Recommended Topic Related To:

Migranal

"Today, the U.S. Food and Drug Administration approved Topamax (topiramate) for prevention (prophylaxis) of migraine headaches in adolescents ages 12 to 17. This is the first FDA approval of a drug for migraine prevention in this age group. The me"...

Migranal

Side Effects
Interactions

SIDE EFFECTS

During clinical studies and the foreign postmarketing experience with Migranal® (dihydroergotamine mesylate, USP) 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 Migranal® (dihydroergotamine mesylate, USP) 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 Migranal® (dihydroergotamine mesylate, USP) 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.

Migranal® (dihydroergotamine mesylate, USP) 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 Migranal® (dihydroergotamine mesylate, USP) 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 events reported by at least 1% of the Migranal® (dihydroergotamine mesylate, USP) Nasal Spray treated patients and occurred more frequently than in the placebo-group in the migraine placebo-controlled trials

    Migranal®
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 Migranal® (dihydroergotamine mesylate, USP) 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 Migranal (dihydroergotamine mesylate spray) ® (dihydroergotamine mesylate, USP) Nasal Spray in placebo-controlled trials and reported an event divided by the total number of patients (n=1796) exposed to Migranal® (dihydroergotamine mesylate, USP) Nasal Spray. All reported events are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; and rare adverse events are those occurring in fewer than 1/1,000 patients.

Skin and Appendages: Infrequent: petechia, pruritus, rash, cold clammy skin; Rare: papular rash, urticaria, herpes simplex.

Musculoskeletal: Infrequent: cramps, myalgia, muscular weakness, dystonia; Rare: arthralgia, involuntary muscle contractions, rigidity.

Central and Peripheral Nervous System: Infrequent: confusion, tremor, hypoesthesia, vertigo; Rare: speech disorder, hyperkinesia, stupor, abnormal gait, aggravated migraine.

Autonomic Nervous System: Infrequent: increased sweating.

Special Senses: Infrequent: sense of smell altered, photophobia, conjunctivitis, abnormal lacrimation, abnormal vision, tinnitus, earache; Rare: eye pain.

Psychiatric: Infrequent: nervousness, euphoria, insomnia, concentration impaired; Rare: anxiety, anorexia, depression.

Gastrointestinal: Infrequent: abdominal pain, dyspepsia, dysphagia, hiccup; Rare: increased salivation, esophagospasm.

Cardiovascular: Infrequent: edema, palpitation, tachycardia; Rare: hypotension, peripheral ischemia, angina.

Respiratory System: Infrequent: dyspnea, upper respiratory tract infections; Rare: bronchospasm, bronchitis, pleural pain, epistaxis.

Urinary System: Infrequent: increased frequency of micturition, cystitis.

Reproductive, Female: Rare: pelvic inflammation, vaginitis.

Body as a Whole - General: Infrequent: feeling cold, malaise, rigors, fever, periorbital edema; Rare: flu-like symptoms, shock, loss of voice, yawning.

Application Site: Infrequent: local anesthesia.

Post-introduction Reports

Voluntary reports of adverse events temporally associated with dihydroergotamine products used in the management of migraine that have been received since the introduction of the injectable formulation are included in this section save for those already listed above. Because of their source (open and uncontrolled clinical use), whether or not events reported in association with the use of dihydroergotamine are causally related to it cannot be determined. There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable dihydroergotamine mesylate. Migranal® (dihydroergotamine mesylate, USP) Nasal Spray is not recommended for prolonged daily use. (See DOSAGE AND ADMINISTRATION)

Drug Abuse And Dependence

Currently available data have not demonstrated drug abuse or psychological dependence with dihydroergotamine. However, cases of drug abuse and psychological dependence in patients on other forms of ergot therapy have been reported. Thus, due to the chronicity of vascular headaches, it is imperative that patients be advised not to exceed recommended dosages.

Read the Migranal (dihydroergotamine mesylate spray) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Vasoconstrictors

Migranal® (dihydroergotamine mesylate, USP) 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 Migranal (dihydroergotamine mesylate spray) ® (dihydroergotamine mesylate, USP) Nasal Spray. Sumatriptan and Migranal (dihydroergotamine mesylate spray) ® (dihydroergotamine mesylate, USP) 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 Migranal (dihydroergotamine mesylate spray) ® (dihydroergotamine mesylate, USP) 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 5HT1 agonists have been co-administered 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 Migranal® (dihydroergotamine mesylate, USP) Nasal Spray or D.H.E. 45®.

Oral Contraceptives

The effect of oral contraceptives on the pharmacokinetics of Migranal® (dihydroergotamine mesylate, USP) Nasal Spray has not been studied.

Read the Migranal Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 5/11/2009
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Living Better

Find the secrets to longer life.