Migraine headache medications

Acronyms

A - approved for acute migraine treatment
C - approved for cluster headache
5-HT - 5-hydroxytryptamine (serotonin)
bpm - beats per minute
CGRP - Calcitonin gene-related peptide
ODT - Orally disintegrating tablet
P - medications with approved pediatric dosing
Mprev - approved for migraine prevention
SC - Subcutaneous

Open all

Almotriptan
Axert®

Dosage forms

Tablet

6.25 mg
12.5 mg
Comes in dose pack of 6 or 12 tablets

Dosing

Acute migraine (12 - 17 years)

Initial: 6.25 - 12.5 mg
May repeat in 2 hours if needed
Do not exceed 25 mg in 24 hours
May take without regard to food

Acute migraine (adults)

Initial: 6.25 - 12.5 mg
In adults, the 12.5 mg dose tends to be more effective
May repeat in 2 hours if needed
Do not exceed 25 mg in 24 hours
May take without regard to food

With strong CYP3A4 inhibitors

Initial: 6.25 mg
Maximum: 12.5 mg in 24 hours
Avoid concomitant CYP3A4 strong inhibitors in patients with kidney or liver disease
See CYP3A4 for a list of inhibitors

Generic / Price

YES/$$$ (12 tablets)

Pharmacokinetics

Time to max level: 1 - 3 hours
Half-life: 3 - 4 hours

Mechanism of action

Almotriptan binds with high affinity to 5-HT1D, 5-HT1B, and 5-HT1F receptors. Almotriptan has weak affinity for 5-HT1A and 5-HT7 receptors, but has no significant affinity or pharmacological activity at 5-HT2, 5-HT3, 5-HT4, 5-HT6; alpha or beta adrenergic; adenosine (A1, A2); angiotensin (AT1, AT2); dopamine (D1, D2); endothelin (ETA, ETB); or tachykinin (NK1, NK2, NK3) binding sites.

FDA-approved indications

Acute migraine headache with or without aura in adults and adolescents

Side effects

Side effect	Almotriptan 12.5 mg (N=182)	Placebo (N=172)
Somnolence	5%	2%
Nausea	3%	0%
Dizziness	3%	2%
Headache	2%	1%
Paresthesia	1%	<1%

Drug interactions

Ergotamines - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
Other 5-HT₁ agonists - DO NOT COMBINE. Triptans should not be taken within 24 hours of other 5-HT₁ agonists including other triptans.
SSRIs/SNRIs - triptans are serotonergic medications, and they may increase the risk of serotonin syndrome (SS) when taken with SSRIs and SNRIs. A study that looked at the risk of SS with this drug combination found it to be very low. [PMID 29482205]
CYP3A4 strong inhibitors - almotriptan is a CYP3A4 sensitive substrate. When taken with a strong CYP3A4 inhibitor, starting dose should be 6.25 mg and daily dose should not exceed 12.5 mg. Avoid concomitant CYP3A4 strong inhibitors in patients with kidney or liver disease.

Contraindications / Precautions

Pregnancy and nursing - see migraine medications in pregnancy and nursing
Cardiovascular disease - triptans have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Prinzmetal's variant angina - DO NOT USE. Triptans may exacerbate vasospastic heart disease.
Hemiplegic or basilar migraine - DO NOT USE
Wolff-Parkinson-White syndrome and other accessory pathway conduction disorders - DO NOT USE
Chest pain and tightness - triptans may cause a sensation of pain and tightness in the chest, neck, and/or throat. These symptoms are more common with injectable drug forms. In most patients, triptan-induced chest pain is not thought to be caused by ischemia and is generally not serious. [1,4]
Raynaud's syndrome - triptans may exacerbate symptoms of Raynaud's syndrome
Hypertension - triptans may cause a short-term rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Cardiac arrhythmias - in a small number of patients, life-threatening arrhythmias have been reported within a few hours of taking triptans
Serotonin syndrome - serotonin syndrome has occurred in patients taking triptans. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including triptans (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Vision changes - rare cases of vision changes and vision loss have been reported with triptan use
Anaphylactic reactions - cases of anaphylaxis including angioedema have been reported in patients taking triptans
Sulfonamide sensitivity - almotriptan contains a sulfonyl group. Patients with sulfonamide allergy may also have an allergic reaction to almotriptan.
Ophthalmic effects - in rat studies, almotriptan was found to bind to melanin in the retina. In another study, almotriptan was associated with corneal opacities in dogs. In both studies, very high doses of almotriptan were used. The significance of these effects in humans is unknown.
Liver disease - starting dose should be 6.25 mg. Do not exceed 12.5 mg in 24 hours.
Kidney disease

CrCl < 30 ml/min: starting dose should be 6.25 mg. Do not exceed 12.5 mg in 24 hours.

Open all

Eletriptan
Relpax®

Dosage forms

Tablet

20 mg
40 mg
40 mg dose comes in package of 6 or 12 tablets
20 mg dose comes in package of 6 tablets

Dosing

Acute migraine (adults)

Initial: 20 - 40 mg
May repeat in 2 hours if needed
More patients responded to the 40 mg dose in trials
Do not exceed 80 mg in 24 hours
May take without regard to food

Generic / Price

YES/$ (6 tablets)

Pharmacokinetics

Time to max level: 1.5 hours
Half-life: 4 hours

Mechanism of action

Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7 receptors.
Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of eletriptan for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

FDA-approved indications

Acute migraine headache with or without aura in adults

Side effects

Side effect	Eletriptan 40 mg (N=1774)	Placebo (N=988)
Dizziness	6%	3%
Somnolence	6%	4%
Weakness	5%	3%
Paresthesia	3%	2%
Dry mouth	3%	2%
Upset stomach	2%	1%
Difficulty swallowing	2%	0.2%
Chest tightness / pain	2%	1%
Abdominal pain	2%	1%

Drug interactions

Ergotamines - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
CYP3A4 strong inhibitors - DO NOT COMBINE. Eletriptan is a CYP3A4 sensitive substrate. Concomitant administration can lead to increased exposure to eletriptan. Eletriptan should not be taken within 72 hours of a CYP3A4 strong inhibitor.
Other 5-HT₁ agonists - DO NOT COMBINE. Triptans should not be taken within 24 hours of other 5-HT₁ agonists including other triptans.
SSRIs/SNRIs - triptans are serotonergic medications, and they may increase the risk of serotonin syndrome (SS) when taken with SSRIs and SNRIs. A study that looked at the risk of SS with this drug combination found it to be very low. [PMID 29482205]

Contraindications / Precautions

Pregnancy and nursing - see migraine medications in pregnancy and nursing
Cardiovascular disease - triptans have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Wolff-Parkinson-White syndrome and other accessory pathway conduction disorders - DO NOT USE
Prinzmetal's variant angina - DO NOT USE. Triptans may exacerbate vasospastic heart disease.
Hemiplegic or basilar migraine - DO NOT USE
Chest pain and tightness - triptans may cause a sensation of pain and tightness in the chest, neck, and/or throat. These symptoms are more common with injectable drug forms. In most patients, triptan-induced chest pain is not thought to be caused by ischemia and is generally not serious. [1,4]
Cardiac arrhythmias - in a small number of patients, life-threatening arrhythmias have been reported within a few hours of taking triptans
Hypertension - triptans may cause a short-term rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Raynaud's syndrome - triptans may exacerbate symptoms of Raynaud's syndrome
Serotonin syndrome - serotonin syndrome has occurred in patients taking triptans. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including triptans (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Vision changes - rare cases of vision changes and vision loss have been reported with triptan use
Anaphylactic reactions - cases of anaphylaxis including angioedema have been reported in patients taking triptans
Kidney disease - no dose adjustment necessary
Liver disease

Mild-to-moderate (Child-Pugh A/B) - no dose adjustment necessary
Severe (Child-Pugh C) - has not been studied. Not recommended.

Open all

Frovatriptan
Frova®

Dosage forms

Tablet

2.5 mg
Comes in dose pack of 9 tablets

Dosing

Acute migraine (adults)

Initial: 2.5 mg
May repeat in 2 hours if needed
Do not exceed 7.5 mg in 24 hours
May take without regard to food

Generic / Price

YES/$ (9 tablets)

Pharmacokinetics

Time to max level: 2 - 4 hours
Half-life: 26 hours

Mechanism of action

Frovatriptan is a 5-HT receptor agonist that binds with high affinity for 5-HT1B and 5-HT1D receptors. Frovatriptan has no significant effects on GABAA mediated channel activity and has no significant affinity for benzodiazepine binding sites.
Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. In anesthetized dogs and cats, intravenous administration of frovatriptan produced selective constriction of the carotid vascular bed and had no effect on blood pressure (both species) or coronary resistance (in dogs).

FDA-approved indications

Acute migraine headache with or without aura in adults

Side effects

Side effect	Frovatriptan 2.5 mg (N=1554)	Placebo (N=838)
Dizziness	4%	3%
Headache	4%	2%
Flushing	4%	2%
Fatigue	3%	2%
Skeletal pain	3%	2%
Dry mouth	2%	1%
Hot or cold sensation	2%	1%

Drug interactions

Ergotamines - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
Other 5-HT₁ agonists - DO NOT COMBINE. Triptans should not be taken within 24 hours of other 5-HT₁ agonists including other triptans.
SSRIs/SNRIs - triptans are serotonergic medications, and they may increase the risk of serotonin syndrome (SS) when taken with SSRIs and SNRIs. A study that looked at the risk of SS with this drug combination found it to be very low. [PMID 29482205]

Contraindications / Precautions

Pregnancy and nursing - see migraine medications in pregnancy and nursing
Cardiovascular disease - triptans have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Wolff-Parkinson-White syndrome and other accessory pathway conduction disorders - DO NOT USE
Prinzmetal's variant angina - DO NOT USE. Triptans may exacerbate vasospastic heart disease.
Hemiplegic or basilar migraine - DO NOT USE
Chest pain and tightness - triptans may cause a sensation of pain and tightness in the chest, neck, and/or throat. These symptoms are more common with injectable drug forms. In most patients, triptan-induced chest pain is not thought to be caused by ischemia and is generally not serious. [1,4]
Cardiac arrhythmias - in a small number of patients, life-threatening arrhythmias have been reported within a few hours of taking triptans
Hypertension - triptans may cause a short-term rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Raynaud's syndrome - triptans may exacerbate symptoms of Raynaud's syndrome
Serotonin syndrome - serotonin syndrome has occurred in patients taking triptans. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including triptans (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Vision changes - rare cases of vision changes and vision loss have been reported with triptan use
Anaphylactic reactions - cases of anaphylaxis including angioedema have been reported in patients taking triptans
Kidney disease - no dose adjustment necessary
Liver disease

Mild-to-moderate (Child-Pugh A/B) - no dose adjustment necessary
Severe (Child-Pugh C) - has not been studied. Use caution.

Open all

Naratriptan
Amerge®

Dosage forms

Tablet

1 mg
2.5 mg
Comes in dose pack of 9 tablets

Dosing

Acute migraine (adults)

Initial: 1 - 2.5 mg
May repeat in 4 hours if needed
Do not exceed 5 mg in 24 hours
May take without regard to food

Generic / Price

YES/$ (9 tablets)

Pharmacokinetics

Time to max level: 2 - 3 hours
Half-life: 6 hours

Mechanism of action

Naratriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (including substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of naratriptan tablets for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

FDA-approved indications

Acute migraine headache with or without aura in adults

Side effects

Side effect	Naratriptan 2.5 mg (N=627)	Placebo (N=498)
Nausea	5%	4%
Paresthesia	2%	<1%
Dizziness	2%	1%
Drowsiness	2%	<1%
Malaise/Fatigue	2%	1%
Throat/neck symptoms	2%	1%

Drug interactions

Ergotamines - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
Other 5-HT₁ agonists - DO NOT COMBINE. Triptans should not be taken within 24 hours of other 5-HT₁ agonists including other triptans.
SSRIs/SNRIs - triptans are serotonergic medications, and they may increase the risk of serotonin syndrome (SS) when taken with SSRIs and SNRIs. A study that looked at the risk of SS with this drug combination found it to be very low. [PMID 29482205]

Contraindications / Precautions

Pregnancy and nursing - see migraine medications in pregnancy and nursing
Cardiovascular disease - triptans have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Wolff-Parkinson-White syndrome and other accessory pathway conduction disorders - DO NOT USE
Prinzmetal's variant angina - DO NOT USE. Triptans may exacerbate vasospastic heart disease.
Hemiplegic or basilar migraine - DO NOT USE
Chest pain and tightness - triptans may cause a sensation of pain and tightness in the chest, neck, and/or throat. These symptoms are more common with injectable drug forms. In most patients, triptan-induced chest pain is not thought to be caused by ischemia and is generally not serious. [1,4]
Cardiac arrhythmias - in a small number of patients, life-threatening arrhythmias have been reported within a few hours of taking triptans
Hypertension - triptans may cause a short-term rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Raynaud's syndrome - triptans may exacerbate symptoms of Raynaud's syndrome
Vision changes - rare cases of vision changes and vision loss have been reported with triptan use
Serotonin syndrome - serotonin syndrome has occurred in patients taking triptans. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including triptans (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Anaphylactic reactions - cases of anaphylaxis including angioedema have been reported in patients taking triptans
Kidney disease

CrCl 30 - 90 ml/min - starting dose is 1 mg; do not exceed 2.5 mg over 24 hours
CrCl < 15 ml/min - DO NOT USE

Liver disease

Mild-to-moderate (Child-Pugh A/B) - starting dose is 1 mg; do not exceed 2.5 mg over 24 hours
Severe (Child-Pugh C) - DO NOT USE

Open all

Rizatriptan
Maxalt®, Maxalt-MLT®

Dosage forms

Maxalt® tablet

5 mg
10 mg
Comes in carton of 18 tablets

Maxalt-MLT® orally disintegrating tablet

5 mg
10 mg
Comes in carton of 18 tablets

Dosing

Acute migraine (6 - 17 years)

< 40 kg (88 lbs): 5 mg
≥ 40 kg (88 lbs): 10 mg
The efficacy and safety of more than one dose in 24 hours has not been established
May take without regard to food

Acute migraine (adults)

Initial: 5 - 10 mg
May repeat in 2 hours if needed
Do not exceed 30 mg in 24 hours
May take without regard to food

When taken with propranolol

Pediatric (6 - 17 years)

< 40 kg (88 lbs): DO NOT COMBINE
≥ 40 kg (88 lbs): Do not exceed a single 5 mg dose in 24 hours

Adults

Initial: 5 mg
Do not exceed 15 mg in 24 hours

Generic / Price

YES/$ (9 tablets)

Other

Maxalt-MLT

Administration with liquid is not necessary
Dissolves on tongue and is swallowed with saliva
Do not remove from blister pack until just prior to dosing

Pharmacokinetics

Maxalt

Time to max level: 1 - 1.5 hours
Half-life: 2 - 3 hours

Maxalt-MLT

Time to max level: 1.7 - 2.2 hours
Half-life: 2 - 3 hours

Mechanism of action

Rizatriptan binds with high affinity to human cloned 5-HT1B and 5-HT1D receptors. Rizatriptan has weak affinity for other 5-HT1 receptor subtypes (5-HT1A, 5-HT1E, 5-HT1F) and the 5-HT7 receptor, but has no significant activity at 5-HT2, 5-HT3, alpha- and beta-adrenergic, dopaminergic, histaminergic, muscarinic or benzodiazepine receptors.
Current theories on the etiology of migraine headache suggest that symptoms are due to local cranial vasodilatation and/or to the release of vasoactive and pro-inflammatory peptides from sensory nerve endings in an activated trigeminal system. The therapeutic activity of rizatriptan in migraine can most likely be attributed to agonist effects at 5-HT1B/1D receptors on the extracerebral, intracranial blood vessels that become dilated during a migraine attack and on nerve terminals in the trigeminal system. Activation of these receptors results in cranial vessel constriction, inhibition of neuropeptide release and reduced transmission in trigeminal pain pathways.

FDA-approved indications

Acute migraine headache with or without aura in adults and pediatric patients 6 - 17 years old

Side effects

Side effect	Rizatriptan 10 mg (N=1167)	Placebo (N=627)
Dizziness	9%	5%
Somnolence	8%	4%
Fatigue	7%	2%
Nausea	6%	4%
Paresthesia	4%	<2%
Chest pain	3%	1%
Pain, location unspecified	3%	<2%
Dry mouth	3%	1%
Neck/throat/jaw pain	2%	1%
Regional pain	2%	0%
Headache	2%	<1%

Drug interactions

MAO-A inhibitors and nonselective MAO inhibitors - DO NOT COMBINE or start rizatriptan within 2 weeks of discontinuing an MAO inhibitor. Rizatriptan is metabolized by MAO-A. Selective MAO-A and nonselective MAO inhibitors may increase blood levels. Selective MAO-B inhibitors would not be expected to affect rizatriptan levels.
Propranolol - propranolol increases rizatriptan levels. See Dosing for dosing recommendations.
Ergotamines - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
Other 5-HT₁ agonists - DO NOT COMBINE. Triptans should not be taken within 24 hours of other 5-HT₁ agonists including other triptans.
SSRIs/SNRIs - triptans are serotonergic medications, and they may increase the risk of serotonin syndrome (SS) when taken with SSRIs and SNRIs. A study that looked at the risk of SS with this drug combination found it to be very low. [PMID 29482205]

Contraindications / Precautions

Pregnancy and nursing - see migraine medications in pregnancy and nursing
Cardiovascular disease - triptans have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Wolff-Parkinson-White syndrome and other accessory pathway conduction disorders - DO NOT USE
Prinzmetal's variant angina - DO NOT USE. Triptans may exacerbate vasospastic heart disease.
Hemiplegic or basilar migraine - DO NOT USE
Chest pain and tightness - triptans may cause a sensation of pain and tightness in the chest, neck, and/or throat. These symptoms are more common with injectable drug forms. In most patients, triptan-induced chest pain is not thought to be caused by ischemia and is generally not serious. [1,4]
Cardiac arrhythmias - in a small number of patients, life-threatening arrhythmias have been reported within a few hours of taking triptans
Hypertension - triptans may cause a short-term rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Raynaud's syndrome - triptans may exacerbate symptoms of Raynaud's syndrome
Vision changes - rare cases of vision changes and vision loss have been reported with triptan use
Serotonin syndrome - serotonin syndrome has occurred in patients taking triptans. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including triptans (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Anaphylactic reactions - cases of anaphylaxis including angioedema have been reported in patients taking triptans
Phenylketonuria - Maxalt-MLT contains phenylalanine. The 5 and 10 mg orally disintegrating tablets contain 1.1 and 2.1 mg phenylalanine, respectively.
Kidney disease

CrCl ≥ 10 ml/min: no dose adjustment necessary

Liver disease

Mild (Child-Pugh A) - no dose adjustment necessary
Moderate-severe (Child-Pugh B/C) - clearance is decreased. Use caution.

Open all

Sumatriptan
Imitrex®, Zembrace®, Onzetra®, Tosymra®, Treximet®

Dosage forms

Imitrex® tablet

25 mg
50 mg
100 mg
Comes in packs of 9 tablets

Imitrex® nasal spray

5 mg
20 mg
Comes in box with 6 single-dose sprays

Imitrex® vial and prefilled syringe

6 mg (6 mg/0.5 ml)

Imitrex® statdose injection

4 mg (4 mg/0.5 ml)
6 mg (6 mg/0.5 ml)
Comes in pack with 2 cartridges

Tosymra® nasal spray

10 mg single-dose spray device
Comes in carton with 6 devices

Zembrace® injection

3 mg single use autoinjector
Comes in pack with 4 injectors

Onzetra® nasal powder

Comes in kit with 8 pouches and 2 delivery systems
Each pouch contains 2 nosepieces
Each nosepiece contains 11 mg sumatriptan

Treximet® tablet

Sumatriptan : naproxen

85 mg : 500 mg

Dosing - Acute migraine

Imitrex tablet

Initial: 25 - 100 mg
May repeat in 2 hours if needed
Do not exceed 200 mg in 24 hours
May take without regard to food
50 mg dose may be more effective than 25 mg dose
If tablet is given after injection, may give up to 100 mg/day of tablet doses

Imitrex nasal spray

Initial: 5, 10, or 20 mg
May repeat one time in 2 hours if needed
Do not exceed 40 mg in 24 hours
If a 10 mg dose is desired, administer a 5 mg dose in each nostril
20 mg dose may be more effective than lower doses

Imitrex injection

Initial: 6 mg subcutaneously
May repeat in 1 hour if needed
Do not exceed 12 mg in 24 hours
If side effects are dose limiting, lower doses (1 - 5 mg) may be used.

Onzetra nasal powder

Initial: 22 mg (2 nosepieces) via delivery device
A second dose (22 mg) may be given 2 hours later
Do not exceed 44 mg in 24 hours

Tosymra nasal spray

Initial: 10 mg in one nostril
May repeat in 1 hour if necessary
Do not exceed 30 mg in 24 hours
May be given at least 1 hour following a dose of another sumatriptan product

Zembrace injection

Initial: 3 mg subcutaneously
May repeat in 1 hour if needed
Do not exceed 12 mg in 24 hours

Treximet

Initial: 1 tablet (85/500)
May repeat one time in 2 hours if needed
Do not exceed 2 tablets in 24 hours
May take without regard to food

Dosing - Cluster headache

Imitrex injections

Initial: 6 mg subcutaneously
May repeat in 1 hour if needed
Do not exceed 12 mg in 24 hours

Generic / Price

Imitrex tablet (9 tablets) - YES/$
Imitrex nasal spray (6 doses) - YES/$$-$$$
Imitrex syringe (2 syringes) - YES/$
Imitrex vial (5 doses) - YES/$
Imitrex statdose (2 doses) - YES/$$
Onzetra (16 nosepieces) - NO/$$$$
Tosymra (6 doses) - NO/$$$$
Zembrace (4 doses) - NO/$$$$
Treximet (9 tablets) - YES/$$$$

Other

Imitrex, Zembrace injections

Injection is typically given in the side of the thigh or the upper arm
Store at room temperature. Protect from light.

Imitrex nasal spray

Blow nose before administering
Store at room temperature. Protect from light.

Onzetra nasal powder

Powder capsule is placed into delivery device
Device is placed in nose and mouth. Patient blows through mouthpiece and powder is delivered into nose.
Store at room temperature

Pharmacokinetics

Imitrex tablet

Time to max level: 2 - 2.5 hours
Half-life: 2.5 hours

Imitrex, Zembrace injections

Time to max level: 12 minutes
Half-life: ∼ 2 hours

Imitrex nasal spray

Time to max level: ?
Half-life: ∼ 2 hours

Onzetra nasal powder

Time to max level: 45 minutes
Half-life: 3 hours

Tosymra nasal spray

Time to max level: 10 minutes
Half-life: 2.4 hours

Mechanism of action

Sumatriptan binds with high affinity to human cloned 5‑HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5‑HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro‑inflammatory neuropeptide release.

FDA-approved indications

Imitrex tablet and nasal spray / Zembrace / Onzetra / Tosymra

Acute migraine headache with or without aura in adults

Imitrex injections

Acute migraine headache with or without aura in adults
Cluster headache

Side effects

Tablet
Side effect	Sumatriptan 50 mg (N=771)	Placebo (N=309)
Paresthesia	5%	2%
Chest pain	2%	1%
Neck / throat / jaw pain	2%	<1%
Fatigue	2%	<1%

Nasal spray
Side effect	Sumatriptan 20 mg (N=1212)	Placebo (N=704)
Bad / Unusual taste	24.5%	1.7%
Nausea / vomiting	13.5%	11.3%
Nasal discomfort	3.8%	2.4%
Throat discomfort	2.4%	0.9%
Burning sensation	1.4%	0.1%

Onzetra nasal powder
Side effect	Sumatriptan (N=151)	Placebo (N=150)
Abnormal taste	20%	3%
Nasal discomfort	11%	1%
Rhinorrhea	5%	2%
Rhinitis	2%	0%

Injection
Side effect	Sumatriptan 6 mg (N=547)	Placebo (N=370)
Injection site reaction	59%	24%
Tingling	14%	3%
Dizziness	12%	4%
Warm sensation	11%	4%
Burning sensation	7%	<1%
Heavy feeling	7%	1%
Pressure sensation	7%	2%
Flushing	7%	2%
Weakness	5%	<1%
Neck pain / stiffness	5%	<1%
Feeling of tightness	5%	<1%
Numbness	5%	2%
Chest discomfort	5%	1%
Chest tightness	3%	<1%
Throat discomfort	3%	<1%
Drowsiness	3%	2%

Drug interactions

MAO-A inhibitors and nonselective MAO inhibitors - DO NOT COMBINE or start sumatriptan within 2 weeks of discontinuing an MAO inhibitor. Sumatriptan is metabolized by MAO-A. Selective MAO-A and nonselective MAO inhibitors may increase blood levels.
Ergotamines - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
Other 5-HT₁ agonists - DO NOT COMBINE. Triptans should not be taken within 24 hours of other 5-HT₁ agonists including other triptans.
SSRIs/SNRIs - triptans are serotonergic medications, and they may increase the risk of serotonin syndrome (SS) when taken with SSRIs and SNRIs. A study that looked at the risk of SS with this drug combination found it to be very low. [PMID 29482205]

Contraindications / Precautions

Pregnancy and nursing - see migraine medications in pregnancy and nursing
Cardiovascular disease - triptans have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Wolff-Parkinson-White syndrome and other accessory pathway conduction disorders - DO NOT USE
Prinzmetal's variant angina - DO NOT USE. Triptans may exacerbate vasospastic heart disease.
Hemiplegic or basilar migraine - DO NOT USE
Chest pain and tightness - triptans may cause a sensation of pain and tightness in the chest, neck, and/or throat. These symptoms are more common with injectable drug forms. In most patients, triptan-induced chest pain is not thought to be caused by ischemia and is generally not serious. [1,4]
Cardiac arrhythmias - in a small number of patients, life-threatening arrhythmias have been reported within a few hours of taking triptans
Hypertension - triptans may cause a short-term rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Raynaud's syndrome - triptans may exacerbate symptoms of Raynaud's syndrome
Vision changes - rare cases of vision changes and vision loss have been reported with triptan use
Serotonin syndrome - serotonin syndrome has occurred in patients taking triptans. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including triptans (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Anaphylactic reactions - cases of anaphylaxis including angioedema have been reported in patients taking triptans
Local irritation (nasal spray) - in trials, symptoms such as burning, numbness, paresthesia, discharge, and pain or soreness were reported in about 5% of patients. Symptoms typically resolved after 2 hours. The long-term effects of imitrex nasal spray on the nose and throat have not been evaluated.
Seizures - in rare cases, patients have experienced seizures after taking sumatriptan. Use caution in susceptible patients.
Corneal opacities - in dogs, sumatriptan has been shown to cause corneal opacities and other defects. It is unknown if similar effects occur in humans.
Kidney disease - has not been studied. Use caution.
Liver disease

Mild to moderate (Child-Pugh A/B) - maximum single dose is 50 mg
Severe (Child-Pugh C) - DO NOT USE

Open all

Zolmitriptan
Zomig®, Zomig-ZMT®

Dosage forms

Zomig® tablet

2.5 mg
5 mg
Comes in pack of 6 tablets for 2.5 mg dose and 3 tablets for 5 mg dose

Zomig-ZMT® orally disintegrating tablet

2.5 mg
5 mg
Comes in pack of 6 tablets for 2.5 mg dose and 3 tablets for 5 mg dose

Zomig® nasal spray

2.5 mg
5 mg
Comes in box with 6 single-dose spray devices

Dosing

Zomig and Zomig-ZMT tablet (acute migraine in adults)

Initial: 2.5 - 5 mg
May repeat in 2 hours if needed
Do not exceed 10 mg in 24 hours
2.5 mg tablet may be broken in half for a lower dose. Do not half oral disintegrating tablet.
In studies, 5 mg dose offered little benefit over 2.5 mg dose

Nasal spray (acute migraine in children ≥ 12 years old and adults)

Initial: 2.5 mg intranasally
May repeat in 2 hours if needed
Dose of 5 mg may be used in some patients
Do not exceed 10 mg in 24 hours

Generic / Price

Zomig® (6 tablets) - YES/$
Zomig-ZMT® (6 tablets) - YES/$
Zomig nasal spray (6 doses) - NO/$$$$

Other

Zomig

May take without regard to food
2.5 mg tablet is scored so it may be broken in half

Zomig-ZMT

Administration with liquid is not necessary
Dissolves on tongue and is swallowed with saliva
Do not remove from blister pack until just prior to dosing
Do not break in half

Nasal spray

Blow nose before use
Store at room temperature

Pharmacokinetics

Zomig tablet

Time to max level: 1.5 hours
Half-life: 3 hours

Zomig-ZMT

Time to max level: 3 hours
Half-life: 3 hours

Zomig nasal spray

Time to max level: 3 hours
Half-life: 3 hours

Mechanism of action

Zolmitriptan binds with high affinity to human recombinant 5-HT1D and 5‑HT1B receptors, and moderate affinity for 5-HT1A receptors. The N-desmethyl metabolite also has high affinity for 5‑HT1B/1D and moderate affinity for 5‑HT1A receptors.
Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of zolmitriptan for the treatment of migraine headache is thought to be due to the agonist effects at the 5‑HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

FDA-approved indications

Tablet and ODT

Acute migraine headache with or without aura in adults

Nasal spray

Acute migraine headache with or without aura in patients ≥ 12 years old

Side effects

Side effect	Zolmitriptan 5 mg tablet (N=1012)	Placebo (N=401)
Neck / throat / jaw pain	10%	3%
Dizziness	10%	4%
Paresthesia	9%	2%
Asthenia	9%	3%
Somnolence	8%	3%
Warm / cold sensation	7%	4%
Nausea	6%	4%
Heaviness other than neck/chest	5%	1%
Chest pain / tightness	4%	1%
Dry mouth	3%	2%
Sweating	3%	1%

Side effect	Zolmitriptan nasal spray 5 mg (N=236)	Placebo (N=228)
Unusual taste	21%	3%
Paraesthesia	10%	6%
Hyperesthesia	5%	0%
Throat pain	4%	1%
Pain (unspecified)	4%	1%
Nausea	4%	1%
Somnolence	4%	2%
Asthenia	3%	1%

Drug interactions

MAO-A inhibitors and nonselective MAO inhibitors - DO NOT COMBINE or start zolmitriptan within 2 weeks of discontinuing an MAO inhibitor. Zolmitriptan is metabolized by MAO-A. Selective MAO-A and nonselective MAO inhibitors may increase blood levels. Selective MAO-B inhibitors would not be expected to affect zolmitriptan levels.
Ergotamines - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
Other 5-HT₁ agonists - DO NOT COMBINE. Triptans should not be taken within 24 hours of other 5-HT₁ agonists including other triptans.
Cimetidine - cimetidine has been shown to double the half-life and AUC of zolmitriptan
SSRIs/SNRIs - triptans are serotonergic medications, and they may increase the risk of serotonin syndrome (SS) when taken with SSRIs and SNRIs. A study that looked at the risk of SS with this drug combination found it to be very low. [PMID 29482205]

Contraindications / Precautions

Pregnancy and nursing - see migraine medications in pregnancy and nursing
Cardiovascular disease - triptans have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Wolff-Parkinson-White syndrome and other accessory pathway conduction disorders - DO NOT USE
Prinzmetal's variant angina - DO NOT USE. Triptans may exacerbate vasospastic heart disease.
Hemiplegic or basilar migraine - DO NOT USE
Chest pain and tightness - triptans may cause a sensation of pain and tightness in the chest, neck, and/or throat. These symptoms are more common with injectable drug forms. In most patients, triptan-induced chest pain is not thought to be caused by ischemia and is generally not serious. [1,4]
Cardiac arrhythmias - in a small number of patients, life-threatening arrhythmias have been reported within a few hours of taking triptans
Hypertension - triptans may cause a short-term rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Raynaud's syndrome - triptans may exacerbate symptoms of Raynaud's syndrome
Vision changes - rare cases of vision changes and vision loss have been reported with triptan use
Serotonin syndrome - serotonin syndrome has occurred in patients taking triptans. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including triptans (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Anaphylactic reactions - cases of anaphylaxis including angioedema have been reported in patients taking triptans
Ophthalmic effects - in rat studies, zolmitriptan at very high doses was found to bind to melanin in the retina. The significance of this in humans is unknown.
Phenylketonuria - Zomig-ZMT contains phenylalanine. The 2.5 mg and 5 mg tablets contain 2.81 mg and 5.62 mg of phenylalanine respectively.
Kidney disease

CrCl ≥ 26 ml/min: no dose adjustment necessary
CrCl 5 - 25 ml/min: clearance is reduced by 25%. Use caution.

Liver disease

Moderate-severe (Child-Pugh B/C) - clearance is decreased. Severe blood pressure elevations may occur. Use doses < 2.5 mg or avoid use.

Open all

Lasmiditan
Reyvow®

Dosage forms

Tablet

50 mg
100 mg
Comes in package of 8 tablets

Dosing

Acute migraine (adults)

Dosing: 50 mg, 100 mg, or 200 mg one time dose with migraine headache
Do not take more than one dose in 24 hours
A second dose has not been shown to be effective for the same migraine attack
Do not take unless can wait at least 8 hours between dosing and driving or operating machinery
May take without regard to food
Do not crush, cut, or chew tablets

Efficacy / Studies

Lasmiditan vs Placebo for Acute Migraine Headache, Brain (2019) [SH review]

Other

Lasmiditan is a Schedule 5 (CV) controlled substance

Generic / Price

NO/$$$$ (8 tablets)

Pharmacokinetics

Time to max level: 1.8 hours
Half-life: 5.7 hours

Mechanism of action

Lasmiditan binds with high affinity to the 5-HT1F receptor. Lasmiditan presumably exerts its therapeutic effects in the treatment of migraine through agonist effects at the 5-HT1F receptor; however, the precise mechanism is unknown.

FDA-approved indications

Acute migraine headache with or without aura in adults

Side effects

Side effect	Las 50 mg (N=654)	Las 100 mg (N=1265)	Las 200 mg (N=1258)	Placebo (N=1262)
Dizziness	9%	15%	17%	3%
Fatigue	4%	5%	6%	1%
Paresthesia	3%	7%	9%	2%
Sedation	6%	6%	7%	2%
Nausea and/or Vomiting	3%	4%	4%	2%
Muscle Weakness	1%	1%	2%	0%

Drug interactions

CNS depressants - lasmiditan can cause sedation, and it may potentiate the effect of other sedating drugs including alcohol. Use caution when combining.
Serotonergic medications - lasmiditan is a serotonergic agonist, and it may increase the risk of serotonin syndrome when taken with other serotonergic drugs. Use caution when combining.
Drugs that slow the heart rate - in trials, the average heart rate decreased by 5 - 10 bpm in lasmiditan-treated patients compared to 2 - 5 bpm in placebo-treated patients. Use caution when prescribing with other medications that slow the heart rate (e.g. beta blockers, clonidine, verapamil, diltiazem, digoxin, amiodarone, fingolimod, ivabradine, siponimod).
P-glycoprotein substrates - coadministration of lasmiditan with P-glycoprotein substrates where a small change in substrate plasma concentration may lead to serious toxicities (e.g. digoxin) is not recommended.
Breast cancer resistant protein (BCRP) substrates - lasmiditan is a BCRP inhibitor in vitro. Combination with BCRP substrates should be avoided.

Contraindications / Precautions

Driving impairment - because of its sedating effect, lasmiditan can cause significant driving impairment. Sleepiness can last for up to 8 hours after a dose. Patients should not engage in potentially hazardous activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery, for at least 8 hours after taking lasmiditan.
CNS depression - lasmiditan can cause sedation and dizziness, and it may potentiate the effect of other sedating drugs including alcohol. Use caution when combining with other CNS depressants and avoid activities that require alertness for at least 8 hours after taking.
Serotonin syndrome - lasmiditan may cause serotonin syndrome. The risk may be increased when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including lasmiditan (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal
Heart rate decrease - in trials, the average heart rate decreased by 5 - 10 bpm in lasmiditan-treated patients compared to 2 - 5 bpm in placebo-treated patients. Use caution when prescribing with other medications that slow the heart rate (e.g. beta blockers, clonidine, verapamil, diltiazem, digoxin, amiodarone, fingolimod, ivabradine, siponimod).
Blood pressure increase - in trials, ambulatory systolic and diastolic blood pressure increased by 2 to 3 mmHg one hour after administration of lasmiditan 200 mg compared to 1 mmHg for placebo. In patients ≥ 65 years, systolic blood pressure increased by 7 mmHg one hour after administration of lasmiditan 200 mg compared to 4 mmHg with placebo. At 2 hours, there was no difference in blood pressure between lasmiditan and placebo.
Liver disease

Mild-to-moderate (Child-Pugh A/B): no dose adjustment necessary
Severe (Child-Pugh C): has not been studied. Not recommended.

Kidney disease - no dose adjustment necessary

Open all

Eptinezumab-jjmr
Vyepti®

Dosage forms

Single dose vial

100 mg
Store refrigerated

Dosing

Migraine prevention (adults)

Dosing: 100 mg by intravenous infusion every 3 months
Some patients may benefit from a dose of 300 mg every 3 months
Infuse over 30 minutes

Efficacy / Studies

Migraine prevention

Acute migraine treatment

Eptinezumab vs Placebo for Treatment of Acute Migraine, JAMA (2021) [PubMed abstract]

Generic / Price

NO/$$$$

Mechanism of action

Eptinezumab-jjmr is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor
Calcitonin gene–related peptide (CGRP) is a chemical mediator involved in eliciting migraine headaches through nociceptive mechanisms in the trigeminovascular system

FDA-approved indications

Prevention of migraines in adults

Side effects

Side effect	Ept 100 mg (N=579)	Ept 300 mg (N=574)	Placebo (N=588)
Nasopharyngitis	6%	8%	6%
Hypersensitivity reactions	1%	2%	0%

Drug interactions

None known

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, facial flushing, dyspnea, and rash, have occurred in trials and the postmarketing setting. Most reactions occurred during infusion and were not serious, but often led to discontinuation of eptinezumab. In trials, 1% of patients treated with eptinezumab 100 mg and 2% treated with eptinezumab 300 mg experienced a hypersensitivity reaction.
Hypertension - Postmarketing reports have linked CGRP antagonists, including eptinezumab, to new-onset or worsening hypertension, with onset occurring at any time but most frequently within 7 days of therapy initiation. In some cases, antihypertensives and even hospitalization were required. Monitor blood pressure in patients receiving eptinezumab and consider discontinuation if new-onset hypertension occurs or existing hypertension worsens.
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including eptinezumab. Symptom onset occurred a median of 71 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue eptinezumab if symptoms develop.
Anti-eptinezumab antibodies - in studies, anti-eptinezumab antibodies developed in up to 21% of patients treated for up to 56 weeks. Of those patients, 41.3% developed neutralizing antibodies. It's unknown if antibody development is associated with reduced efficacy or increased hypersensitivity.
Kidney disease - has not been studied. Kidney disease is not expected to affect the pharmacokinetics of eptinezumab.
Liver disease - has not been studied. Liver disease is not expected to affect the pharmacokinetics of eptinezumab.

Open all

Erenumab-aooe
Aimovig®

Dosage forms

SureClick Autoinjector

70 mg/ml
140 mg/ml
Store refrigerated

Prefilled syringe

70 mg/ml
140 mg/ml
Store refrigerated

Dosing

Migraine prevention (adults)

Dosing: 70 mg subcutaneous injection once monthly
Some patients may benefit from 140 mg once monthly which is given as two consecutive 70 mg doses
If a dose is missed, administer as soon as possible and give next dose in 1 month
Administer in the abdomen, thigh, or upper arm

Efficacy / Studies

Migraine prevention

Rosacea

Open-label, Nonrandomized Study of Erenumab for Rosacea, JAMA Dermatol (2024) [PubMed abstract]

Generic / Price

NO/$$$$

Other

Store in refrigerator protected from light
At room temperature, Aimovig is good for 7 days

Mechanism of action

Erenumab-aooe is a human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor and antagonizes CGRP receptor function
Calcitonin gene–related peptide (CGRP) is a chemical mediator involved in eliciting migraine headaches through nociceptive mechanisms in the trigeminovascular system

FDA-approved indications

Prevention of migraines in adults

Side effects

^✝Pain, itching, swelling, and/or erythema
Side effect	Erenumab 70 mg (N=787)	Erenumab 140 mg (N=507)	Placebo (N=890)
Injection site reactions^✝	6%	5%	3%
Constipation	1%	3%	1%
Muscle cramps	<1%	2%	<1%

Drug interactions

None known

Contraindications / Precautions

Anti-erenumab-aooe antibodies - in studies, anti-erenumab-aooe antibodies developed in 6.2% (48/778) of patients receiving 70 mg once monthly and 2.6% (13/504) of patients receiving 140 mg once monthly. It's unknown if antibody development is associated with reduced efficacy or increased hypersensitivity.
Hypersensitivity reactions - hypersensitivity reactions, including rash, angioedema, and anaphylaxis, have been reported. Most hypersensitivity reactions were not serious and occurred within hours of administration, although some occurred more than one week after administration.
Hypertension - cases of new hypertension and worsening hypertension have been reported in patients receiving erenumab. Hypertension may occur at any time during therapy, but it was most frequently seen within the first seven days after receiving the initial dose. All patients should monitor their blood pressure after starting erenumab, and patients with pre-existing hypertension should be particularly cautious. An observational study published in 2021 that combined data from four randomized controlled trials (N=2443) found no significant difference in vascular events or hypertension events between erenumab-treated patients and placebo-treated patients. [PMID 32381555]
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including erenumab. Symptom onset occurred a median of 71 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue ubrogepant if symptoms develop.
Constipation with serious complications - constipation with serious complications has been reported in postmarketing use. Some cases required hospitalization and surgery. The majority of the cases happened after the first dose, but other cases happened later in treatment. In trials, constipation was reported in up to 3% of patients using the 140 mg dose once monthly.
Kidney disease - in patients with mild or moderate renal impairment, pharmacokinetics were not affected. Erenumab-aooe has not been studied in severe renal impairment (CrCl < 30 ml/min). Renal impairment is not expected to affect the pharmacokinetics of erenumab-aooe.
Liver disease - has not been studied. Hepatic impairment is not expected to affect the pharmacokinetics of erenumab-aooe.

Open all

Fremanezumab-vfrm
Ajovy™

Dosage forms

Single-dose prefilled syringe

225 mg/1.5 ml
Comes in carton with one syringe
Keep refrigerated. Good for 7 days at room temp.

Single-dose autoinjector

225 mg/1.5 ml
Comes in package with 1 or 3 autoinjectors
Keep refrigerated. Good for 7 days at room temp.

Dosing

Migraine prevention (adults)

Dosing: 225 mg SC monthly OR 675 mg SC every 3 months (given as three consecutive subcutaneous injections of 225 mg each)
Inject in abdomen, thigh, or upper arm. For multiple injections, you may use the same body site, but not the exact location of the previous injection.
If a dose is missed, administer as soon as possible. Thereafter, fremanezumab can be scheduled from the date of the last dose.
When switching dosage options, administer the first dose of the new regimen on the next scheduled date of administration

Efficacy / Studies

Migraine prevention

Generic / Price

NO/$$$$

Other

Store in refrigerator protected from light
May be kept at room temperature for up to 24 hours

Mechanism of action

Fremanezumab-vfrm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor
Calcitonin gene–related peptide (CGRP) is a chemical mediator involved in eliciting migraine headaches through nociceptive mechanisms in the trigeminovascular system

FDA-approved indications

Prevention of migraines in adults

Side effects

Side effect	Fremanezumab 225 mg monthly (N=290)	Fremanezumab 675 mg quarterly (N=667)	Placebo (N=668)
Injection site reactions (e.g., pain, induration, and/or erythema)	43%	45%	38%

Drug interactions

None known

Contraindications / Precautions

Anti-fremanezumab antibodies - in trials, anti-fremanezumab antibodies were detected in 1.6% of patients (30 out of 1888). Out of 30 antibody-positive patients, 17 had a neutralizing activity in their post-dose samples.
Hypersensitivity reactions - hypersensitivity reactions, including rash, pruritus, and urticaria were reported with fremanezumab in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration. Cases of anaphylaxis and angioedema have been reported in the postmarketing setting. Fremanezumab is contraindicated in patients with a history of serious hypersensitivity reactions to it or any of its excipients.
Hypertension - Postmarketing reports have linked CGRP antagonists, including fremanezumab, to new-onset or worsening hypertension, with onset occurring at any time but most frequently within 7 days of therapy initiation. In some cases, antihypertensives and even hospitalization were required. Monitor blood pressure in patients receiving fremanezumab and consider discontinuation if new-onset hypertension occurs or existing hypertension worsens.
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including fremanezumab. Symptom onset occurred a median of 71 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue fremanezumab if symptoms develop.
Kidney disease - has not been studied. Renal impairment is not expected to affect the pharmacokinetics of fremanezumab.
Liver disease - has not been studied. Hepatic impairment is not expected to affect the pharmacokinetics of fremanezumab.

Open all

Galcanezumab-gnlm
Emgality™

Dosage forms

Single-dose prefilled pen

120 mg/ml
Comes in carton with 1 or 2 pens

Single-dose prefilled syringe

120 mg/ml
Comes in carton with 1 or 2 syringes

Single-dose prefilled syringe

100 mg/ml
Comes in carton with 3 syringes

Dosing

Migraine prevention (adults)

Dosing: 240 mg (two consecutive subcutaneous injections of 120 mg each) once as a loading dose, followed by monthly doses of 120 mg injected subcutaneously
Administer in the abdomen, thigh, back of the upper arm, or buttocks subcutaneously
If a dose of galcanezumab is missed, administer as soon as possible. Thereafter, galcanezumab can be scheduled monthly from the date of the last dose.

Treatment of cluster headache

Dosing: 300 mg (three consecutive subcutaneous injections of 100 mg each) at the onset of cluster period, followed by monthly doses of 300 mg until the end of the cluster period
Administer in the abdomen, thigh, back of the upper arm, or buttocks subcutaneously
If a dose of galcanezumab is missed, administer as soon as possible. Thereafter, galcanezumab can be scheduled monthly from the date of the last dose.

Efficacy / Studies

Cluster headache

Galcanezumab vs Placebo for Prevention of Episodic Cluster Headache, NEJM (2019) [PubMed abstract]

Migraine prevention

Galcanezumab vs Placebo for Migraine Prevention, J Headache Pain (2018) [PubMed abstract]

Generic / Price

NO/$$$$

Other

Store in refrigerator protected from light
May be kept at room temperature for up to 7 days

Mechanism of action

Galcanezumab-gnlm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.
Calcitonin gene–related peptide (CGRP) is a chemical mediator involved in eliciting migraine headaches through nociceptive mechanisms in the trigeminovascular system

FDA-approved indications

Prevention of migraines in adults
Treatment of episodic cluster headache in adults

Side effects

Side effect	Galcanezumab 120 mg monthly (N=705)	Placebo (N=1451)
Injection site reactions (e.g., pain, itching, and/or erythema	18%	13%

Drug interactions

None known

Contraindications / Precautions

Anti-galcanezumab antibodies - in trials, up to 12.5% (16/128) of galcanezumab-treated patients developed anti-galcanezumab antibodies. Most of these patients tested positive for neutralizing antibodies.
Hypersensitivity reactions - hypersensitivity reactions including rash, urticaria, and dyspnea were reported in clinical trials. Cases of anaphylaxis and angioedema have been reported in the postmarketing setting.
Hypertension - Postmarketing reports have linked CGRP antagonists, including galcanezumab, to new-onset or worsening hypertension, with onset occurring at any time but most frequently within 7 days of therapy initiation. In some cases, antihypertensives and even hospitalization were required. Monitor blood pressure in patients receiving galcanezumab and consider discontinuation if new-onset hypertension occurs or existing hypertension worsens.
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including galcanezumab. Symptom onset occurred a median of 71 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue galcanezumab if symptoms develop.
Kidney disease - has not been studied. Renal impairment is not expected to affect the pharmacokinetics of galcanezumab.
Liver disease - has not been studied. Hepatic impairment is not expected to affect the pharmacokinetics of galcanezumab.

Open all

Atogepant
Qulipta®

Dosage forms

Tablet

10 mg
30 mg
60 mg

Dosing

Episodic migraine prevention (adults)

Dosing: 10, 30, or 60 mg once daily
In trials, there was no significant difference in efficacy between the 3 doses
May take without regard to food

Chronic migraine (≥ 15 days/month) prevention (adults)

Dosing: 60 mg once daily
May take without regard to food

With CYP3A4 modifiers

Episodic migraine

Strong CYP3A4 inhibitors: 10 mg once daily
Strong, moderate, or weak CYP3A4 inducers: 30 or 60 mg once daily
See CYP3A4 inducers and inhibitors for more

Chronic migraine

Strong CYP3A4 inhibitors: DO NOT USE
Strong, moderate, or weak CYP3A4 inducers: DO NOT USE

With OATP inhibitors

Episodic migraine

10 or 30 mg once daily
See OATP inhibitors for more

Chronic migraine

30 mg once daily

Kidney disease

Episodic migraine

CrCl ≥ 30 ml/min: no dose adjustment necessary
CrCl < 30 ml/min: 10 mg once daily

Chronic migraine

CrCl ≥ 30 ml/min: no dose adjustment necessary
CrCl < 30 ml/min: DO NOT USE

Liver disease

Child-Pugh A and B: no dose adjustment necessary
Child-Pugh C: not recommended

Efficacy / Studies

Migraine prevention

Generic / Price

NO/$$$$

Pharmacokinetics

Time to max level: 1 - 2 hours
Half-life: 11 hours

Mechanism of action

Atogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist

FDA-approved indications

Preventive treatment of episodic and chronic migraine (≥ 15 days/month) in adults

Side effects

Side effect	Atogepant 60 mg (N=678)	Placebo (N=663)
Nausea	9%	3%
Constipation	8%	2%
Fatigue	5%	4%
Decreased appetite	3%	<1%
Dizziness	3%	2%

Drug interactions

CYP3A4 modifiers - atogepant is a CYP3A4 sensitive substrate. See Dosing above for recommendations on combining with CYP3A4 modifiers.
OATP inhibitors - atogepant is a OATP1B1/1B3 substrate. See Dosing above for recommendations on combining with OATP inhibitors.

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions, including anaphylaxis, dyspnea, rash, pruritus, urticaria, and facial edema, have been reported with atogepant, with some occurring days after administration. Discontinue atogepant if a significant reaction occurs.
Hypertension - Postmarketing reports have linked CGRP antagonists, including atogepant, to new-onset or worsening hypertension, with onset occurring at any time but most frequently within 7 days of therapy initiation. In some cases, antihypertensives and even hospitalization were required. Monitor blood pressure in patients receiving atogepant and consider discontinuation if new-onset hypertension occurs or existing hypertension worsens.
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including atogepant. Symptom onset occurred a median of 1.5 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue atogepant if symptoms develop.
Liver disease - see Dosing above
Kidney disease - see Dosing above

Open all

Rimegepant
Nurtec®

Dosage forms

Orally disintegrating tablet

75 mg
Comes in package of 8 tablets

Dosing

Acute migraine headache (adults)

Dosing: 75 mg one time dose with migraine headache
Do not take more than one dose in 24 hours
In trials, rimegepant was taken without regard to food. High-fat meals have been shown to reduce bioavailability by up to 38%.

Migraine prevention (adults)

Dosing: 75 mg every other day
In trials, rimegepant was taken without regard to food. High-fat meals have been shown to reduce bioavailability by up to 38%.

With CYP3A4 modifiers

Strong CYP3A4 inhibitors: DO NOT COMBINE
Moderate CYP3A4 inhibitors: Do not take two doses of rimegepant within 48 hours of each other
Strong or moderate CYP3A4 inducers: DO NOT COMBINE
See CYP3A4 inhibitors and inducers for more

With Potent P-glycoprotein inhibitors

Do not take two doses of rimegepant within 48 hours of each other
Examples of potent P-glycoprotein inhibitors include amiodarone, cyclosporine, lapatinib, quinidine, and ranolazine
See P-glycoprotein for more

Efficacy / Studies

Acute migraine

Rimegepant vs Placebo for Acute Migraine Headache, Lancet (2019) [SH review]

Migraine prevention

Rimegepant vs Placebo for Migraine Prevention, Lancet (2021) [SH review]

Generic / Price

NO/$$$$ (8 tablets)

Pharmacokinetics

Time to max level: 1.5 hours
Half-life: 11 hours

Mechanism of action

Rimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist

FDA-approved indications

Acute migraine headache with or without aura in adults
Preventive treatment of episodic migraine in adults

Side effects

In trials, the incidence of side effects in the rimegepant group was similar to placebo. The most common adverse event was nausea, which occurred in 2% of rimegepant-treated patients and 0.4% of placebo-treated patients.

Drug interactions

CYP3A4 strong inhibitors - DO NOT COMBINE. Rimegepant is a CYP3A4 sensitive substrate, and strong CYP3A4 inhibitors increase its exposure.
CYP3A4 moderate inhibitors - rimegepant is a CYP3A4 sensitive substrate. When taking rimegepant with CYP3A4 moderate inhibitors, do not take two rimegepant doses within 48 hours of each other.
CYP3A4 strong and moderate inducers - DO NOT COMBINE. Rimegepant is a CYP3A4 sensitive substrate and CYP3A4 moderate and strong inducers reduce its exposure.
P-glycoprotein potent inhibitors - rimegepant is a p-glycoprotein substrate. When taking rimegepant with P-glycoprotein potent inhibitors (e.g. amiodarone, cyclosporine, lapatinib, quinidine, ranolazine), do not take two rimegepant doses within 48 hours of each other.

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions including shortness of breath and rash have been reported. Reactions have occurred days after administration. If a reaction occurs, discontinue rimegepant.
Hypertension - Postmarketing reports have linked CGRP antagonists, including rimegepant, to new-onset or worsening hypertension, with onset occurring at any time but most frequently within 7 days of therapy initiation. In some cases, antihypertensives and even hospitalization were required. Monitor blood pressure in patients receiving rimegepant and consider discontinuation if new-onset hypertension occurs or existing hypertension worsens.
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including rimegepant. Symptom onset occurred a median of 1.5 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue rimegepant if symptoms develop.
Liver disease

Mild-to-moderate (Child-Pugh A/B): no dose adjustment necessary
Severe (Child-Pugh C): exposure is increased. Do not use.

Kidney disease

CrCl ≥ 15 ml/min: no dose adjustment necessary
CrCl < 15 ml/min: has not been studied. Not recommended.

Open all

Ubrogepant
Ubrelvy®

Dosage forms

Tablet

50 mg
100 mg
Comes in packages of 6, 8, 10, 12, and 30 tablets

Dosing

Acute migraine (adults)

Dosing: 50 - 100 mg with migraine headache. May repeat in 2 hours if necessary.
Max: 200 mg in 24 hours
May take without regard to food

Efficacy / Studies

Acute migraine

Ubrogepant vs Placebo for Acute Migraine Headache, NEJM (2019) [SH review]

Prevention of acute migraine during prodromal phase

Ubrogepant vs Placebo to Prevent Migraine when Given During Prodromal Phase, Lancet (2023) [PubMed abstract]

Generic / Price

NO/$$$$ (6 tablets)

Pharmacokinetics

Time to max level: 1.5 hours
Half-life: 5 - 7 hours

Mechanism of action

Rimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist

FDA-approved indications

Acute migraine headache with or without aura in adults

Side effects

Side effect	Placebo (N=984)	Ubro 50 mg (N=954)	Ubro 100 mg (N=485)
Nausea	2%	2%	4%
Somnolence	1%	2%	3%
Dry mouth	1%	<1%	2%

Drug interactions

Breast cancer resistant protein (BCRP) inhibitors - first dose should be 50 mg. Second dose (if needed) should also be 50 mg. Do not exceed 100 mg in 24 hours.
CYP3A4 strong inhibitors - DO NOT COMBINE. Ubrogepant exposure is increased.
CYP3A4 moderate inhibitors - do not exceed 50 mg in 24 hours. Ubrogepant exposure is increased.
CYP3A4 weak inhibitors - first dose should be 50 mg. Second dose (if needed) should also be 50 mg. Do not exceed 100 mg in 24 hours.
CYP3A4 strong inducers - DO NOT COMBINE. Ubrogepant exposure is decreased.
CYP3A4 weak and moderate inducers - first dose should be 100 mg. Second dose (if needed) should also be 100 mg. Ubrogepant exposure is decreased.
P-glycoprotein inhibitors - first dose should be 50 mg. Second dose (if needed) should also be 50 mg. Do not exceed 100 mg in 24 hours.

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions, including anaphylaxis, dyspnea, facial or throat edema, rash, urticaria, and pruritus, have been reported in patients receiving ubrogepant. Most reactions were mild and occurred within hours of dosing, but reactions have been reported days after administration. If a serious reaction occurs, ubrogepant should be permanently discontinued.
Hypertension - Postmarketing reports have linked CGRP antagonists, including ubrogepant, to new-onset or worsening hypertension, with onset occurring at any time but most frequently within 7 days of therapy initiation. In some cases, antihypertensives and even hospitalization were required. Monitor blood pressure in patients receiving ubrogepant and consider discontinuation if new-onset hypertension occurs or existing hypertension worsens.
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including ubrogepant. Symptom onset occurred a median of 1.5 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue ubrogepant if symptoms develop.
Liver disease

Mild-to-moderate (Child-Pugh A/B): no dose adjustment necessary
Severe (Child-Pugh C): first dose should be 50 mg. Second dose (if needed) should also be 50 mg. Do not exceed 100 mg in 24 hours.

Kidney disease

CrCl ≥ 30 ml/min: no dose adjustment necessary
CrCl 15 - 29 ml/min: first dose should be 50 mg. Second dose (if needed) should also be 50 mg. Do not exceed 100 mg in 24 hours.
CrCl < 15 ml/min: do not use

Open all

Zavegepant
Zavzpret®

Dosage forms

Nasal spray

10 mg single-dose spray device
Comes in carton with 6 devices

Dosing

Acute migraine (adults)

Dosing: 10 mg given as a single spray in one nostril
Max: 10 mg (one spray) in 24 hours

Efficacy / Studies

Acute migraine

Zavegepant vs Placebo for Acute Migraine, Lancet Neurol (2023) [PubMed abstract]

Generic / Price

NO/$$$$ (6 sprays)

Pharmacokinetics

Time to max level: 30 minutes
Half-life: 6.55 hours

Mechanism of action

Zavegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist.

FDA-approved indications

Acute treatment of migraine with or without aura in adults

Side effects

Side effect	Zavegepant (N=1023)	Placebo (N=1056)
Altered taste or no taste	18%	4%
Nausea	4%	1%
Nasal discomfort	3%	1%
Vomiting	2%	<1%

Drug interactions

OATP1B3 inhibitors and inducers - zavegepant is a OATP1B3 sensitive substrate and should not be given with OATP1B3 inhibitors or inducers
Sodium taurocholate co-transporting polypeptide (NTCP) inhibitors and inducers - zavegepant is an NTCP sensitive substrate and should not be given with NTCP inhibitors or inducers
Intranasal decongestants - intranasal decongestants may reduce zavegepant absorption, and concomitant use should be avoided. If concomitant use is unavoidable, intranasal decongestants should be given one hour after zavegepant.

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions, including facial swelling and urticaria, have occurred in patients receiving zavegepant. If a reaction occurs, discontinue zavegepant and treat appropriately.
Hypertension - Postmarketing reports have linked CGRP antagonists, including zavegepant, to new-onset or worsening hypertension, with onset occurring at any time but most frequently within 7 days of therapy initiation. In some cases, antihypertensives and even hospitalization were required. Monitor blood pressure in patients receiving zavegepant and consider discontinuation if new-onset hypertension occurs or existing hypertension worsens.
Raynaud's phenomenon - Postmarketing reports of new-onset or worsening Raynaud's phenomenon have been reported with CGRP antagonists, including zavegepant. Symptom onset occurred a median of 1.5 days following dosing, and many cases had serious outcomes, including hospitalizations and disability. In most cases, symptoms resolved after the CGRP antagonist was discontinued. Use caution in patients with a history of Raynaud's phenomenon and discontinue zavegepant if symptoms develop.
Liver disease

Mild-to-moderate (Child-Pugh A or B): no dose adjustment necessary
Severe (Child-Pugh C): has not been studied. Not recommended.

Kidney disease

CrCl ≥ 30 ml/min: no dose adjustment necessary
CrCl < 30 ml/min: do not use

Open all

Ergotamine
Cafergot®, Migergot®

Dosage forms

Cafergot® tablet

Ergotamine : Caffeine

1 mg : 100 mg

Migergot® suppository

Ergotamine : Caffeine

2 mg : 100 mg
Comes in boxes of 12 suppositories

Dosing

Cafergot (acute migraine in adults)

Initial: 2 tablets with first sign of headache
May take 1 additional tablet every 30 minutes if needed
May take without regard to food
Do not exceed 6 tablets
Total weekly dose should not exceed 10 tablets

Migergot (acute migraine in adults)

Initial: one suppository at start of headache
May repeat one time in 1 hour if needed
Do not exceed 2 suppositories
Total weekly dose should not exceed 5 suppositories
Store in refrigerator

Generic / Price

NO/$$$$

Pharmacokinetics

Time to max level: ?
Half-life: 2 hours [5]

Mechanism of action

Ergotamine is a serotonergic agonist that has a high affinity for 5-HT_1B/1D receptors. It also binds dopamine and noradrenaline receptors. [5]
The mechanism by which ergotamine alleviates migraine headaches is not completely understood. Proposed theories include the following:

Cranial vasoconstriction
Inhibition of vasoactive peptide release
Blockade of neurotransmitter release in the dorsal horn
Facilitation of descending pain inhibitory systems [1]

FDA-approved indications

Migraine headache in adults

Side effects

The incidence of ergotamine side effects is not well defined

Paraesthesia
Nausea and vomiting
Numbness
Weakness
Vertigo
Edema
Itching
Anal ulcer (suppository)

Drug interactions

CYP3A4 inhibitors - DO NOT COMBINE with strong CYP3A4 inhibitors. Ergotamine is a sensitive CYP3A4 substrate. Life-threatening peripheral ischemia has been reported with combined use. Use caution with mild to moderate CYP3A4 inhibitors.
Vasoconstrictors - DO NOT COMBINE. May cause elevated blood pressure.
Other 5HT₁ agonists (ex. triptans) - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use within 24 hours of each other.
Propranolol - propranolol may potentiate the vasoconstrictive properties of ergotamines
Nicotine - nicotine may potentiate the vasoconstrictive properties of ergotamines
SSRIs/SNRIs - ergotamine is a serotonergic medication, and it may increase the risk of serotonin syndrome when taken with SSRIs and SNRIs

Contraindications / Precautions

Cardiovascular disease - ergotamines have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Prinzmetal's variant angina - DO NOT USE. Ergotamines may exacerbate vasospastic heart disease.
Pregnancy and nursing - DO NOT USE. Ergotamines may cause fetal harm, and they possess oxytocic properties. Ergotamines may inhibit prolactin and suppress lactation.
Hemiplegic or basilar migraine - DO NOT USE
Fibrosis - there have been case reports of pleural, retroperitoneal, and cardiac valvular fibrosis following long-term use of ergotamines
Hypertension - ergotamines may cause a rise in blood pressure. Use caution in patients with uncontrolled hypertension.
Raynaud's syndrome - ergotamines may exacerbate symptoms of Raynaud's syndrome
Serotonin syndrome - serotonin syndrome has occurred in patients taking ergotamines. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications including ergotamines (e.g. ≥ 10 days a month) may cause an increase in headache frequency and worsening headache with drug withdrawal.
Kidney disease - has not been studied. Do not use in severe kidney disease (CrCl < 30 ml/min).
Liver disease - has not been studied. Do not use in severe liver disease (Child-Pugh C)

Open all

Dihydroergotamine
D.H.E. 45®, Migranal®, Trudhesa®

Dosage forms

D.H.E. 45® injection

1 mg (1 mg/ml)
Comes in single-dose vials and ampules
Comes in packs of 10 vials/ampules

Migranal® nasal spray

0.5 mg/spray
Comes in vial that is attached to spray device
Each 4 mg vial delivers 4 doses
Comes in pack of 8 vials

Trudhesa® nasal spray

0.725 mg/spray
Comes in vial that is attached to spray device
Each vial delivers two sprays (one in each nostril)
Comes in package with 4 vials

Dosing - Acute migraine (adults)

D.H.E. 45 injection

Initial: 1 mg given intramuscularly or subcutaneously
May repeat in 1 hour if needed
Do not exceed 3 mg in 24 hours
Total weekly dose should not exceed 6 mg
For subcutaneous injection, inject in the middle of the thigh

Migranal nasal spray

One spray (0.5mg) in each nostril. Fifteen minutes later, an additional spray should be administered in each nostril (total dose of 2 mg).
No benefit of doses greater than 2 mg has been demonstrated
The safety of doses greater than 3 mg in 24 hours has not been evaluated

Trudhesa nasal spray

The recommended dose is 1.45 mg administered as two metered sprays into the nose (one spray of 0.725 mg into each nostril)
The dose may be repeated, if needed, a minimum of 1 hour after the first dose
Do not use more than 2 doses within a 24-hour period or 3 doses within a 7-day period

Dosing - Cluster headache (adults)

D.H.E. 45 injection

Initial: 1 mg given intramuscularly or subcutaneously
May repeat in 1 hour if needed
Do not exceed 3 mg in 24 hours
Total weekly dose should not exceed 6 mg

Generic / Price

D.H.E. 45® (10 ampules) - YES/$$$$
Migranal® (8 vials) - YES/$$$$
Trudhesa® (4 vials) - NO/$$$$

Pharmacokinetics

D.H.E. 45 injection

Time to max level: ?
Half-life: 9 hours

Migranal

Time to max level: ?
Half-life: 10 hours

Trudhesa

Time to max level: 0.5 hours
Half-life: 12 hours

Mechanism of action

Dihydroergotamine is a serotonergic agonist that has a high affinity for 5-HT_1D receptors. It also binds with high affinity to 5-HT_1A, 5-HT_2A, 5-HT_2C, noradrenaline α2A, α2B α1, and dopamine D2L and D3 receptors.
The mechanism by which dihydroergotamine alleviates migraine headaches is not completely understood. Proposed theories include the following:

Cranial vasoconstriction
Inhibition of vasoactive peptide release
Blockade of neurotransmitter release in the dorsal horn
Facilitation of descending pain inhibitory systems [1]

FDA-approved indications

D.H.E. 45

Acute migraine headache with or without aura in adults
Cluster headache

Migranal, Trudhesa

Acute migraine headache with or without aura in adults

Side effects

Side effect	Migranal nasal spray (N=597)	Placebo (N=631)
Runny nose	26%	7%
Nausea	10%	4%
Altered sense of taste	8%	1%
Application site reaction	6%	2%
Dizziness	4%	2%
Vomiting	4%	1%
Pharyngitis	3%	1%
Somnolence	3%	2%
Diarrhea	2%	<1%

Drug interactions

CYP3A4 inhibitors - DO NOT COMBINE with strong CYP3A4 inhibitors. Dihydroergotamine is a sensitive CYP3A4 substrate. Life-threatening peripheral ischemia has been reported with combined use. Use caution with mild to moderate CYP3A4 inhibitors.
Vasoconstrictors - DO NOT COMBINE. May cause elevated blood pressure.
Other 5HT₁ agonists (ex. triptans) - DO NOT COMBINE. May cause prolonged vasospastic reactions. Do not use triptans and ergotamine products within 24 hours of each other.
Propranolol - propranolol may potentiate the vasoconstrictive properties of ergotamines
Nicotine - nicotine may potentiate the vasoconstrictive properties of ergotamines
SSRIs/SNRIs - dihydroergotamine is a serotonergic medication, and it may increase the risk of serotonin syndrome when taken with SSRIs and SNRIs

Contraindications / Precautions

Cardiovascular disease - ergotamines have the potential to cause coronary, cerebral, and peripheral vasospasm. Because of this, they should not be used in patients with known cardiac ischemia, cerebral ischemia (TIA and stroke), or peripheral ischemia (bowel ischemia, intermittent claudication, etc.). Patients at high-risk for having vascular disease (e.g. diabetics, smokers, obese, etc.) should also use caution.
Prinzmetal's variant angina - DO NOT USE. Ergotamines may exacerbate vasospastic heart disease.
Pregnancy and nursing - DO NOT USE. Ergotamines may cause fetal harm, and they possess oxytocic properties. Ergotamines may inhibit prolactin and suppress lactation.
Hemiplegic or basilar migraine - DO NOT USE
Fibrosis - there have been case reports of pleural, retroperitoneal, and cardiac valvular fibrosis following prolonged daily use of injectable dihydroergotamine mesylate
Hypertension - ergotamines may cause a rise in blood pressure. Do not use in patients with uncontrolled hypertension.
Raynaud's syndrome - ergotamines may exacerbate symptoms of Raynaud's syndrome
Serotonin syndrome - serotonin syndrome has occurred in patients taking ergotamines. The risk may be higher when taken with other serotonergic medications.
Medication overuse headache - overuse of headache medications (e.g. ≥ 10 days a month), including ergotamines, may cause an increase in headache frequency and worsening symptoms with drug withdrawal.
Kidney disease - has not been studied. Do not use in severe kidney disease (CrCl < 30 ml/min).
Liver disease - has not been studied. Do not use in severe liver disease (Child-Pugh C)

PRICE ($) INFO / PATIENT ASSISTANCE

$ = 0 - $50
$$ = $51 - $100
$$$ = $101 - $150
$$$$ = > $151

Pricing based on one month of therapy at standard dosing in an adult
Pricing based on information from GoodRX.com®
Pricing may vary by region and availability

Patient Assistance Programs for Migraine Medications
Drug	Manufacturer	Ships to	PAP info	Application
Eptinezumab (Vyepti®)	Lundbeck	Doctor	Link	Link
Erenumab (Aimovig®)	Amgen	Patient	Link	Link
Galcanezumab (Emgality™)	Lilly	Patient or doctor	Link	PDF and online
Lasmiditan (Reyvow®)	Lilly	Patient or doctor	Link	PDF and online
Sumatriptan (Imitrex nasal spray®)	GlaxoSmithKline	Patient or other	Link	Link
Rizatriptan (Maxalt®)	Merck	Patient or doctor	Link	Link
Ubrogepant (Ubrelvy®)	Allergen	Doctor	Link	Link

BIBLIOGRAPHY

Manufacturer's package insert

MIGRAINE HEADACHE MEDICATIONS

Acronyms

Dosage forms

Dosing

Generic / Price

Pharmacokinetics

Mechanism of action

FDA-approved indications

Side effects

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FDA-approved indications

Side effects

Drug interactions

Contraindications / Precautions

Dosage forms

Dosing - Acute migraine

Dosing - Cluster headache

Generic / Price

Other

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Mechanism of action

FDA-approved indications

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