Dosing and uses of Migranal (dihydroergotamine intranasal)
Adult dosage forms and strengths
intranasal solution
- 0.5mcg/actuation (4mg/ampule with intranasal sprayer)
- Also contains caffeine (10 mg/ampule; 1.25mg/actuation)
Migraine Headache
Indicated for acute treatment of migraine with or without aura
1 spray (0.5 mg) in each nostril, repeat after 15-30 minutes for a total of 4 sprays (2 mg); not to exceed 6 sprays (3mg)/24 hr or 8 sprays (4 mg)/week
Dosing Considerations
Not intended for prophylaxis of migraine
Not for chronic, daily use
Not for management of hemiplegic or basilar migraine
Administration
Prior to administration, the pump must be primed (ie, squeeze 4 times) before use
Once the nasal spray applicator has been prepared, it should be discarded (with any remaining drug in opened vial) after 8 hr
Store below 25°C (77°F)
Do not refrigerate or freeze
Pediatric dosage forms and strengths
Safety and efficacy not established
Migranal (dihydroergotamine intranasal) adverse (side) effects
>10%
Rhinitis (26%)
1-10%
Nausea (10%)
Altered taste (8%)
Application site reactions (6%)
Vomiting (4%)
Somnolence (3%)
Paraesthesia (2%)
Pharyngitis (3%)
Diarrhea (2%)
Sinusitis (1%)
Hot flashes (1%)
Fatigue (1%)
Asthenia (1%)
Dry mouth (1%)
Stiffness (1%)
Warnings
Black box warnings
Serious and/or life-threatening peripheral ischemia has been reported with coadministration of this drug with potent CYP 3A4 inhibitors (including protease inhibitors and macrolide antibiotics)
Because CYP3A4 inhibition elevates the serum ergotamine levels, the risk of vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased
Concurrent use of these potent CYP3A4 inhibitors are contraindicated
Contraindications
Hypersensitivity
Peripheral vascular disease, severe hepatic/renal impairment, ischemic heart disease, uncontrolled hypertension, sepsis, pregnancy, breastfeeding women
Recent vascular surgery
Hemiplegic or basilar migraine
Coadministration with potent CYP3A4 inhibitors
Peripheral or central vasoconstrictors
Cautions
Coadministration with less potent CYP3A4 inhibitors
Fibrotic complications reported (pleural and retroperitoneal fibrosis with prolonged parenteral use)
May cause coronary vasospasm
Avoid in patients with unrecognized CAD (ie, patient with risk factors)
May cause vasospastic reactions including myocardial, peripheral vascular, and colonic ischemia
May elevate blood pressure
Pregnancy and lactation
Pregnancy category: X
Lactation: Contraindicated; excreted in human milk and is known to inhibit prolactin
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Migranal (dihydroergotamine intranasal)
Mechanism of action
Binds with high affinity to 5-HT-1Dα and 5-HT-1Dβ; also bind to serotonin 5-HT-1A, -2A, and -2C receptors, noradrenaline α2A, α2B, and alpha receptors, and dopamine D2L and D3 receptors
Therapeutic activity attributed to agonist effect at 5-HT-1D receptors, which includes vasoconstriction of intracranial blood vessels, or activation of 5-HT1D may inhibit proinflammatory neuropeptide release
Absorption
Bioavailability: 32%
Distribution
Protein bound: 93%
Vd: 800 L
Metabolism
Metabolites: 8'-β-hydroxydihydroergotamine (active); metabolites represent 20-30% of plasma AUC
Elimination
Half-life: 10 hr
Renal clearance: 0.1 L/min
Total body clearance: 1.5 mL/min
Excretion: Major excretory route is in the bile and feces; urine 2%
