Adult: For the treatment of acute episodes with or without aura: 1 mg as a single dose via IM or SC inj. Doses may be repeated at 1-hour intervals, as needed. Max: 3 mg/24 hours; 6 mg weekly.
Intramuscular, Subcutaneous Acute attack of cluster headache
Adult: 1 mg as a single dose via IM or SC inj. Doses may be repeated at 1-hour intervals, as needed. Max: 3 mg/24 hours; 6 mg weekly.
Intravenous Acute migraine attacks
Adult: For the treatment of acute episodes with or without aura: 1 mg as a single dose via IV inj. Doses may be repeated at 1-hour intervals, as needed. Max: 2 mg/24 hours; 6 mg weekly.
Intravenous Acute attack of cluster headache
Adult: Initially, 1 mg as a single dose via IV inj. Doses may be repeated at 1-hour intervals, as needed. Max: 2 mg/24 hours; 6 mg weekly.
Nasal Acute migraine attacks
Adult: For the treatment of acute episodes with or without aura: As 0.4% solution or 0.5 mg/spray: Initially, 1 spray (0.5 mg) into each nostril, then another 1 spray into each nostril after 15 minutes (total dose of 4 sprays [2 mg] per attack). Max dose: 4 sprays (2 mg)/24 hours. As 0.725 mg/spray: 1 spray (0.725 mg) into each nostril (total of 2 sprays [1.45 mg] per dose), may repeat dose after ≥1 hour as needed (total dose of 4 sprays [2.9 mg] per attack). Max dose: 2 doses or 4 sprays (2.9 mg)/24 hours; 3 doses or 6 sprays (4.35 mg) weekly. Dosage recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal Impairment
Severe: Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Administration
Should be taken with food.
Contraindications
Ischaemic heart disease (e.g. angina pectoris, silent ischaemia, history of MI), coronary artery vasospasm (including Prinzmetal's angina), uncontrolled hypertension, obliterative vascular disease, peripheral vascular disease (e.g. Raynaud's syndrome), temporal arteritis, cerebral injury, septic conditions, shock. Post-vascular surgery. Use for haemiplegic or basilar migraine. Severe renal and hepatic impairment. Pregnancy and lactation. Concomitant use with peripheral or central vasoconstrictors and potent CYP3A4 inhibitors (e.g. protease inhibitors, azole antifungals, or macrolide antibiotics).
Special Precautions
Patient with risk factors for CAD (e.g. hypertension, hypercholesterolaemia, diabetes, obesity, smoking, family history of CAD, postmenopausal women, men who are >40 years); history of drug-induced fibrotic disorders (e.g. retroperitoneal and pleural fibrosis); rhinitis or allergic rhinitis, nasal congestion (nasal). Not intended for use as prophylaxis for migraine. Avoid prolonged use of nasal spray. Avoid use within 24 hours of 5-HT1 agonists (e.g. sumatriptan), other serotonin agonists, and ergotamine-containing or ergot-like agents. Mild to moderate hepatic impairment (particularly in patients with cholestatic hepatitis). Elderly.
Adverse Reactions
Significant: Vasospastic reactions (e.g. myocardial, peripheral vascular, colonic ischaemia), rebound headache (chronic use); porphyria. Rarely, hypertension. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain. General disorders and administration site conditions: Local (nasal) site reactions (e.g. pain, dryness, irritation, congestion, burning sensation, epistaxis). Immune system disorders: Rarely, hypersensitivity reactions (e.g. skin rash, face oedema, urticaria, and dyspnoea). Musculoskeletal and connective tissue disorders: Muscular spasms. Nervous system disorders: Dizziness, anxiety, paraesthesia or hypoaesthesia. Respiratory, thoracic and mediastinal disorders: Rhinitis (for nasal spray). Rarely, pharyngitis (for nasal spray). Skin and subcutaneous tissue disorders: Rash, Diaphoresis. Vascular disorders: Flushing. Potentially Fatal: CV events (e.g. acute MI, disturbance of cardiac rhythm); fibrosis (e.g. retroperitoneal, cardiac, pulmonary, pleural); persistent vasospasm which may lead to gangrene (patients with compromised circulation); cerebrovascular events (e.g. cerebral or subarachnoid haemorrhage, stroke).
This drug may cause dizziness or visual disturbances, if affected, do not drive or operate machinery.
Monitoring Parameters
Evaluate CV status in patients with risk factors for CAD prior to treatment initiation. Monitor ECG in patients with CAD risk factors (immediately after the first dose).
Overdosage
Symptoms: Headache, vertigo, nausea, vomiting, abdominal pain, peripheral signs and symptoms of vasospasm (e.g. tingling, pain, and numbness of the extremities), respiratory depression, symptoms of myocardial ischaemia and chest pain; increased and/or decreased blood pressure, tachycardia, confusion, delirium, convulsions, and coma. Management: Supportive and symptomatic treatment. Apply warmth to the local affected area and provide nursing care to prevent tissue damage. Administer IV peripheral vasodilators (e.g. nitroprusside, phentolamine, dihydralazine) once severe vasospastic reactions occur. In the event of coronary constriction, may initiate the administration of glyceryl trinitrate.
Drug Interactions
Enhanced vasoconstriction with peripheral or central vasoconstrictors, β-blockers (e.g. propranolol), triptans (e.g. sumatriptan), or other ergot alkaloids. May cause serotonin-like syndrome (e.g. weakness, incoordination, hyperreflexia) when used with SSRIs (e.g. fluoxetine, fluvoxamine, paroxetine, sertraline). Increased serum concentration or exposure with moderate to weak CYP3A4 inhibitors (e.g. saquinavir, quinupristin/dalfopristin, metronidazole, clotrimazole, fluconazole, nefazodone, zileuton, or cimetidine). Potentially Fatal: May increase serum concentration when given concomitantly with potent CYP3A4 inhibitors such as protease inhibitors (e.g. ritonavir, nelfinavir, indinavir), reverse transcriptase inhibitors (e.g. efavirenz), azole antifungals (e.g. ketoconazole, itraconazole), tetracyclines, or macrolides (e.g. erythromycin, clarithromycin, troleandomycin).
Food Interaction
Increased exposure with grapefruit juice.
Action
Description: Mechanism of Action: Dihydroergotamine, a semisynthetic ergot alkaloid, is a potent 5-HT1D receptor agonist. It activates 5-HT1D receptors located in the intracranial blood vessels (including those on arterio-venous anastomoses) and in the sensory nerve endings of the trigeminal system which leads to vasoconstriction and inhibition of pro-inflammatory neuropeptide release, thus resulting in relief of migraine headache. Onset: Variable, commonly <5 minutes (IV); 15-30 minutes (IM); approx 30 minutes (nasal). Duration: Approx 8 hours (IV, SC); approx 4 hours (nasal). Pharmacokinetics: Absorption: Bioavailability: 100% (IV, IM); 43% (nasal). Time to peak plasma concentration: 1-2 minutes (IV); approx 30 minutes (IM); approx 15-45 minutes (SC); 30-60 minutes (nasal). Distribution: Plasma protein binding: 90-95%. Metabolism: Extensively metabolised in the liver by CYP3A4 enzymes into 8'-β-hydroxydihydroergotamine (major active metabolite) and further metabolised via oxidation into 8',10'-dihydroxydihydroergotamine (active metabolite); undergoes extensive first-pass metabolism. Excretion: Mainly via faeces; urine (6-7% [IM]; approx 2% [nasal], both as unchanged drug). Elimination half-life: Approx 9-10 hours (IM, IV, nasal [0.5 mg/spray]); 12 hours (nasal [0.725 mg/spray]).
Chemical Structure
Dihydroergotamine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 10531, Dihydroergotamine. https://pubchem.ncbi.nlm.nih.gov/compound/Dihydroergotamine. Accessed Jan. 25, 2024.
Storage
Solution for inj: Store between 15-30°C. Do not refrigerate or freeze. Protect from light and heat. Nasal spray: Store below 25°C. Do not refrigerate or freeze. Once the nasal spray applicator has been prepared or the vial has been opened, use within 8 hours.
N02CA01 - dihydroergotamine ; Belongs to the class of ergot alkaloids preparations. Used to relieve migraine.
References
Anon. Dihydroergotamine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 21/09/2023.Anon. Dihydroergotamine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/09/2023.Buckingham R (ed). Dihydroergotamine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/09/2023.Dihydroergotamine Mesylate Injection (Gland Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/09/2023.Migranal 4 mg/mL Nasal Spray Solution (Amdipharm UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2023.Migranal Spray (Bausch Health US, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/09/2023.Trudhesa Spray, Metered (Impel Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/09/2023.
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