </p> <ul class="Circle"> <li>temporary squeezing of arteries that supply the heart (coronary artery vasospasm)</li> <li>temporary decrease of blood flow to the heart (transient myocardial ischemia)</li> <li>heart rhythm problems (ventricular tachycardia and ventricular fibrillation)</li> </ul> <p>Symptoms of these heart problems include:</p> <p>See “<span class="Bold">heart attack and other heart problems</span>.”</p> <ul class="Disc"> <li>numbness or tingling in your fingers and toes.</li> <li>muscle pain or cramps in your arms and legs.</li> <li>weakness in your legs.</li> <li>temporary speeding or slowing of your heart rate.</li> <li>swelling or itching.</li> </ul> <p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of BREKIYA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">How should I store </span><span class="Bold">BREKIYA</span><span class="Bold">?</span> </p> <ul class="Disc"> <li>Store BREKIYA at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Do not refrigerate or freeze BREKIYA. </li> <li>Protect BREKIYA from light. </li> <li>Keep BREKIYA in the original pack until ready to use.</li> </ul> <span class="Bold">Keep </span><span class="Bold">BREKIYA </span><span class="Bold">and all medicines out of the reach of children. </span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">General information about the safe and effective use of </span><span class="Bold">BREKIYA</span><span class="Bold">. </span> </p> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use BREKIYA for a condition for which it was not prescribed. Do not give BREKIYA to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about BREKIYA that is written for health professionals. </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">What are the ingredients in </span><span class="Bold">BREKIYA</span><span class="Bold">? </span> </p> <p> <span class="Bold">Active ingredient:</span> dihydroergotamine mesylate, USP </p> <p> <span class="Bold">Inactive ingredients:</span> ethanol, glycerin, water for injection, methanesulfonic acid or sodium hydroxide.<br/> <br/> Distributed by:</p> <p> <span class="Bold">Amneal Specialty, a division of Amneal Pharmaceuticals LLC</span> </p> <p>Bridgewater, NJ  08807<br/> <br/>Manufactured by:</p> <p> <span class="Bold">Amneal Pharmaceuticals Pvt. Ltd.</span> </p> <p>Ahmedabad 382213, INDIA<br/> <br/> <span class="Bold">For more information </span><span class="Bold">or to report side-effects, call 1-877-835-5472.</span> </p> <p> <span class="Bold"> <br/> </span>Rev. 05-2025-00</p>  </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"17px\"/>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">BREKIYA<span class=\"Sup\">®</span></span><span class=\"Bold\">[breh-kee-yah]</span>\n</p>\n<p>\n<span class=\"Bold\"> </span><span class=\"Bold\">(dihydroergotamine mesylate)</span>\n</p>\n<p>\n<span class=\"Bold\"> </span><span class=\"Bold\">injection, for subcutaneous use</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about BREKIYA?</span>\n</p>\n<p>\n<span class=\"Bold\">BREKIYA can cause serious side effects, including: </span>\n</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Serious problems with blood circulation to your legs and feet (peripheral ischemia)</span>. BREKIYA can cause peripheral ischemia when you take it with certain medicines known as CYP3A4 inhibitors. Peripheral ischemia may lead to a stroke and death. Stop taking BREKIYA and get emergency medical help right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Circle\">\n<li>cramping and pain in your legs or hips</li>\n<li>feeling of heaviness or tightness in your leg muscles</li>\n<li>burning or aching pain in your feet or toes while resting</li>\n<li>numbness, tingling, or weakness in your legs</li>\n<li>cold feeling or color changes in 1 or both legs or feet</li>\n<li>slurred speech</li>\n<li>sudden weakness</li>\n</ul>\n<p class=\"First\">Do not take medicines known as strong CYP3A4 inhibitors, such as:</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li> ritonavir </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>indinavir </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>clarithromycin </li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Circle\">\n<li>itraconazole </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>nelfinavir </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>erythromycin </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>ketoconazole </li>\n</ul>\n</td><td class=\"Rrule\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\">These are not all of the medicines that could affect how BREKIYA works. Your healthcare provider can tell you if it is safe to take BREKIYA with other medicines. </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What is BREKIYA?</span>\n</p>\n<p>BREKIYA is a prescription medicine used for the acute treatment of migraine with or without aura and acute cluster headaches in adults.</p>\n<ul class=\"Disc\">\n<li>BREKIYA is not used to prevent migraine.</li>\n<li>BREKIYA is not used to treat other types of headaches such as hemiplegic migraines (that make you unable to move on one side of your body) or basilar migraines (rare form of migraine with aura).</li>\n</ul>\n It is not known if BREKIYA is safe and effective in children. </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not take BREKIYA? Do not use BREKIYA if you:</span>\n</p>\n<ul class=\"Disc\">\n<li>are taking medicines known as strong CYP3A4 inhibitors.</li>\n<li>have heart problems or a history of heart problems.</li>\n<li>have uncontrolled high blood pressure.</li>\n<li>have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease).</li>\n<li>have sepsis.</li>\n<li>have had vascular surgery.</li>\n<li>have severe liver problems.</li>\n<li>have severe kidney problems.</li>\n<li>are allergic to dihydroergotamine, ergot alkaloids, latex, or any of the ingredients in BREKIYA. See the end of this Medication Guide for a complete list of ingredients in BREKIYA.</li>\n<li>have taken any of the following medicines in the last 24 hours: </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>sumatriptan </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>almotriptan </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>eletriptan </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>frovatriptan </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>naratriptan </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>rizatriptan </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>ergotamine or ergotamine-type medicines </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>zolmitriptan </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>have taken any medicines that constrict your blood vessels or raise your blood pressure. </li>\n</ul>\n<p class=\"First\">Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take BREKIYA with other medicines. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">Before you take BREKIYA, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<ul class=\"Disc\">\n<li>have high blood pressure.</li>\n<li>have liver problems.</li>\n<li>have kidney problems.</li>\n</ul>\n<ul class=\"Disc\">\n<li>have risk factors for heart disease. You have a higher risk for heart disease if you:\n <ul class=\"Circle\">\n<li>have high blood pressure</li>\n<li>have high cholesterol levels</li>\n<li>smoke</li>\n<li>are overweight</li>\n<li>have diabetes</li>\n<li>have a family history of heart disease</li>\n</ul>\n</li>\n<li>are taking medicines known as strong CYP3A4 inhibitors.</li>\n</ul>\n<ul class=\"Disc\">\n<li>are pregnant or plan to become pregnant. BREKIYA may cause preterm labor. BREKIYA should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant. </li>\n<li>are breastfeeding or plan to breastfeed. BREKIYA may reduce breast milk supply and pass into your breast milk. BREKIYA may be harmful to your baby. Do not breastfeed your baby while taking BREKIYA and for 3 days after you use BREKIYA. Talk with your healthcare provider about the best way to feed your baby if you take BREKIYA.</li>\n</ul>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider will decide if you can take BREKIYA with your other medicines.</p>\n<p>\n<span class=\"Bold\">Especially tell your healthcare provider if you take:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>sumatriptan </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>fluconazole </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>propranolol or other medicines that can lower your heart rate </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>ergot-type medicine </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>grapefruit juice </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>any medicines that can increase your blood pressure </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>saquinavir </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>zileuton </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>selective serotonin reuptake inhibitors </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>nefazodone </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>nicotine </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\">These are not all of the medicines that could affect how BREKIYA works. Your healthcare provider can tell you if it is safe to take BREKIYA with other medicines. </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use BREKIYA? </span>\n</p>\n<ul class=\"Disk\">\n<li>Certain people should take their first dose of BREKIYA in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li>\n<li>BREKIYA is for injection under the skin (subcutaneous) only.</li>\n<li>Use BREKIYA exactly as your healthcare provider tells you to use it. </li>\n<li>See the detailed Instructions for Use that comes with BREKIYA for information about how to use BREKIYA. </li>\n<li>Each autoinjector contains 1 dose (1 mg) of BREKIYA. </li>\n<li>If your headache comes back after the first complete dose, you may give yourself up to 2 more doses as needed. Wait at least 1 hour between doses.</li>\n<li>\n<span class=\"Bold\">Do not</span> inject more than 3 doses (3 mg) of BREKIYA in a 24-hour period or 6 doses (6 mg) in a 1-week (7 day) period. </li>\n<li>Using BREKIYA for 10 or more days in 1 month may make your headache worse. You should write down when you have headaches and when you take BREKIYA so that you can talk with your healthcare provider about how BREKIYA is working for you.</li>\n<li>If you use too much BREKIYA, call your healthcare provider or the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of </span><span class=\"Bold\">BREKIYA</span><span class=\"Bold\">?</span>\n</p>\n<p>\n<span class=\"Bold\">BREKIYA can cause serious side effects, including: </span>\n</p>\n<p>See<span class=\"Bold\"> “What is the most important information I should know about BREKIYA?”</span>\n</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Heart attack and other heart problems. </span>Heart problems may lead to death. Stop taking BREKIYA and get emergency medical help right away if you have any of the following symptoms of a heart attack:\n <ul class=\"Circle\">\n<li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li>\n<li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li>\n<li>pain or discomfort in your arms, back, neck, jaw, or stomach</li>\n<li>shortness of breath with or without chest discomfort</li>\n<li>breaking out in a cold sweat</li>\n<li>nausea or vomiting</li>\n<li>feeling lightheaded</li>\n</ul>\n<p class=\"First\"> BREKIYA is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. See <span class=\"Bold\">“Before you take BREKIYA, tell your healthcare provider about all of your medical conditions, including if you:” </span>for the risk factors for heart disease.</p>\n</li>\n<li>\n<span class=\"Bold\">Stroke. </span>Stop using BREKIYA and get emergency medical help right away if you have any of the following symptoms of a stroke:</li>\n</ul>\n<ul class=\"Circle\">\n<li>face drooping</li>\n<li>unusual weakness or numbness</li>\n<li>slurred speech</li>\n</ul>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Changes in color or sensation in your fingers and toes (Raynaud’s syndrome).</span>\n</li>\n</ul>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Stomach and intestinal problems</span> (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include: </li>\n</ul>\n  </td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>sudden or severe stomach pain </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>constipation or diarrhea </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>stomach pain after meals </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>bloody diarrhea </li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>weight loss </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>fever </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>nausea or vomiting </li>\n</ul>\n</td><td> </td><td class=\"Rrule\" colspan=\"2\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Increased blood pressure.</span>\n</li>\n<li>\n<span class=\"Bold\">Medicine overuse headache. </span>Some people who use too much BREKIYA may make their headaches worse (medicine overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with BREKIYA.</li>\n<li>\n<span class=\"Bold\">Preterm labor.</span>\n</li>\n<li>\n<span class=\"Bold\">Tissue changes (fibrotic complications).</span> Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach.</li>\n</ul>\n<p class=\"First\">\n<span class=\"Bold\">The most common but serious side effects of BREKIYA are heart problems that happen but may lead to death. These heart problems include:</span>\n</p>\n<ul class=\"Circle\">\n<li>temporary squeezing of arteries that supply the heart (coronary artery vasospasm)</li>\n<li>temporary decrease of blood flow to the heart (transient myocardial ischemia)</li>\n<li>heart rhythm problems (ventricular tachycardia and ventricular fibrillation)</li>\n</ul>\n<p>Symptoms of these heart problems include:</p>\n<p>See “<span class=\"Bold\">heart attack and other heart problems</span>.”</p>\n<ul class=\"Disc\">\n<li>numbness or tingling in your fingers and toes.</li>\n<li>muscle pain or cramps in your arms and legs.</li>\n<li>weakness in your legs.</li>\n<li>temporary speeding or slowing of your heart rate.</li>\n<li>swelling or itching.</li>\n</ul>\n<p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of BREKIYA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store </span><span class=\"Bold\">BREKIYA</span><span class=\"Bold\">?</span>\n</p>\n<ul class=\"Disc\">\n<li>Store BREKIYA at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Do not refrigerate or freeze BREKIYA. </li>\n<li>Protect BREKIYA from light. </li>\n<li>Keep BREKIYA in the original pack until ready to use.</li>\n</ul>\n<span class=\"Bold\">Keep </span><span class=\"Bold\">BREKIYA </span><span class=\"Bold\">and all medicines out of the reach of children. </span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of </span><span class=\"Bold\">BREKIYA</span><span class=\"Bold\">. </span>\n</p>\n Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use BREKIYA for a condition for which it was not prescribed. Do not give BREKIYA to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about BREKIYA that is written for health professionals. </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in </span><span class=\"Bold\">BREKIYA</span><span class=\"Bold\">? </span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span> dihydroergotamine mesylate, USP </p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> ethanol, glycerin, water for injection, methanesulfonic acid or sodium hydroxide.<br/>\n<br/>\n Distributed by:</p>\n<p>\n<span class=\"Bold\">Amneal Specialty, a division of Amneal Pharmaceuticals LLC</span>\n</p>\n<p>Bridgewater, NJ  08807<br/>\n<br/>Manufactured by:</p>\n<p>\n<span class=\"Bold\">Amneal Pharmaceuticals Pvt. Ltd.</span>\n</p>\n<p>Ahmedabad 382213, INDIA<br/>\n<br/>\n<span class=\"Bold\">For more information </span><span class=\"Bold\">or to report side-effects, call 1-877-835-5472.</span>\n</p>\n<p>\n<span class=\"Bold\">\n<br/>\n</span>Rev. 05-2025-00</p>\n  </td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration                                                                                                                          Issued: 05/2025

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration                                                                                                                          Issued: 05/2025" }

<div class="scrollingtable"><table width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-2.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/> </td><td class="Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-3.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First">This Instructions for Use contains information on how to inject BREKIYA.</p> If there are any questions concerning the use of BREKIYA autoinjector, ask your healthcare provider, pharmacist or visit www.brekiya.com. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Important Information You Need to Know Before Injecting BREKIYA</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Warnings</span> </p> <ul class="Circle"> <li>BREKIYA is for injection under the skin (subcutaneous) only.</li> <li>The rigid needle shield of the BREKIYA autoinjector contains a needle cover (located inside the cap) that contains dry natural rubber, which is made from latex. Tell your healthcare provider if you are allergic to latex. </li> <li> <span class="Bold">Do not</span> remove the red needle cap until you are ready to inject BREKIYA. Inject BREKIYA right away after removing the red needle cap. </li> <li> <span class="Bold">Do not</span> inject BREKIYA if the autoinjector appears damaged, if the expiration date has passed, if the liquid medicine is cloudy, discolored or has floating flakes or particles. </li> <li> <span class="Bold">Do not</span> throw away (dispose of) the autoinjector into the household trash. Throw away (dispose of) the autoinjector into a FDA-cleared sharps disposal container. </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Dosing</span> </p> <ul class="Circle"> <li>Follow your healthcare provider’s dosing instructions for how often to inject BREKIYA autoinjector. </li> <li>Each autoinjector contains 1 dose (1 mg) of BREKIYA. After your first dose of BREKIYA, you may give yourself 2 more doses (for a total of 3 mg) as needed. Wait at least 1 hour between doses.</li> <li> <span class="Bold">Do not</span> inject more than 3 doses (3 mg) of BREKIYA in 1 day (24-hour) period.</li> <li> <span class="Bold">Do not</span> inject more than 6 doses (6 mg) during a 1-week (7-day) period. </li> </ul>  </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Storing BREKIYA Autoinjector</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <ul class="Circle"> <li>Store the BREKIYA autoinjector at room temperature between 68°F to 77°F (20°C to 25°C). </li> <li>Protect BREKIYA from light.</li> <li>Keep BREKIYA in the carton until ready to use. </li> <li> <span class="Bold">Do not</span> refrigerate or freeze BREKIYA.</li> </ul> <p class="First"> <span class="Bold">Keep BREKIYA and all medicines out of the reach of children.  </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Autoinjector Parts</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">This autoinjector is a prefilled single dose (1 time use), disposable device that gives a 1 mg subcutaneous (under the skin) injection of BREKIYA. Figure A shows a new and used autoinjector.</p> <img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-4.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-5.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p> <span class="Bold"> </span> </p> <p> <span class="Bold">Figure A</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Preparing to Inject BREKIYA </span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Step 1: Wash Hands and Gather Supplies</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">1.1</span> Before you begin, wash your hands with soap and water (See Figure B). </p>  </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-6.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure B</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">1.2</span> Gather the following supplies (See Figure C): </p> <ul class="Circle"> <li>BREKIYA autoinjector foil pouch (inside carton)</li> <li>Alcohol swab</li> <li>Cotton balls or gauze</li> <li>Sharps container [See “Throwing Away (Disposing of) BREKIYA”]</li> </ul>  </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-7.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/></span> </p> <p> <span class="Bold">Figure C</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Step 2: Remove and Inspect the Autoinjector</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">2.1</span> Tear open the foil pouch from the notch to remove the autoinjector (See Figure D). </p>  </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-8.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure D</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">  <p class="First"> <span class="Bold">2.2</span> Check the expiration date printed on the autoinjector (See Figure E). Do not use the autoinjector if the expiration date has passed. </p> <p> <span class="Bold">2.3</span> Check the liquid medicine in BREKIYA by looking through the viewing window (See Figure E). The liquid medicine in BREKIYA should be clear and colorless. It is normal to see one or more air bubbles.</p> <p> <span class="Bold">Do not </span>inject if the liquid medicine appears cloudy, discolored, or has floating flakes or particles. </p> <p> <span class="Bold">Do not </span>inject if the autoinjector appears to be damaged or broken. </p> </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-9.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure E</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Step 3: Select and Prepare Injection Site</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">3.1</span> Locate your injection site. BREKIYA autoinjector should be injected into the skin in the middle of your thigh (See Figure F). </p> <p> <span class="Bold">Do not</span> inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard. </p> <p> <span class="Bold">Do not </span>inject through clothing. </p> <p> <span class="Bold">Do not </span>inject into the same spot 2 times in a row. </p> <span class="Bold">Important:</span> This injection should be at least 2 inches away from the last injection site.  </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-10.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure F</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">3.2</span> Clean the injection site with an alcohol swab (See Figure G). </p> <p>Wait for the injection site to air dry before giving the injection. Do not touch the clean injection site again before you inject BREKIYA.</p>  </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-11.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure G</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Injecting BREKIYA </span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Step 4: Remove Red Needle Cap and Position the Autoinjector</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">4.1</span> Remove the red needle cap by pulling it straight off (See Figure H) and throw it away in the household trash. </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Do not </span>bend or twist the cap while removing. </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Do not </span>touch the white safety guard after the red needle cap is removed. </p>  </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-12.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure H</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">4.2</span> Position the autoinjector straight onto the cleaned injection site with the white safety guard resting on the skin (See Figure I). </p>  </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-13.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/></span> </p> <p> <span class="Bold">Figure I</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Step 5: Give Injection</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">5.1</span> Push the autoinjector down against the skin until you do not see the white safety guard (See Figure J). </p> <span class="Bold">Important:</span> Keep downward pressure on the skin throughout the injection process. <span class="Italics"> </span> </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-14.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure J</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">5.2</span> Press and release the gray activation button to start the injection (See Figure K). You will hear a “click” sound when the injection starts. </p> <p> <span class="Bold">Be Patient. Do not </span>lift the autoinjector after the first click. </p> <span class="Bold">Important: </span>If you do not hear a “click” when you press the gray activation button, make sure that the autoinjector is pressed down against the skin, then try again. </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-15.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure K</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">5.3</span> Hold the autoinjector down against the skin for at least 10 seconds to make sure you get the full dose of BREKIYA (See Figure L).</p> <p> <span class="Bold">Note:</span> You may hear a second “click”, which means you are close to the end of the injection. Whether or not you hear a second “click” you must hold down the autoinjector against your skin for at least 10 seconds. </p> Do not lift up the autoinjector early. </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-16.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure L</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">5.4</span> Make sure the injection is finished by looking at the viewing window. The viewing window will turn completely blue (See Figure M) when the full dose of BREKIYA has been given. </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Note: </span>Even if the inspection window is not completely blue, do not try to use the autoinjector again.</p>  </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-17.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure M</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Throwing Away (Disposing of) BREKIYA Autoinjector</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Step 6: Lift and Throw away (dispose of)</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">6.1</span> Lift the autoinjector straight up, away from the skin. The white safety guard will drop down and lock over the needle (See Figure N).  </p> <p> <span class="Bold"> </span> </p> <span class="Bold">Note:</span> If you think that you have not received the full dose, do not repeat the injection using a new autoinjector. Call your healthcare provider right away for assistance. </td><td class="Botrule Lrule Rrule Toprule"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-18.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/><p class="First"> <span class="Bold">Figure N</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">6.2</span> Throw away (dispose of) the used autoinjector into a FDA-cleared sharps disposal container (See Figure O). </p> <p> <span class="Bold">Do not </span>throw away (dispose of) the autoinjector into household trash. </p>  </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-19.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/></span> </p> <p> <span class="Bold">Figure O</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">6.3 </span>Treat the injection site as needed (See Figure P). It is normal to see a drop of blood or medicine at the injection site. It will not affect your dose.  </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold"><img alt="1" src="/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-20.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2"/></span> </p> <p> <span class="Bold">Figure P</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Additional Information on how to Throw Away (Dispose of) BREKIYA</span> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <ul class="Circle"> <li>Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. <span class="Bold">Do not throw away (dispose of) loose needles and syringes in your household trash.</span> </li> <li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: </li> </ul> <ul class="Circle"> <li>made of a heavy-duty plastic,</li> <li>can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, </li> <li>upright and stable during use, </li> <li>leak-resistant, and</li> <li>properly labeled to warn of hazardous waste inside the container. </li> </ul> <ul class="Disc"> <li>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: <a href="http://www.fda.gov/safesharpsdisposal">http://www.fda.gov/safesharpsdisposal</a> </li> <li>Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</li> </ul> <p class="First">Distributed by:</p> <p> <span class="Bold">Amneal Specialty, a division of Amneal Pharmaceuticals LLC</span> </p> <p>Bridgewater, NJ  08807<br/> <br/> Manufactured by:</p> <p> <span class="Bold">Amneal Pharmaceuticals Pvt. Ltd.</span> </p> <p>Ahmedabad 382213, INDIA<br/> <br/> <span class="Bold">For more information or to report side-effects, call 1-877-835-5472.<br/> <br/> </span>Rev. 05-2025-00 </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"17px\"/>\n<col width=\"17px\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Lrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-2.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/> </td><td class=\"Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-3.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/> </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">This Instructions for Use contains information on how to inject BREKIYA.</p>\n If there are any questions concerning the use of BREKIYA autoinjector, ask your healthcare provider, pharmacist or visit www.brekiya.com. </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Important Information You Need to Know Before Injecting BREKIYA</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Warnings</span>\n</p>\n<ul class=\"Circle\">\n<li>BREKIYA is for injection under the skin (subcutaneous) only.</li>\n<li>The rigid needle shield of the BREKIYA autoinjector contains a needle cover (located inside the cap) that contains dry natural rubber, which is made from latex. Tell your healthcare provider if you are allergic to latex. </li>\n<li>\n<span class=\"Bold\">Do not</span> remove the red needle cap until you are ready to inject BREKIYA. Inject BREKIYA right away after removing the red needle cap. </li>\n<li>\n<span class=\"Bold\">Do not</span> inject BREKIYA if the autoinjector appears damaged, if the expiration date has passed, if the liquid medicine is cloudy, discolored or has floating flakes or particles. </li>\n<li>\n<span class=\"Bold\">Do not</span> throw away (dispose of) the autoinjector into the household trash. Throw away (dispose of) the autoinjector into a FDA-cleared sharps disposal container. </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Dosing</span>\n</p>\n<ul class=\"Circle\">\n<li>Follow your healthcare provider’s dosing instructions for how often to inject BREKIYA autoinjector.\n </li>\n<li>Each autoinjector contains 1 dose (1 mg) of BREKIYA. After your first dose of BREKIYA, you may give yourself 2 more doses (for a total of 3 mg) as needed. Wait at least 1 hour between doses.</li>\n<li>\n<span class=\"Bold\">Do not</span> inject more than 3 doses (3 mg) of BREKIYA in 1 day (24-hour) period.</li>\n<li>\n<span class=\"Bold\">Do not</span> inject more than 6 doses (6 mg) during a 1-week (7-day) period. </li>\n</ul>\n  </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Storing BREKIYA Autoinjector</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>Store the BREKIYA autoinjector at room temperature between 68°F to 77°F (20°C to 25°C). </li>\n<li>Protect BREKIYA from light.</li>\n<li>Keep BREKIYA in the carton until ready to use. </li>\n<li>\n<span class=\"Bold\">Do not</span> refrigerate or freeze BREKIYA.</li>\n</ul>\n<p class=\"First\">\n<span class=\"Bold\">Keep BREKIYA and all medicines out of the reach of children.  </span> </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Autoinjector Parts</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">This autoinjector is a prefilled single dose (1 time use), disposable device that gives a 1 mg subcutaneous (under the skin) injection of BREKIYA. Figure A shows a new and used autoinjector.</p>\n<img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-4.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-5.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Figure A</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Preparing to Inject BREKIYA </span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Step 1: Wash Hands and Gather Supplies</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">1.1</span> Before you begin, wash your hands with soap and water (See Figure B). </p>\n  </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-6.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure B</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">1.2</span> Gather the following supplies (See Figure C): </p>\n<ul class=\"Circle\">\n<li>BREKIYA autoinjector foil pouch (inside carton)</li>\n<li>Alcohol swab</li>\n<li>Cotton balls or gauze</li>\n<li>Sharps container [See “Throwing Away (Disposing of) BREKIYA”]</li>\n</ul>\n  </td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-7.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/></span>\n</p>\n<p>\n<span class=\"Bold\">Figure C</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Step 2: Remove and Inspect the Autoinjector</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">2.1</span> Tear open the foil pouch from the notch to remove the autoinjector (See Figure D). </p>\n  </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-8.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure D</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> \n <p class=\"First\">\n<span class=\"Bold\">2.2</span> Check the expiration date printed on the autoinjector (See Figure E). Do not use the autoinjector if the expiration date has passed.\n </p>\n<p>\n<span class=\"Bold\">2.3</span> Check the liquid medicine in BREKIYA by looking through the viewing window (See Figure E). The liquid medicine in BREKIYA should be clear and colorless. It is normal to see one or more air bubbles.</p>\n<p>\n<span class=\"Bold\">Do not </span>inject if the liquid medicine appears cloudy, discolored, or has floating flakes or particles. </p>\n<p>\n<span class=\"Bold\">Do not </span>inject if the autoinjector appears to be damaged or broken. </p>\n</td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-9.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure E</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Step 3: Select and Prepare Injection Site</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">3.1</span> Locate your injection site. BREKIYA autoinjector should be injected into the skin in the middle of your thigh (See Figure F). </p>\n<p>\n<span class=\"Bold\">Do not</span> inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard. </p>\n<p>\n<span class=\"Bold\">Do not </span>inject through clothing. </p>\n<p>\n<span class=\"Bold\">Do not </span>inject into the same spot 2 times in a row. </p>\n<span class=\"Bold\">Important:</span> This injection should be at least 2 inches away from the last injection site.  </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-10.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure F</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">3.2</span> Clean the injection site with an alcohol swab (See Figure G). </p>\n<p>Wait for the injection site to air dry before giving the injection. Do not touch the clean injection site again before you inject BREKIYA.</p>\n  </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-11.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure G</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Injecting BREKIYA </span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Step 4: Remove Red Needle Cap and Position the Autoinjector</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">4.1</span> Remove the red needle cap by pulling it straight off (See Figure H) and throw it away in the household trash. </p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Do not </span>bend or twist the cap while removing. </p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Do not </span>touch the white safety guard after the red needle cap is removed. </p>\n  </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-12.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure H</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">4.2</span> Position the autoinjector straight onto the cleaned injection site with the white safety guard resting on the skin (See Figure I). </p>\n  </td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-13.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/></span>\n</p>\n<p>\n<span class=\"Bold\">Figure I</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Step 5: Give Injection</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">5.1</span> Push the autoinjector down against the skin until you do not see the white safety guard (See Figure J). </p>\n<span class=\"Bold\">Important:</span> Keep downward pressure on the skin throughout the injection process. <span class=\"Italics\"> </span> </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-14.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure J</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">5.2</span> Press and release the gray activation button to start the injection (See Figure K). You will hear a “click” sound when the injection starts. </p>\n<p>\n<span class=\"Bold\">Be Patient. Do not </span>lift the autoinjector after the first click. </p>\n<span class=\"Bold\">Important: </span>If you do not hear a “click” when you press the gray activation button, make sure that the autoinjector is pressed down against the skin, then try again. </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-15.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure K</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">5.3</span> Hold the autoinjector down against the skin for at least 10 seconds to make sure you get the full dose of BREKIYA (See Figure L).</p>\n<p>\n<span class=\"Bold\">Note:</span> You may hear a second “click”, which means you are close to the end of the injection. Whether or not you hear a second “click” you must hold down the autoinjector against your skin for at least 10 seconds. </p>\n Do not lift up the autoinjector early. </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-16.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure L</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">5.4</span> Make sure the injection is finished by looking at the viewing window. The viewing window will turn completely blue (See Figure M) when the full dose of BREKIYA has been given. </p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Note: </span>Even if the inspection window is not completely blue, do not try to use the autoinjector again.</p>\n  </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-17.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure M</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Throwing Away (Disposing of) BREKIYA Autoinjector</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Step 6: Lift and Throw away (dispose of)</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">6.1</span> Lift the autoinjector straight up, away from the skin. The white safety guard will drop down and lock over the needle (See Figure N).  </p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<span class=\"Bold\">Note:</span> If you think that you have not received the full dose, do not repeat the injection using a new autoinjector. Call your healthcare provider right away for assistance. </td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-18.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/><p class=\"First\">\n<span class=\"Bold\">Figure N</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">6.2</span> Throw away (dispose of) the used autoinjector into a FDA-cleared sharps disposal container (See Figure O). </p>\n<p>\n<span class=\"Bold\">Do not </span>throw away (dispose of) the autoinjector into household trash. </p>\n  </td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-19.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/></span>\n</p>\n<p>\n<span class=\"Bold\">Figure O</span> </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">6.3 </span>Treat the injection site as needed (See Figure P). It is normal to see a drop of blood or medicine at the injection site. It will not affect your dose.  </td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"1\" src=\"/dailymed/image.cfm?name=brekiya---dihydroergotamine-mesylate-injection-20.jpg&amp;setid=cdbf5619-767f-4165-aec2-17bdd92d9ca2\"/></span>\n</p>\n<p>\n<span class=\"Bold\">Figure P</span> </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Additional Information on how to Throw Away (Dispose of) BREKIYA</span> </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. <span class=\"Bold\">Do not throw away (dispose of) loose needles and syringes in your household trash.</span>\n</li>\n<li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: </li>\n</ul>\n<ul class=\"Circle\">\n<li>made of a heavy-duty plastic,</li>\n<li>can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, </li>\n<li>upright and stable during use, </li>\n<li>leak-resistant, and</li>\n<li>properly labeled to warn of hazardous waste inside the container. </li>\n</ul>\n<ul class=\"Disc\">\n<li>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: <a href=\"http://www.fda.gov/safesharpsdisposal\">http://www.fda.gov/safesharpsdisposal</a>\n</li>\n<li>Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</li>\n</ul>\n<p class=\"First\">Distributed by:</p>\n<p>\n<span class=\"Bold\">Amneal Specialty, a division of Amneal Pharmaceuticals LLC</span>\n</p>\n<p>Bridgewater, NJ  08807<br/>\n<br/>\n Manufactured by:</p>\n<p>\n<span class=\"Bold\">Amneal Pharmaceuticals Pvt. Ltd.</span>\n</p>\n<p>Ahmedabad 382213, INDIA<br/>\n<br/>\n<span class=\"Bold\">For more information or to report side-effects, call 1-877-835-5472.<br/>\n<br/>\n</span>Rev. 05-2025-00 </p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Instructions for Use have been approved by the U.S. Food and Drug Administration                                                                                                                     Issued: 05/2025

{ "type": "p", "children": [], "text": "This Instructions for Use have been approved by the U.S. Food and Drug Administration                                                                                                                     Issued: 05/2025" }

NDC 64896-509-01

BREKIYA® (dihydroergotamine mesylate) injection, 1 mg/mL

Rx only

Autoinjector Label

Amneal Pharmaceuticals LLC

NDC 64896-509-01

BREKIYA® (dihydroergotamine mesylate) injection, 1 mg/mL

Rx only

Pouch

Amneal Pharmaceuticals LLC

NDC 64896-509-02

BREKIYA® (dihydroergotamine mesylate) injection, 1 mg/mL

Rx only

Carton

Amneal Pharmaceuticals LLC

Limitations of Use

TRUDHESA is not indicated for the preventive treatment of migraine.

TRUDHESA is not indicated for the management of hemiplegic or basilar migraine.

The recommended dose of TRUDHESA is 1.45 mg administered as two metered sprays into the nose (one spray of 0.725 mg into each nostril).

The dose may be repeated, if needed, a minimum of 1 hour after the first dose. Do not use more than 2 doses of TRUDHESA within a 24-hour period or 3 doses within a 7-day period.

Prior to initiation of TRUDHESA, a cardiovascular evaluation is recommended [see Warnings and Precautions (5.2)]. For patients with risk factors predictive of coronary artery disease who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of TRUDHESA take place in the setting of an equipped healthcare facility.

TRUDHESA is for nasal administration only and must not be injected.

TRUDHESA must be assembled prior to use (see Instructions for Use). Use or discard TRUDHESA within 8 hours once the vial has been opened or the product has been assembled.

Prime the assembled TRUDHESA before initial use by releasing 4 sprays. Use TRUDHESA immediately after priming. Discard TRUDHESA immediately after use. Open and prepare a new TRUDHESA if an additional dose is needed.

TRUDHESA (dihydroergotamine mesylate) nasal spray is a single-dose, drug-device combination product containing a vial of dihydroergotamine mesylate with a clear and colorless to faintly yellow solution and an intranasal delivery device. Each spray delivers 0.725 mg of dihydroergotamine mesylate.

{ "type": "p", "children": [], "text": "TRUDHESA (dihydroergotamine mesylate) nasal spray is a single-dose, drug-device combination product containing a vial of dihydroergotamine mesylate with a clear and colorless to faintly yellow solution and an intranasal delivery device. Each spray delivers 0.725 mg of dihydroergotamine mesylate." }

TRUDHESA is contraindicated in patients:

{ "type": "p", "children": [], "text": "TRUDHESA is contraindicated in patients:" }

{ "type": "ul", "children": [ "with concomitant use of strong CYP3A4 inhibitors, such as protease inhibitors (e.g., ritonavir, nelfinavir, or indinavir), macrolide antibiotics (e.g., erythromycin or clarithromycin), and antifungals (ketoconazole or itraconazole) [see Warnings and Precautions (5.1) and Drug Interactions (7.1)]\n", "with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina [see Warnings and Precautions (5.4)]\n", "with uncontrolled hypertension [see Warnings and Precautions (5.5)]\n", "with peripheral arterial disease", "with sepsis", "following vascular surgery", "with severe hepatic impairment", "with severe renal impairment", "with known hypersensitivity to ergot alkaloids", "with recent use (i.e., within 24 hours) of other 5-HT1 agonists (e.g., sumatriptan) or ergotamine-containing or ergot-type medications [see Drug Interactions (7.2)]\n", "with concomitant use of peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure [see Warnings and Precautions (5.5)]\n" ], "text": "" }

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors, including protease inhibitors, macrolide antibiotics, and antifungals. 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 TRUDHESA with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4) and Drug Interactions (7.1)].

The potential for adverse cardiac adverse reactions exists with TRUDHESA treatment. Serious adverse cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine mesylate. These events have included acute myocardial infarction, life-threatening disturbances of cardiac rhythm (e.g., ventricular tachycardia and ventricular fibrillation), coronary artery vasospasm, and transient myocardial ischemia.

Prior to initiation of TRUDHESA, a cardiovascular evaluation is recommended to determine if the patient is free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. If, during the cardiovascular evaluation, the patient's medical history (including risk factors), or electrocardiographic investigation, findings are consistent with coronary artery vasospasm or myocardial ischemia, TRUDHESA should not be administered [see Contraindications (4)].

For patients with risk factors predictive of coronary artery disease (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of coronary artery disease, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of TRUDHESA take place in the setting of an equipped healthcare facility, unless the patient has previously received dihydroergotamine mesylate. During the interval immediately following the first use of TRUDHESA, an electrocardiogram is recommended in those patients with risk factors because ischemia can occur in the absence of clinical symptoms.

The potential for adverse cerebrovascular adverse reactions exists with TRUDHESA treatment. Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with dihydroergotamine mesylate; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the dihydroergotamine mesylate having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack). Discontinue TRUDHESA if a cerebrovascular event is suspected.

TRUDHESA, like other ergot alkaloids, may cause vasospastic reactions other than coronary artery vasospasm. Myocardial, peripheral vascular, and colonic ischemia have been reported with dihydroergotamine mesylate.

Dihydroergotamine mesylate associated vasospastic phenomena may also cause muscle pains, numbness, coldness, pallor, and cyanosis of the digits. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. TRUDHESA should be discontinued immediately if signs or symptoms of vasoconstriction develop.

Patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud's syndrome, following the use of any 5-HT agonist, including TRUDHESA, should be evaluated by a healthcare provider.

Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension treated with dihydroergotamine mesylate. TRUDHESA is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].

An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5-HT1 agonist in a study evaluating subjects undergoing cardiac catheterization.

Overuse of acute migraine drugs (e.g., ergotamines, triptans, opioids, or a combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

Based on the mechanism of action of dihydroergotamine and findings from the published literature, TRUDHESA may cause preterm labor. Avoid use of TRUDHESA during pregnancy [see Use in Specific Populations (8.1)].

The potential for fibrotic complications exists with TRUDHESA treatment. There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of dihydroergotamine mesylate. Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis. Rare cases have also been reported in association with the use of dihydroergotamine mesylate; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis.

Administration of TRUDHESA should not exceed the dosing guidelines and should not be used for chronic daily administration [see Dosage and Administration (2.1)].

Local irritative symptoms were reported in 52% of patients treated with at least one dose of TRUDHESA in an open-labeled trial, which allowed repeated use of TRUDHESA over 6 to 12 months. The most common local irritative symptoms (at least 1% of patients) were nasopharyngitis (21%), rhinitis (19%), nasal discomfort (7%), product taste abnormal/dysgeusia (6%), sinusitis (5%), sinus discomfort (4%), olfactory test abnormal [defined based on a change in score at a prespecified threshold on the University of Pennsylvania Smell Identification Test (UPSIT)] (4%), epistaxis (3%), pharyngitis (3%), nasal mucosal disorder (2%), change in smell (1%), ear discomfort (1%), and rhinorrhea (1%). If a severe local irritation event occurs for no other attributable reasons, TRUDHESA should be temporarily suspended until the event resolves. If the event does not resolve, or it recurs with re-challenge, TRUDHESA should be discontinued permanently. Administration of TRUDHESA should not exceed the dosing guidelines and should not be used for chronic daily administration [see Dosage and Administration (2.1)].

Nasal tissue in animals treated with dihydroergotamine mesylate daily showed mild mucosal irritation characterized by mucous cell and transitional cell hyperplasia and squamous cell metaplasia. Changes in rat nasal mucosa at 64 weeks were less severe than at 13 weeks. Local effects on respiratory tissue after chronic intranasal dosing in animals have not been evaluated.

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.

Adverse Reactions in Placebo-Controlled Trials with Dihydroergotamine (DHE) Mesylate Nasal Spray [see Clinical Studies (14)]

Of the 1,796 patients and subjects treated with DHE nasal spray doses 2 mg or less in U.S. and foreign clinical studies, 26 (1.4%) discontinued because of adverse events. The adverse events associated with discontinuation were, in decreasing order of frequency: rhinitis (13), dizziness (2), facial edema (2), and one patient each due to cold sweats, accidental trauma, depression, elective surgery, somnolence, allergy, vomiting, hypotension, and paraesthesia.

Table 1 summarizes the incidence rates of adverse reactions reported by at least 1% of patients who received DHE nasal spray for the treatment of migraine during placebo-controlled, double-blind clinical studies and were more frequent than in those patients receiving placebo. The most commonly reported adverse reactions (greater than 1% of patients who received DHE nasal spray) were rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea. In most instances these events were transient and self-limited and did not result in patient discontinuation from a study.

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 1 Adverse Reactions Reported by at Least 1% of the DHE Nasal Spray Treated Patients and Occurred more Frequently than in the Placebo-Group in the Migraine Placebo-Controlled Trials</span> </caption> <col align="left" valign="top" width="30%"/> <col align="center" valign="top" width="30%"/> <col align="center" valign="top" width="40%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">DHE Nasal Spray<br/>N=597<br/>%</th><th align="center" class="Rrule">Placebo<br/>N=631<br/>%</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Respiratory System</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Rhinitis</td><td align="center" class="Rrule">26</td><td align="center" class="Rrule">7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Pharyngitis</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Gastrointestinal System</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Nausea</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Vomiting</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Diarrhea</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Special Senses, Other</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Altered Sense of Taste</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Application Site</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Application Site Reaction</td><td align="center" class="Rrule">6</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Central and Peripheral Nervous System</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Dizziness</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Somnolence</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Body as a Whole, General</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Hot Flashes</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Asthenia</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Musculoskeletal System</span></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Stiffness</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">&lt;1</td> </tr> </tbody> </table></div>

Adverse Reactions in Studies with TRUDHESA

An open-label study in adults (18 to 66 years of age) was conducted to evaluate the safety and tolerability of TRUDHESA, repeated use of TRUDHESA was allowed over the course of 6 to 12 months. A total of 354 patients with migraine received at least one dose of TRUDHESA. One hundred and eighty-five patients treated on average at least two migraines per month for 6 months, and 55 patients treated on average at least two migraines per month for 12 months. Of the patients who received at least one dose of TRUDHESA, 185 (52.3%) patients experienced local irritative symptoms. Of these, the most common local irritative symptoms were nasopharyngitis, rhinitis, nasal discomfort, product taste abnormal/dysgeusia, sinusitis, sinus discomfort, olfactory test abnormal, epistaxis, pharyngitis, nasal mucosal disorder, change in smell, ear discomfort, and rhinorrhea [see Warnings and Precautions (5.9)].

The following adverse reactions have been identified during postapproval use of dihydroergotamine mesylate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Vasospasm, paresthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use of dihydroergotamine. Cases of myocardial infarction and stroke have been reported following the use of dihydroergotamine mesylate [see Warnings and Precautions (5.2)].

There have been rare reports of serious adverse events in connection with the coadministration of intravenous administration of dihydroergotamine and strong CYP3A4 inhibitors, such as protease inhibitors (e.g., ritonavir, nelfinavir, indinavir), macrolide antibiotics (e.g., erythromycin, clarithromycin), and antifungals (e.g., ketoconazole, itraconazole), resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities [see Warnings and Precautions (5.1)]. The use of strong CYP3A4 inhibitors with dihydroergotamine is contraindicated [see Contraindications (4)]. Administer moderate CYP3A4 inhibitors (e.g., saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, clotrimazole) with caution.

Triptans (serotonin [5-HT] 1B/1D receptor agonists) have been reported to cause coronary artery vasospasm, and its effect could be additive with TRUDHESA. Therefore, triptans and TRUDHESA should not be taken within 24 hours of each other [see Contraindications (4)].

There have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.

TRUDHESA is contraindicated for use with peripheral and central vasoconstrictors because the combination may cause synergistic elevation of blood pressure [see Warnings and Precautions (5.5)].

Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy [see Warnings and Precautions (5.1, 5.5)].

Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT1 agonists have been coadministered with selective serotonin reuptake inhibitors (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline).

Risk Summary

Available data from published literature indicate an increased risk of preterm delivery with TRUDHESA use during pregnancy. Avoid use of TRUDHESA during pregnancy [see Warnings and Precautions (5.7)]. Data collected over decades have shown no increased risk of major birth defects or miscarriage with use of dihydroergotamine mesylate during pregnancy.

In animal studies, adverse effects on embryofetal development were observed following administration of dihydroergotamine mesylate during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation in rats (decreased body weight and impaired reproductive function in the offspring) in rats at doses less than those used clinically and which were not associated with maternal toxicity (see Data).

The estimated rate of major birth defects (2.2% to 2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

Intranasal administration of dihydroergotamine mesylate to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weight and/or skeletal ossification at doses of 0.16 mg/day (associated with plasma exposures [AUC] less than that in humans at the maximum recommended human dose [MRHD] of 2.9 mg) or greater. A no-effect level for embryofetal toxicity was not identified in rats. Intranasal administration of dihydroergotamine mesylate to pregnant rabbits throughout organogenesis resulted in decreased skeletal ossification at 3.6 mg/day. At the no-effect dose (1.2 mg/day) for adverse effects on embryofetal development in rabbits, plasma exposures (AUC) were less than that in humans at the MRHD.

Intranasal administration of dihydroergotamine mesylate to female rats throughout pregnancy and lactation resulted in decreased body weight and impaired reproductive function (decreased mating indices) were observed in the offspring at doses of 0.16 mg/day or greater. A no-effect dose for adverse developmental effects in rats was not established.

Effects on development occurred at doses below those that produced evidence of significant maternal toxicity in these studies.

Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.

Risk Summary

There are no data on the presence of dihydroergotamine in human milk; however, ergotamine, a related drug, is present in human milk. There are reports of diarrhea, vomiting, weak pulse, and unstable blood pressure in breastfed infants exposed to ergotamine. TRUDHESA may reduce milk supply because it may decrease prolactin levels. Because of the potential for reduced milk supply and serious adverse events in the breastfed infant, including diarrhea, vomiting, weak pulse, and unstable blood pressure, advise patients not to breastfeed during treatment with TRUDHESA and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded.

Safety and effectiveness in pediatric patients have not been established.

Clinical studies of TRUDHESA and other dihydroergotamine mesylate products did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

TRUDHESA contains dihydroergotamine (as the mesylate salt), which is not a controlled substance.

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Currently available data have not demonstrated drug abuse with dihydroergotamine. However, cases of drug abuse in patients on other forms of ergot therapy have been reported.

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Currently available data have not demonstrated physical or psychological dependence with dihydroergotamine. However, cases of psychological dependence in patients on other forms of ergot therapy have been reported.

Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism. In general, the symptoms of an acute TRUDHESA overdose are similar to those of an ergotamine overdose, although there may be less pronounced nausea and vomiting with TRUDHESA. The symptoms of an ergotamine overdose include the following: numbness, tingling, pain, and cyanosis of the extremities associated with diminished or absent peripheral pulses; respiratory depression; an increase and/or decrease in blood pressure, usually in that order; confusion, delirium, convulsions, and coma; and/or some degree of nausea, vomiting, and abdominal pain.

In laboratory animals, dihydroergotamine was lethal when given at intravenous doses of 44 mg/kg in mice, 130 mg/kg in rats, and 37 mg/kg in rabbits.

Treatment includes discontinuance of the drug, local application of warmth to the affected area, the administration of vasodilators, and nursing care to prevent tissue damage. Up-to-date information about the treatment of overdosage can often be obtained from a certified Regional Poison Control Center.

TRUDHESA (dihydroergotamine mesylate) nasal spray is a single-dose, drug-device combination product containing a dihydroergotamine mesylate drug constituent and a nasal spray device constituent.

{ "type": "p", "children": [], "text": "TRUDHESA (dihydroergotamine mesylate) nasal spray is a single-dose, drug-device combination product containing a dihydroergotamine mesylate drug constituent and a nasal spray device constituent. " }

The chemical name for dihydroergotamine mesylate is ergotaman-3', 6', 18-trione, 9,10-dihydro-12'-hydroxy-2'-methyl-5'- (phenylmethyl)-, (5'α)-, monomethanesulfonate. Its molecular weight is 679.78, and its molecular formula is C33H37N5O5∙CH4O3S.

{ "type": "p", "children": [], "text": "The chemical name for dihydroergotamine mesylate is ergotaman-3', 6', 18-trione, 9,10-dihydro-12'-hydroxy-2'-methyl-5'- (phenylmethyl)-, (5'α)-, monomethanesulfonate. Its molecular weight is 679.78, and its molecular formula is C33H37N5O5∙CH4O3S." }

The chemical structure is:

{ "type": "p", "children": [], "text": "The chemical structure is:" }

{ "type": "", "children": [], "text": "" }

The drug constituent is a dihydroergotamine mesylate solution. Each milliliter (mL) of solution contains dihydroergotamine mesylate 4.0 mg (equivalent to 3.43 mg dihydroergotamine), and the following inactive ingredients: caffeine (10.0 mg), carbon dioxide (q.s.), dextrose (50.0 mg), and water (q.s. to 1.0 mL).

{ "type": "p", "children": [], "text": "The drug constituent is a dihydroergotamine mesylate solution. Each milliliter (mL) of solution contains dihydroergotamine mesylate 4.0 mg (equivalent to 3.43 mg dihydroergotamine), and the following inactive ingredients: caffeine (10.0 mg), carbon dioxide (q.s.), dextrose (50.0 mg), and water (q.s. to 1.0 mL). " }

TRUDHESA nasal spray, after assembly and priming, delivers 0.725 mg dihydroergotamine mesylate per spray. A total dose of 1.45 mg of dihydroergotamine mesylate is delivered in 2 sprays. The nasal spray device contains hydrofluoroalkane-134a (HFA) propellant.

{ "type": "p", "children": [], "text": "TRUDHESA nasal spray, after assembly and priming, delivers 0.725 mg dihydroergotamine mesylate per spray. A total dose of 1.45 mg of dihydroergotamine mesylate is delivered in 2 sprays. The nasal spray device contains hydrofluoroalkane-134a (HFA) propellant." }

Dihydroergotamine binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effects at 5-HT1D receptors.

Significant elevation in blood pressure has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.5)].

Dihydroergotamine possesses oxytocic properties [see Warnings and Precautions (5.7)].

Absorption

The mean time from dosing to maximum plasma concentration following TRUDHESA administration was approximately 0.5 hours.

Distribution

Dihydroergotamine mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.

Elimination

Metabolism

Four dihydroergotamine mesylate metabolites have been identified in human plasma following oral administration. The major metabolite, 8'-β-hydroxy dihydroergotamine, exhibits affinity equivalent to its parent for adrenergic and 5-HT receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites, i.e., dihydrolysergic acid, dihydrolysergic amide, and a metabolite formed by oxidative opening of the proline ring, are of minor importance. Following nasal administration, total metabolites represent only 20% to 30% of plasma AUC. The systemic clearance of dihydroergotamine mesylate following intravenous and intramuscular administration is 1.5 L/min. Quantitative pharmacokinetic characterization of the four metabolites has not been performed.

Excretion

The major excretory route of dihydroergotamine is via the bile in the feces. The total body clearance is 1.5 L/min, which reflects mainly hepatic clearance. Only 6% to 7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection. The renal clearance (0.1 L/min) is unaffected by the route of dihydroergotamine administration.

The mean apparent half-life of TRUDHESA nasal administration in healthy subjects is approximately 12 hours.

Specific Populations

No studies have been conducted on the effect of renal or hepatic impairment, gender, race, ethnicity, or pregnancy on dihydroergotamine pharmacokinetics [see Contraindications (4), Use in Specific Populations (8.1)].

Drug Interaction Studies

CYP3A4 Inhibitors

Rare reports of ergotism have been obtained from patients treated with dihydroergotamine and macrolide antibiotics (e.g., clarithromycin, erythromycin) and from patients treated with dihydroergotamine and protease inhibitors (e.g., ritonavir), presumably due to inhibition of CYP3A metabolism of ergotamine [see Contraindications (4)].

Other Drugs

The pharmacokinetics of dihydroergotamine did not appear to be significantly affected by the concomitant use of a local vasoconstrictor.

Multiple oral doses of the β-adrenoceptor antagonist propranolol, used for migraine prophylaxis, had no significant influence on the Cmax, tmax, or AUC of dihydroergotamine doses up to 4 mg. However, propranolol may potentiate the vasoconstrictive action of ergotamine [see Drug Interactions (7.3)].

The effect of oral contraceptives on the pharmacokinetics of TRUDHESA has not been studied.

Carcinogenesis

Assessment of the carcinogenic potential of dihydroergotamine mesylate in mice and rats has not been assessed.

Mutagenesis

Dihydroergotamine mesylate was negative in an in vitro mutagenicity (Ames) assay and positive in in vitro chromosomal aberration (V79 Chinese hamster cell assay with metabolic activation, and human peripheral blood lymphocyte) assays. Dihydroergotamine was negative in in vivo micronucleus assays in mouse and hamster.

Impairment of Fertility

There was no evidence of impairment of fertility in rats given intranasal doses of dihydroergotamine mesylate up to 1.6 mg/day, which was associated with plasma exposures (AUC) approximately 3 times that in humans at the maximum recommended human dose of 2.9 mg/day.

The efficacy of TRUDHESA is based on the relative bioavailability of TRUDHESA nasal spray compared to dihydroergotamine mesylate nasal spray in healthy subjects.

{ "type": "p", "children": [], "text": "The efficacy of TRUDHESA is based on the relative bioavailability of TRUDHESA nasal spray compared to dihydroergotamine mesylate nasal spray in healthy subjects.\n" }

The clinical studies described below were conducted using dihydroergotamine mesylate nasal spray.

{ "type": "p", "children": [], "text": "The clinical studies described below were conducted using dihydroergotamine mesylate nasal spray." }

The efficacy of dihydroergotamine mesylate nasal spray for the acute treatment of migraine headaches was evaluated in four randomized, double-blind, placebo controlled studies in the U.S. The patient population for the trials was predominantly female (87%) and Caucasian (95%) with a mean age of 39 years (range 18 to 65 years). Patients treated a single moderate to severe migraine headache with a single dose of study medication 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 four-point pain intensity scale was utilized; in studies 3 and 4, a five-point scale was used to record pain response. Although rescue medication was allowed in all four studies, patients were instructed not to use them during the four hour observation period. In studies 3 and 4, a total dose of 2 mg was compared to placebo. In studies 1 and 2, doses of 2 and 3 mg were evaluated, and showed no advantage of the higher dose for a single treatment. In all studies, patients received a regimen consisting of 0.5 mg in each nostril, repeated in 15 minutes (and again in another 15 minutes for the 3 mg dose in studies 1 and 2).

{ "type": "p", "children": [], "text": "The efficacy of dihydroergotamine mesylate nasal spray for the acute treatment of migraine headaches was evaluated in four randomized, double-blind, placebo controlled studies in the U.S. The patient population for the trials was predominantly female (87%) and Caucasian (95%) with a mean age of 39 years (range 18 to 65 years). Patients treated a single moderate to severe migraine headache with a single dose of study medication 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 four-point pain intensity scale was utilized; in studies 3 and 4, a five-point scale was used to record pain response. Although rescue medication was allowed in all four studies, patients were instructed not to use them during the four hour observation period. In studies 3 and 4, a total dose of 2 mg was compared to placebo. In studies 1 and 2, doses of 2 and 3 mg were evaluated, and showed no advantage of the higher dose for a single treatment. In all studies, patients received a regimen consisting of 0.5 mg in each nostril, repeated in 15 minutes (and again in another 15 minutes for the 3 mg dose in studies 1 and 2)." }

The percentage of patients achieving headache response 4 hours after treatment was significantly greater in patients receiving 2 mg doses of dihydroergotamine mesylate nasal spray compared to those receiving placebo in 3 of the 4 studies (see Table 2 and Table 3 and Figure 1 and Figure 2).

{ "type": "p", "children": [], "text": "The percentage of patients achieving headache response 4 hours after treatment was significantly greater in patients receiving 2 mg doses of dihydroergotamine mesylate nasal spray compared to those receiving placebo in 3 of the 4 studies (see Table 2 and Table 3 and Figure 1 and Figure 2)." }

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 2 Studies 1 and 2: Percentage of Patients with Headache Response<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo)</span> </caption> <col align="left" valign="middle" width="13%"/> <col align="left" valign="middle" width="44%"/> <col align="center" valign="middle" width="9%"/> <col align="center" valign="middle" width="17%"/> <col align="center" valign="middle" width="17%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="left" class="Rrule"></th><th align="center" class="Rrule" valign="bottom">N</th><th align="center" class="Rrule" valign="bottom">2 hours</th><th align="center" class="Rrule" valign="bottom">4 hours</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale.</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>p value &lt; 0.001</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>p value &lt; 0.01</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" rowspan="2"><span class="Bold">Study 1</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">105</td><td align="center" class="Rrule">61%<a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a></td><td align="center" class="Rrule">70%<a class="Sup" href="#footnote-2">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">98</td><td align="center" class="Rrule">23%</td><td align="center" class="Rrule">28%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">37%</td><td align="center" class="Rrule">42%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2"><span class="Bold">Study 2</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">103</td><td align="center" class="Rrule">47%</td><td align="center" class="Rrule">56%<a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">102</td><td align="center" class="Rrule">33%</td><td align="center" class="Rrule">35%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">14%</td><td align="center" class="Rrule">21%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<caption>\n<span>Table 2 Studies 1 and 2: Percentage of Patients with Headache Response<a class=\"Sup\" href=\"#footnote-1\" name=\"footnote-reference-1\">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo)</span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"13%\"/>\n<col align=\"left\" valign=\"middle\" width=\"44%\"/>\n<col align=\"center\" valign=\"middle\" width=\"9%\"/>\n<col align=\"center\" valign=\"middle\" width=\"17%\"/>\n<col align=\"center\" valign=\"middle\" width=\"17%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Lrule Rrule\"></th><th align=\"left\" class=\"Rrule\"></th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">N</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">2 hours</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">4 hours</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-1\" name=\"footnote-1\">*</a>\n</dt>\n<dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale.</dd>\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">†</a>\n</dt>\n<dd>p value &lt; 0.001</dd>\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">‡</a>\n</dt>\n<dd>p value &lt; 0.01</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\"><span class=\"Bold\">Study 1</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">105</td><td align=\"center\" class=\"Rrule\">61%<a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">†</a></td><td align=\"center\" class=\"Rrule\">70%<a class=\"Sup\" href=\"#footnote-2\">†</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">98</td><td align=\"center\" class=\"Rrule\">23%</td><td align=\"center\" class=\"Rrule\">28%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">37%</td><td align=\"center\" class=\"Rrule\">42%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\"><span class=\"Bold\">Study 2</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">103</td><td align=\"center\" class=\"Rrule\">47%</td><td align=\"center\" class=\"Rrule\">56%<a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">‡</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">102</td><td align=\"center\" class=\"Rrule\">33%</td><td align=\"center\" class=\"Rrule\">35%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">14%</td><td align=\"center\" class=\"Rrule\">21%</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 3 Studies 3 and 4: Percentage of Patients with Headache Response<a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo)</span> </caption> <col align="left" valign="middle" width="13%"/> <col align="left" valign="middle" width="44%"/> <col align="center" valign="middle" width="9%"/> <col align="center" valign="middle" width="17%"/> <col align="center" valign="middle" width="17%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="left" class="Rrule"></th><th align="center" class="Rrule" valign="bottom">N</th><th align="center" class="Rrule" valign="bottom">2 hours</th><th align="center" class="Rrule" valign="bottom">4 hours</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was evaluated on a five-point scale that included pain response.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">†</a> </dt> <dd>p value &lt; 0.01</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" rowspan="2" valign="top"><span class="Bold">Study 3</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">32%</td><td align="center" class="Rrule">48%<a class="Sup" href="#footnote-5" name="footnote-reference-5">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">20%</td><td align="center" class="Rrule">22%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">26%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2" valign="top"><span class="Bold">Study 4</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">47</td><td align="center" class="Rrule">30%</td><td align="center" class="Rrule">47%</td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">20%</td><td align="center" class="Rrule">30%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">10%</td><td align="center" class="Rrule">17%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<caption>\n<span>Table 3 Studies 3 and 4: Percentage of Patients with Headache Response<a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo)</span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"13%\"/>\n<col align=\"left\" valign=\"middle\" width=\"44%\"/>\n<col align=\"center\" valign=\"middle\" width=\"9%\"/>\n<col align=\"center\" valign=\"middle\" width=\"17%\"/>\n<col align=\"center\" valign=\"middle\" width=\"17%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Lrule Rrule\"></th><th align=\"left\" class=\"Rrule\"></th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">N</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">2 hours</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">4 hours</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">*</a>\n</dt>\n<dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was evaluated on a five-point scale that included pain response.</dd>\n<dt>\n<a href=\"#footnote-reference-5\" name=\"footnote-5\">†</a>\n</dt>\n<dd>p value &lt; 0.01</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\" valign=\"top\"><span class=\"Bold\">Study 3</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">50</td><td align=\"center\" class=\"Rrule\">32%</td><td align=\"center\" class=\"Rrule\">48%<a class=\"Sup\" href=\"#footnote-5\" name=\"footnote-reference-5\">†</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">50</td><td align=\"center\" class=\"Rrule\">20%</td><td align=\"center\" class=\"Rrule\">22%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">12%</td><td align=\"center\" class=\"Rrule\">26%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\" valign=\"top\"><span class=\"Bold\">Study 4</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">47</td><td align=\"center\" class=\"Rrule\">30%</td><td align=\"center\" class=\"Rrule\">47%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">50</td><td align=\"center\" class=\"Rrule\">20%</td><td align=\"center\" class=\"Rrule\">30%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">10%</td><td align=\"center\" class=\"Rrule\">17%</td>\n</tr>\n</tbody>\n</table></div>" }

The Kaplan-Meier plots below (Figure 1 and Figure 2) provides an estimate of the probability that a patient will have responded to a single 2 mg dose of dihydroergotamine mesylate nasal spray as a function of the time elapsed since initiation of treatment.

{ "type": "p", "children": [], "text": "The Kaplan-Meier plots below (Figure 1 and Figure 2) provides an estimate of the probability that a patient will have responded to a single 2 mg dose of dihydroergotamine mesylate nasal spray as a function of the time elapsed since initiation of treatment." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="top" width="100%"/> <tfoot> <tr> <td align="left" colspan="1"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale. Patients not achieving response within 4 hours were censored to 4 hours.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left"><span class="Bold"><a name="fig1"></a>Figure 1 Estimated Probability of a Patient Responding During the Four Hours Following a Single 2 mg Dose of Dihydroergotamine Mesylate Nasal Spray as a Function of the Time Elapsed Since Initiation of Treatment<a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a></span></td> </tr> <tr> <td align="center"><img alt="Figure 1" src="/dailymed/image.cfm?name=trudhesa-02.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"center\" valign=\"top\" width=\"100%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"1\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-6\" name=\"footnote-6\">*</a>\n</dt>\n<dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale. Patients not achieving response within 4 hours were censored to 4 hours.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\"><a name=\"fig1\"></a>Figure 1 Estimated Probability of a Patient Responding During the Four Hours Following a Single 2 mg Dose of Dihydroergotamine Mesylate Nasal Spray as a Function of the Time Elapsed Since Initiation of Treatment<a class=\"Sup\" href=\"#footnote-6\" name=\"footnote-reference-6\">*</a></span></td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure 1\" src=\"/dailymed/image.cfm?name=trudhesa-02.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="top" width="100%"/> <tfoot> <tr> <td align="left" colspan="1"> <dl class="Footnote"> <dt> <a href="#footnote-reference-7" name="footnote-7">*</a> </dt> <dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was evaluated on a five-point scale that included pain response. Patients not achieving response within 4 hours were censored to 4 hours.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left"><span class="Bold"><a name="fig2"></a>Figure 2 Estimated Probability of a Patient Responding to Dihydroergotamine Mesylate Nasal Spray During the Four Hours Following Dosing<a class="Sup" href="#footnote-7" name="footnote-reference-7">*</a></span></td> </tr> <tr> <td align="center"><img alt="Figure 2" src="/dailymed/image.cfm?name=trudhesa-03.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"center\" valign=\"top\" width=\"100%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"1\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-7\" name=\"footnote-7\">*</a>\n</dt>\n<dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was evaluated on a five-point scale that included pain response. Patients not achieving response within 4 hours were censored to 4 hours.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\"><a name=\"fig2\"></a>Figure 2 Estimated Probability of a Patient Responding to Dihydroergotamine Mesylate Nasal Spray During the Four Hours Following Dosing<a class=\"Sup\" href=\"#footnote-7\" name=\"footnote-reference-7\">*</a></span></td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure 2\" src=\"/dailymed/image.cfm?name=trudhesa-03.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></td>\n</tr>\n</tbody>\n</table></div>" }

For patients with migraine-associated nausea, photophobia, and phonophobia at baseline, there was a lower incidence of these symptoms at 2 and 4 hours following administration of dihydroergotamine mesylate nasal spray compared to placebo.

{ "type": "p", "children": [], "text": "For patients with migraine-associated nausea, photophobia, and phonophobia at baseline, there was a lower incidence of these symptoms at 2 and 4 hours following administration of dihydroergotamine mesylate nasal spray compared to placebo." }

Patients were not allowed to use additional treatments for 8 hours prior to study medication dosing and during the 4-hour observation period following study treatment. Following the 4-hour observation period, patients were allowed to use additional treatments. For all studies, the estimated probability of patients using additional treatments for their migraines over the 24 hours following the single 2 mg dose of study treatment is summarized in Figure 3 below.

{ "type": "p", "children": [], "text": "Patients were not allowed to use additional treatments for 8 hours prior to study medication dosing and during the 4-hour observation period following study treatment. Following the 4-hour observation period, patients were allowed to use additional treatments. For all studies, the estimated probability of patients using additional treatments for their migraines over the 24 hours following the single 2 mg dose of study treatment is summarized in Figure 3 below." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="top" width="100%"/> <tfoot> <tr> <td align="left" colspan="1"> <dl class="Footnote"> <dt> <a href="#footnote-reference-8" name="footnote-8">*</a> </dt> <dd>Kaplan-Meier plot based on data obtained from all studies with patients not using additional treatments censored to 24 hours. All patients received a single treatment of study medication for their migraine attack. The plot also includes patients who had no response to the initial dose.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left"><span class="Bold"><a name="fig3"></a>Figure 3 Estimated Probability of a Patient Using Additional Treatments for Migraine Over the 24 Hours Following Either Dihydroergotamine Mesylate Nasal Spray 2 mg (or Placebo)<a class="Sup" href="#footnote-8" name="footnote-reference-8">*</a></span></td> </tr> <tr> <td align="center"><img alt="Figure 3" src="/dailymed/image.cfm?name=trudhesa-04.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"center\" valign=\"top\" width=\"100%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"1\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-8\" name=\"footnote-8\">*</a>\n</dt>\n<dd>Kaplan-Meier plot based on data obtained from all studies with patients not using additional treatments censored to 24 hours. All patients received a single treatment of study medication for their migraine attack. The plot also includes patients who had no response to the initial dose.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\"><a name=\"fig3\"></a>Figure 3 Estimated Probability of a Patient Using Additional Treatments for Migraine Over the 24 Hours Following Either Dihydroergotamine Mesylate Nasal Spray 2 mg (or Placebo)<a class=\"Sup\" href=\"#footnote-8\" name=\"footnote-reference-8\">*</a></span></td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure 3\" src=\"/dailymed/image.cfm?name=trudhesa-04.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></td>\n</tr>\n</tbody>\n</table></div>" }

Neither age nor sex appear to affect the patient's response to dihydroergotamine mesylate nasal spray. The racial distribution of patients was insufficient to determine the effect of race on the efficacy of dihydroergotamine mesylate nasal spray.

{ "type": "p", "children": [], "text": "Neither age nor sex appear to affect the patient's response to dihydroergotamine mesylate nasal spray. The racial distribution of patients was insufficient to determine the effect of race on the efficacy of dihydroergotamine mesylate nasal spray." }

TRUDHESA (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) is supplied as a package of 4 single-dose units (NDC 77530-725-04). Each single-dose unit contains:

Store TRUDHESA at controlled room temperature, 20°C to 25°C (68°F to 77°F), with excursions allowed between 15°C to 30°C (59°F to 86°F). Do not refrigerate or freeze.

Serious and/or Life-Threatening Reactions with Coadministration of CYP3A4 Inhibitors

Inform patients that serious and/or life-threatening peripheral ischemia (cerebral ischemia and/or ischemia of the extremities) has been associated with the coadministration of dihydroergotamine mesylate and strong CYP3A4 inhibitors, such as macrolide antibiotics and protease inhibitors [see Contraindications (4), Warnings and Precautions (5.1), and Drug Interactions (7.1)].

Myocardial Ischemia and/or Infarction, Other Cardiac Events, Cerebrovascular Events, and Fatalities

Inform patients of the risk for serious cardiac, cerebrovascular, and other vasospasm related events. Advise patients to notify their healthcare provider if they develop any risk factors or symptoms while taking TRUDHESA. Inform patients that nicotine may provoke vasoconstriction predisposing to a greater ischemic response [see Warnings and Precautions (5.2, 5.3, 5.4)].

Medication Overuse Headache

Inform patients that use of drugs to treat migraine attacks for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].

Local Irritation

Advise patients to notify their healthcare provider if they have bothersome local irritation [see Warnings and Precautions (5.9)].

Drug Interactions

Advise patients to inform their healthcare providers if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7)].

Pregnancy

Advise patients of the risk for preterm birth. Advise women to inform their healthcare provider if they are pregnant or intend to become pregnant [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)].

Lactation

Advise patients not to breastfeed during treatment with TRUDHESA [see Use In Specific Populations (8.2)].

Important Administration Instructions

Advise patients that TRUDHESA must be assembled prior to use and that, prior to administration, the device must be primed (i.e., pumped 4 times). Instruct patients to use or discard TRUDHESA within 8 hours once the vial has been opened or the product has been assembled.

Manufactured by: Mipharm, S.p.A. Milano, Italy

{ "type": "p", "children": [], "text": "Manufactured by: Mipharm, S.p.A. Milano, Italy" }

Manufactured for: Impel NeuroPharma Inc 201 Elliott Ave West, Suite 260 Seattle, WA 98119 USA

{ "type": "p", "children": [], "text": "Manufactured for: Impel NeuroPharma Inc 201 Elliott Ave West, Suite 260 Seattle, WA 98119 USA" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="16%"/> <col align="left" valign="top" width="22%"/> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="30%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align="right">Issued: 9/2021      </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule Toprule" colspan="5"><span class="Bold">MEDICATION GUIDE<br/>TRUDHESA™ (true - deh - sa)<br/>(dihydroergotamine mesylate)<br/>nasal spray</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold"><a name="important"></a>What is the most important information I should know about TRUDHESA?<br/>TRUDHESA can cause serious side effects, including:</span> <ul> <li>Serious problems with blood circulation to your legs and feet (peripheral ischemia). TRUDHESA can cause peripheral ischemia when you take it with certain medicines known as CYP3A4 inhibitors. Peripheral ischemia may lead to a stroke and death. Stop taking TRUDHESA and get emergency medical help right away if you have any of the following symptoms:<ul> <li>cramping and pain in your legs or hips</li> <li>feeling of heaviness or tightness in your leg muscles</li> <li>burning or aching pain in your feet or toes while resting</li> <li>numbness, tingling, or weakness in your legs</li> <li>cold feeling or color changes in 1 or both legs or feet</li> <li>slurred speech</li> <li>sudden weakness</li> </ul> </li> </ul>Do not take medicines known as strong CYP3A4 inhibitors, such as: </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>ritonavir</li> <li>nelfinavir</li> </ul> </td><td align="left"> <ul class="Circle"> <li>erythromycin</li> <li>clarithromycin</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>ketoconazole</li> <li>itraconazole</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">These are not all of the medicines that could affect how TRUDHESA works. Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What is TRUDHESA?</span> <br/>TRUDHESA is a prescription medicine used for the acute treatment of migraine with or without aura in adults.<ul> <li>TRUDHESA is not used to prevent migraine.</li> <li>TRUDHESA is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.</li> </ul>It is not known if TRUDHESA is safe and effective in children.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Do not take TRUDHESA if you:</span> <ul> <li>are taking medicines known as strong CYP3A4 inhibitors.</li> <li>have heart problems or a history of heart problems.</li> <li>have uncontrolled high blood pressure.</li> <li>have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease).</li> <li>have sepsis.</li> <li>have had vascular surgery.</li> <li>have severe liver problems.</li> <li>have severe kidney problems.</li> <li>are allergic to dihydroergotamine mesylate, ergot alkaloids, or any ingredients in TRUDHESA. See the end of this Medication Guide for a complete list of ingredients.</li> <li>have taken any of the following medicines in the last 24 hours:<ul> <li>sumatriptan</li> <li>almotriptan</li> <li>eletriptan</li> <li>frovatriptan</li> <li>naratriptan</li> <li>rizatriptan</li> <li>ergotamine or ergotamine-type medicines</li> </ul> </li> <li>have taken any medicines that constrict your blood vessels or raise your blood pressure.</li> </ul>Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Before you take TRUDHESA, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul> <li>have high blood pressure.</li> <li>have liver problems.</li> <li>have kidney problems.</li> <li>smoke.</li> <li>are pregnant or plan to become pregnant. TRUDHESA may cause preterm labor. TRUDHESA should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant.</li> <li>are breastfeeding or plan to breastfeed. TRUDHESA may reduce breast milk supply and pass into your breast milk. TRUDHESA may be harmful to your baby. Do not breastfeed your baby while taking TRUDHESA and for 3 days after you use TRUDHESA. Talk with your healthcare provider about the best way to feed your baby if you take TRUDHESA.</li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider will decide if you can take TRUDHESA with your other medicines.<br/> <span class="Bold">Especially tell your healthcare provider if you take:</span></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>sumatriptan</li> <li>ergot-type medicine</li> <li>saquinavir</li> <li>nefazodone</li> </ul> </td><td align="left"> <ul class="Circle"> <li>fluconazole</li> <li>grapefruit juice</li> <li>zileuton</li> <li>nicotine</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>propranolol or other medicines that can lower your heart rate</li> <li>any medicines that can increase your blood pressure</li> <li>selective serotonin reuptake inhibitors</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">These are not all of the medicines that could affect how TRUDHESA works. Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">How should I take TRUDHESA?</span> <ul> <li>Certain people should take their first dose of TRUDHESA in their doctor's office or in another medical setting. Ask your doctor if you should take your first dose in a medical setting.</li> <li>Use TRUDHESA exactly as your healthcare provider tells you to use it. Read and follow the instructions in the <span class="Bold">Instructions for Use</span> which is provided with the TRUDHESA package before using.</li> <li>You should use TRUDHESA as soon as the symptoms of your headache start, but it may be given at any time during a migraine.</li> <li>After putting TRUDHESA together and priming the device, spray 1 time in each nostril (a complete dose).</li> <li>If your headache comes back after the first complete dose or you only get some relief from your headache, you can use a second dose 1 hour after the first complete dose. Use a new TRUDHESA nasal spray device for the second dose.</li> <li>Do not use more than 2 doses of TRUDHESA within a 24-hour period or 3 doses within a 7-day period.</li> <li>If you use too much TRUDHESA, call your healthcare provider or go to the nearest hospital emergency room right away.</li> <li>Taking TRUDHESA for 10 or more days in 1 month may make your headaches worse. You should write down when you have headaches and when you take TRUDHESA so that you can talk with your healthcare provider about how TRUDHESA is working for you.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What are the possible side effects of TRUDHESA?<br/>TRUDHESA can cause serious side effects, including:</span> <br/>See "<span class="Bold"><a href="#important">What is the most important information I should know about TRUDHESA?</a></span>"<ul> <li> <span class="Bold">Heart attack and other heart problems.</span> Heart problems may lead to death. Stop taking TRUDHESA and get emergency medical help right away if you have any of the following symptoms of a heart attack:<ul class="Circle"> <li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li> <li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li> <li>pain or discomfort in your arms, back, neck, jaw, or stomach</li> <li>shortness of breath with or without chest discomfort</li> <li>breaking out in a cold sweat</li> <li>nausea or vomiting</li> <li>feeling lightheaded</li> </ul> </li> </ul>TRUDHESA is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <ul class="Circle"> <li>have high blood pressure</li> <li>smoke</li> <li>have diabetes</li> </ul> </td><td align="left"></td><td align="left"> <ul class="Circle"> <li>have high cholesterol levels</li> <li>are overweight</li> <li>have a family history of heart disease</li> </ul> </td><td align="left" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <ul> <li> <span class="Bold">Stroke.</span> Stop taking TRUDHESA and get emergency medical help right away if you have any of the following symptoms of a stroke:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <ul class="Circle"> <li>face drooping</li> <li>slurred speech</li> </ul> </td><td align="left"></td><td align="left"> <ul class="Circle"> <li>unusual weakness or numbness</li> </ul> </td><td align="left" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <ul> <li> <span class="Bold">Changes in color or sensation in your fingers and toes (Raynaud's syndrome).</span> </li> <li> <span class="Bold">Stomach and intestinal problems </span>(gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <ul class="Circle"> <li>sudden or severe stomach pain</li> <li>stomach pain after meals</li> <li>weight loss</li> <li>nausea or vomiting</li> </ul> </td><td align="left"></td><td align="left"> <ul class="Circle"> <li>constipation or diarrhea</li> <li>bloody diarrhea</li> <li>fever</li> </ul> </td><td align="left" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <ul> <li> <span class="Bold">Increase blood pressure.</span> </li> <li> <span class="Bold">Medicine overuse headache.</span> Some people who use too much TRUDHESA may make their headaches worse (medicine overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with TRUDHESA.</li> <li> <span class="Bold">Preterm labor</span>.</li> <li> <span class="Bold">Tissue changes (fibrotic complications).</span> Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach.</li> <li> <span class="Bold">Burning feelings in your nose, mouth and throat and abnormal taste</span>.</li> </ul>The most common side effects of TRUDHESA include:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>runny nose</li> <li>nausea</li> <li>abnormal taste</li> </ul> </td><td align="left"> <ul class="Disc"> <li>application site reactions</li> <li>dizziness</li> <li>vomiting</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>sleepiness</li> <li>sore throat</li> <li>diarrhea</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">These are not all the possible side effects TRUDHESA.<br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">How should I store TRUDHESA?</span> <br/>Keep TRUDHESA away from heat and light.<ul> <li>Store TRUDHESA at room temperature between 68°F to 77°F (20°C to 25°C). </li> <li>Do not refrigerate or freeze.</li> <li>After a TRUDHESA vial has been opened, it must be thrown away after 8 hours.</li> </ul>Keep TRUDHESA and all medicines out of the reach of children.<br/>Do not throw TRUDHESA into fire or incinerators as the canister inside the device may explode.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">General information about the safe and effective use of TRUDHESA.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TRUDHESA for a condition for which it was not prescribed. Do not give TRUDHESA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TRUDHESA that is written for health professionals.</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What are the ingredients in TRUDHESA?</span> <br/> <span class="Bold">Active ingredient:</span> Dihydroergotamine mesylate <br/> <span class="Bold">Inactive ingredients:</span> Caffeine, carbon dioxide, dextrose, and water. The nasal spray device canister contains hydrofluoroalkane-134a (HFA) propellant. The vial stopper is not made with natural rubber latex.<br/>TRUDHESA is a trademark of Impel NeuroPharma Inc.<br/>Marketed by: Impel NeuroPharma, Seattle, WA 98119, USA<br/>www.impelnp.com<br/>Manufactured by: Mipharm, S.p.A. Milano, Italy<br/>Manufactured for: Impel NeuroPharma Inc. 201 Elliott Ave West, Suite 260 Seattle, WA 98119 USA<br/>For more information, go to www.trudhesa.com or call 1-833-878-3437.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"16%\"/>\n<col align=\"left\" valign=\"top\" width=\"22%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"4\">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align=\"right\">Issued: 9/2021      </td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">MEDICATION GUIDE<br/>TRUDHESA™ (true - deh - sa)<br/>(dihydroergotamine mesylate)<br/>nasal spray</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\"><a name=\"important\"></a>What is the most important information I should know about TRUDHESA?<br/>TRUDHESA can cause serious side effects, including:</span>\n<ul>\n<li>Serious problems with blood circulation to your legs and feet (peripheral ischemia). TRUDHESA can cause peripheral ischemia when you take it with certain medicines known as CYP3A4 inhibitors. Peripheral ischemia may lead to a stroke and death. Stop taking TRUDHESA and get emergency medical help right away if you have any of the following symptoms:<ul>\n<li>cramping and pain in your legs or hips</li>\n<li>feeling of heaviness or tightness in your leg muscles</li>\n<li>burning or aching pain in your feet or toes while resting</li>\n<li>numbness, tingling, or weakness in your legs</li>\n<li>cold feeling or color changes in 1 or both legs or feet</li>\n<li>slurred speech</li>\n<li>sudden weakness</li>\n</ul>\n</li>\n</ul>Do not take medicines known as strong CYP3A4 inhibitors, such as: </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>ritonavir</li>\n<li>nelfinavir</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Circle\">\n<li>erythromycin</li>\n<li>clarithromycin</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>ketoconazole</li>\n<li>itraconazole</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">These are not all of the medicines that could affect how TRUDHESA works. Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What is TRUDHESA?</span>\n<br/>TRUDHESA is a prescription medicine used for the acute treatment of migraine with or without aura in adults.<ul>\n<li>TRUDHESA is not used to prevent migraine.</li>\n<li>TRUDHESA is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.</li>\n</ul>It is not known if TRUDHESA is safe and effective in children.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Do not take TRUDHESA if you:</span>\n<ul>\n<li>are taking medicines known as strong CYP3A4 inhibitors.</li>\n<li>have heart problems or a history of heart problems.</li>\n<li>have uncontrolled high blood pressure.</li>\n<li>have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease).</li>\n<li>have sepsis.</li>\n<li>have had vascular surgery.</li>\n<li>have severe liver problems.</li>\n<li>have severe kidney problems.</li>\n<li>are allergic to dihydroergotamine mesylate, ergot alkaloids, or any ingredients in TRUDHESA. See the end of this Medication Guide for a complete list of ingredients.</li>\n<li>have taken any of the following medicines in the last 24 hours:<ul>\n<li>sumatriptan</li>\n<li>almotriptan</li>\n<li>eletriptan</li>\n<li>frovatriptan</li>\n<li>naratriptan</li>\n<li>rizatriptan</li>\n<li>ergotamine or ergotamine-type medicines</li>\n</ul>\n</li>\n<li>have taken any medicines that constrict your blood vessels or raise your blood pressure.</li>\n</ul>Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Before you take TRUDHESA, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul>\n<li>have high blood pressure.</li>\n<li>have liver problems.</li>\n<li>have kidney problems.</li>\n<li>smoke.</li>\n<li>are pregnant or plan to become pregnant. TRUDHESA may cause preterm labor. TRUDHESA should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant.</li>\n<li>are breastfeeding or plan to breastfeed. TRUDHESA may reduce breast milk supply and pass into your breast milk. TRUDHESA may be harmful to your baby. Do not breastfeed your baby while taking TRUDHESA and for 3 days after you use TRUDHESA. Talk with your healthcare provider about the best way to feed your baby if you take TRUDHESA.</li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider will decide if you can take TRUDHESA with your other medicines.<br/>\n<span class=\"Bold\">Especially tell your healthcare provider if you take:</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>sumatriptan</li>\n<li>ergot-type medicine</li>\n<li>saquinavir</li>\n<li>nefazodone</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Circle\">\n<li>fluconazole</li>\n<li>grapefruit juice</li>\n<li>zileuton</li>\n<li>nicotine</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>propranolol or other medicines that can lower your heart rate</li>\n<li>any medicines that can increase your blood pressure</li>\n<li>selective serotonin reuptake inhibitors</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">These are not all of the medicines that could affect how TRUDHESA works. Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">How should I take TRUDHESA?</span>\n<ul>\n<li>Certain people should take their first dose of TRUDHESA in their doctor's office or in another medical setting. Ask your doctor if you should take your first dose in a medical setting.</li>\n<li>Use TRUDHESA exactly as your healthcare provider tells you to use it. Read and follow the instructions in the <span class=\"Bold\">Instructions for Use</span> which is provided with the TRUDHESA package before using.</li>\n<li>You should use TRUDHESA as soon as the symptoms of your headache start, but it may be given at any time during a migraine.</li>\n<li>After putting TRUDHESA together and priming the device, spray 1 time in each nostril (a complete dose).</li>\n<li>If your headache comes back after the first complete dose or you only get some relief from your headache, you can use a second dose 1 hour after the first complete dose. Use a new TRUDHESA nasal spray device for the second dose.</li>\n<li>Do not use more than 2 doses of TRUDHESA within a 24-hour period or 3 doses within a 7-day period.</li>\n<li>If you use too much TRUDHESA, call your healthcare provider or go to the nearest hospital emergency room right away.</li>\n<li>Taking TRUDHESA for 10 or more days in 1 month may make your headaches worse. You should write down when you have headaches and when you take TRUDHESA so that you can talk with your healthcare provider about how TRUDHESA is working for you.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What are the possible side effects of TRUDHESA?<br/>TRUDHESA can cause serious side effects, including:</span>\n<br/>See \"<span class=\"Bold\"><a href=\"#important\">What is the most important information I should know about TRUDHESA?</a></span>\"<ul>\n<li>\n<span class=\"Bold\">Heart attack and other heart problems.</span> Heart problems may lead to death. Stop taking TRUDHESA and get emergency medical help right away if you have any of the following symptoms of a heart attack:<ul class=\"Circle\">\n<li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li>\n<li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li>\n<li>pain or discomfort in your arms, back, neck, jaw, or stomach</li>\n<li>shortness of breath with or without chest discomfort</li>\n<li>breaking out in a cold sweat</li>\n<li>nausea or vomiting</li>\n<li>feeling lightheaded</li>\n</ul>\n</li>\n</ul>TRUDHESA is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>have high blood pressure</li>\n<li>smoke</li>\n<li>have diabetes</li>\n</ul>\n</td><td align=\"left\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>have high cholesterol levels</li>\n<li>are overweight</li>\n<li>have a family history of heart disease</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<ul>\n<li>\n<span class=\"Bold\">Stroke.</span> Stop taking TRUDHESA and get emergency medical help right away if you have any of the following symptoms of a stroke:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>face drooping</li>\n<li>slurred speech</li>\n</ul>\n</td><td align=\"left\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>unusual weakness or numbness</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<ul>\n<li>\n<span class=\"Bold\">Changes in color or sensation in your fingers and toes (Raynaud's syndrome).</span>\n</li>\n<li>\n<span class=\"Bold\">Stomach and intestinal problems </span>(gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>sudden or severe stomach pain</li>\n<li>stomach pain after meals</li>\n<li>weight loss</li>\n<li>nausea or vomiting</li>\n</ul>\n</td><td align=\"left\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>constipation or diarrhea</li>\n<li>bloody diarrhea</li>\n<li>fever</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<ul>\n<li>\n<span class=\"Bold\">Increase blood pressure.</span>\n</li>\n<li>\n<span class=\"Bold\">Medicine overuse headache.</span> Some people who use too much TRUDHESA may make their headaches worse (medicine overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with TRUDHESA.</li>\n<li>\n<span class=\"Bold\">Preterm labor</span>.</li>\n<li>\n<span class=\"Bold\">Tissue changes (fibrotic complications).</span> Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach.</li>\n<li>\n<span class=\"Bold\">Burning feelings in your nose, mouth and throat and abnormal taste</span>.</li>\n</ul>The most common side effects of TRUDHESA include:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>runny nose</li>\n<li>nausea</li>\n<li>abnormal taste</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>application site reactions</li>\n<li>dizziness</li>\n<li>vomiting</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>sleepiness</li>\n<li>sore throat</li>\n<li>diarrhea</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">These are not all the possible side effects TRUDHESA.<br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">How should I store TRUDHESA?</span>\n<br/>Keep TRUDHESA away from heat and light.<ul>\n<li>Store TRUDHESA at room temperature between 68°F to 77°F (20°C to 25°C). </li>\n<li>Do not refrigerate or freeze.</li>\n<li>After a TRUDHESA vial has been opened, it must be thrown away after 8 hours.</li>\n</ul>Keep TRUDHESA and all medicines out of the reach of children.<br/>Do not throw TRUDHESA into fire or incinerators as the canister inside the device may explode.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">General information about the safe and effective use of TRUDHESA.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TRUDHESA for a condition for which it was not prescribed. Do not give TRUDHESA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TRUDHESA that is written for health professionals.</td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What are the ingredients in TRUDHESA?</span>\n<br/>\n<span class=\"Bold\">Active ingredient:</span> Dihydroergotamine mesylate <br/>\n<span class=\"Bold\">Inactive ingredients:</span> Caffeine, carbon dioxide, dextrose, and water. The nasal spray device canister contains hydrofluoroalkane-134a (HFA) propellant. The vial stopper is not made with natural rubber latex.<br/>TRUDHESA is a trademark of Impel NeuroPharma Inc.<br/>Marketed by: Impel NeuroPharma, Seattle, WA 98119, USA<br/>www.impelnp.com<br/>Manufactured by: Mipharm, S.p.A. Milano, Italy<br/>Manufactured for: Impel NeuroPharma Inc. 201 Elliott Ave West, Suite 260 Seattle, WA 98119 USA<br/>For more information, go to www.trudhesa.com or call 1-833-878-3437.</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="8%"/> <col align="left" valign="top" width="42%"/> <col align="left" valign="top" width="50%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="3"><span class="Bold">INSTRUCTIONS FOR USE<br/>Trudhesa™<br/>(true-deh-sa)</span> <br/>(dihydroergotamine mesylate)<br/>nasal spray<br/>For Nasal Use Only</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"> <p class="First"> <img alt="Image" src="/dailymed/image.cfm?name=trudhesa-05.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <br/>622344<br/> <span class="Bold">Remove and Follow When Dosing</span> <br/>This Instructions for Use contains information on how to deliver Trudhesa.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Introduction</span> <br/>Read this Instructions for Use before you start to use Trudhesa and each time you get a prescription refill. There may be new information.<br/>This information does not take the place of talking with your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about Trudhesa when you start taking it and at regular checkups.<br/>It is important to follow these directions accurately in order to receive the correct dose. Contact your healthcare provider if you have any questions about how to use this product.<br/> <p class="First"> <img alt="Figure" src="/dailymed/image.cfm?name=trudhesa-06.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Nasal Spray Device Parts</span> <br/> <p class="First"> <img alt="Figure" src="/dailymed/image.cfm?name=trudhesa-07.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <br/> <span class="Bold">Glass Vial Parts</span> <br/> <p> <img alt="Figure" src="/dailymed/image.cfm?name=trudhesa-08.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Important Information You Need To Know Before Dosing with Trudhesa</span> <ul> <li>For nasal use only.</li> <li>Always prime the nasal spray device before dosing by pumping the finger grips and glass vial together <span class="Bold">exactly 4 times.</span> </li> <li>The purpose of priming is to bring the medicine to the tip of the spray nozzle. You may or may not see liquid or spray come out of the nozzle during each priming action.</li> <li>During priming, make sure to aim the spray nozzle away from your face and anything that you do not want coming into contact with the spray of medicine.</li> <li>A complete dose is 2 sprays; 1 spray in each nostril.</li> <li> <span class="Bold">Do not</span> take more than 2 doses within a 24-hour period. <span class="Bold">Do not</span> take more than 3 doses in a 7-day period.</li> <li>Always hold the nasal spray device perfectly upright when priming and when dosing.</li> <li>Sniffing while dosing is not necessary. However, sniffing will not hurt you nor make the medicine less effective.</li> <li>This nasal spray device product is single-dose (for one complete dose only) and should be thrown away (discarded) after use. You will need a new kit for each dose.</li> <li>Keep the product in the case until ready to use.</li> <li>After a TRUDHESA vial has been opened, it must be thrown away after 8 hours.</li> <li> <span class="Bold">Do not</span> open the glass vial and expose to air until ready to use.</li> <li>Store at room temperature in a clean, dry area.</li> <li> <span class="Bold">Do not</span> use if product is damaged.</li> <li> <span class="Bold">Do not</span> use if product is expired.</li> <li>Each glass vial and nasal spray device can only be used 1 time. Throw away the entire nasal spray device after dosing, without removing the glass vial.</li> <li>You can take another complete dose at least 1 hour after your first dose if your symptoms persist</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"> <p class="First"> <span class="Bold">Storing Trudhesa</span> </p> <ul> <li>Store Trudhesa at room temperature between 68 °F to 77°F (20 °C to 25°C).</li> <li>Store Trudhesa in the original packaging in a clean, dry area away from heat and light (Figure A).</li> <li>Keep Trudhesa in the original packaging until you are ready to use.</li> <li> <span class="Bold">Do not</span> refrigerate or freeze Trudhesa.</li> <li> <span class="Bold">Keep Trudhesa and all medicines out of the reach of children.</span> </li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"> <p class="First"> <img alt="Figure A" src="/dailymed/image.cfm?name=trudhesa-09.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                    Figure A</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Preparing to Dose with Trudhesa<br/>Step 1: Gather and Check Supplies</span> <dl> <dt class="Bold">1.1</dt> <dd>Check to make sure you are using the right medicine for your migraine (see <a href="#figb">Figure B</a>).<p class="First"> <a name="figb"></a><img alt="Figure B" src="/dailymed/image.cfm?name=trudhesa-10.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                                  Figure B</span> </dd> <dt class="Bold">1.2</dt> <dd>Check to make sure Trudhesa is not expired (EXP) (see <a href="#figc">Figure C</a>).<ul> <li>If expired, throw away and get a new glass vial.</li> </ul> <p class="First"> <a name="figc"></a><img alt="Figure C" src="/dailymed/image.cfm?name=trudhesa-11.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                                  Figure C</span> </dd> <dt class="Bold">1.3</dt> <dd>Check to make sure that the glass vial and blue plastic cover do not look damaged.</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 2: Remove Blue Plastic Cover, Metal Foil and Grey Rubber Stopper from Glass Vial</span> <dl> <dt class="Bold">2.1</dt> <dd>Remove (flip up) the blue plastic cover from the glass vial (see <a href="#figd">Figure D</a>).</dd> <dt class="Bold">2.2</dt> <dd>Use the blue plastic cover to slowly peel away all the metal foil from the grey rubber stopper in a circular motion (see <a href="#fige">Figure E</a>).<br/> <span class="Bold">NOTE:</span> The metal foil may come off in 2 or more pieces. Make sure to remove all of the metal foil.</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <p class="First"> <a name="figd"></a><img alt="Figure D" src="/dailymed/image.cfm?name=trudhesa-12.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                     Figure D</span></td><td align="left" class="Rrule"> <p class="First"> <a name="fige"></a><img alt="Figure E" src="/dailymed/image.cfm?name=trudhesa-13.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                     Figure E</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"> <dl> <dt class="Bold">2.3</dt> <dd>Pull the grey rubber stopper up and out of the glass vial (Figure F and Figure G).</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <p class="First"> <a name="figf"></a><img alt="Figure F" src="/dailymed/image.cfm?name=trudhesa-14.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                     Figure F</span></td><td align="left" class="Rrule"> <p class="First"> <a name="figg"></a><img alt="Figure G" src="/dailymed/image.cfm?name=trudhesa-15.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                     Figure G</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"> <dl> <dt class="Bold">2.4</dt> <dd>Throw away (discard) cover, foil and grey rubber stopper into the trash.</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 3: Remove the Clear Plastic Cover from the Nasal Spray Device</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"> <dl> <dt class="Bold">3.1</dt> <dd>Hold the nasal spray device upright.</dd> <dt class="Bold">3.2</dt> <dd>Pull down on the clear plastic cover and remove it from the nasal spray device (Figure H).<ul> <li>Throw away the clear plastic cover.<p class="First"> <a name="figh"></a><img alt="Figure H" src="/dailymed/image.cfm?name=trudhesa-16.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                                  Figure H</span> </li> </ul> </dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 4: Screw the Glass Vial into the Nasal Spray Device</span> <dl> <dt class="Bold">4.1</dt> <dd>Hold the nasal spray device upright.</dd> <dt class="Bold">4.2</dt> <dd>Gently push glass vial into the bottom of the nasal spray device (see <a href="#figi">Figure I</a>) and screw it on until it is secured as shown in Figure J.</dd> </dl> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule"></td><td align="left"> <p class="First"> <a name="figi"></a><img alt="Figure I" src="/dailymed/image.cfm?name=trudhesa-17.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                     Figure I</span></td><td align="left" class="Rrule"> <p class="First"> <a name="figj"></a><img alt="Figure J" src="/dailymed/image.cfm?name=trudhesa-18.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                     Figure J</span></td> </tr> <tr> <td align="left" class="Lrule" colspan="2" valign="top"><span class="Bold">Step 5: Prime the Nasal Spray Device by Pumping Four Times with Fin and Thumb</span> <dl> <dt class="Bold">5.1</dt> <dd>Hold the nasal spray device <span class="Bold">upright.</span> </dd> <dt class="Bold">5.2</dt> <dd>Point the spray nozzle away from your face.</dd> <dt class="Bold">5.3</dt> <dd>Place your thumb on the bottom of the glass vial and place your pointer (index) and middle fingers on the finger grips (see <a href="#figk">Figure K</a>).</dd> <dt class="Bold">5.4</dt> <dd>Pump the nasal spray device <span class="Bold">exactly 4 times.</span> <ul class="Disc"> <li>To pump the nasal spray device, firmly press the finger grips down and press the glass vial up at the same time. Then release (see <a href="#figk">Figure K</a>).</li> <li>You may see some medicine spray out during priming. This is normal. It is okay if you do not see medicine spray out on the first few pumps.</li> </ul> </dd> </dl> </td><td align="center" class="Rrule" valign="top"><a name="figk"></a><img alt="Figure K" src="/dailymed/image.cfm?name=trudhesa-19.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/><br/> <span class="Bold">You may or may not see liquid each time you pump.<br/>Only pump 4 times to prime.<br/>Figure K</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Important Tip:</span> The purpose of priming is to bring the medicine to the tip of the spray nozzle. If you do not prime the nasal spray device, you will not get your correct dose of medicine.<br/>Always prime the nasal spray device before use by pumping <span class="Bold">exactly 4 times.</span> <br/>During priming, make sure to aim the nozzle away from your face and anything that you do not want coming into contact with the spray of medicine.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Using Trudhesa</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 6: Position the Nasal Spray Device</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"> <dl> <dt class="Bold">6.1</dt> <dd>Turn or re-grip the nasal spray device so that the spray nozzle faces you.</dd> <dt class="Bold">6.2</dt> <dd>Make sure your head is straight and the nasal spray device is upright.</dd> <dt class="Bold">6.3</dt> <dd>Insert the spray nozzle into your first nostril as far as comfortable (see <a href="#figl">Figure L</a>).</dd> </dl> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule"></td><td align="left" class="Rrule" colspan="2"> <p class="First"> <a name="figl"></a><img alt="Figure L" src="/dailymed/image.cfm?name=trudhesa-20.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                                  Figure L</span></td> </tr> <tr> <td align="left" class="Lrule" colspan="2"><span class="Bold">Step 7: Spray the First Spray into 1 Nostril</span></td><td align="left" class="Rrule"><span class="Bold">Step 8: Spray the Second Spray into Other Nostril</span></td> </tr> <tr> <td align="left" class="Lrule" colspan="2"> <dl> <dt class="Bold">7.1</dt> <dd>Firmly press the finger grips down and press the glass vial up at the same time to deliver the first spray (see <a href="#figm">Figure M</a>). Then release.<ul class="Disc"> <li>Only deliver 1 spray into this nostril.<p class="First"> <a name="figm"></a><img alt="Figure M" src="/dailymed/image.cfm?name=trudhesa-21.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                                  Figure M</span> </li> </ul> </dd> </dl> </td><td align="left" class="Rrule"> <dl> <dt class="Bold">8.1</dt> <dd>Move the spray nozzule into your other nostril.</dd> <dt class="Bold">8.2</dt> <dd>Firmly press the finger grips down and press the glass vial up at the same time to deliver the second spray (see <a href="#fign">Figure N</a>). Then release.<ul class="Disc"> <li>Only deliver 1 spray into this nostril.<p class="First"> <a name="fign"></a><img alt="Figure N" src="/dailymed/image.cfm?name=trudhesa-22.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                                  Figure N</span> </li> </ul> </dd> </dl> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Important Tip: A complete dose is 2 sprays; 1 spray in each nostril.</span> <br/> <span class="Bold">Do not</span> take more than 2 doses within a 24-hour period. <span class="Bold">Do not</span> take more than 3 doses in a 7-day period. Please refer to the prescribing information for more information.<br/>Sniffing while or after dosing is not necessary. However, sniffing will not hurt you or make the medicine less effective.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 9: Throw away Trudhesa</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"> <dl> <dt class="Bold">9.1</dt> <dd>Throw away the entire nasal spray device, with the glass vial attached, into your household trash (Figure O).<p class="First"> <a name="figo"></a><img alt="Figure O" src="/dailymed/image.cfm?name=trudhesa-23.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63"/></p> <span class="Bold">                                      Figure O</span> </dd> </dl> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"> <ul> <li> <span class="Bold">Do not</span> separate the glass vial from the nasal spray device.</li> <li> <span class="Bold">Do not</span> reuse the glass vial or the nasal spray device. The glass vial and nasal spray device can only be used 1 time.</li> <li> <span class="Bold">Do not</span> throw Trudhesa into fire or incinerators.</li> </ul> <span class="Bold">Important Tip:</span> Some medicine may remain in the glass vial. This is normal. Remaining medicine cannot be used for later dosing.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Important Frequently Asked Questions (FAQs)</span> <br/> <span class="Bold">Question: Can I save medicine by skipping the 4 pumps in "Step 5: Prime the Nasal Spray Device"?</span> <br/> <span class="Bold">Answer:</span> No. Skipping the 4 pumps to prime the nasal spray device can result in you not getting your correct dose of medicine.<br/> <span class="Bold">Question: When I first pumped the nasal spray device to prime nothing seemed to happen. Why?</span> <br/> <span class="Bold">Answer:</span> The purpose of priming is to bring the medicine up to the tip of the nozzle. Even though you may not see or hear anything on your first pump or two, the pumping action will move the medicine from the glass vial through the inside of the nasal spray device and into the nozzle. You should see a spray by your fourth pump attempt. Always prime by pumping exactly 4 times prior to dosing.<br/> <span class="Bold">Question: Can I reuse the nasal spray device with a new glass vial?</span> <br/> <span class="Bold">Answer:</span> No. The nasal spray device is for one-time use only and must be thrown away after you have dosed (1 spray in each nostril). This is because the device may clog. After dosing, leave the glass vial screwed onto the nasal spray device and throw away the assembled nasal spray device into the trash. Do not recycle any part of the product.<br/> <span class="Bold">Question: Can I use the medicine that remains in the glass vial for a later dose?</span> <br/> <span class="Bold">Answer:</span> No. Although it is normal for some medicine to remain in the glass vial, it can not be used for later dosing. Any leftover medicine will become ineffective.<br/> <span class="Bold">Question: What happens if I spray more than one time in the same nostril?</span> <br/> <span class="Bold">Answer:</span> A complete and correct dose is one spray into each nostril. Do not dose in your other nostril if you already sprayed two times in one nostril. Talk to your healthcare provider if you have moderate to severe irritation in your nose or changes in smell.<br/> <span class="Bold">Question: How soon can I take another dose if I am not getting relief from my migraine?</span> <br/> <span class="Bold">Answer:</span> You can take another dose at least 1 hour after your first dose if your symptoms persist. <span class="Bold">Do not</span> take more than 2 doses within a 24-hour period. <span class="Bold">Do not</span> take more than 3 doses in a 7-day period. Please refer to the prescribing information for more information. </td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule" colspan="2">This Instructions for Use has been approved by the U.S. Food and Drug Administration.</td><td align="right" class="Rrule">Issued: 9/2021          </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"8%\"/>\n<col align=\"left\" valign=\"top\" width=\"42%\"/>\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"3\"><span class=\"Bold\">INSTRUCTIONS FOR USE<br/>Trudhesa™<br/>(true-deh-sa)</span>\n<br/>(dihydroergotamine mesylate)<br/>nasal spray<br/>For Nasal Use Only</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<p class=\"First\">\n<img alt=\"Image\" src=\"/dailymed/image.cfm?name=trudhesa-05.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<br/>622344<br/>\n<span class=\"Bold\">Remove and Follow When Dosing</span>\n<br/>This Instructions for Use contains information on how to deliver Trudhesa.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Introduction</span>\n<br/>Read this Instructions for Use before you start to use Trudhesa and each time you get a prescription refill. There may be new information.<br/>This information does not take the place of talking with your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about Trudhesa when you start taking it and at regular checkups.<br/>It is important to follow these directions accurately in order to receive the correct dose. Contact your healthcare provider if you have any questions about how to use this product.<br/>\n<p class=\"First\">\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=trudhesa-06.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Nasal Spray Device Parts</span>\n<br/>\n<p class=\"First\">\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=trudhesa-07.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<br/>\n<span class=\"Bold\">Glass Vial Parts</span>\n<br/>\n<p>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=trudhesa-08.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Important Information You Need To Know Before Dosing with Trudhesa</span>\n<ul>\n<li>For nasal use only.</li>\n<li>Always prime the nasal spray device before dosing by pumping the finger grips and glass vial together <span class=\"Bold\">exactly 4 times.</span>\n</li>\n<li>The purpose of priming is to bring the medicine to the tip of the spray nozzle. You may or may not see liquid or spray come out of the nozzle during each priming action.</li>\n<li>During priming, make sure to aim the spray nozzle away from your face and anything that you do not want coming into contact with the spray of medicine.</li>\n<li>A complete dose is 2 sprays; 1 spray in each nostril.</li>\n<li>\n<span class=\"Bold\">Do not</span> take more than 2 doses within a 24-hour period. <span class=\"Bold\">Do not</span> take more than 3 doses in a 7-day period.</li>\n<li>Always hold the nasal spray device perfectly upright when priming and when dosing.</li>\n<li>Sniffing while dosing is not necessary. However, sniffing will not hurt you nor make the medicine less effective.</li>\n<li>This nasal spray device product is single-dose (for one complete dose only) and should be thrown away (discarded) after use. You will need a new kit for each dose.</li>\n<li>Keep the product in the case until ready to use.</li>\n<li>After a TRUDHESA vial has been opened, it must be thrown away after 8 hours.</li>\n<li>\n<span class=\"Bold\">Do not</span> open the glass vial and expose to air until ready to use.</li>\n<li>Store at room temperature in a clean, dry area.</li>\n<li>\n<span class=\"Bold\">Do not</span> use if product is damaged.</li>\n<li>\n<span class=\"Bold\">Do not</span> use if product is expired.</li>\n<li>Each glass vial and nasal spray device can only be used 1 time. Throw away the entire nasal spray device after dosing, without removing the glass vial.</li>\n<li>You can take another complete dose at least 1 hour after your first dose if your symptoms persist</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<p class=\"First\">\n<span class=\"Bold\">Storing Trudhesa</span>\n</p>\n<ul>\n<li>Store Trudhesa at room temperature between 68 °F to 77°F (20 °C to 25°C).</li>\n<li>Store Trudhesa in the original packaging in a clean, dry area away from heat and light (Figure A).</li>\n<li>Keep Trudhesa in the original packaging until you are ready to use.</li>\n<li>\n<span class=\"Bold\">Do not</span> refrigerate or freeze Trudhesa.</li>\n<li>\n<span class=\"Bold\">Keep Trudhesa and all medicines out of the reach of children.</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<p class=\"First\">\n<img alt=\"Figure A\" src=\"/dailymed/image.cfm?name=trudhesa-09.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                    Figure A</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Preparing to Dose with Trudhesa<br/>Step 1: Gather and Check Supplies</span>\n<dl>\n<dt class=\"Bold\">1.1</dt>\n<dd>Check to make sure you are using the right medicine for your migraine (see <a href=\"#figb\">Figure B</a>).<p class=\"First\">\n<a name=\"figb\"></a><img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=trudhesa-10.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                                  Figure B</span>\n</dd>\n<dt class=\"Bold\">1.2</dt>\n<dd>Check to make sure Trudhesa is not expired (EXP) (see <a href=\"#figc\">Figure C</a>).<ul>\n<li>If expired, throw away and get a new glass vial.</li>\n</ul>\n<p class=\"First\">\n<a name=\"figc\"></a><img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=trudhesa-11.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                                  Figure C</span>\n</dd>\n<dt class=\"Bold\">1.3</dt>\n<dd>Check to make sure that the glass vial and blue plastic cover do not look damaged.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 2: Remove Blue Plastic Cover, Metal Foil and Grey Rubber Stopper from Glass Vial</span>\n<dl>\n<dt class=\"Bold\">2.1</dt>\n<dd>Remove (flip up) the blue plastic cover from the glass vial (see <a href=\"#figd\">Figure D</a>).</dd>\n<dt class=\"Bold\">2.2</dt>\n<dd>Use the blue plastic cover to slowly peel away all the metal foil from the grey rubber stopper in a circular motion (see <a href=\"#fige\">Figure E</a>).<br/>\n<span class=\"Bold\">NOTE:</span> The metal foil may come off in 2 or more pieces. Make sure to remove all of the metal foil.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<p class=\"First\">\n<a name=\"figd\"></a><img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=trudhesa-12.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                     Figure D</span></td><td align=\"left\" class=\"Rrule\">\n<p class=\"First\">\n<a name=\"fige\"></a><img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=trudhesa-13.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                     Figure E</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<dl>\n<dt class=\"Bold\">2.3</dt>\n<dd>Pull the grey rubber stopper up and out of the glass vial (Figure F and Figure G).</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<p class=\"First\">\n<a name=\"figf\"></a><img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=trudhesa-14.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                     Figure F</span></td><td align=\"left\" class=\"Rrule\">\n<p class=\"First\">\n<a name=\"figg\"></a><img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=trudhesa-15.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                     Figure G</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<dl>\n<dt class=\"Bold\">2.4</dt>\n<dd>Throw away (discard) cover, foil and grey rubber stopper into the trash.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 3: Remove the Clear Plastic Cover from the Nasal Spray Device</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<dl>\n<dt class=\"Bold\">3.1</dt>\n<dd>Hold the nasal spray device upright.</dd>\n<dt class=\"Bold\">3.2</dt>\n<dd>Pull down on the clear plastic cover and remove it from the nasal spray device (Figure H).<ul>\n<li>Throw away the clear plastic cover.<p class=\"First\">\n<a name=\"figh\"></a><img alt=\"Figure H\" src=\"/dailymed/image.cfm?name=trudhesa-16.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                                  Figure H</span>\n</li>\n</ul>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 4: Screw the Glass Vial into the Nasal Spray Device</span>\n<dl>\n<dt class=\"Bold\">4.1</dt>\n<dd>Hold the nasal spray device upright.</dd>\n<dt class=\"Bold\">4.2</dt>\n<dd>Gently push glass vial into the bottom of the nasal spray device (see <a href=\"#figi\">Figure I</a>) and screw it on until it is secured as shown in Figure J.</dd>\n</dl>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<p class=\"First\">\n<a name=\"figi\"></a><img alt=\"Figure I\" src=\"/dailymed/image.cfm?name=trudhesa-17.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                     Figure I</span></td><td align=\"left\" class=\"Rrule\">\n<p class=\"First\">\n<a name=\"figj\"></a><img alt=\"Figure J\" src=\"/dailymed/image.cfm?name=trudhesa-18.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                     Figure J</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">Step 5: Prime the Nasal Spray Device by Pumping Four Times with Fin and Thumb</span>\n<dl>\n<dt class=\"Bold\">5.1</dt>\n<dd>Hold the nasal spray device <span class=\"Bold\">upright.</span>\n</dd>\n<dt class=\"Bold\">5.2</dt>\n<dd>Point the spray nozzle away from your face.</dd>\n<dt class=\"Bold\">5.3</dt>\n<dd>Place your thumb on the bottom of the glass vial and place your pointer (index) and middle fingers on the finger grips (see <a href=\"#figk\">Figure K</a>).</dd>\n<dt class=\"Bold\">5.4</dt>\n<dd>Pump the nasal spray device <span class=\"Bold\">exactly 4 times.</span>\n<ul class=\"Disc\">\n<li>To pump the nasal spray device, firmly press the finger grips down and press the glass vial up at the same time. Then release (see <a href=\"#figk\">Figure K</a>).</li>\n<li>You may see some medicine spray out during priming. This is normal. It is okay if you do not see medicine spray out on the first few pumps.</li>\n</ul>\n</dd>\n</dl>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"><a name=\"figk\"></a><img alt=\"Figure K\" src=\"/dailymed/image.cfm?name=trudhesa-19.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/><br/>\n<span class=\"Bold\">You may or may not see liquid each time you pump.<br/>Only pump 4 times to prime.<br/>Figure K</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Important Tip:</span> The purpose of priming is to bring the medicine to the tip of the spray nozzle. If you do not prime the nasal spray device, you will not get your correct dose of medicine.<br/>Always prime the nasal spray device before use by pumping <span class=\"Bold\">exactly 4 times.</span>\n<br/>During priming, make sure to aim the nozzle away from your face and anything that you do not want coming into contact with the spray of medicine.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Using Trudhesa</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 6: Position the Nasal Spray Device</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<dl>\n<dt class=\"Bold\">6.1</dt>\n<dd>Turn or re-grip the nasal spray device so that the spray nozzle faces you.</dd>\n<dt class=\"Bold\">6.2</dt>\n<dd>Make sure your head is straight and the nasal spray device is upright.</dd>\n<dt class=\"Bold\">6.3</dt>\n<dd>Insert the spray nozzle into your first nostril as far as comfortable (see <a href=\"#figl\">Figure L</a>).</dd>\n</dl>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<p class=\"First\">\n<a name=\"figl\"></a><img alt=\"Figure L\" src=\"/dailymed/image.cfm?name=trudhesa-20.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                                  Figure L</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\"><span class=\"Bold\">Step 7: Spray the First Spray into 1 Nostril</span></td><td align=\"left\" class=\"Rrule\"><span class=\"Bold\">Step 8: Spray the Second Spray into Other Nostril</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\">\n<dl>\n<dt class=\"Bold\">7.1</dt>\n<dd>Firmly press the finger grips down and press the glass vial up at the same time to deliver the first spray (see <a href=\"#figm\">Figure M</a>). Then release.<ul class=\"Disc\">\n<li>Only deliver 1 spray into this nostril.<p class=\"First\">\n<a name=\"figm\"></a><img alt=\"Figure M\" src=\"/dailymed/image.cfm?name=trudhesa-21.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                                  Figure M</span>\n</li>\n</ul>\n</dd>\n</dl>\n</td><td align=\"left\" class=\"Rrule\">\n<dl>\n<dt class=\"Bold\">8.1</dt>\n<dd>Move the spray nozzule into your other nostril.</dd>\n<dt class=\"Bold\">8.2</dt>\n<dd>Firmly press the finger grips down and press the glass vial up at the same time to deliver the second spray (see <a href=\"#fign\">Figure N</a>). Then release.<ul class=\"Disc\">\n<li>Only deliver 1 spray into this nostril.<p class=\"First\">\n<a name=\"fign\"></a><img alt=\"Figure N\" src=\"/dailymed/image.cfm?name=trudhesa-22.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                                  Figure N</span>\n</li>\n</ul>\n</dd>\n</dl>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Important Tip: A complete dose is 2 sprays; 1 spray in each nostril.</span>\n<br/>\n<span class=\"Bold\">Do not</span> take more than 2 doses within a 24-hour period. <span class=\"Bold\">Do not</span> take more than 3 doses in a 7-day period. Please refer to the prescribing information for more information.<br/>Sniffing while or after dosing is not necessary. However, sniffing will not hurt you or make the medicine less effective.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 9: Throw away Trudhesa</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<dl>\n<dt class=\"Bold\">9.1</dt>\n<dd>Throw away the entire nasal spray device, with the glass vial attached, into your household trash (Figure O).<p class=\"First\">\n<a name=\"figo\"></a><img alt=\"Figure O\" src=\"/dailymed/image.cfm?name=trudhesa-23.jpg&amp;setid=b81397b0-910d-4eb4-8fee-a9a3c9d94d63\"/></p>\n<span class=\"Bold\">                                      Figure O</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> separate the glass vial from the nasal spray device.</li>\n<li>\n<span class=\"Bold\">Do not</span> reuse the glass vial or the nasal spray device. The glass vial and nasal spray device can only be used 1 time.</li>\n<li>\n<span class=\"Bold\">Do not</span> throw Trudhesa into fire or incinerators.</li>\n</ul>\n<span class=\"Bold\">Important Tip:</span> Some medicine may remain in the glass vial. This is normal. Remaining medicine cannot be used for later dosing.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Important Frequently Asked Questions (FAQs)</span>\n<br/>\n<span class=\"Bold\">Question: Can I save medicine by skipping the 4 pumps in \"Step 5: Prime the Nasal Spray Device\"?</span>\n<br/>\n<span class=\"Bold\">Answer:</span> No. Skipping the 4 pumps to prime the nasal spray device can result in you not getting your correct dose of medicine.<br/>\n<span class=\"Bold\">Question: When I first pumped the nasal spray device to prime nothing seemed to happen. Why?</span>\n<br/>\n<span class=\"Bold\">Answer:</span> The purpose of priming is to bring the medicine up to the tip of the nozzle. Even though you may not see or hear anything on your first pump or two, the pumping action will move the medicine from the glass vial through the inside of the nasal spray device and into the nozzle. You should see a spray by your fourth pump attempt. Always prime by pumping exactly 4 times prior to dosing.<br/>\n<span class=\"Bold\">Question: Can I reuse the nasal spray device with a new glass vial?</span>\n<br/>\n<span class=\"Bold\">Answer:</span> No. The nasal spray device is for one-time use only and must be thrown away after you have dosed (1 spray in each nostril). This is because the device may clog. After dosing, leave the glass vial screwed onto the nasal spray device and throw away the assembled nasal spray device into the trash. Do not recycle any part of the product.<br/>\n<span class=\"Bold\">Question: Can I use the medicine that remains in the glass vial for a later dose?</span>\n<br/>\n<span class=\"Bold\">Answer:</span> No. Although it is normal for some medicine to remain in the glass vial, it can not be used for later dosing. Any leftover medicine will become ineffective.<br/>\n<span class=\"Bold\">Question: What happens if I spray more than one time in the same nostril?</span>\n<br/>\n<span class=\"Bold\">Answer:</span> A complete and correct dose is one spray into each nostril. Do not dose in your other nostril if you already sprayed two times in one nostril. Talk to your healthcare provider if you have moderate to severe irritation in your nose or changes in smell.<br/>\n<span class=\"Bold\">Question: How soon can I take another dose if I am not getting relief from my migraine?</span>\n<br/>\n<span class=\"Bold\">Answer:</span> You can take another dose at least 1 hour after your first dose if your symptoms persist. <span class=\"Bold\">Do not</span> take more than 2 doses within a 24-hour period. <span class=\"Bold\">Do not</span> take more than 3 doses in a 7-day period. Please refer to the prescribing information for more information. \t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t</td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule\" colspan=\"2\">This Instructions for Use has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\" class=\"Rrule\">Issued: 9/2021          </td>\n</tr>\n</tbody>\n</table></div>" }

Trudhesa™(dihydroergotamine mesylate) nasal spray

{ "type": "p", "children": [], "text": "Trudhesa™(dihydroergotamine mesylate) nasal spray" }

0.725 mg per spray

{ "type": "p", "children": [], "text": "0.725 mg per spray" }

Recommended Dosage: See Prescribing Information

{ "type": "p", "children": [], "text": "Recommended Dosage: See Prescribing Information" }

Contains: 4 Nasal Spray Devices, 4 Trudhesa Vials,Instructions for Use and Prescribing Information

{ "type": "p", "children": [], "text": "Contains: 4 Nasal Spray Devices, 4 Trudhesa Vials,Instructions for Use and Prescribing Information\n" }

NOT FOR INDIVIDUAL SALEContents are disposable; discard used nasal spray deviceand vial after use. For nasal use only.

{ "type": "p", "children": [], "text": "NOT FOR INDIVIDUAL SALEContents are disposable; discard used nasal spray deviceand vial after use. For nasal use only." }

RX ONLY

{ "type": "p", "children": [], "text": "RX ONLY" }

622338

{ "type": "p", "children": [], "text": "622338" }

Limitations of Use

ATZUMI is not indicated for the preventive treatment of migraine.

ATZUMI is not indicated for the management of hemiplegic migraine or migraine with brainstem aura.

ATZUMI is for nasal administration only.

The recommended dose of ATZUMI is 5.2 mg (the contents of one nasal device) and is administered as a powdered medicine into one nostril [see Dosage and Administration (2.3)].

The dose may be repeated, if needed, a minimum of 1 hour after the first dose. The maximum dose in a 24-hour period is 10.4 mg (two doses of ATZUMI 5.2 mg). The safety of taking more than 4 doses in a 7-day period or 12 doses within a 30-day period has not been established.

Prior to initiation of ATZUMI, a cardiovascular evaluation is recommended [see Warnings and Precautions (5.2)]. For patients with risk factors predictive of coronary artery disease who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of ATZUMI take place in the setting of an equipped healthcare facility.

Nasal Powder: 5.2 mg dihydroergotamine as a white powder in a single-dose nasal device.

{ "type": "p", "children": [], "text": "Nasal Powder: 5.2 mg dihydroergotamine as a white powder in a single-dose nasal device." }

ATZUMI is contraindicated in patients:

{ "type": "p", "children": [], "text": "ATZUMI is contraindicated in patients:" }

{ "type": "ul", "children": [ "with concomitant use of strong CYP3A4 inhibitors [see Warnings and Precautions (5.1) and Drug Interactions (7.1)]\n", "with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina [see Warnings and Precautions (5.4)]\n", "with uncontrolled hypertension [see Warnings and Precautions (5.5)]\n", "with peripheral arterial disease", "with sepsis", "following vascular surgery", "with severe hepatic impairment", "with severe renal impairment", "with known hypersensitivity to ergot alkaloids", "with recent use (i.e., within 24 hours) of other 5-HT1 agonists or ergotamine-containing or ergot-type medications [see Drug Interactions (7.2)]\n", "with concomitant use of peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure [see Warnings and Precautions (5.5)]\n" ], "text": "" }

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors, including protease inhibitors, macrolide antibiotics, and antifungals. 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 ATZUMI with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4) and Drug Interactions (7.1)].

The potential for cardiac adverse reactions exists with ATZUMI treatment. Serious adverse cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine. These events have included acute myocardial infarction, life-threatening disturbances of cardiac rhythm (e.g., ventricular tachycardia and ventricular fibrillation), coronary artery vasospasm, and transient myocardial ischemia.

Prior to initiation of ATZUMI, a cardiovascular evaluation is recommended to determine if the patient is free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. If, during the cardiovascular evaluation, the patient's medical history (including risk factors), or electrocardiographic investigation, findings are consistent with coronary artery vasospasm or myocardial ischemia, ATZUMI should not be administered [see Contraindications (4)].

For patients with risk factors predictive of coronary artery disease (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of coronary artery disease, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of ATZUMI take place in the setting of an equipped healthcare facility, unless the patient has previously received dihydroergotamine. During the interval immediately following the first use of ATZUMI, an electrocardiogram is recommended in those patients with risk factors because ischemia can occur in the absence of clinical symptoms.

The potential for adverse cerebrovascular adverse reactions exists with ATZUMI treatment. Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with dihydroergotamine; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the dihydroergotamine having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack).

Discontinue ATZUMI if a cerebrovascular event is suspected.

ATZUMI, like other ergot alkaloids, may cause vasospastic reactions other than coronary artery vasospasm. Myocardial, peripheral vascular, and colonic ischemia have been reported with dihydroergotamine.

Dihydroergotamine associated vasospastic phenomena may also cause muscle pains, numbness, coldness, pallor, and cyanosis of the digits. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. ATZUMI should be discontinued immediately if signs or symptoms of vasoconstriction develop.

Patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud's syndrome, following the use of any 5-HT1 agonist, including ATZUMI, should be evaluated by a healthcare provider.

Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension treated with dihydroergotamine. ATZUMI is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].

An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5-HT1 agonist in a study evaluating subjects undergoing cardiac catheterization.

Overuse of acute migraine drugs (e.g., ergotamines, triptans, opioids, or a combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

Based on the mechanism of action of dihydroergotamine and findings from the published literature, ATZUMI may cause preterm labor. Avoid use of ATZUMI during pregnancy [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.2)].

The potential for fibrotic complications exists with ATZUMI treatment. There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of dihydroergotamine . Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis. Rare cases have also been reported in association with the use of dihydroergotamine; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis.

Administration of ATZUMI should not exceed the dosing guidelines and should not be used for chronic daily administration [see Dosage and Administration (2.1)].

Local irritative symptoms were reported in 29% of patients treated with at least one dose of ATZUMI in an open-labeled trial, which allowed repeated use of ATZUMI up to 12 months. The common local irritative symptoms (at least 1% of patients) were nasal discomfort (11%), altered taste (8%), nasal congestion (5%), nasopharyngitis (5%), rhinorrhea (4%), cough (3%), nasal pain (3%), epistaxis (2%), sneezing (2%), nasal pruritus (1%), and increased lacrimation (1%). If a severe local irritation event occurs for no other attributable reasons, avoid further use of ATZUMI until the event resolves. Monitor patients for severe recurrent local irritation.

Nasal tissue in animals treated with dihydroergotamine mesylate daily showed mild mucosal irritation characterized by mucous cell and transitional cell hyperplasia and squamous cell metaplasia. Changes in rat nasal mucosa at 64 weeks were less severe than at 13 weeks. Local effects on respiratory tissue after chronic intranasal dosing in animals have not been evaluated.

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 studies described below were conducted with dihydroergotamine mesylate nasal spray; adverse reactions with ATZUMI nasal powder are expected to be similar to adverse reactions with dihydroergotamine mesylate nasal spray.

Adverse Reactions in Placebo-Controlled Trials with Dihydroergotamine Mesylate Nasal Spray [see Clinical Studies (14)]

Of the 1,796 patients and subjects treated with dihydroergotamine mesylate nasal spray doses 2 mg or less in U.S. and foreign clinical studies, 26 (1.4%) discontinued because of adverse events. The adverse events associated with discontinuation were, in decreasing order of frequency: rhinitis (13), dizziness (2), facial edema (2), and one patient each due to cold sweats, accidental trauma, depression, elective surgery, somnolence, allergy, vomiting, hypotension, and paraesthesia.

Table 1 summarizes the incidence rates of adverse reactions reported by at least 1% of patients who received dihydroergotamine mesylate nasal spray for the treatment of migraine during placebo-controlled, double-blind clinical studies and were more frequent than in those patients receiving placebo. The most commonly reported adverse reactions (greater than 1% of patients who received dihydroergotamine mesylate nasal spray) were rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea. In most instances these events were transient and self-limited and did not result in patient discontinuation from a study.

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 1 Adverse Reactions Reported by at Least 1% of the Dihydroergotamine Mesylate Nasal Spray Treated Patients and Occurred more Frequently than in the Placebo-Group in the Migraine Placebo-Controlled Trials </span> </caption> <col align="left" valign="middle" width="40%"/> <col align="center" valign="middle" width="30%"/> <col align="center" valign="middle" width="30%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">Dihydroergotamine Mesylate Nasal Spray <br/> N=597 <br/> %</th><th align="center" class="Rrule" valign="top">Placebo <br/> N=631 <br/> %</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Respiratory System</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Rhinitis</td><td align="center" class="Rrule">26</td><td align="center" class="Rrule">7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Pharyngitis</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Gastrointestinal System</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Nausea</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Vomiting</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Diarrhea</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Special Senses, Other</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Altered Sense of Taste</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Application Site</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Application Site Reaction</td><td align="center" class="Rrule">6</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Central and Peripheral Nervous System</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Dizziness</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Somnolence</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Body as a Whole, General</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Hot Flashes</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   Asthenia</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Musculoskeletal System</span></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">   Stiffness</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">&lt;1</td> </tr> </tbody> </table></div>

Adverse Reactions in Studies with ATZUMI

An open-label study in adults was conducted to evaluate the safety and tolerability of ATZUMI, with repeated use of ATZUMI over the course of 6 to 12 months. A total of 344 patients with migraine received at least one dose of ATZUMI. One hundred and eighty-eight patients treated on average at least two migraines per month for at least 6 months, and 86 patients treated at least two migraines per month for at least one year. Of the patients who received at least one dose of ATZUMI, 99 (29%) experienced local irritative symptoms. Of these, the most common local irritative symptoms (at least 5% of patients) were nasal discomfort, altered taste, nasal congestion, and nasopharyngitis [see Warnings and Precautions (5.9)]. The most common adverse reaction resulting in discontinuation in the long-term safety study was nasal discomfort (1.5%).

The following adverse reactions have been identified during postapproval use of dihydroergotamine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

There have been rare reports of serious adverse events in connection with the coadministration of intravenous administration of dihydroergotamine and strong CYP3A4 inhibitors, resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities [see Warnings and Precautions (5.1)]. The use of strong CYP3A4 inhibitors with ATZUMI is contraindicated [see Contraindications (4)]. Administer moderate CYP3A4 inhibitors with caution.

Triptans (serotonin [5-HT] 1B/1D receptor agonists) have been reported to cause coronary artery vasospasm, and its effects could be additive with ATZUMI. Therefore, triptans and ATZUMI should not be taken within 24 hours of each other [see Contraindications (4)].

There have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.

ATZUMI is contraindicated for use with peripheral and central vasoconstrictors because the combination may cause synergistic elevation of blood pressure [see Warnings and Precautions (5.5)].

Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy [see Warnings and Precautions (5.2, 5.4)].

Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT1 agonists have been co-administered with selective serotonin reuptake inhibitors (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline).

Risk Summary

Available data from published literature indicate an increased risk of preterm delivery with dihydroergotamine, the active moiety in ATZUMI, use during pregnancy. Avoid use of ATZUMI during pregnancy [see Warnings and Precautions (5.7)]. Data collected over decades have shown no increased risk of major birth defects or miscarriage with the use of dihydroergotamine during pregnancy.

In animal reproduction studies, adverse effects on development were observed following intranasal administration of dihydroergotamine mesylate during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation in rats (decreased body weight and impaired reproductive function in the offspring) at doses that were not associated with maternal toxicity (see Data).

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated rate of major birth defects (2.2% to 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

Intranasal administration of dihydroergotamine mesylate to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weight and/or skeletal ossification at doses of 0.16 mg/day and greater. A no-effect level for adverse effects on embryofetal development was not identified in rats.

Intranasal administration of dihydroergotamine mesylate to pregnant rabbits throughout organogenesis resulted in decreased skeletal ossification at 3.6 mg/day. The no-effect dose for adverse effects on embryofetal development in rabbits was 1.2 mg/day.

Intranasal administration of dihydroergotamine mesylate to female rats throughout pregnancy and lactation resulted in decreased body weight and impaired reproductive function (decreased mating indices) in the offspring at doses of 0.16 mg/day or greater. A no-effect dose for adverse effects on pre- and postnatal development in rats was not established. Effects on offspring development occurred at doses below those that produced evidence of significant maternal toxicity in these studies.

Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.

Risk Summary

There are no data on the presence of dihydroergotamine in human milk; however, ergotamine, a related drug, is present in human milk. There are reports of diarrhea, vomiting, weak pulse, and unstable blood pressure in breastfed infants exposed to ergotamine. ATZUMI may reduce milk supply because it may decrease prolactin levels. Because of the potential for reduced milk supply and serious adverse events in the breastfed infant, including diarrhea, vomiting, weak pulse, and unstable blood pressure, advise patients not to breastfeed during treatment with ATZUMI and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded.

The safety and effectiveness of ATZUMI have not been established in pediatric patients.

Clinical studies of ATZUMI and other dihydroergotamine products did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

ATZUMI contains dihydroergotamine (as the mesylate salt), which is not a controlled substance.

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Currently available data have not demonstrated drug abuse with dihydroergotamine. However, cases of drug abuse in patients on other forms of ergot therapy have been reported.

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Currently available data have not demonstrated physical or psychological dependence with dihydroergotamine. However, cases of psychological dependence in patients on other forms of ergot therapy have been reported.

Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism. In general, the symptoms of an acute ATZUMI overdose may be similar to those of an ergotamine overdose, although there may be less pronounced nausea and vomiting with ATZUMI. The symptoms of an ergotamine overdose include the following: numbness, tingling, pain, and cyanosis of the extremities associated with diminished or absent peripheral pulses; respiratory depression; an increase and/or decrease in blood pressure, usually in that order; confusion, delirium, convulsions, and coma; and/or some degree of nausea, vomiting, and abdominal pain.

In laboratory animals, dihydroergotamine mesylate was lethal when given at intravenous doses of 44 mg/kg in mice, 130 mg/kg in rats, and 37 mg/kg in rabbits.

Treatment of an overdose of ATZUMI should consist of discontinuation of the drug, general supportive measures including monitoring of vital signs, and observation of the clinical status of the patient for at least 24 hours, or while symptoms or signs persist. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

ATZUMI contains dihydroergotamine, an ergotamine derivative, as the mesylate salt. Dihydroergotamine mesylate is a white or almost white crystalline powder. It is slightly soluble in water and chloroform and sparingly soluble in methanol. The chemical designation for dihydroergotamine mesylate is (6aR,9R,10aR)-N-[(2R,5S,10aS,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxo-octahydro-8H-oxazolo[3,2-α]pyrrolo[2,1-c]pyrazin-2-yl]-7-methyl- 4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide methanesulphonate. The empirical formula is C33H37N5O5 ∙ CH4O3S. The molecular weight is 679.80, and it has the following structure:

{ "type": "p", "children": [], "text": "ATZUMI contains dihydroergotamine, an ergotamine derivative, as the mesylate salt. Dihydroergotamine mesylate is a white or almost white crystalline powder. It is slightly soluble in water and chloroform and sparingly soluble in methanol. The chemical designation for dihydroergotamine mesylate is (6aR,9R,10aR)-N-[(2R,5S,10aS,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxo-octahydro-8H-oxazolo[3,2-α]pyrrolo[2,1-c]pyrazin-2-yl]-7-methyl- 4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide methanesulphonate. The empirical formula is C33H37N5O5 ∙ CH4O3S. The molecular weight is 679.80, and it has the following structure:" }

ATZUMI contains dihydroergotamine 5.2 mg (equivalent to 6.0 mg dihydroergotamine mesylate).

{ "type": "p", "children": [], "text": "ATZUMI contains dihydroergotamine 5.2 mg (equivalent to 6.0 mg dihydroergotamine mesylate)." }

ATZUMI nasal powder is a drug-device combination product consisting of a powder prefilled in a single-dose delivery device for nasal administration into one nostril. ATZUMI does not need to be assembled or primed before use. Inactive ingredients are hypromellose, mannitol, and microcrystalline cellulose.

{ "type": "p", "children": [], "text": "ATZUMI nasal powder is a drug-device combination product consisting of a powder prefilled in a single-dose delivery device for nasal administration into one nostril. ATZUMI does not need to be assembled or primed before use. Inactive ingredients are hypromellose, mannitol, and microcrystalline cellulose." }

Dihydroergotamine binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors.

The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effects at 5-HT1D receptors.

Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine with and without a history of hypertension [see Warnings and Precautions (5.5)].

Dihydroergotamine possesses oxytocic properties [see Warnings and Precautions (5.7)].

Absorption

Following ATZUMI administration, the mean maximum plasma concentration was 2.1 ng/mL, and the median time from dosing to maximum plasma concentration was approximately 0.5 hours.

Distribution

Dihydroergotamine is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.

Elimination

The mean apparent half-life of dihydroergotamine following nasal administration of ATZUMI in healthy subjects is approximately 13 hours.

Metabolism

Four dihydroergotamine mesylate metabolites have been identified in human plasma following oral administration. The major metabolite, 8'-β-hydroxydihydroergotamine, exhibits affinity equivalent to its parent for adrenergic and 5-HT1 receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites, (i.e., dihydrolysergic acid, dihydrolysergic amide) and a metabolite formed by oxidative opening of the proline ring are of minor importance.

Following nasal administration of ATZUMI, the 8'-β-hydroxydihydroergotamine metabolite plasma AUC was approximately 16% of the plasma AUC of dihydroergotamine, and the mean Cmax (5.7% of parent) was below the minimal concentrations required for receptor binding for adrenergic and 5-HT1 receptors.

Excretion

The major excretory route of dihydroergotamine is via the bile in the feces. The total body clearance following ATZUMI administration is 1.5 L/min which reflects mainly hepatic clearance. The renal clearance (0.1 L/min) is unaffected by the route of dihydroergotamine administration based on other dihydroergotamine products.

Specific Populations

No studies have been conducted on the effect of renal or hepatic impairment, gender, race, ethnicity, or pregnancy on dihydroergotamine pharmacokinetics [see Contraindications (4), Use in Specific Populations (8.1)].

Drug Interaction Studies

CYP3A4 Inhibitors

In a drug interaction study, administration of ATZUMI with itraconazole increased dihydroergotamine plasma exposure by 14% for Cmax and 19% for AUC while the plasma exposures (Cmax and AUC0-inf) of 8'-β-hydroxy dihydroergotamine (8'-OH-DHE, active metabolite) were increased by approximately 4-fold and 3-fold, respectively [see Contraindications (4), Warnings and Precautions (5.1), Drug Interactions (7.1)].

Other Drugs

The pharmacokinetics of dihydroergotamine did not appear to be significantly affected by the concomitant use of a local vasoconstrictor.

Multiple oral doses of the β-adrenoceptor antagonist propranolol, used for preventive treatment of migraine, had no significant influence on the Cmax, Tmax or AUC of dihydroergotamine doses up to 4 mg [see Drug Interactions (7.3)].

The effect of oral contraceptives on the pharmacokinetics of dihydroergotamine has not been studied.

Carcinogenesis

In a 2-year mouse carcinogenicity study, subcutaneous administration of dihydroergotamine mesylate (0, 0.5, 1.5, or 5 mg/kg/day) resulted in an increased incidence of fibrosarcoma at the injection sites in males and females at the high dose.

In a 2-year rat carcinogenicity study, intranasal administration of dihydroergotamine mesylate (0, 0.4, 0.8, or 1.6 mg/day for 13 weeks, followed by 0, 0.08, 0.24, or 0.8 mg/day for the remainder of the study) did not result in an increase in tumors.

Mutagenesis

Dihydroergotamine mesylate was negative in an in vitro mutagenicity (Ames) assay and positive in in vitro chromosomal aberration (V79 Chinese hamster cell assay with metabolic activation, and human peripheral blood lymphocyte) assays. Dihydroergotamine was negative in in vivo micronucleus assays in mouse and hamster.

Impairment of Fertility

Intranasal administration of dihydroergotamine to rats at doses up to 1.6 mg/day was not associated with adverse effects on fertility.

The efficacy of ATZUMI for the acute treatment of migraine with or without aura in adults was based on the relative bioavailability of ATZUMI nasal powder compared to dihydroergotamine mesylate nasal spray.

{ "type": "p", "children": [], "text": "The efficacy of ATZUMI for the acute treatment of migraine with or without aura in adults was based on the relative bioavailability of ATZUMI nasal powder compared to dihydroergotamine mesylate nasal spray.\n" }

The clinical trials described below were conducted using dihydroergotamine mesylate nasal spray.

{ "type": "p", "children": [], "text": "The clinical trials described below were conducted using dihydroergotamine mesylate nasal spray." }

The efficacy of dihydroergotamine mesylate nasal spray for the acute treatment of migraine headaches was evaluated in four randomized, double-blind, placebo controlled studies in the U.S. The patient population for the trials was predominantly female (87%) and Caucasian (95%) with a mean age of 39 years (range 18 to 65 years). Patients treated a single moderate to severe migraine headache with a single dose of study medication 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 four-point pain intensity scale was utilized; in studies 3 and 4, a five-point scale was used to record pain response. Although rescue medication was allowed in all four studies, patients were instructed not to use them during the four hour observation period. In studies 3 and 4, a total dose of 2 mg was compared to placebo. In studies 1 and 2, doses of 2 and 3 mg were evaluated, and showed no advantage of the higher dose for a single treatment. In all studies, patients received a regimen consisting of 0.5 mg in each nostril, repeated in 15 minutes (and again in another 15 minutes for the 3 mg dose in studies 1 and 2).

{ "type": "p", "children": [], "text": "The efficacy of dihydroergotamine mesylate nasal spray for the acute treatment of migraine headaches was evaluated in four randomized, double-blind, placebo controlled studies in the U.S. The patient population for the trials was predominantly female (87%) and Caucasian (95%) with a mean age of 39 years (range 18 to 65 years). Patients treated a single moderate to severe migraine headache with a single dose of study medication 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 four-point pain intensity scale was utilized; in studies 3 and 4, a five-point scale was used to record pain response. Although rescue medication was allowed in all four studies, patients were instructed not to use them during the four hour observation period. In studies 3 and 4, a total dose of 2 mg was compared to placebo. In studies 1 and 2, doses of 2 and 3 mg were evaluated, and showed no advantage of the higher dose for a single treatment. In all studies, patients received a regimen consisting of 0.5 mg in each nostril, repeated in 15 minutes (and again in another 15 minutes for the 3 mg dose in studies 1 and 2). " }

The percentage of patients achieving headache response 4 hours after treatment was significantly greater in patients receiving 2 mg doses of dihydroergotamine mesylate nasal spray compared to those receiving placebo in 3 of the 4 studies (see Table 2 and Table 3 and Figure 1 and Figure 2).

{ "type": "p", "children": [], "text": "The percentage of patients achieving headache response 4 hours after treatment was significantly greater in patients receiving 2 mg doses of dihydroergotamine mesylate nasal spray compared to those receiving placebo in 3 of the 4 studies (see Table 2 and Table 3 and Figure 1 and Figure 2). " }

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 2 Studies 1 and 2: Percentage of Patients with Headache Response<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo)</span> </caption> <col align="left" valign="middle" width="10%"/> <col align="left" valign="middle" width="30%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="20%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="left" class="Rrule"></th><th align="center" class="Rrule" valign="bottom">N</th><th align="center" class="Rrule" valign="bottom">2 hours</th><th align="center" class="Rrule" valign="bottom">4 hours</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale.</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>p value &lt; 0.001</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>p value &lt; 0.01</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" rowspan="2"><span class="Bold">Study 1</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">105</td><td align="center" class="Rrule">61%<a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a></td><td align="center" class="Rrule">70%<a class="Sup" href="#footnote-2">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">98</td><td align="center" class="Rrule">23%</td><td align="center" class="Rrule">28%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">37%</td><td align="center" class="Rrule">42%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2"><span class="Bold">Study 2</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">103</td><td align="center" class="Rrule">47%</td><td align="center" class="Rrule">56%<a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">102</td><td align="center" class="Rrule">33%</td><td align="center" class="Rrule">35%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">14%</td><td align="center" class="Rrule">21%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"85%\">\n<caption>\n<span>Table 2 Studies 1 and 2: Percentage of Patients with Headache Response<a class=\"Sup\" href=\"#footnote-1\" name=\"footnote-reference-1\">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo)</span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"10%\"/>\n<col align=\"left\" valign=\"middle\" width=\"30%\"/>\n<col align=\"center\" valign=\"middle\" width=\"20%\"/>\n<col align=\"center\" valign=\"middle\" width=\"20%\"/>\n<col align=\"center\" valign=\"middle\" width=\"20%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Lrule Rrule\"></th><th align=\"left\" class=\"Rrule\"></th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">N</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">2 hours</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">4 hours</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-1\" name=\"footnote-1\">*</a>\n</dt>\n<dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale.</dd>\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">†</a>\n</dt>\n<dd>p value &lt; 0.001</dd>\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">‡</a>\n</dt>\n<dd>p value &lt; 0.01</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\"><span class=\"Bold\">Study 1</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">105</td><td align=\"center\" class=\"Rrule\">61%<a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">†</a></td><td align=\"center\" class=\"Rrule\">70%<a class=\"Sup\" href=\"#footnote-2\">†</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">98</td><td align=\"center\" class=\"Rrule\">23%</td><td align=\"center\" class=\"Rrule\">28%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">37%</td><td align=\"center\" class=\"Rrule\">42%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\"><span class=\"Bold\">Study 2</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">103</td><td align=\"center\" class=\"Rrule\">47%</td><td align=\"center\" class=\"Rrule\">56%<a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">‡</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">102</td><td align=\"center\" class=\"Rrule\">33%</td><td align=\"center\" class=\"Rrule\">35%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">14%</td><td align=\"center\" class=\"Rrule\">21%</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 3 Studies 3 and 4: Percentage of Patients with Headache Response<a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo) </span> </caption> <col align="left" valign="middle" width="10%"/> <col align="left" valign="middle" width="30%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="20%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="left" class="Rrule"></th><th align="center" class="Rrule" valign="bottom">N</th><th align="center" class="Rrule" valign="bottom">2 hours</th><th align="center" class="Rrule" valign="bottom">4 hours</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was evaluated on a five-point scale that included pain response.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">†</a> </dt> <dd>p value &lt; 0.01</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" rowspan="2" valign="top"><span class="Bold">Study 3</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">32%</td><td align="center" class="Rrule">48%<a class="Sup" href="#footnote-5" name="footnote-reference-5">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">20%</td><td align="center" class="Rrule">22%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">26%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2" valign="top"><span class="Bold">Study 4</span></td><td align="left" class="Rrule">Dihydroergotamine mesylate nasal spray</td><td align="center" class="Rrule">47</td><td align="center" class="Rrule">30%</td><td align="center" class="Rrule">47%</td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Placebo</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">20%</td><td align="center" class="Rrule">30%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">Difference from Placebo</td><td align="center" class="Rrule"></td><td align="center" class="Rrule">10%</td><td align="center" class="Rrule">17%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"85%\">\n<caption>\n<span>Table 3 Studies 3 and 4: Percentage of Patients with Headache Response<a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">*</a> 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo) </span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"10%\"/>\n<col align=\"left\" valign=\"middle\" width=\"30%\"/>\n<col align=\"center\" valign=\"middle\" width=\"20%\"/>\n<col align=\"center\" valign=\"middle\" width=\"20%\"/>\n<col align=\"center\" valign=\"middle\" width=\"20%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Lrule Rrule\"></th><th align=\"left\" class=\"Rrule\"></th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">N</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">2 hours</th><th align=\"center\" class=\"Rrule\" valign=\"bottom\">4 hours</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">*</a>\n</dt>\n<dd>Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was evaluated on a five-point scale that included pain response.</dd>\n<dt>\n<a href=\"#footnote-reference-5\" name=\"footnote-5\">†</a>\n</dt>\n<dd>p value &lt; 0.01</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\" valign=\"top\"><span class=\"Bold\">Study 3</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">50</td><td align=\"center\" class=\"Rrule\">32%</td><td align=\"center\" class=\"Rrule\">48%<a class=\"Sup\" href=\"#footnote-5\" name=\"footnote-reference-5\">†</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">50</td><td align=\"center\" class=\"Rrule\">20%</td><td align=\"center\" class=\"Rrule\">22%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">12%</td><td align=\"center\" class=\"Rrule\">26%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\" valign=\"top\"><span class=\"Bold\">Study 4</span></td><td align=\"left\" class=\"Rrule\">Dihydroergotamine mesylate nasal spray</td><td align=\"center\" class=\"Rrule\">47</td><td align=\"center\" class=\"Rrule\">30%</td><td align=\"center\" class=\"Rrule\">47%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">50</td><td align=\"center\" class=\"Rrule\">20%</td><td align=\"center\" class=\"Rrule\">30%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"left\" class=\"Rrule\">Difference from Placebo</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\">10%</td><td align=\"center\" class=\"Rrule\">17%</td>\n</tr>\n</tbody>\n</table></div>" }

The Kaplan-Meier plots below (Figure 1 and Figure 2) provides an estimate of the probability that a patient will have responded to a single 2 mg dose of dihydroergotamine mesylate nasal spray as a function of the time elapsed since initiation of treatment.

{ "type": "p", "children": [], "text": "The Kaplan-Meier plots below (Figure 1 and Figure 2) provides an estimate of the probability that a patient will have responded to a single 2 mg dose of dihydroergotamine mesylate nasal spray as a function of the time elapsed since initiation of treatment. " }

<div class="scrollingtable"><table class="Noautorules" width="85%"> <caption> <span>Figure 1 Estimated Probability of a Patient Responding During the Four Hours Following a Single 2 mg Dose of Dihydroergotamine Mesylate Nasal Spray as a Function of the Time Elapsed Since Initiation of Treatment<a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a></span> </caption> <col align="center" valign="middle" width="100%"/> <tfoot> <tr> <td align="left" colspan="1"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale. Patients not achieving response within 4 hours were censored to 4 hours.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=atzumi-02.jpg&amp;setid=0982a44a-dc0c-75c0-e063-6394a90a6d6c"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"85%\">\n<caption>\n<span>Figure 1 Estimated Probability of a Patient Responding During the Four Hours Following a Single 2 mg Dose of Dihydroergotamine Mesylate Nasal Spray as a Function of the Time Elapsed Since Initiation of Treatment<a class=\"Sup\" href=\"#footnote-6\" name=\"footnote-reference-6\">*</a></span>\n</caption>\n<col align=\"center\" valign=\"middle\" width=\"100%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"1\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-6\" name=\"footnote-6\">*</a>\n</dt>\n<dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale. Patients not achieving response within 4 hours were censored to 4 hours.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=atzumi-02.jpg&amp;setid=0982a44a-dc0c-75c0-e063-6394a90a6d6c\"/></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="85%"> <caption> <span>Figure 2 Estimated Probability of a Patient Responding to Dihydroergotamine Mesylate Nasal Spray During the Four Hours Following Dosing<a class="Sup" href="#footnote-7" name="footnote-reference-7">*</a></span> </caption> <col align="center" valign="middle" width="100%"/> <tfoot> <tr> <td align="left" colspan="1"> <dl class="Footnote"> <dt> <a href="#footnote-reference-7" name="footnote-7">*</a> </dt> <dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was evaluated on a five-point scale that included pain response. Patients not achieving response within 4 hours were censored to 4 hours.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=atzumi-03.jpg&amp;setid=0982a44a-dc0c-75c0-e063-6394a90a6d6c"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"85%\">\n<caption>\n<span>Figure 2 Estimated Probability of a Patient Responding to Dihydroergotamine Mesylate Nasal Spray During the Four Hours Following Dosing<a class=\"Sup\" href=\"#footnote-7\" name=\"footnote-reference-7\">*</a></span>\n</caption>\n<col align=\"center\" valign=\"middle\" width=\"100%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"1\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-7\" name=\"footnote-7\">*</a>\n</dt>\n<dd>The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray. Headache response was evaluated on a five-point scale that included pain response. Patients not achieving response within 4 hours were censored to 4 hours.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=atzumi-03.jpg&amp;setid=0982a44a-dc0c-75c0-e063-6394a90a6d6c\"/></td>\n</tr>\n</tbody>\n</table></div>" }

For patients with migraine-associated nausea, photophobia, and phonophobia at baseline, there was a lower incidence of these symptoms at 2 and 4 hours following administration of dihydroergotamine mesylate nasal spray compared to placebo.

{ "type": "p", "children": [], "text": "For patients with migraine-associated nausea, photophobia, and phonophobia at baseline, there was a lower incidence of these symptoms at 2 and 4 hours following administration of dihydroergotamine mesylate nasal spray compared to placebo." }

Patients were not allowed to use additional treatments for 8 hours prior to study medication dosing and during the 4-hour observation period following study treatment. Following the 4-hour observation period, patients were allowed to use additional treatments. For all studies, the estimated probability of patients using additional treatments for their migraines over the 24 hours following the single 2 mg dose of study treatment is summarized in Figure 3 below.

{ "type": "p", "children": [], "text": "Patients were not allowed to use additional treatments for 8 hours prior to study medication dosing and during the 4-hour observation period following study treatment. Following the 4-hour observation period, patients were allowed to use additional treatments. For all studies, the estimated probability of patients using additional treatments for their migraines over the 24 hours following the single 2 mg dose of study treatment is summarized in Figure 3 below." }

<div class="scrollingtable"><table class="Noautorules" width="85%"> <caption> <span>Figure 3 Estimated Probability of a Patient Using Additional Treatments for Migraine Over the 24 Hours Following Either Dihydroergotamine Mesylate Nasal Spray 2 mg (or Placebo)<a class="Sup" href="#footnote-8" name="footnote-reference-8">*</a></span> </caption> <col align="center" valign="middle" width="100%"/> <tfoot> <tr> <td align="left" colspan="1"> <dl class="Footnote"> <dt> <a href="#footnote-reference-8" name="footnote-8">*</a> </dt> <dd>Kaplan-Meier plot based on data obtained from all studies with patients not using additional treatments censored to 24 hours. All patients received a single treatment of study medication for their migraine attack. The plot also includes patients who had no response to the initial dose.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=atzumi-04.jpg&amp;setid=0982a44a-dc0c-75c0-e063-6394a90a6d6c"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"85%\">\n<caption>\n<span>Figure 3 Estimated Probability of a Patient Using Additional Treatments for Migraine Over the 24 Hours Following Either Dihydroergotamine Mesylate Nasal Spray 2 mg (or Placebo)<a class=\"Sup\" href=\"#footnote-8\" name=\"footnote-reference-8\">*</a></span>\n</caption>\n<col align=\"center\" valign=\"middle\" width=\"100%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"1\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-8\" name=\"footnote-8\">*</a>\n</dt>\n<dd>Kaplan-Meier plot based on data obtained from all studies with patients not using additional treatments censored to 24 hours. All patients received a single treatment of study medication for their migraine attack. The plot also includes patients who had no response to the initial dose.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=atzumi-04.jpg&amp;setid=0982a44a-dc0c-75c0-e063-6394a90a6d6c\"/></td>\n</tr>\n</tbody>\n</table></div>" }

Neither age nor sex appear to affect the patient's response to dihydroergotamine mesylate nasal spray. The racial distribution of patients was insufficient to determine the effect of race on the efficacy of dihydroergotamine mesylate nasal spray.

{ "type": "p", "children": [], "text": "Neither age nor sex appear to affect the patient's response to dihydroergotamine mesylate nasal spray. The racial distribution of patients was insufficient to determine the effect of race on the efficacy of dihydroergotamine mesylate nasal spray." }

ATZUMI (dihydroergotamine) nasal powder is supplied in a single-dose nasal device with white powder containing 5.2 mg of dihydroergotamine. ATZUMI is available in a carton of 8 nasal devices each individually packaged in a protective foil pouch (NDC 76978-101-08).

Store ATZUMI at controlled room temperature, 20°C to 25°C (68°F to 77°F), with excursions allowed between 15°C to 30°C (59°F to 86°F).

Store ATZUMI in its protective foil pouch until ready to use.

Serious and/or Life-Threatening Reactions with Coadministration of CYP3A4 Inhibitors

Inform patients that serious and/or life-threatening peripheral ischemia (cerebral ischemia and/or ischemia of the extremities) has been associated with the coadministration of dihydroergotamine and strong CYP3A4 inhibitors, such as macrolide antibiotics and protease inhibitors [see Contraindications (4), Warnings and Precautions (5.1), and Drug Interactions (7.1)].

Myocardial Ischemia and/or Infarction, Other Cardiac Events, Cerebrovascular Events, and Fatalities

Inform patients of the risk for serious cardiac, cerebrovascular, and other vasospasm related events. Advise patients to notify their healthcare provider if they develop any risk factors or symptoms while taking ATZUMI. Inform patients that nicotine may provoke vasoconstriction predisposing to a greater ischemic response [see Warnings and Precautions (5.2, 5.3, 5.4)].

Increase in Blood Pressure

Inform patients of the risk for significant elevation in blood pressure [see Warnings and Precautions (5.5)].

Medication Overuse Headache

Inform patients that use of drugs to treat migraine attacks for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].

Local Irritation

Advise patients to notify their healthcare provider if they have bothersome local irritation [see Warning and Precautions (5.9)].

Drug Interactions

Advise patients to inform their healthcare providers if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7)].

Pregnancy

Advise patients of the risk for preterm birth. Advise women to inform their healthcare provider if they are pregnant or intend to become pregnant [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)].

Lactation

Advise patients not to breastfeed during treatment with ATZUMI [see Use In Specific Populations (8.2)].

Administration Instructions

Instruct patients not to squeeze ATZUMI before inserting it into the nostril because priming is not required. Inform patients that they will need to squeeze the air pump on the ATZUMI device three separate times into one nostril to give a dose. Instruct the patient to squeeze while inhaling, release to allow the air pump to expand back to its original shape, then repeat two more times [see Instructions for Use]. Tell patients to use fast, complete, pulse-like squeezes to deliver their dose. [see Dosage and Administration (2.3)].

Manufactured for Satsuma Pharmaceuticals, Inc., 4819 Emperor Blvd., Suite 340, Durham, NC 27703

{ "type": "p", "children": [], "text": "Manufactured for Satsuma Pharmaceuticals, Inc., 4819 Emperor Blvd., Suite 340, Durham, NC 27703" }

© 2025. Satsuma Pharmaceuticals, Inc. All rights reserved. ATZUMI is a trademark of Satsuma Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "© 2025. Satsuma Pharmaceuticals, Inc. All rights reserved. ATZUMI is a trademark of Satsuma Pharmaceuticals, Inc." }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="middle" width="5%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="30%"/> <col align="left" valign="middle" width="45%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" colspan="4">MEDICATION GUIDE <br/> ATZUMI™ (at zoo' mee) <br/> (dihydroergotamine) <br/> nasal powder</th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="3">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align="right">Issued: 04/2025</td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold"><a name="mostimportantinformation"></a>What is the most important information I should know about ATZUMI? <br/> ATZUMI can cause serious side effects, including:</span> <ul class="Disc"> <li> <span class="Bold">Serious problems with blood circulation to your legs and feet (peripheral ischemia).</span> ATZUMI can cause peripheral ischemia when you take it with certain medicines known as CYP3A4 inhibitors. Peripheral ischemia may lead to a stroke and death. Stop taking ATZUMI and get emergency medical help right away if you have any of the following symptoms: <ul class="Circle"> <li>cramping and pain in your legs or hips</li> <li>feeling of heaviness or tightness in your leg muscles</li> <li>burning or aching pain in your feet or toes while resting</li> <li>numbness, tingling, or weakness in your legs</li> <li>cold feeling or color changes in 1 or both legs or feet</li> <li>slurred speech</li> <li>sudden weakness</li> </ul> </li> </ul> Do not take medicines known as strong CYP3A4 inhibitors, such as:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <ul class="Circle"> <li>ritonavir</li> <li>nelfinavir</li> </ul> </td><td align="left"> <ul class="Circle"> <li>erythromycin</li> <li>clarithromycin</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>ketoconazole</li> <li>itraconazole</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">These are not all of the medicines that could affect how ATZUMI works. Your healthcare provider can tell you if it is safe to take ATZUMI with other medicines. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What is ATZUMI?</span> <br/> ATZUMI is a prescription medicine used for the acute treatment of migraine with or without aura in adults. <ul class="Disc"> <li>ATZUMI is not used to prevent migraine.</li> <li>ATZUMI is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.</li> </ul> It is not known if ATZUMI is safe and effective in children.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Who should not take ATZUMI? <br/> Do not take ATZUMI if you: </span> <ul class="Disc"> <li>are taking medicines known as strong CYP3A4 inhibitors.</li> <li>have heart problems or a history of heart problems.</li> <li>have uncontrolled high blood pressure.</li> <li>have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease).</li> <li>have sepsis.</li> <li>have had vascular surgery.</li> <li>have severe liver problems.</li> <li>have severe kidney problems.</li> <li>are allergic to dihydroergotamine, ergot alkaloids, or any of the ingredients in ATZUMI. See the end of this Medication Guide for a complete list of ingredients in ATZUMI.</li> <li>have taken any of the following medicines in the last 24 hours: <ul class="Circle"> <li>sumatriptan</li> <li>almotriptan</li> <li>eletriptan</li> <li>frovatriptan</li> <li>naratriptan</li> <li>rizatriptan</li> <li>zolmitriptan</li> <li>ergotamine or ergotamine-type medicines</li> </ul> </li> <li>have taken any medicines that constrict your blood vessels or raise your blood pressure.</li> </ul> Ask your healthcare provider if you are not sure if you are taking any of these medicines. <br/> Your healthcare provider can tell you if it is safe to take ATZUMI with other medicines.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold"><a name="beforeyoutake"></a>Before you take ATZUMI, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have high blood pressure.</li> <li>have liver problems.</li> <li>have kidney problems.</li> <li>have risk factors for heart disease. You have a higher risk for heart disease if you: <ul class="Circle"> <li>have high blood pressure</li> <li>have high cholesterol levels</li> <li>smoke</li> <li>are overweight</li> <li>have diabetes</li> <li>have a family history of heart disease</li> </ul> </li> <li>are taking medicines known as strong CYP3A4 inhibitors.</li> <li>are pregnant or plan to become pregnant. ATZUMI may cause preterm labor. ATZUMI should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant.</li> <li>are breastfeeding or plan to breastfeed. ATZUMI may reduce breast milk supply and pass into your breast milk. ATZUMI may be harmful to your baby. Do not breastfeed your baby while taking ATZUMI and for 3 days after you use ATZUMI. Talk with your healthcare provider about the best way to feed your baby if you take ATZUMI.</li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider will decide if you can take ATZUMI with your other medicines. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">How should I take ATZUMI?</span> <ul class="Disc"> <li>ATZUMI is for nasal use only (use in the nose).</li> <li>Certain people should take their first dose of ATZUMI in their healthcare provider's office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li> <li>Use ATZUMI exactly as your healthcare provider tells you to use it. Read and follow the instructions in the Instructions for Use or use the Quick Reference Guide located on the ATZUMI protective foil pouch.</li> <li>If your headache comes back after the first complete dose or you only get some relief from your headache, you can use a second dose 1 hour after the first complete dose. Use a new ATZUMI nasal powder device for the second dose, if needed.</li> <li>Do not take more than 2 doses of ATZUMI within a 24-hour period. It is not known if it is safe to take more than 4 doses of ATZUMI in a 7-day period or 12 doses in a 30-day period.</li> <li>Taking ATZUMI for 10 or more days in 1 month may make your headaches worse. You should write down when you have headaches and when you take ATZUMI so that you can talk with your healthcare provider about how ATZUMI is working for you. See "<a href="#whatarethepossible">What are the possible side effects of ATZUMI?</a>".</li> </ul> If you use too much ATZUMI, call your healthcare provider or Poison Help line at 1-800-222-1222, or go to the nearest hospital emergency room right away.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold"><a name="whatarethepossible"></a>What are the possible side effects of ATZUMI? <br/> ATZUMI can cause serious side effects, including:</span> <br/> See <span class="Bold">"<a href="#mostimportantinformation">What is the most important information I should know about ATZUMI?</a>"</span> <ul class="Disc"> <li> <span class="Bold">Heart attack and other heart problems.</span> Heart problems may lead to death. Stop taking ATZUMI and get emergency medical help right away if you have any of the following symptoms of a heart attack: <ul class="Circle"> <li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li> <li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li> <li>pain or discomfort in your arms, back, neck, jaw, or stomach</li> <li>shortness of breath with or without chest discomfort</li> <li>breaking out in a cold sweat</li> <li>feeling lightheaded</li> <li>nausea or vomiting</li> </ul> </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" class="Rrule" colspan="3">ATZUMI is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. See <span class="Bold">"<a href="#beforeyoutake">Before you take ATZUMI, tell your healthcare provider about all of your medical conditions, including if you:</a>"</span> for the risk factors for heart disease.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">Stroke.</span> Stop taking ATZUMI and get emergency medical help right away if you have any of the following symptoms of a stroke: <ul class="Circle"> <li>face drooping</li> <li>unusual weakness or numbness</li> <li>slurred speech</li> </ul> </li> <li> <span class="Bold">Changes in color or sensation in your fingers and toes (Raynaud's syndrome).</span> </li> <li> <span class="Bold">Stomach and intestinal problems</span> (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include<span class="Bold">:</span> <ul class="Circle"> <li>sudden or severe stomach pain</li> <li>constipation or diarrhea</li> <li>stomach pain after meals</li> <li>bloody diarrhea</li> <li>weight loss</li> <li>fever</li> <li>nausea or vomiting</li> </ul> </li> <li> <span class="Bold">Increased blood pressure.</span> </li> <li> <span class="Bold">Medicine overuse headache.</span> Some people who use too much ATZUMI may make their headaches worse (medicine overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with ATZUMI.</li> <li> <span class="Bold">Preterm labor.</span> </li> <li> <span class="Bold">Tissue changes (fibrotic complications).</span> Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach.</li> <li> <span class="Bold">Nose irritation.</span> Discomfort in your nose, change in taste, stuffy nose, and cold-type symptoms, (such as, runny nose, sneezing, and cough) can occur.</li> </ul> <span class="Bold">The most common side effects of ATZUMI include</span>:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <ul class="Disc"> <li>runny nose</li> <li>nausea</li> <li>abnormal taste</li> </ul> </td><td align="left"> <ul class="Disc"> <li>application site reactions</li> <li>dizziness</li> <li>vomiting</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>sleepiness</li> <li>sore throat</li> <li>diarrhea</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">These are not all of the possible side effects of ATZUMI. <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">How should I store ATZUMI?</span> <ul class="Disc"> <li>Store ATZUMI at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Store ATZUMI in its protective foil pouch until ready to use.</li> </ul> <span class="Bold">Keep ATZUMI and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">General information about the safe and effective use of ATZUMI. </span> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ATZUMI for a condition for which it was not prescribed. Do not give ATZUMI to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ATZUMI that is written for health professionals.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are the ingredients in ATZUMI?</span> <br/> <span class="Bold">Active ingredient:</span> Dihydroergotamine <br/> <span class="Bold">Inactive ingredients:</span> Hypromellose, mannitol, and microcrystalline cellulose <br/> ATZUMI is a trademark of Satsuma Pharmaceuticals, Inc. <br/> Manufactured for Satsuma Pharmaceuticals, Inc., Durham, NC 27703 <br/> © 2025. Satsuma Pharmaceuticals, Inc. All rights reserved. <br/> For more information, go to www.atzumi.com or call 1-888-273-2480.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"middle\" width=\"5%\"/>\n<col align=\"left\" valign=\"middle\" width=\"20%\"/>\n<col align=\"left\" valign=\"middle\" width=\"30%\"/>\n<col align=\"left\" valign=\"middle\" width=\"45%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\" colspan=\"4\">MEDICATION GUIDE <br/> ATZUMI™ (at zoo' mee) <br/> (dihydroergotamine) <br/> nasal powder</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"3\">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\">Issued: 04/2025</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\"><a name=\"mostimportantinformation\"></a>What is the most important information I should know about ATZUMI? <br/> ATZUMI can cause serious side effects, including:</span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Serious problems with blood circulation to your legs and feet (peripheral ischemia).</span> ATZUMI can cause peripheral ischemia when you take it with certain medicines known as CYP3A4 inhibitors. Peripheral ischemia may lead to a stroke and death. Stop taking ATZUMI and get emergency medical help right away if you have any of the following symptoms: \t\t\t\t\t\t\t\t\t\t<ul class=\"Circle\">\n<li>cramping and pain in your legs or hips</li>\n<li>feeling of heaviness or tightness in your leg muscles</li>\n<li>burning or aching pain in your feet or toes while resting</li>\n<li>numbness, tingling, or weakness in your legs</li>\n<li>cold feeling or color changes in 1 or both legs or feet</li>\n<li>slurred speech</li>\n<li>sudden weakness</li>\n</ul>\n</li>\n</ul>\t\t\t\t\t\t\t\t\tDo not take medicines known as strong CYP3A4 inhibitors, such as:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>ritonavir</li>\n<li>nelfinavir</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Circle\">\n<li>erythromycin</li>\n<li>clarithromycin</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>ketoconazole</li>\n<li>itraconazole</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">These are not all of the medicines that could affect how ATZUMI works. Your healthcare provider can tell you if it is safe to take ATZUMI with other medicines. </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What is ATZUMI?</span>\n<br/> ATZUMI is a prescription medicine used for the acute treatment of migraine with or without aura in adults. \t\t\t\t\t\t\t\t\t<ul class=\"Disc\">\n<li>ATZUMI is not used to prevent migraine.</li>\n<li>ATZUMI is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.</li>\n</ul>\t\t\t\t\t\t\t\t\tIt is not known if ATZUMI is safe and effective in children.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Who should not take ATZUMI? <br/> Do not take ATZUMI if you: </span>\n<ul class=\"Disc\">\n<li>are taking medicines known as strong CYP3A4 inhibitors.</li>\n<li>have heart problems or a history of heart problems.</li>\n<li>have uncontrolled high blood pressure.</li>\n<li>have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease).</li>\n<li>have sepsis.</li>\n<li>have had vascular surgery.</li>\n<li>have severe liver problems.</li>\n<li>have severe kidney problems.</li>\n<li>are allergic to dihydroergotamine, ergot alkaloids, or any of the ingredients in ATZUMI. See the end of this Medication Guide for a complete list of ingredients in ATZUMI.</li>\n<li>have taken any of the following medicines in the last 24 hours: <ul class=\"Circle\">\n<li>sumatriptan</li>\n<li>almotriptan</li>\n<li>eletriptan</li>\n<li>frovatriptan</li>\n<li>naratriptan</li>\n<li>rizatriptan</li>\n<li>zolmitriptan</li>\n<li>ergotamine or ergotamine-type medicines</li>\n</ul>\n</li>\n<li>have taken any medicines that constrict your blood vessels or raise your blood pressure.</li>\n</ul>\t\t\t\t\t\t\t\t\tAsk your healthcare provider if you are not sure if you are taking any of these medicines. <br/> Your healthcare provider can tell you if it is safe to take ATZUMI with other medicines.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\"><a name=\"beforeyoutake\"></a>Before you take ATZUMI, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have high blood pressure.</li>\n<li>have liver problems.</li>\n<li>have kidney problems.</li>\n<li>have risk factors for heart disease. You have a higher risk for heart disease if you: \t\t\t\t\t\t\t\t\t\t<ul class=\"Circle\">\n<li>have high blood pressure</li>\n<li>have high cholesterol levels</li>\n<li>smoke</li>\n<li>are overweight</li>\n<li>have diabetes</li>\n<li>have a family history of heart disease</li>\n</ul>\n</li>\n<li>are taking medicines known as strong CYP3A4 inhibitors.</li>\n<li>are pregnant or plan to become pregnant. ATZUMI may cause preterm labor. ATZUMI should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant.</li>\n<li>are breastfeeding or plan to breastfeed. ATZUMI may reduce breast milk supply and pass into your breast milk. ATZUMI may be harmful to your baby. Do not breastfeed your baby while taking ATZUMI and for 3 days after you use ATZUMI. Talk with your healthcare provider about the best way to feed your baby if you take ATZUMI.</li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider will decide if you can take ATZUMI with your other medicines. </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">How should I take ATZUMI?</span>\n<ul class=\"Disc\">\n<li>ATZUMI is for nasal use only (use in the nose).</li>\n<li>Certain people should take their first dose of ATZUMI in their healthcare provider's office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li>\n<li>Use ATZUMI exactly as your healthcare provider tells you to use it. Read and follow the instructions in the Instructions for Use or use the Quick Reference Guide located on the ATZUMI protective foil pouch.</li>\n<li>If your headache comes back after the first complete dose or you only get some relief from your headache, you can use a second dose 1 hour after the first complete dose. Use a new ATZUMI nasal powder device for the second dose, if needed.</li>\n<li>Do not take more than 2 doses of ATZUMI within a 24-hour period. It is not known if it is safe to take more than 4 doses of ATZUMI in a 7-day period or 12 doses in a 30-day period.</li>\n<li>Taking ATZUMI for 10 or more days in 1 month may make your headaches worse. You should write down when you have headaches and when you take ATZUMI so that you can talk with your healthcare provider about how ATZUMI is working for you. See \"<a href=\"#whatarethepossible\">What are the possible side effects of ATZUMI?</a>\".</li>\n</ul>\t\t\t\t\t\t\t\t\tIf you use too much ATZUMI, call your healthcare provider or Poison Help line at 1-800-222-1222, or go to the nearest hospital emergency room right away.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\"><a name=\"whatarethepossible\"></a>What are the possible side effects of ATZUMI? <br/> ATZUMI can cause serious side effects, including:</span>\n<br/> See <span class=\"Bold\">\"<a href=\"#mostimportantinformation\">What is the most important information I should know about ATZUMI?</a>\"</span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Heart attack and other heart problems.</span> Heart problems may lead to death. Stop taking ATZUMI and get emergency medical help right away if you have any of the following symptoms of a heart attack: \t\t\t\t\t\t\t\t\t\t<ul class=\"Circle\">\n<li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li>\n<li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li>\n<li>pain or discomfort in your arms, back, neck, jaw, or stomach</li>\n<li>shortness of breath with or without chest discomfort</li>\n<li>breaking out in a cold sweat</li>\n<li>feeling lightheaded</li>\n<li>nausea or vomiting</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" class=\"Rrule\" colspan=\"3\">ATZUMI is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. See <span class=\"Bold\">\"<a href=\"#beforeyoutake\">Before you take ATZUMI, tell your healthcare provider about all of your medical conditions, including if you:</a>\"</span> for the risk factors for heart disease.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Stroke.</span> Stop taking ATZUMI and get emergency medical help right away if you have any of the following symptoms of a stroke: <ul class=\"Circle\">\n<li>face drooping</li>\n<li>unusual weakness or numbness</li>\n<li>slurred speech</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Changes in color or sensation in your fingers and toes (Raynaud's syndrome).</span>\n</li>\n<li>\n<span class=\"Bold\">Stomach and intestinal problems</span> (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include<span class=\"Bold\">:</span>\n<ul class=\"Circle\">\n<li>sudden or severe stomach pain</li>\n<li>constipation or diarrhea</li>\n<li>stomach pain after meals</li>\n<li>bloody diarrhea</li>\n<li>weight loss</li>\n<li>fever</li>\n<li>nausea or vomiting</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Increased blood pressure.</span>\n</li>\n<li>\n<span class=\"Bold\">Medicine overuse headache.</span> Some people who use too much ATZUMI may make their headaches worse (medicine overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with ATZUMI.</li>\n<li>\n<span class=\"Bold\">Preterm labor.</span>\n</li>\n<li>\n<span class=\"Bold\">Tissue changes (fibrotic complications).</span> Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach.</li>\n<li>\n<span class=\"Bold\">Nose irritation.</span> Discomfort in your nose, change in taste, stuffy nose, and cold-type symptoms, (such as, runny nose, sneezing, and cough) can occur.</li>\n</ul>\n<span class=\"Bold\">The most common side effects of ATZUMI include</span>:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>runny nose</li>\n<li>nausea</li>\n<li>abnormal taste</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>application site reactions</li>\n<li>dizziness</li>\n<li>vomiting</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>sleepiness</li>\n<li>sore throat</li>\n<li>diarrhea</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">These are not all of the possible side effects of ATZUMI. <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">How should I store ATZUMI?</span>\n<ul class=\"Disc\">\n<li>Store ATZUMI at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Store ATZUMI in its protective foil pouch until ready to use.</li>\n</ul>\n<span class=\"Bold\">Keep ATZUMI and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">General information about the safe and effective use of ATZUMI. </span>\n<br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ATZUMI for a condition for which it was not prescribed. Do not give ATZUMI to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ATZUMI that is written for health professionals.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are the ingredients in ATZUMI?</span>\n<br/>\n<span class=\"Bold\">Active ingredient:</span> Dihydroergotamine <br/>\n<span class=\"Bold\">Inactive ingredients:</span> Hypromellose, mannitol, and microcrystalline cellulose <br/> ATZUMI is a trademark of Satsuma Pharmaceuticals, Inc. <br/> Manufactured for Satsuma Pharmaceuticals, Inc., Durham, NC 27703 <br/> © 2025. Satsuma Pharmaceuticals, Inc. All rights reserved. <br/> For more information, go to www.atzumi.com or call 1-888-273-2480.</td>\n</tr>\n</tbody>\n</table></div>" }

ATZUMI™ (at zoo' mee) (dihydroergotamine) nasal powder

{ "type": "p", "children": [], "text": "ATZUMI™ (at zoo' mee) (dihydroergotamine) nasal powder" }

For Nasal Use Only

{ "type": "p", "children": [], "text": "For Nasal Use Only" }

This Instructions for Use contains information on how to use ATZUMI.

{ "type": "p", "children": [], "text": "This Instructions for Use contains information on how to use ATZUMI." }

Read this Instructions for Use before using ATZUMI.

{ "type": "p", "children": [], "text": "\nRead this Instructions for Use before using ATZUMI.\n" }

Important Information You Need to Know Before Using ATZUMI

{ "type": "p", "children": [], "text": "\nImportant Information You Need to Know Before Using ATZUMI\n" }

{ "type": "ul", "children": [ "ATZUMI contains 1 complete dose of medicine and should be thrown away after each use.", "ATZUMI is for nasal (nose) use only.", "Deliver all the powdered medicine into only 1 nostril.", "\nDo not use ATZUMI if it is damaged or expired.", "\nDo not squeeze ATZUMI before inserting it into the nostril. Priming is not required.", "Powdered medicine is inside the blue nozzle. When you squeeze the white air pump, air is pushed into the blue nozzle and pushes the powdered medicine into your nose.", "\nDo not squeeze slowly, partially or with any hesitation. When dosing, you must fully squeeze the white air pump as fast as you can. A fast, pulse-like squeezing action is needed." ], "text": "" }

How often can you use ATZUMI?

{ "type": "p", "children": [], "text": "\nHow often can you use ATZUMI?\n" }

{ "type": "ul", "children": [ "If needed, you may take a second dose 1 hour after your first dose. Wait at least 1 hour before taking the second dose.", "\nDo not take more than 2 doses within a 24-hour period.", "It is not known if it is safe to take more than 4 doses of ATZUMI in a 7-day period or 12 doses in a 30-day period." ], "text": "" }

Storing ATZUMI

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{ "type": "ul", "children": [ "Store ATZUMI at room temperature between 68°F to 77°F (20°C to 25°C).", "Store ATZUMI in its protective foil pouch until ready to use (Figure C).", "\nKeep ATZUMI and all medicines out of the reach of children.\n\n\n" ], "text": "" }

Step 1. Preparing to Use ATZUMI

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Step 2. Using ATZUMI

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Step 3. Inspecting ATZUMI

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{ "type": "", "children": [], "text": "" }

Step 4. Throwing Away ATZUMI

{ "type": "p", "children": [], "text": "Step 4. Throwing Away ATZUMI" }

{ "type": "", "children": [], "text": "" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration. Approved: 4/2025

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Quick Reference Guide

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This is a Quick Reference Guide. Read the full Instructions for Use before using ATZUMI. Deliver ATZUMI into only 1 nostril.

{ "type": "p", "children": [], "text": "This is a Quick Reference Guide. Read the full Instructions for Use before using ATZUMI. Deliver ATZUMI into only 1 nostril.\n" }

{ "type": "", "children": [], "text": "" }

This Quick Reference Guide has been approved by the U.S. Food and Drug Administration. Approved: 04/2025

{ "type": "p", "children": [], "text": "This Quick Reference Guide has been approved by the U.S. Food and Drug Administration. Approved: 04/2025" }

Atzumi™ (dihydroergotamine) nasal powder

{ "type": "p", "children": [], "text": "Atzumi™ (dihydroergotamine) nasal powder" }

5.2 mg

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For nasal use only. Discard after use. Contains:

{ "type": "p", "children": [], "text": "For nasal use only. Discard after use. Contains:" }

{ "type": "ul", "children": [ "8 prefilled single-dose devices", "Instructions for Use", "Medication Guide", "Prescribing Information" ], "text": "" }

Nasal devices not for individual sale. Dispense entire carton and accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Nasal devices not for individual sale. Dispense entire carton and accompanying Medication Guide to each patient." }

Rx Only NDC 76978-101-08

{ "type": "p", "children": [], "text": "Rx Only NDC 76978-101-08" }

© 2025 Satsuma Pharmaceuticals, Inc. All rights reserved.

{ "type": "p", "children": [], "text": "© 2025 Satsuma Pharmaceuticals, Inc. All rights reserved." }

Atzumi™ (dihydroergotamine) nasal powder

{ "type": "p", "children": [], "text": "Atzumi™ (dihydroergotamine) nasal powder" }

5.2 mg

{ "type": "p", "children": [], "text": "5.2 mg" }

For nasal use only. Discard after use. Recommended Dosage: See Prescribing Information. Contains 1 prefilled single-dose device. Nasal devices not for individual sale. Store ATZUMI in its protective pouch at room temperature 68°F to 77°F (20°C to 25°C). Excursions allowed between 59°F to 86°F (15°C to 30°C).

{ "type": "p", "children": [], "text": "For nasal use only. Discard after use. Recommended Dosage: See Prescribing Information. Contains 1 prefilled single-dose device. Nasal devices not for individual sale. Store ATZUMI in its protective pouch at room temperature 68°F to 77°F (20°C to 25°C). Excursions allowed between 59°F to 86°F (15°C to 30°C). " }

Keep out of reach of children. INSTRUCTIONS ON REVERSE

{ "type": "p", "children": [], "text": "Keep out of reach of children. INSTRUCTIONS ON REVERSE" }

Rx Only NDC 76978-101-01

{ "type": "p", "children": [], "text": "Rx Only NDC 76978-101-01" }

Manufactured for Satsuma Pharmaceuticals, Inc. Durham, NC 27703

{ "type": "p", "children": [], "text": "Manufactured for Satsuma Pharmaceuticals, Inc. Durham, NC 27703 " }

© 2025 Satsuma Pharmaceuticals, Inc. All rights reserved.

{ "type": "p", "children": [], "text": "© 2025 Satsuma Pharmaceuticals, Inc. All rights reserved." }