MIGRAINE HEADACHE MEDICATIONS









Almotriptan (Axert®)

Dosage forms

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

Dosing - Migraine headache

Adolescents 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
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

  • Triptans are serotonergic agonists that have a high affinity for 5-HT1D and 5-HT1B receptors
  • The mechanism by which they alleviate 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

- Acute migraine headache with or without aura in adults and adolescents

Side effects



Side effect Almotriptan 12.5 mg Placebo
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

  • 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.

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

Migraine headache
  • 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

  • Triptans are serotonergic agonists that have a high affinity for 5-HT1D and 5-HT1B receptors
  • The mechanism by which they alleviate 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

- Acute migraine headache with or without aura in adults

Side effects



Side effect Eletriptan 40 mg Placebo
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 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

  • 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.

Frovatriptan (Frova®)

Dosage forms

Tablet
  • 2.5 mg
  • Comes in dose pack of 9 tablets

Dosing

Migraine headache
  • 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

  • Triptans are serotonergic agonists that have a high affinity for 5-HT1D and 5-HT1B receptors
  • The mechanism by which they alleviate 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

- Acute migraine headache with or without aura in adults

Side effects



Side effect Frovatriptan 2.5 mg Placebo
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

  • 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.

Naratriptan (Amerge®)

Dosage forms

Tablet
  • 1 mg
  • 2.5 mg
  • Comes in dose pack of 9 tablets

Dosing

Migraine headache
  • 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

  • Triptans are serotonergic agonists that have a high affinity for 5-HT1D and 5-HT1B receptors
  • The mechanism by which they alleviate 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

- Acute migraine headache with or without aura in adults

Side effects



Side effect Naratriptan 2.5 mg Placebo
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

  • 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

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 - Migraine headache

Pediatric (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
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

  • Triptans are serotonergic agonists that have a high affinity for 5-HT1D and 5-HT1B receptors
  • The mechanism by which they alleviate 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

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

Side effects



Side effect Rizatriptan 10 mg tablet Placebo
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

  • 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.

Sumatriptan | Imitrex® | Zembrace® | Onzetra®

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 spray devices
Imitrex® prefilled syringe and vial
  • 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
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 - Migraine headache

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.
Zembrace injection
  • Initial: 3 mg subcutaneously
  • May repeat in 1 hour if needed
  • Do not exceed 12 mg in 24 hours
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
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/$$
  • Imitrex vial (5 doses) - YES/$
  • Imitrex statdose (2 doses) - YES/$$
  • Zembrace (4 doses) - NO/$$$$
  • Onzetra (16 nosepieces) - NO/$$$$
  • Treximet (9 tablets) - YES/$$$$

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

Mechanism of action

  • Triptans are serotonergic agonists that have a high affinity for 5-HT1D and 5-HT1B receptors
  • The mechanism by which they alleviate 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

Imitrex tablet and nasal spray / Zembrace / Onzetra
  • 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 Placebo
Paresthesia 5% 2%
Chest pain 2% 1%
Neck / throat / jaw pain 2% <1%
Fatigue 2% <1%
Nasal spray
Side effect Sumatriptan 20 mg Placebo
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 Placebo
Abnormal taste 20% 3%
Nasal discomfort 11% 1%
Rhinorrhea 5% 2%
Rhinitis 2% 0%
Injection
Side effect Sumatriptan 6 mg Placebo
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%


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

  • 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

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 - Migraine headache

Zomig and Zomig-ZMT tablet
  • 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
  • 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

  • Triptans are serotonergic agonists that have a high affinity for 5-HT1D and 5-HT1B receptors
  • The mechanism by which they alleviate 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

- Acute migraine headache with or without aura in adults

Side effects



Side effect Zolmitriptan 2.5 mg tablet Placebo
Nausea 9% 4%
Dizziness 8% 4%
Paresthesia 7% 2%
Neck / throat / jaw pain 7% 3%
Somnolence 6% 3%
Chest pain 3% 1%
Other pressure / tightness / heaviness 2% 0%


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

  • 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.



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 - Migraine headache

Cafergot
  • 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
  • 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-HT1B/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

NOTE: Incidence of side effects with ergotamine 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 possesses 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)

Dihydroergotamine | D.H.E. 45® | Migranal®

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
  • 4 mg
  • Comes in vial that is attached to spray device
  • Comes in pack of 8 vials

Dosing - Migraine headache

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
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

Dosing - Cluster headache

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/$$$$
  • Migranal® (8 vials) - YES/$$$$

Other

D.H.E. 45
  • For subcutaneous injection, inject in the middle of the thigh
  • Store below 25°C (77°F), in light-resistant containers
  • Do not refrigerate or freeze
  • Solution should be clear and colorless
Migranal
  • Sprayer must be primed 4 times prior to administration
  • Once sprayer is assembled, drug is good for 8 hours
  • Store below 25°C (77°F). Do not refrigerate or freeze.

Pharmacokinetics

D.H.E. 45 injection
  • Time to max level: ?
  • Half-life: 9 hours
Migranal
  • Time to max level: ?
  • Half-life: 10 hours

Mechanism of action

  • Dihydroergotamine is a serotonergic agonist that has a high affinity for 5-HT1D receptors. It also binds with high affinity to 5-HT1A, 5-HT2A, 5-HT2C, 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
  • Acute migraine headache with or without aura in adults

Side effects

Migranal nasal spray
Side effect Migranal Placebo
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%
Diarrhea 2% <1%
D.H.E. 45
  • NOTE: Incidence of side effects is not well-defined
  • Paraesthesia
  • Dizziness
  • Anxiety
  • Shortness of breath
  • Headache
  • Flushing
  • Diarrhea
  • Rash
  • Increased sweating


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 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 possesses 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. 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)



Erenumab-aooe (Aimovig™)

Dosage forms

SureClick Autoinjector
  • 70 mg/ml
  • Comes as single autoinjector or carton with 2 autoinjectors

Dosing

Prevention of migraine headache
  • 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


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



Side effect Erenumab 70 mg once monthly Placebo
Injection site reactions 6% 3%
Constipation 1% 1%
Muscle cramps <1% <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.
  • 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.

Fremanezumab-vfrm (Ajovy™)

Dosage forms

Single-dose prefilled syringe
  • 225 mg/1.5 ml
  • Comes in carton with one syringe

Dosing

Prevention of migraine headache
  • Dosing: 225 mg SQ monthly OR 675 mg SQ 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


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 monthly Placebo
Injection site reactions 43% 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.
  • 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.

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

Prevention of migraine headache
  • 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


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 Placebo
Injection site reactions 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 (e.g. rash, urticaria, and dyspnea) have been reported with galcanezumab in clinical studies
  • 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.



Erenumab vs Placebo for Episodic Migraine, NEJM (2017) [PubMed abstract]
  • The trial enrolled 955 patients with episodic migraine headache
Main inclusion criteria
  • History of migraine with or without aura for at least 12 months before screening
  • 4 - 15 migraine days per month
Main exclusion criteria
  • Older than 50 years of age at migraine onset
  • History of hemiplegic migraine or cluster headache
  • Prior nonresponse to more than two migraine-preventive treatment categories
  • Taking ≥ 2 migraine preventive medications
Baseline characteristics
  • Average age - 41 years
  • Female sex - 85%
  • Taking preventive migraine medication at baseline - 3%
  • Average migraine days per month - 8.3
  • Failed previous preventive treatment - 40%
Randomized treatment groups
  • Group 1 (316 patients) - Placebo injection
  • Group 2 (312 patients) - Erenumab 70 mg SQ once monthly
  • Group 3 (318 patients) - Erenumab 140 mg SQ once monthly
  • Abortive medications including triptans and ergotamines were allowed for acute treatment
  • The trial had a 4-week run-in phase before patients were randomized to the 6-month double-blind treatment phase
Primary outcome: Change in mean number of migraine days per month from baseline to the final 3 months (months 4 through 6) of the double-blind treatment phase
Results

Duration: 6 months
Outcome Placebo Erenumab 70 Erenumab 140 Comparisons
Primary outcome (decrease in migraine days/month) 1.8 3.2 3.7 Group 2 or 3 vs 1 p<0.001
Reduction of ≥ 50% in migraine days/month 27% 43% 50% Group 2 or 3 vs 1 p<0.001
Reduction in days/month of use of acute migraine–specific medications 0.2 1.1 1.6 Group 2 or 3 vs 1 p<0.001
  • Adverse event rates were similar between the two treatment groups and placebo

Findings: Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study.

LIBERTY Study - Erenumab vs Placebo for Migraines that Failed 2 - 4 Previous Preventive Treatments, Lancet (2018) [PubMed abstract]
  • The trial enrolled 246 patients with episodic migraine who had failed previous treatment
Main inclusion criteria
  • History of episodic migraine with or without aura for at least 12 months
  • Failed previous treatment (in terms of either efficacy or tolerability, or both) with 2 - 4 migraine preventive therapies. Preventive therapies included propranolol, metoprolol, topiramate, flunarizine, valproate, amitriptyline, venlafaxine, lisinopril, candesartan, or other locally approved preventives.
Main exclusion criteria
  • Older than 50 years at migraine onset
  • Active chronic pain syndrome
Baseline characteristics
  • Average age - 44 years
  • Female - 80%
  • Average monthly migraine days - 9.2
  • Previous unsuccessful treatments: Topiramate - 85%, Propranolol - 45%, Amitriptyline - 45%, Metoprolol - 38%, Valproate - 28%
Randomized treatment groups
  • Group 1 (121 patients): Erenumab 140 mg SQ once monthly
  • Group 2 (125 patients): Placebo
Primary outcome: Proportion of patients who achieved at least a 50% reduction from their individual baseline in the number of monthly migraine days during the third month of the double-blind treatment phase (ie, weeks 9–12)
Results

Duration: 12 weeks
Outcome Erenumab Placebo Comparisons
Primary outcome (≥ 50% reduction) 30% 14% OR 2.7 95%CI [1.4 - 5.2], p=0.002
Primary outcome (≥ 75% reduction) 12% 4% OR 3.2 95%CI [1.1 - 9.0], p=0.025
Primary outcome (100% reduction) 6% 0% N/A
Reduction in monthly migraine days (weeks 9 - 12) 1.8 days 0.2 days Diff 1.6 95%CI [0.5 - 2.7], p=0.004
  • Adverse events were similar between the two groups

Findings: Compared with placebo, erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and four previous migraine preventive treatments. Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options.

Fremanezumab vs Placebo for Migraine Prevention, NEJM (2017) [PubMed abstract]
  • The trial enrolled 1130 patients with episodic migraine
Main inclusion criteria
  • Age 18 to 70 years with migraine onset at ≤ 50 years of age
  • History of migraine for ≥ 12 months prior to screening
  • Headache occurring on ≥ 15 days each month
  • Using ≤ 1 preventive medication
Main exclusion criteria
  • Patients using opioids or barbiturates
  • Taking preventive treatment and previously failed ≥ 2 previous preventive treatments
  • Unremitting headaches (headaches for > 80% of awake time)
Baseline characteristics
  • Average age - 41 years
  • Female - 87%
  • Average monthly headache days - 13
  • Taking preventive medication - 21%
  • Previous use of topiramate - 30%
Randomized treatment groups
  • Group 1 (376 patients): Fremanezumab 675 mg once every 3 months
  • Group 2 (379 patients): Fremanezumab 675 mg one time followed by 225 mg at weeks 4 and 8
  • Group 3 (375 patients): Placebo
Primary outcome: Mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine–specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose
Results

Duration: 12 weeks
Outcome Fremanezumab 1 Fremanezumab 2 Placebo Comparisons
Primary outcome -4.3 -4.6 -2.5 1 or 2 vs 3 p<0.001
Change in days/month of use of acute migraine–specific medications -3.7 -4.2 -1.9 1 or 2 vs 3 p<0.001
≥ 50% reduction in mean HA days/month 38% 41% 18% N/A
  • Injection site reactions were slightly more common in the fremanezumab groups - 47% vs 40%
  • Other adverse events were similar between fremanezumab and placebo

Findings: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study.



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