dihydroergotamine mesylate
Dihydroergotamine Mesylate is an ergotamine derivative used to treat Cluster Headache, Postpartum Hemorrhage, Orthostatic Hypotension, Migraine Disorders.
Ergotamine Derivative · by Somerset Theraps LLC
Generic of Brekiya (Autoinjector)
Key facts
- Active ingredient
- Dihydroergotamine Mesylate
- Drug class
- Ergotamine Derivative
- Form
- Injectable, Solution, Spray/Inhaler, Spray/Inhaler, metered
- Strength
- Dihydroergotamine Mesylate 0.5MG/SPRAY
- Type
- Prescription (Rx)
- Brand or generic
- Generic
- Manufacturer
- Somerset Theraps LLC
- Half-life
- about 9 to 13 hours, depending on the form (how long it stays in your system)
- What the pharmacy pays
- ~$34.84 per ml — not your price
- FDA application
- ANDA215228
- FDA boxed warning
- Yes — see the boxed warning
What is Dihydroergotamine Mesylate?
From the FDA label:Dihydroergotamine mesylate is ergotamine hydrogenated in the 9,10 position as the mesylate salt. Dihydroergotamine mesylate is known chemically as ergotaman-3', 6', 18-trione, 9,10-dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-, (5'α)-, monomethane-sulfonate. Its molecular weight is 679.78 and its empirical formula is C 33 H 37 N 5 O 5 •CH 4 O 3 S. The chemical structure is: Dihydroergotamine mesylate nasal spray is provided for intranasal administration as a clear, colorless to light yellow aqueous solution in an amber glass vial containing: Dihydroergotamine mesylate ……………………………………… 4 mg caffeine, anhydrous………………………………………………… 10 mg dextrose, anhydrous ……………………………………………….. 50 mg carbon dioxide …………………………………………………….. qs purified water ……………………………………………………… qs 1 mL Each milliliter contains Dihydroergotamine mesylate ……………………………………… 4 mg (equivalent to 3.43 mg dihydroergotamine) Image
How to use
Dihydroergotamine Mesylate is sold in more than one form (Injectable, Solution, Spray/Inhaler and Spray/Inhaler, metered), and each is dosed differently. The instructions below come from the FDA label for application ANDA215228 — follow the label that came with the product you were actually prescribed.
The solution used in dihydroergotamine mesylate nasal spray (4 mg/mL) is intended for intranasal use and must not be injected. In clinical trials, dihydroergotamine mesylate nasal spray has been effective for the acute treatment of migraine headaches with or without aura. One spray (0.5 mg) of dihydroergotamine mesylate nasal spray should be administered in each nostril. Fifteen minutes later, an additional one spray (0.5 mg) of dihydroergotamine mesylate nasal spray should be administered in each nostril, for a total dosage of four sprays (2 mg) of dihydroergotamine mesylate nasal spray. Studies have shown no additional benefit from acute doses greater than 2 mg for a single migraine administration. The safety of doses greater than 3 mg in a 24 hour period and 4 mg in a 7 day period has not been established. Dihydroergotamine mesylate nasal spray, should not be used for chronic daily administration. Prior to administration, the pump must be primed (i.e., squeeze 4 times) before use (see administration instructions). Once the nasal spray applicator has been prepared, it should be discarded (with any remaining drug in opened vial) after 8 hours. Prior to administration, the pump must be primed (i.e., squeeze 4 times) before use. (See administration instructions) Once the nasal spray applicator has been prepared, it should be discarded (with any remaining drug in opened vial…
Side effects
During clinical studies and the foreign postmarketing experience with dihydroergotamine mesylate nasal spray there have been no fatalities due to cardiac events. Serious cardiac events, including some that have been fatal, have occurred following use of the parenteral form of dihydroergotamine mesylate (D.H.E. 45 ® Injection), but are extremely rare. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation. ( see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS ). Fibrotic complications have been reported in association with long term use of injectable dihydroergotamine mesylate ( see WARNINGS: Fibrotic Complications ). Incidence in Controlled Clinical Trials 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 each due to cold sweats, accidental trauma, depression, elective surgery, somnolence, allergy, vomiting, hypotension, and paraesthesia. The most commonly reported adverse events associated with the use of dihydroergotamine mesylate nasal spray during placebo-controlled, double-blind studies…
FDA Boxed Warning (the FDA’s most serious warning)
Boxed (black-box) warning — from the FDA label
Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated. (see also CONTRAINDICATIONS and WARNINGS section)
Warnings
Important safety information
Dihydroergotamine mesylate nasal spray should only be used where a clear diagnosis of migraine headache has been established . CYP 3A4 Inhibitors (e.g. Macrolide Antibiotics and Protease Inhibitors) There have been rare reports of serious adverse events in connection with the coadministration of dihydroergotamine and potent CYP 3A4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or and ischemia of the extremities. The use of potent CYP 3A4 inhibitors with dihydroergotamine should therefore be avoided (see CONTRAINDICATIONS) . Examples of some of the more potent CYP 3A4 inhibitors include: antifungals ketoconazole and itraconazole, the protease inhibitors ritonavir, nelfinavir, and indinavir, and macrolide antibiotics erythromycin, clarithromycin, and troleandomycin. Other less potent CYP 3A4 inhibitors should be administered with caution. Less potent inhibitors include saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, and clotrimazole. These lists are not exhaustive, and the prescriber should consider the effects on CYP 3A4 of other agents being considered for concomitant use with dihydroergotamine . Fibrotic Complications There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable 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 injectable dihydroergotamine mesylate; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis. Administration of dihydroergotamine mesylate nasal spray, should not exceed the dosing guidelines and should not be used for chronic daily administration (see DOSAGE AND ADMINISTRATION). Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events: Dihydroergotamine mesylate nasal spray should not be used by patients with documented ischemic or vasospastic coronary artery disease. (see CONTRAINDICATIONS) It is strongly recommended that dihydroergotamine mesylate nasal spray not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient's medical history or electrocardiographic investigations reveal findings indicative of or consistent with coronary artery vasospasm or myocardial ischemia, dihydroergotamine mesylate nasal spray should not be administered. (see CONTRAINDICATIONS) For patients with risk factors predictive of CAD who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of dihydroergotamine mesylate nasal spray take place in the setting of a physician's office or similar medically staffed and equipped facility unless the patient has previously received dihydroergotamine mesylate . Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion of use an electrocardiogram (ECG) during the interval immediately following dihydroergotamine mesylate nasal spray , in these patients with risk factors. It is recommended that patients who are intermittent long-term users of dihydroergotamine mesylate nasal spray and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use dihydroergotamine mesylate nasal spray . The systematic approach described above is currently recommended as a method to identify patients in whom dihydroergotamine mesylate nasal spray may be used to treat migraine headaches with an acceptable margin of cardiovascular safety. Cardiac Events and Fatalities No deaths have been reported in patients using dihydroergotamine mesylate nasal spray. However, the potential for adverse cardiac events exists. Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported to have occurred following the administration of dihydroergotamine mesylate injection (e.g., D.H.E. 45 ® Injection). Considering the extent of use of dihydroergotamine mesylate in patients with migraine, the incidence of these events is extremely low. Drug-Associated Cerebrovascular Events and Fatalities Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with D.H.E. 45 ® Injection; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the D.H.E. 45 ® Injection 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). Other Vasospasm Related Events Dihydroergotamine mesylate nasal spray, like other ergot alkaloids, may cause vasospastic reactions other than coronary artery vasospasm. Myocardial and peripheral vascular ischemia have been reported with dihydroergotamine mesylate nasal spray. Dihydroergotamine mesylate nasal spray 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, dihydroergotamine mesylate nasal spray should be discontinued immediately if signs or symptoms of vasoconstriction develop. Increase in Blood Pressure Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension treated with dihydroergotamine mesylate nasal spray and dihydroergotamine mesylate injection. Dihydroergotamine mesylate nasal spray is contraindicated in patients with uncontrolled hypertension. (see CONTRAINDICATIONS) An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5HT 1 agonist in a study evaluating subjects undergoing cardiac catheterization. Local Irritation Approximately 30% of patients using dihydroergotamine mesylate nasal spray (compared to 9% of placebo patients) have reported irritation in the nose, throat, and/or disturbances in taste. Irritative symptoms include congestion, burning sensation, dryness, paraesthesia, discharge, epistaxis, pain, or soreness. The symptoms were predominantly mild to moderate in severity and transient. In approximately 70% of the above mentioned cases, the symptoms resolved within four hours after dosing with dihydroergotamine mesylate nasal spray. Examinations of the nose and throat in a small subset (N = 66) of study participants treated for up to 36 months (range 1-36 months) did not reveal any clinically noticeable injury. Other than this limited number of patients, the consequences of extended and repeated use of dihydroergotamine mesylate nasal spray on the nasal and/or respiratory mucosa have not been systematically evaluated in patients. Nasal tissue in animals treated with dihydroergotamine mesylate daily at nasal cavity surface area exposures (in mg/mm2) that were equal to or less than those…
Who should not take Dihydroergotamine Mesylate
There have been a few reports of serious adverse events associated with the coadministration of dihydroergotamine and potent CYP 3A4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities. The use of potent CYP 3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) with dihydroergotamine is, therefore contraindicated ( see WARNINGS: CYP 3A4 Inhibitors ). Dihydroergotamine mesylate nasal spray should not be given to patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina. ( see WARNINGS ) Because dihydroergotamine mesylate nasal spray may increase blood pressure, it should not be given to patients with uncontrolled hypertension. Dihydroergotamine mesylate nasal spray , 5-HT1 agonists (e.g., sumatriptan), ergotamine-containing or ergot-type medications or methysergide should not be used within 24 hours of each other. Dihydroergotamine mesylate nasal spray should not be administered to patients with hemiplegic or basilar migraine. In addition to those conditions mentioned above, dihydroergotamine mesylate nasal spray is also contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery, and severely impaired hepatic or renal function. Dihydroergotamine mesylate nasal spray is contraindicated in patients who have previously shown hypersensitivity to ergot alkaloids. Dihydroergotamine mesylate nasal spray should not be used with peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure.
Overdose — what happens if you take too much
To date, there have been no reports of acute overdosage with this drug. Due to the risk of vascular spasm, exceeding the recommended dosages of dihydroergotamine mesylate nasal spray is to be avoided. Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism. 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. In general, the symptoms of an acute dihydroergotamine mesylate nasal spray overdose are similar to those of an ergotamine overdose, although there is less pronounced nausea and vomiting with dihydroergotamine mesylate nasal spray. 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, significant lethality occurs when dihydroergotamine is given at I.V. doses of 44 mg/kg in mice, 130 mg/kg in rats, and 37 mg/kg in rabbits. Up-to-date information about the treatment of overdosage can often be obtained from a certified Regional Poison Control Center. Telephone numbers of certified…
U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.
How long does Dihydroergotamine Mesylate stay in your body?
The elimination half-life of dihydroergotamine mesylate is about 9 to 13 hours, depending on the form — the time it takes the body to clear about half of it. As a rule of thumb, a medicine is mostly gone after roughly 4 to 5 half-lives, though this varies from person to person with age and kidney or liver function. The injection label states a terminal half-life of about 9 hours after intramuscular or intravenous dosing, with a multi-exponential decline. Nasal forms read slightly longer because absorption is slower: the nasal spray label gives about 10 hours (biphasic decline) and the Atzumi nasal powder label gives an apparent half-life of about 13 hours. The major metabolite, 8'-beta-hydroxydihydroergotamine, binds adrenergic and 5-HT receptors as strongly as the parent drug and is equally potent at constricting veins, so its effects can outlast what the parent's half-life suggests — but the label explicitly says its pharmacokinetics have not been quantified, so no metabolite half-life exists in the labeling. No studies have been done on how kidney or liver impairment, age, sex, or race change these numbers; the drug is contraindicated outright in severe hepatic or renal impairment. Clearance is 1.5 L/min and mainly hepatic (excreted in bile and feces; only 6-7% of unchanged drug appears in urine), so liver disease and CYP3A4 inhibitors such as ritonavir, clarithromycin, and erythromycin are the real-world drivers of accumulation. There is no extended-release dihydroergotamine.
This is general information, not medical advice. It doesn’t tell you when a drug test would read negative (tests detect substances for different, often longer, windows) or when it’s safe to take another dose — ask your pharmacist or prescriber. Source: Dihydroergotamine Mesylate Injection, USP — FDA label, Clinical Pharmacology (DailyMed).
Drug class
May treat (source: NIH RxClass)
See how Dihydroergotamine Mesylate ranks — best-rated ergotamine derivative for:
Dosage forms
Injectable, Solution, Spray/Inhaler and Spray/Inhaler, metered
The forms currently marketed in the U.S., per the FDA National Drug Code Directory.
Ways to save
Ask for the generic
Same active ingredient, far cheaper. Is there a generic? →
Request a 90-day supply
Bulk fills usually lower the per-dose price vs monthly refills.
Use copay cards
Manufacturer copay cards & patient-assistance programs — especially for brand drugs.
Compare alternatives
A same-class option may cost less. See alternatives →
Frequently asked questions
- What does Dihydroergotamine Mesylate treat?
- Dihydroergotamine Mesylate (Dihydroergotamine Mesylate) may be used to treat cluster headache, postpartum hemorrhage, orthostatic hypotension, migraine disorders, xerostomia, based on NIH RxClass drug-classification data (conditions a drug may treat — not a verbatim copy of the FDA-approved label). This is general reference, not medical advice.
- How much does Dihydroergotamine Mesylate cost?
- Nobody can tell you what you will pay — your price is set by your insurer's formulary, your deductible and the pharmacy's markup, and none of those are published. What IS published is what the pharmacy paid to acquire it: about $34.84 per ml, per the CMS NADAC survey. Treat that as the floor, not the quote — ask the pharmacist for the cash price as well as your copay, because for cheap generics the cash price often wins.
- Is there a coupon or discount for Dihydroergotamine Mesylate?
- pharmaranks is an independent ratings site, not a pharmacy — we don't issue coupons or sell Dihydroergotamine Mesylate. To pay less, Dihydroergotamine Mesylate is already a generic — usually the lowest-cost version — so the main levers are comparing cash prices between pharmacies and using a pharmacy discount-card service. Prices vary by pharmacy, insurance, and location, so always confirm at the counter. This is general reference, not medical or financial advice.
- Who makes Dihydroergotamine Mesylate?
- Dihydroergotamine Mesylate is marketed by Somerset Theraps LLC. You can see Somerset Theraps LLC's full profile, rating, and other products on pharmaranks.
- Is Dihydroergotamine Mesylate a brand-name or generic drug?
- Dihydroergotamine Mesylate is a generic medication; its active ingredient is Dihydroergotamine Mesylate. Generics contain the same active ingredient as the brand-name original and are usually lower cost.
- Is Dihydroergotamine Mesylate available over the counter?
- No. Dihydroergotamine Mesylate is a prescription (Rx) medication in the US — you need a prescription from a licensed clinician (in person or via telehealth); it isn't sold over the counter. For some conditions there are OTC alternatives — ask your pharmacist.
- What forms does Dihydroergotamine Mesylate come in?
- Dihydroergotamine Mesylate is currently marketed as injectable, solution, spray/inhaler and spray/inhaler, metered, per the FDA's National Drug Code Directory.
- What class of drug is Dihydroergotamine Mesylate?
- Dihydroergotamine Mesylate is classified as ergotamine derivative, per the FDA's Established Pharmacologic Class.
- Is Dihydroergotamine Mesylate FDA-registered?
- Dihydroergotamine Mesylate is on record with the U.S. FDA under application number ANDA215228. You can verify this on its official FDA label.
- Is Dihydroergotamine Mesylate safe?
- There's no single safe-or-not verdict, and we don't yet have a composite recall-safety score for Dihydroergotamine Mesylate. Review its FDA-label side effects and warnings below, and always consult a licensed professional.
- What are the side effects of Dihydroergotamine Mesylate?
- Dihydroergotamine Mesylate's side effects are taken directly from its FDA label. From the label: During clinical studies and the foreign postmarketing experience with dihydroergotamine mesylate nasal spray there have been no fatalities due to cardiac events. Serious cardiac events, including some that have been fatal,… Both common and serious reactions are documented in full on this page. This is general reference from the FDA, not medical advice — always consult a professional.
Clinical content sourced from the FDA label via openFDA (U.S. FDA). View the FDA label on DailyMed → Provided for general reference only — not medical advice. Always consult a licensed professional and the current prescribing information.
Reviews
No reviews yet. Be the first to write one.
People also viewed
Compare Dihydroergotamine Mesylate head-to-head
Browse medications A–Z
Research products from A to Z, compare independent ratings, and find alternatives.
dihydroergotamine mesylate
New