Dihydroergotamine Mesylate 4 mg/mL Spray, 8 vials
Other active recalls for Dihydroergotamine Mesylate (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Ergotamine Derivative class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- This medication is used to treat a migraine attack while it's happening — it's not something you take every day to stop migraines from starting. It works on migraines with or witho...
- What exactly is this medication for? My doctor said it's for migraines, but I want to understand more.
- The technique matters with these products. If you're using Atzumi (the nasal powder), you remove the blue tab, insert the nozzle into one nostril, and squeeze the white pump three...
- How do I actually use the nasal spray or powder correctly?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Dihydroergotamine Mesylate — tap one for details:
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 5SL0G7R0OK
A simple sugar made from corn or other plants, used in medicines as a filler and sweetener. It helps create the right texture and taste in tablets, powders, and liquid formulations.
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UNII 3G6A5W338E
Caffeine is a natural stimulant compound commonly extracted from coffee beans and tea leaves. In medicines, it serves as an active booster in pain relievers and cold products to enhance alertness and improve the effectiveness of other ingredients.
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UNII 142M471B3J
Carbon dioxide is a colorless gas used in medicines as a propellant in pressurized inhalers and aerosol sprays to help deliver the active medication to where it's needed.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
4 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $34.212 | $273.69 / 8 ml |
| Medicaid paysCMS SDUD · 12 mo | $40.39 | $323.11 / 8 ml |
| Medicare drug plans payPart D · Q2 2026 | $79.27 | $634.17 / 8 ml |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Dihydroergotamine Mesylate Nasal 4 mg/mL 69097-0503-27 | Cipla | 8 vials | $30.148 | AB | Availability likely | save 12% |
| Dihydroergotamine Mesylate 4 mg/mL 70069-0880-08 | Somerset | 1 kit | $30.148 | AB | Availability likely | save 12% |
| Dihydroergotamine mesylate 4 mg/mL 72888-0096-19 | Advagen | 8 kits | $30.148 | AB | Availability likely | save 12% |
| Dihydroergotamine mesylate 4 mg/mL 73352-0096-19 | Trifluent | 8 kits | $30.148 | AB | Availability likely | save 12% |
| Dihydroergotamine Mesylate 4 mg/mLthis 68682-0357-10 | Oceanside | 8 vials | $34.212 | AB | FDA listed | — |
| Dihydroergotamine Mesylate 4 mg/mL 24201-0463-01 | Hikma | 1 vial | $50.117 | AB | Availability likely | +46% |
| Trudhesa 4 mg/mL 77530-0725-00 | Impel | 1 vial | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68682-0357-10 You're viewing this | 8 VIAL in 1 KIT (68682-357-10) / 1 mL in 1 VIAL | 2013-03-18 | Active |
🧭 About this NDC listing & data coverage
Kit / multi-component package
This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS 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 CONTRAINDICATIONS and WARNINGS ).
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Dihydroergotamine Mesylate Nasal Spray is indicated for the acute treatment of migraine headaches with or without aura. Dihydroergotamine Mesylate Nasal Spray is not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION 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 after 8 hours).
⛔ Contraindications ▾
CONTRAINDICATIONS 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-HT 1 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 should not be used with peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure.
⚠️ Warnings ▾
WARNINGS 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 Dihydroerg…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS 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 for the treatment of migraine headache and not reported at an equal incidence by placebo-treated patients were rhinitis, altered sense of taste, application site reactions, dizziness, nausea, and vomiting.
The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ. Dihydroergotamine Mesylate Nasal Spray was generally well tolerated.
In most instances these events were transient and self-limited and did not result in patient discontinuation from a study. The following table summarizes the incidence rates of adverse events reported by at least 1% of patients who received Dihydroergotamine Mesylate Nasal Spray for the treatment of migraine headaches during placebo-controlled, double-blind clinical studies and were more frequent than in those patients receiving placebo. Table 3: 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 Dihydroergotamine Mesylate Nasal Spray N=597 Placebo N=631 Respiratory System Rhinitis 26% 7% Pharyngitis 3% 1% Sinusitis 1% 1% Gastrointestinal System Nausea 10% 4% Vomiting 4% 1% Diarrhea 2% <1% Special Senses, Other Altered Sense of Taste 8% 1% Application Site Application Site Reaction 6% 2% Central and Peripheral Nervous System Dizziness 4% 2% Somnolence 3% 2% Paraesthesia 2% 2% Body as a Whole, General Hot Flashes 1% <1% Fatigue 1% 1% Asthenia 1% 0% Autonomic Nervous System Mouth Dry 1% 1% Musculoskeletal System Stiffness 1% <1% Other Adverse Events During Clinical Trials In the paragraphs that follow, the frequencies of less commonly reported adverse clinical events are presented.
Because the reports include events observed in open and uncontrolled studies, the role of Dihydroergotamine Mesylate Nasal Spray in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, etc., limit the value of the quantitative frequency estimates provided. Event frequencies are calculated as the number of patients who used Dihydroergotamine Mesylate Nasal Spray in placebo-controlled trials and reported an event divided by the total number of patients (n=1796) exposed to Dihydroergotamine Mesylate Nasal Spray.
All repo…
🔄 Drug Interactions ▾
Drug Interactions Vasoconstrictors Dihydroergotamine Mesylate Nasal Spray should not be used with peripheral vasoconstrictors because the combination may cause synergistic elevation of blood pressure. Sumatriptan Sumatriptan has been reported to cause coronary artery vasospasm, and its effect could be additive with Dihydroergotamine Mesylate Nasal Spray. Sumatriptan and Dihydroergotamine Mesylate Nasal Spray should not be taken within 24 hours of each other ( see CONTRAINDICATIONS ).
Beta-Blockers Although the results of a clinical study did not indicate a safety problem associated with the administration of Dihydroergotamine Mesylate Nasal Spray to subjects already receiving propranolol, there have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine. Nicotine Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy. CYP 3A4 Inhibitors (e.g., Macrolide Antibiotics and Protease Inhibitors) See CONTRAINDICATIONS and WARNINGS.
SSRI’s Weakness, hyperreflexia, and incoordination have been reported rarely when 5HT 1 agonists have been coadministered with SSRI’s (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline). There have been no reported cases from spontaneous reports of drug interaction between SSRI’s and Dihydroergotamine Mesylate Nasal Spray or D.H.E. 45.
Oral Contraceptives The effect of oral contraceptives on the pharmacokinetics of Dihydroergotamine Mesylate Nasal Spray has not been studied.
🤰 Pregnancy ▾
Pregnancy Risk Summary Available data from published literature indicate an increased risk of preterm delivery with Dihydroergotamine Mesylate Nasal Spray use during pregnancy. Avoid use of Dihydroergotamine Mesylate Nasal Spray during pregnancy (see WARNINGS) . 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 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). 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 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 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.
🧒 Pediatric Use ▾
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
Use in the Elderly There is no information about the safety and effectiveness of Dihydroergotamine Mesylate Nasal Spray in this population because patients over age 65 were excluded from the controlled clinical trials.
🆘 Overdosage ▾
Medication Overuse Headache 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.
OVERDOSAGE 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 Poison Control Centers are listed in the Physicians’ Desk Reference (PDR). *
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Mechanism of Action Dihydroergotamine binds with high affinity to 5-HT 1Dα and 5-HT 1Dβ receptors. It also binds with high affinity to serotonin 5-HT 1A , 5-HT 2A , and 5-HT 2C receptors, noradrenaline α 2A , α 2B and α 1 receptors, and dopamine D 2L and D 3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT 1D receptors.
Two current theories have been proposed to explain the efficacy of 5-HT 1D receptor agonists in migraine. One theory suggests that activation of 5-HT 1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT 1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
In addition, dihydroergotamine possesses oxytocic properties. Pharmacokinetics Absorption Dihydroergotamine mesylate is poorly bioavailable following oral administration. Following intranasal administration, however, the mean bioavailability of dihydroergotamine mesylate is 32% relative to the injectable administration.
Absorption is variable, probably reflecting both intersubject differences of absorption and the technique used for self-administration. Distribution Dihydroergotamine mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.
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%-30% of plasma AUC. The systemic clearance of dihydroergotamine mesylate following I.V. and I.M. administration is
1.5L/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. After intranasal administration the urinary recovery of parent drug amounts to about 2% of the administered dose compared to 6% after I.M. administration. The total body clearance is
1.5L/min which reflects mainly hepatic clearance. The renal clearance (0.1 L/min) is unaffected by the route of dihydroergotamine administration. The decline of plasma dihydroergotamine is biphasic with a terminal half-life of about 10 hours.
Subpopulations No studies have been conducted on the effect of renal or hepatic impairment, gender, race, or ethnicity on dihydroergotamine pharmacokinetics. Dihydroergotamine Mesylate Nasal Spray is contraindicated in patients with severely impaired hepatic or renal function ( see CONTRAINDICATIONS ). Interactions The pharmacokinetics of dihydroergotamine did not appear to be significantly affected by the concomitant use of a local vasoconstrictor (e.g., fenoxazoline).
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. Pharmacokinetic interactions have been reported in patients treated orally with other ergot alkaloids (e.g., increased levels of ergotamine) and macrolide antibiotics, principally troleandomycin, presumably due to inhibition of cytochrome P450 3A metabolism of the alkaloids by troleandomycin. 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 d…
🧬 Mechanism of Action ▾
Mechanism of Action Dihydroergotamine binds with high affinity to 5-HT 1Dα and 5-HT 1Dβ receptors. It also binds with high affinity to serotonin 5-HT 1A , 5-HT 2A , and 5-HT 2C receptors, noradrenaline α 2A , α 2B and α 1 receptors, and dopamine D 2L and D 3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT 1D receptors.
Two current theories have been proposed to explain the efficacy of 5-HT 1D receptor agonists in migraine. One theory suggests that activation of 5-HT 1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT 1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
In addition, dihydroergotamine possesses oxytocic properties.
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Dihydroergotamine Mesylate Nasal Spray is available (as a clear, colorless to light yellow aqueous solution) in 3.5 mL amber glass vials containing 4 mg of dihydroergotamine mesylate. Dihydroergotamine Mesylate Nasal Spray is provided as a package of 8 units, administration instruction sheet, and one package insert. Each unit consists of one vial and one sprayer (NDC 68682-357-10).
Store below 25°C (77°F). Do not refrigerate or freeze. * Trademark of PDR Network, LLC Distributed by: Oceanside Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Mipharm, S.p.A. Milano, Italy © 2022 Bausch Health Companies Inc. or its affiliates Rev.
09/2022 9606502
📦 Storage and Handling ▾
Store below 25°C (77°F). Do not refrigerate or freeze. * Trademark of PDR Network, LLC Distributed by: Oceanside Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Mipharm, S.p.A. Milano, Italy © 2022 Bausch Health Companies Inc. or its affiliates Rev. 09/2022 9606502
📋 Description ▾
DESCRIPTION Dihydroergotamine mesylate is ergotamine hydrogenated in the 9,10 position as the mesylate salt. Dihydroergotamine Mesylate Nasal Spray 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) Chemical Structure
💬 Information for Patients ▾
Information for Patients The text of a patient information sheet is printed at the end of this insert. To assure safe and effective use of Dihydroergotamine Mesylate Nasal Spray, the information and instructions provided in the patient information sheet should be discussed with patients. Once the nasal spray applicator has been prepared, it should be discarded (with any remaining drug) after 8 hours.
Patients should be advised to report to the physician immediately any of the following: numbness or tingling in the fingers and toes, muscle pain in the arms and legs, weakness in the legs, pain in the chest, temporary speeding or slowing of the heart rate, swelling, or itching. Prior to the initial use of the product by a patient, the prescriber should take steps to ensure that the patient understands how to use the product as provided (see Patient Information Sheet and product packaging). 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 ).