Dihydroergotamine mesylate injection

Dihydroergotamine is a prescription medication indicated for the acute treatment of migraine with or without aura and the acute treatment of cluster headaches in adults

• Dihydroergotamine is available under the following different brand names: Brekiya, D.H.E. 45 (discontinued)

Common side effects of Dihydroergotamine include:

• numbness or tingling in the fingers and toes
• pain, tightness, or discomfort in the chest
• muscle pain or cramps in the arms and legs
• weakness in the legs
• irregular heart rate
• swelling or itching

Serious side effects of Dihydroergotamine include:

• symptoms of peripheral ischemia may include cramping and pain in the legs or hips, feeling of heaviness or tightness in the leg muscles, burning or aching pain in the feet or toes while resting, numbness, tingling, or weakness in the legs, cold feeling or color changes in one or both legs or feet, slurred speech, and sudden weakness
• heart problems may cause symptoms like chest discomfort that lasts for more than a few minutes or comes and goes, severe tightness, pain, pressure, or heaviness in the chest, throat, neck, or jaw pain or discomfort in the arms, back, neck, jaw, or stomach, shortness of breath with or without chest discomfort, cold sweat, nausea or vomiting, lightheadedness.
• symptoms of stroke may include face drooping, unusual weakness or numbness, and slurred speech
• symptoms of gastrointestinal and colonic ischemic events may include sudden or severe stomach pain, constipation or diarrhea, stomach pain after meals, bloody diarrhea, weight loss, fever, nausea, or vomiting
• Raynaud’s syndrome may cause changes in the color or sensation of the fingers or toes
• increased blood pressure
• medicine overuse headache 
• preterm labor
• complications that may arise from fibrosis around the lungs and stomach

Rare side effects of Dihydroergotamine include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• 1 mg/mL single-dose autoinjector

Migraine & Cluster Headaches

Adult dosage

• 1 mg SC; may repeat dose as the need arises at 1-hour interval (maximum 3 mg [3 doses] per 24-hour period)
• Not to exceed 6 mg per week

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Drug interaction overview

• Serious adverse events reported 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 extremities
• Administer other less potent CYP 3A4 inhibitors with caution; less potent inhibitors include saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, and clotrimazole (list not exhaustive)
• Not for use with a peripheral vasoconstrictor, as it may cause synergistic elevation of blood pressure
• Effects of this drug in coronary artery vasospasm may be additive if coadministered with sumatriptan; should not be taken within 24 hours of each other
• There are reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine
• Weakness, hyperreflexia, and incoordination are reported rarely when 5-HT 1 agonists are coadministered with  selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline); there have been no reported cases from spontaneous reports of drug interaction between SSRIs and this drug

Contraindications

• Coadministration with potent CYP 3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole)
• Patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal’s variant angina
• Uncontrolled hypertension
• Within 24 hours of 5-HT 1 agonists (e.g., sumatriptan), ergotamine-containing or ergot-type medications, or methysergide
• Patients with hemiplegic or basilar migraine
• Patients with known peripheral arterial disease, sepsis, following vascular surgery, and severely impaired hepatic or renal function
• During pregnancy
• Documented hypersensitivity to the drug or excipients
• Nursing mothers
• Coadministration with peripheral and central vasoconstrictors

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dihydroergotamine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dihydroergotamine?”

Cautions

• Only for use where a clear diagnosis of migraine has been established
• Pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable Dihydroergotamine mesylate reported; prolonged daily use of other ergot alkaloid drugs is associated with cardiac valvular fibrosis (rare); therapy should not exceed dosing guidelines and should not be used for chronic daily administration
• Potential for adverse cardiac events exists; serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death reported to have occurred following administration of Dihydroergotamine mesylate injection; considering the extent of use of dihydroergotamine mesylate in patients with migraine, the incidence of these events is extremely low
• Significant elevation in blood pressure reported on rare occasions in patients with and without a history of hypertension treated with this drug; therapy is contraindicated in patients with uncontrolled hypertension
• Therapy may cause coronary artery vasospasm; patients who experience signs or symptoms suggestive of angina following its administration should be evaluated for the presence of coronary artery disease (CAD) or a predisposition to variant angina before receiving additional doses
• Patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud’s syndrome, following the use of any 5-HT agonist are candidates for further evaluation

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 (e.g., 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 overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache), may be necessary

Vasospasm related events

• Therapy may cause vasospastic reactions other than coronary artery vasospasm; myocardial, peripheral vascular, and colonic ischemia have been reported with therapy; treatment associated with 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; therapy should be discontinued immediately if signs or symptoms of vasoconstriction develop

Cardiovascular events

• Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events reported in patients receiving therapy; some have resulted in fatalities
• In several cases, it appears possible that the cerebrovascular events were primary, the drug 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)

Risk of myocardial ischemia and/or infarction

• Not for use by patients with documented ischemic or vasospastic coronary artery disease; strongly recommended not to be given to patients in whom unrecognized CAD predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, women who are surgically or physiologically postmenopausal, or men 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 cardiovascular evaluation, the patient’s medical history or electrocardiographic investigations reveal findings indicative of or consistent with coronary artery vasospasm or myocardial ischemia, do not administer
• For patients with risk factors predictive of CAD who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that the administration of the first dose 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 therapy administration in those patients with risk factors
• Recommended that patients who are intermittent long-term users of this drug and who have or acquire risk factors predictive of CAD, undergo periodic interval cardiovascular evaluation as they continue to receive therapy
• The systematic approach described above is currently recommended as a method to identify patients in whom this drug may be used to treat migraine headaches with an acceptable margin of cardiovascular safety

Pregnancy and Lactation

• Available data from published literature indicate an increased risk of preterm delivery with use during pregnancy; avoid use during pregnancy. Data collected over decades has shown no increased risk of major birth defects or miscarriage with use

Fertility

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

Lactation

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