Dihydroergotamine is a semisynthetic ergot alkaloid that is structurally and pharmacologically related to ergotamine.129, 139, 148, 149, 150
Dihydroergotamine mesylate is used for the acute management of migraine attacks with or without aura in adults.129, 139, 148, 149, 150 .)
Dihydroergotamine is commercially available in parenteral (IV, IM, and subcutaneous injection) and intranasal preparations for this indication.129, 139, 148, 149, 150
Because dihydroergotamine rarely can cause potentially serious or life-threatening adverse effects, the drug should be used only in patients in whom a clear diagnosis of migraine has been established.129, 139 The manufacturer states that the drug should not be used for the management of hemiplegic or basilar migraine.129, 139, 148, 149, 150 In addition, dihydroergotamine should not be used for the prophylaxis of migraine headache.129, 139, 148, 149, 150
The efficacy of dihydroergotamine nasal spray for the acute treatment of migraine headache was established in four randomized, double-blind, placebo-controlled trials.130, 133, 134, 135, 149, 150 The majority (87%) of patients included in clinical trials were female with a mean age of 39 years (range: 18—65 years).149, 150 Patients with moderate-to-severe migraine headache were given a single dose of dihydroergotamine and were assessed for pain severity for 24 hours following treatment.149, 150 A positive response to treatment was defined as a reduction in headache severity to either mild or no pain.149, 150 Use of additional rescue medications was allowed in all studies, although patients were instructed not to take other rescue medications for 8 hours prior to or during a 4-hour observation period of the trial; additional rescue medications were allowed after the 4-hour observation period.149, 150 In two of the studies, a dose of 2 mg was administered and compared to placebo.149, 150 In the remaining 2 studies, doses of 2 mg and 3 mg were evaluated, although no advantage was noted in those patients that received the higher dose (3 mg) as a single treatment.149, 150 In all studies, patients received dihydroergotamine 0.5 mg in each nostril, which was repeated in 15 minutes (and repeated a third time in another 15 minutes in the participants that received a 3 mg dose).149, 150 The number of patients achieving a positive headache response was significantly greater in patients who received dihydroergotamine compared with those who received placebo in 3 of the 4 trials.149, 150 In patients who experienced 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 compared to placebo.149, 150
Guidelines from the American Headache Society (AHS) include dihydroergotamine as one of several drugs with efficacy in the acute treatment of migraine and recommend its use as a treatment option for moderate or severe attacks or for mild-to-moderate migraine attacks that respond poorly to alternate agents.151, 152 Subcutaneous or intranasal dihydroergotamine can also be considered as an alternative to 5-HT1 receptor agonists (triptans) or ketorolac in patients with severe nausea and vomiting when a non-oral route of medication administration is needed.151, 152 Intravenous dihydroergotamine, in combination with an antiemetic, can be considered for refractory migraine headaches.151, 152
Dihydroergotamine mesylate is used for the acute management of cluster headaches in adults.139, 148 Dihydroergotamine is commercially available as a parenteral (IV, IM, and subcutaneous injection) preparation for this indication.139, 148
Guidelines from AHS recommend 5-HT1 receptor agonists (triptans) and high flow oxygen for the treatment of cluster headache.153 The AHS guideline states that there is insufficient evidence to provide a recommendation regarding the use of dihydroergotamine for the treatment of acute cluster headache.153
Dispensing and Administration Precautions
Administer dihydroergotamine intranasally or by IM, IV, or subcutaneous injection for acute treatment of migraine.129, 139, 148, 149, 150 Administer by direct IV injection or continuous IV infusion† for the acute treatment of intractable migraines in an inpatient setting.139, 155
Administer dihydroergotamine by IM, IV, or subcutaneous injection for acute treatment of cluster headaches.139, 148
If the drug is being self-administered, the patient should be counseled on proper use and administration technique.129, 139, 148, 149, 150
Dihydroergotamine may be administered via IV, IM, or subcutaneous routes.139
If given by continuous IV infusion†, add 3 mg of dihydroergotamine mesylate into 1 liter of sodium chloride 0.9%, resulting in a final concentration of 3 mcg/mL.155 Continuous IV infusion†of dihydroergotamine has been administered at a rate of 126 mcg (42 mL) per hour.155
Dihydroergotamine is also available for subcutaneous self-administration via a prefilled, single-dose disposable autoinjector.148 Prior to injection, the expiration date and contents of the autoinjector should be inspected; the drug should be clear and colorless and should not be used if it appears cloudy, discolored, or has floating particles.148 The autoinjector is equipped with an attached needle, which is exposed by pulling the needle cap straight off.148 The injection should be administered into the skin in the middle of the thigh at least 2 inches away from the prior injection site; do not inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard.148 The same injection site should not be used 2 times in a row.148 The autoinjector should be placed straight (at a 90° angle) into the injection site and pushed down against the skin until the white safety guard is no longer visible prior to pressing the activation button.148 Press and release the gray activation button and a "click" will sound when the injection starts.148 The autoinjector should be held against the skin for at least 10 seconds to deliver the dose; when the viewing window is fully blocked (completely blue), the full dose has been administered.148 See full prescribing details for additional information.148
Store dihydroergotamine ampule at 20—25°C; excursions are permitted between 15—30°C.139 Do not refrigerate or freeze.139 Protect from light and heat.139
Store dihydroergotamine subcutaneous autoinjector at 20—25°C; excursions are permitted between 15—30°C.148 Do not refrigerate or freeze.148 Protect from light and retain in the original pack until time of use.148
Dihydroergotamine is available as an intranasal solution and powder.129, 149, 150 Prior to use, the intranasal delivery device should be prepared according to the manufacturer's instructions.129, 149, 150 Each device is intended for single use and should be disposed of after each use.129, 149, 150
Prior to use of dihydroergotamine nasal spray, the delivery device should be primed.129, 149 A complete dose using the Trudehsa® device consists of 2 sprays, 1 in each nostril; do not tilt head back or inhale through nose while administering the drug or immediately after.149 A complete dose of the generic dihydroergotamine mesylate nasal preparation is 1 spray in each nostril followed in 15 minutes by an additional spray in each nostril, for a total of 4 sprays.129 After the product is opened, it should be used within 8 hours or must be discarded.129, 149 See full prescribing information for additional details on individual preparations.129, 149
Dihydroergotamine intranasal powder is ready for use and does not require priming.150 Immediately prior to use, the round blue tab should be removed from the blue nozzle of the delivery device and the blue nozzle should be placed into one nostril.150 While inhaling, the white air pump should be squeezed 3 separate times into 1 nostril, allowing the white air pump to expand back to its original shape between squeezes.150 After use, the blue nozzle should be inspected for loose powder.150 Repeat until no loose powder medication remains.150 See full prescribing information for additional details.150
Store dihydroergotamine intranasal solution at controlled room temperature; do not refrigerate or freeze.129, 149 Consult labeling for product-specific recommendations.129, 149
Store dihydroergotamine powder for intranasal use at 20—25°C; excursions are permitted between 15-30°C.150 Store in protective foil pouch until ready to use.150
Available as dihydroergotamine mesylate; dosage expressed in terms of the salt.129, 139, 148, 149, 150
For the acute management of migraine headaches with or without aura, the usual adult IV, IM, or subcutaneous dose of dihydroergotamine mesylate is 1 mg initially, followed by 1 mg at 1-hour intervals until the attack has abated or until a total of 2 mg IV or 3 mg IM or subcutaneous has been given in a 24-hour period.139, 148 The total weekly IM, subcutaneous, or IV dosage should not exceed 6 mg.139, 148
Alternatively, dihydroergotamine mesylate 3 mg has been administered by continuous IV infusion†over 24 hours for the treatment of intractable migraine.155
For the acute management of migraine headaches with or without aura, the usual adult intranasal dose of dihydroergotamine mesylate is 0.5 mg (1 spray) administered in each nostril (1 mg total) initially, followed by 1 mg (1 spray [0.5 mg] in each nostril) 15 minutes later for a total dose of 2 mg.129 Intranasal dihydroergotamine mesylate doses exceeding 2 mg for a single migraine episode do not appear to provide additional therapeutic benefit.129 In addition, the safety of intranasal dihydroergotamine mesylate dosages exceeding 3 mg daily or 4 mg weekly has not been established.129 Intranasal dihydroergotamine mesylate is not recommended for prolonged daily use.129
When given intranasally using the Trudhesa®device, the usual adult intranasal dose of dihydroergotamine mesylate is 0.725 mg (1 spray) into each nostril (1.45 mg total).149 The dose may be repeated, if needed, a minimum of 1 hour after the first dose.149 The maximum recommended dosage is 2 doses within a 24-hour period or 3 doses within a 7-day period.149
When given intranasally as a powder for the acute management of migraine headaches with or without aura, the usual adult dose is 5.2 mg (the contents of 1 nasal device) into 1 nostril.150 The dose may be repeated, if needed, a minimum of 1 hour after the first dose.150 The maximum dosage in a 24-hour period is 10.4 mg (two doses of 5.2 mg).150 The safety of intranasal dihydroergotamine mesylate powder dosages exceeding more than 4 doses in a 7-day period or 12 doses within a 30-day period has not been established.150
For the acute management of cluster headaches, the usual adult IV, IM, or subcutaneous dose of dihydroergotamine mesylate is 1 mg initially, followed by 1 mg at 1-hour intervals until the attack has abated or until a total of 2 mg IV or 3 mg IM or subcutaneous has been given in a 24-hour period.139, 148 The total weekly IM, subcutaneous, or IV dosage should not exceed 6 mg.139
The manufacturers make no specific dosage recommendations for patients with hepatic impairment; use is contraindicated in patients with severe hepatic impairment.129, 139, 148, 149, 150
The manufacturers make no specific dosage recommendations for patients with renal impairment; use is contraindicated in patients with severe renal impairment.129, 139, 148, 149, 150
The manufacturers make no specific dosage recommendations for geriatric patients.148, 149, 150 In general, dose selection should be cautious, 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.148, 149, 150
Peripheral Ischemia Following Coadministration with Strong Cytochrome P-450 (CYP) 3A4 Inhibitors
A boxed warning regarding the risk of peripheral ischemia following coadministration with strong CYP3A4 inhibitors is included in the prescribing information for dihydroergotamine.129, 139, 148, 149, 150 There have been rare reports of serious and/or life-threatening adverse events associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities.129, 139, 148, 149, 150
Concomitant therapy with strong CYP3A4 inhibitors, including azole antifungal agents itraconazole and ketoconazole, protease inhibitors ritonavir and nelfinavir, and macrolide antibiotic agents erythromycin and clarithromycin should be avoided and is contraindicated.129, 139, 148, 149, 150 Other less potent CYP3A4 inhibitors (e.g., clotrimazole, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, nefazodone, zileuton) should be administered with caution.129, 139 Consider the effects on CYP3A4 of other agents being considered for concomitant use with dihydroergotamine.129, 139
Pleural and retroperitoneal fibrosis have occurred in patients following prolonged daily use of parenteral dihydroergotamine mesylate.129, 139, 148, 149, 150 Cardiac valvular fibrosis has occurred rarely in patients receiving parenteral dihydroergotamine.129, 139, 148, 149, 150 The manufacturers state that dihydroergotamine mesylate should not be used for prolonged daily administration and dosages of the drug should not exceed those recommended by the manufacturer.129, 139, 148, 149, 150
Risk of myocardial ischemia and/or infarction, coronary vasospasm, life-threatening cardiac rhythm disturbance (e.g., ventricular tachycardia and ventricular fibrillation), and death associated with use of dihydroergotamine.129, 139, 148, 149, 150 Dihydroergotamine should not be used in patients with known ischemic or vasospastic coronary artery disease.129, 139 Use not recommended in patients in whom unrecognized coronary artery disease is likely (e.g., postmenopausal women, men >40 years of age, patients with risk factors such as hypertension, hypercholesterolemia, obesity, diabetes mellitus, smoking, or family history of coronary artery disease) unless a prior cardiovascular evaluation provides satisfactory evidence that the patient does not have coronary artery disease, ischemic heart disease, or other clinically important underlying cardiovascular disease.129, 139, 148, 149, 150 For patients with risk factors for coronary artery disease who nevertheless have completed a satisfactory cardiovascular evaluation, the manufacturer strongly recommends that administration of an initial dose of dihydroergotamine take place under medical supervision (e.g., in the clinician's office, possibly followed by an ECG) unless such patients have previously received the drug.129, 139, 148, 149, 150 Periodic cardiovascular evaluation is recommended for patients with risk factors for coronary artery disease who are receiving intermittent long-term therapy with dihydroergotamine.129, 139, 148, 149, 150
Cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, some of which resulted in death, have occurred in patients treated with parenteral dihydroergotamine.129, 139, 148, 149, 150 In a number of patients, it appears that dihydroergotamine might have been used to treat symptoms thought to be a consequence of migraine, but actually related to a cerebrovascular event.129, 139, 148, 149, 150 Patients with a history of migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack).129, 139, 148, 149, 150 Discontinue dihydroergotamine if a cerebrovascular event is suspected.148, 149, 150
Other Vasospasm-related Events
Dihydroergotamine may cause vasospastic reactions other than coronary artery vasospasm.129, 139, 148, 149, 150 Myocardial, peripheral vascular, and colonic ischemia have been reported with use of dihydroergotamine.129, 139, 148, 149, 150
Vasospastic phenomena associated with the drug may result in muscle pain, numbness, coldness, pallor, and cyanosis of the digits.129, 139, 148, 149, 150 Because persistent vasospasm may result in gangrene or death in patients with compromised circulation, dihydroergotamine should be discontinued immediately if signs or symptoms of vasoconstriction develop.129, 139, 148, 149, 150 Patients who experience other symptoms suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud's syndrome following use should be evaluated by a clinician.148, 149, 150
Substantial increases in systemic blood pressure have been reported rarely in patients with or without a history of hypertension receiving dihydroergotamine.129, 139, 148, 149, 150 Use in patients with uncontrolled hypertension is contraindicated.129, 139, 148, 149, 150
Overuse of drugs used for acute migraine treatment (e.g., ergotamines, 5-HT1 receptor agonists [i.e., triptans], opioids, or a combination of these drugs for ≥10 days per month) may lead to exacerbation of headache (i.e., medication overuse headache).129, 139, 148, 149, 150 Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks.129, 139, 148, 149, 150 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.129, 139, 148, 149, 150
Based on the mechanism of action and findings from published literature, dihydroergotamine may cause preterm labor.129, 139, 148, 149, 150 Avoid use of dihydroergotamine during pregnancy.129, 139, 148, 149, 150
Local Effects of Intranasal Administration
Local irritative symptoms have been reported in patients receiving dihydroergotamine nasal spray.129, 149, 150 Symptoms include nasal pain/discomfort (including burning sensation), altered taste or smell, nasal congestion, nasopharyngitis, rhinorrhea, cough, epistaxis, sneezing, nasal pruritis, and increased lacrimation.129, 149, 150 If severe irritation occurs for no other attributable reasons, temporarily discontinue use until the event resolves.149, 150 If the event does not resolve or recurs with rechallenge, discontinue permanently.149, 150 Monitor patients for severe recurrent local irritation.150
The rigid needle shield of the dihydroergotamine autoinjector for subcutaneous injection contains a needle cover (located inside the cap) that contains dry natural rubber, which is made from latex.148 This product is contraindicated in patients who have shown previous hypersensitivity to latex.148
Available data from published literature indicate an increased risk of preterm delivery associated with dihydroergotamine use during pregnancy.129, 139, 148, 149, 150 Data collected over decades have found no increased risk of major birth defects or miscarriage.129, 139, 148, 149, 150 In animal reproduction studies, adverse developmental effects were observed in rats and rabbits following intranasal administration of dihydroergotamine during pregnancy (decreased fetal body weight and/or skeletal ossification) and lactation (decreased body weight and impaired reproductive function in offspring) at doses not associated with maternal toxicity.129, 139, 148, 149, 150 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.129, 139, 148, 149, 150
Avoid use of dihydroergotamine during pregnancy.129, 139, 148, 149, 150
There are no data on the presence of dihydroergotamine in human milk; however, ergotamine is present in human milk.129, 139, 148, 149, 150 Vomiting, diarrhea, weak pulse, and unstable blood pressure have been reported in breast-fed infants exposed to ergotamine.129, 139, 148, 149, 150 Ergot alkaloids inhibit prolactin secretion, which may reduce milk supply.129, 139, 148, 149, 150 Because of the potential for reduced milk supply and serious adverse effects in the breast-fed infant, advise patients not to breast-feed during treatment with dihydroergotamine and for 3 days after the last dose.129, 139, 148, 149, 150 Breast milk supply during this time should be pumped and discarded.129, 139, 148, 149, 150
Safety and efficacy of dihydroergotamine not established in children.129, 139, 148, 149, 150
Experience with intranasal dihydroergotamine in patients 65 years of age and older is insufficient to determine whether they respond differently than younger adults.129, 148, 149, 150 In general, dose selection should be cautious, 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.148, 149, 150
Contraindicated in patients with severe renal impairment.129, 139, 148, 149, 150 The effect of renal impairment on the pharmacokinetics of dihydroergotamine has not been evaluated in controlled studies.129, 139, 148, 149, 150
Contraindicated in patients with severe hepatic impairment.129, 139, 148, 149, 150 The effect of hepatic impairment on the pharmacokinetics of dihydroergotamine has not been evaluated in controlled studies. 129, 139, 148, 149, 150
Adverse effects of dihydroergotamine injection include vasospasm, paresthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use.139
The most common adverse effects of dihydroergotamine nasal spray and powder (>1% of patients) include rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea.149, 150
Drugs Affecting Hepatic Microsomal Enzymes
Potential pharmacologic and pharmacokinetic interaction (serious vasospastic effects secondary to increased plasma concentrations of dihydroergotamine) with inhibitors of cytochrome P-450 (CYP) 3A4 isoenzyme. 129, 139, 148, 149, 150 Serious and/or life-threatening cerebral and/or peripheral ischemia has been reported in patients receiving dihydroergotamine concomitantly with strong CYP3A4 inhibitors such as protease inhibitors (e.g., nelfinavir, ritonavir), macrolide antibiotics (e.g., clarithromycin, erythromycin), and azole antifungal agents (e.g., itraconazole, ketoconazole).129, 139, 148, 149, 150 Concomitant use with such agents is contraindicated.129, 139, 148, 149, 150 Caution is advised if dihydroergotamine is used concurrently with less potent CYP3A4 inhibitors (e.g., nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, clotrimazole).129, 148, 149 Clinicians should consider the effects on CYP3A4 of other agents being considered for concomitant use with dihydroergotamine.129, 139
Peripheral or Central Vasoconstrictors
Potential pharmacologic interaction (additive increases in blood pressure).129, 139, 148, 149, 150 Concomitant use of dihydroergotamine with these agents is contraindicated.129, 139, 148, 149, 150
Serotonin (5-HT1) Receptor Agonists (Triptans)
Triptans (5-HT1 receptor agonists) reported to cause coronary artery vasospasm and therefore have a potential pharmacologic interaction (additive vasospastic effects).129, 139, 148, 149, 150 Use within 24 hours of dihydroergotamine is contraindicated.129, 139, 148, 149, 150
Beta-Adrenergic Blocking Agents
Potential pharmacologic interaction.129, 139, 148, 149, 150 There have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.129, 139, 148, 149, 150
Potential pharmacologic interaction.129, 139, 148, 149, 150 Nicotine may provoke vasoconstriction in some patients, predisposing them to a greater ischemic response to ergot alkaloid therapy.129, 139, 148, 149, 150
Selective Serotonin-Reuptake Inhibitors
Potential pharmacologic interaction (weakness, hyperreflexia, incoordination) reported rarely when 5-HT1 receptor agonists were used concomitantly with selective serotonin-reuptake inhibitors (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline);129, 139, 148, 149, 150 no such interactions have been reported thus far between dihydroergotamine and selective serotonin-reuptake inhibitors.129, 139
The effect of oral contraceptives on the pharmacokinetics of dihydroergotamine has not been studied.129, 139
Dihydroergotamine is a semisynthetic ergot alkaloid that is structurally and pharmacologically related to ergotamine.129, 139, 148, 150 The mechanism of action of dihydroergotamine in the acute management of migraine headaches generally is attributed to the agonist effect at serotonin (5-hydroxytryptamine; 5-HT) type 1D receptors.129, 139, 148, 149, 150 Some clinicians suggest that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arteriovenous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache.129, 139 Alternatively, other clinicians have suggested that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of proinflammatory neuropeptide release.129, 139 Dihydroergotamine also exhibits oxytocic activity.129, 139, 148, 149, 150
Dihydroergotamine has poor oral bioavailability.129, 139 Following intranasal administration, mean bioavailability is 32% relative to parenteral administration; absorption is variable, reflecting both intersubject differences in absorption and technique used for self-administration.129 Absolute bioavailability for subcutaneous and IM routes has not been determined, however, no difference was observed in bioavailability from IM and subcutaneous doses.139, 148, 149, 150 The median time to maximum plasma concentration is 0.4 hours after subcutaneous administration and 0.5 hours after intranasal administration.148, 149, 150 Dihydroergotamine is 93% plasma protein bound.129, 139, 148, 149, 150 Dihydroergotamine is extensively metabolized in the liver by cytochrome P-450 3A4; the major metabolite (8'-β-hydroxydihydroergotamine) exhibits affinity for adrenergic and serotonergic receptors similar to the parent drug.129, 139, 148, 149, 150 Dihydroergotamine is eliminated principally in the feces via the bile; 6—7% is excreted unchanged in the urine after IM injection.129, 139, 148, 149 The decline of plasma dihydroergotamine after IM or IV injection is multi-exponential with a terminal half life of ~9 hours.139, 148 The decline of plasma dihydroergotamine after intranasal administration is biphasic with a terminal half-life of ~10 hours.129 No studies have been performed on the effect of renal or hepatic impairment, gender, race, or ethnicity on the pharmacokinetics of dihydroergotamine.129, 148, 149, 150
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Intranasal | Solution | 0.5 mg/metered spray (4 mg/mL)* | Dihydroergotamine Nasal Spray (with anhydrous caffeine 10 mg/mL ; available in ampul with a nasal spray applicator) | |
0.725 mg/metered spray (4 mg/mL) | Trudhesa® (with anhydrous caffeine 10 mg; available in glass vial with nasal spray device) | Impel Pharmaceuticals | ||
Powder | 5.2 mg/device | Atzumi® (available in single-dose nasal device) | Satsuma Pharmaceuticals | |
Parenteral | Injection, for IV, IM, and subcutaneous use | 1 mg/mL* | Dihydroergotamine Mesylate Injection | |
Injection, for subcutaneous use | 1 mg/mL | Brekiya® (available as prefilled autoinjector) | Amneal Pharmaceuticals |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
129. Trifluent Pharma, LLC. Dihydroergotamine mesylate nasal spray prescribing information. San Antonio, TX; 2025 Feb.
130. Ziegler D, Ford R, Kriegler J et al. Dihydroergotamine nasal spray for the acute treatment of migraine. Neurology . 1994; 44:
133. Massiou H. Dihydroergotamine nasal spray in prevention and treatment of migraine attacks: two controlled trials versus placebo. Cephalgia . 1987 (suppl. 6): 440-1.
134. Dihydroergotamine Nasal Spray Multicenter Investigators. Efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine. Headache . 1995; 35:177-84. [PubMed 7775172]
135. Gallagher RM. Acute treatment of migraine with dihydroergotamine nasal spray. Arch Neurol . 1996; 53:1285-91. [PubMed 8970458]
139. Baxter Healthcare Corporation. Ddihydroergotamine mesylate injection prescribing information. Deerfield, IL; 2023 Jul.
148. Amneal Pharmaceuticals LLC. Brekiya® (dihydoergotamine mesylate) injection prescribing information. Bridgewater, NJ; 2025 May.
149. Impel Pharmaceuticals LLC. Trudhesa® (dihydroergotamine mesylate) nasal spray prescribing information. Seattle, WA; 2021 Sep.
150. Satsuma Pharmaceuticals, Inc. Atzumi® (dihydroergotamine mesylate) powder for intranasal use prescribing information. Durham, NC; 2025 Apr.
151. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache . 2019; 59:1-18.
152. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society consensus statement: Update on integrating new migraine treatments into clinical practice. Headache . 2021; 61:1021-39.
153. Robbins MS, Starling AJ, Pringsheim et al. Treatment of cluster headache: The American Headache Society evidence-based guidelines. Headache . 2016; 56:1093-1106.
154. Centers for Disease Control and Prevention National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2024. From CDC website. http://www.cdc.gov/niosh/docs/2025-103/pdfs/2025-103.pdf
155. Ford RG, Ford KT. Continuous infusion dihydroergotamine in the treatment of intractable migraine. Headache . 1997; 37:129-136.