Migraine:

Prevention and Treatment Options

Hannah Cooper, PharmD

PGY1 Pharmacy Resident
April 2020
  Summarize the relationship between CGRP and migraines

 Identify who would qualify for migraine prevention therapy

Objectives
 Compare and contrast migraine medication options for the
treatment and prophylaxis
  Headache that lasts 4-72 hours
 At least 2 of the following characteristics
 Unilateral localization
Definition of  Pulsating quality
 Moderate to severe pain intensity
Migraine
 At least 1 of the following symptoms
 Nausea and/or vomiting
 Photophobia and phonophobia

Headache. 2019;59(1):1-18.
Pathophysiology

 Neuronal and vascular component

 Trigeminovasclar (TMV) system
 Once activated  increased CGRP + decreased 5-HT  vasodilation
and inflammation of the surrounding vessels
 Dilation + inflammation  pain

Annu Rev Pharmacol Toxicol. 2015;55:533-52.

Image: http://flipper.diff.org/app/items/info/5242
  Associated with migraines since 1990’s
Calcitonin  Role related to migraine:
Gene-Related  Vasodilation
 Neurogenic inflammation
Peptide  Peripheral sensitization
(CGRP)  Enhances nociceptor sensitization
 Enhances sensory input in CNS

Annu Rev Pharmacol Toxicol. 2015;55:533-52.

  Elevations in CGRP found in serum and saliva during
migraine attacks
 Levels reduced by the use of triptans
Evidence of
 When CGRP injected  criteria met for experimentally
CGRP induced migraine
 CGRP receptor antagonists relive pain and associated
symptoms of migraine

Annu Rev Pharmacol Toxicol. 2015;55:533-52.

 Prevention Treatment

Migraine Beta Blockers Ergot derivatives

Therapy SSRI/SNRI/TCA NSAIDs
Options Antiepileptics  Triptans
 CGRP Antagonist  CGRP Receptor Antagonist

Neurology. 2012;78(17):1337-45
  Attacks significantly interfere with patients daily
routine DESPITE rescue therapy
 Frequent attacks (≥ 4 monthly headache days)
Indications for  Contraindication, failure, or overuse of acute
treatments
Preventive  10 or more days a month using rescue therapies
Therapy  Ergot derivatives, triptans, opioids, combo analgesics, etc.
 15 or more days a month using NSAIDs, APAP, ASA
 Adverse effects with acute treatment
 Patient preference

Headache. 2019;59(1):1-18.
 Prevention should Headache days/month Degree of disability
Patient be…
6 or more
required
None
Identification Offered 4 or more Some

for 3 or more
4 or 5
Severe
None
Preventative Considered 3 Some
Therapy 2 Severe

Headache. 2019;59(1):1-18.
  Evaluate for BEFORE beginning preventive therapy

 Headache occurring ≥ 15 days/month

Medication  Regular overuse of 1 medication (or more) for > 3
Over-Use months
Headache  10 or more days a month using rescue therapies
 Ergot derivatives, triptans, opioids, combo analgesics, etc.
 15 or more days a month using NSAIDs, APAP, ASA
 Not better accounted for by any other diagnosis

Headache. 2019;59(1):1-18.
Calcitonin-Gene
Related Peptide (CGRP)
Antagonists
 Erenumab (Aimovig)

Fremanezumab (Ajovy)
CGRP
Galcanezumab (Emgality)
Antagonists
Rimegepant (Nurtec)

Ubrogepant (Ubrelvy)
  Indication: migraine prophylaxis
 MOA: antagonizes CGRP-receptor function
 70 mg SubQ once monthly
 Can go up to 140 mg

Erenumab  Missed dose?

 Administer ASAP, schedule next dose 1 month from last dose
(Aimovig)  Adverse effects: constipation, injection site reactions
 Price: $723.82/pen

Lexi-Comp Online
Novartis. Paying for Aimovig.
  Indication: migraine prophylaxis
 MOA: binds to CGRP inhibiting binding to receptor
 225 mg SubQ monthly
Fremanezumab  675 mg SubQ every 3 months
(Ajovy)  3 consecutive 225 mg injections
 Adverse effects: injection site reactions
 Price: $723.84/pen

Lexi-Comp Online
Teva. Ajovy.
  Indication: migraine prophylaxis
 MOA: binds to CGRP inhibiting binding to receptor
 240 mg SubQ as loading dose, followed by 120 mg SubQ once
monthly
 Loading dose given as 2 injections of 120 mg
Galcanezumab  Missed dose?
(Emgality)  Administer ASAP, schedule next dose 1 month from last dose
 Adverse effects: injection site reaction
 CV and peripheral vascular disease- patients excluded from trials,
use with caution
 Price: $724.32/pen (120 mg/mL)

Lexi-Comp Online
Lilly. Emgality.
  Indication: migraine treatment
 MOA: CGRP receptor antagonist
 75 mg PO as single dose
 Max: 75 mg/24 hours
Rimegepant  Safety of treating >15 headaches in 30-day period is not established

(Nurtec)  Disintegrating tablet

 Dose adjustment with strong CYP3A4 inhibitors
 Adverse effects: nausea
 Price: $127.50/tablet

Lexi-Comp Online
Biohaven. Nurtec.
  Indication: migraine treatment
 MOA: CGRP receptor antagonist
 50-100 mg PO as single dose; may repeat once after ≥ 2 hours
 Max: 200 mg/24 hours
Ubrogepant  Safety of treating >8 migraines/month has not been established

(Ubrelvy)  Contraindicated with strong CYP3A4 inhibitors

 Dose adjustment in renal and hepatic impairment
 Adverse effects: drowsiness, nausea
 Price: $102/tablet

Lexi-Comp Online
Allegran. Ubrelvy.
 Eptinezumab (Vyepti)

• FDA approved February 2020,

anticipated availability April 2020
Coming Soon! • IV infusion
• 100 mg over 30 minutes every 3
months
• Price: $1,794/mL (100 mg/mL)

Lexi-Comp Online
Triptans
Mechanism of
 Selective agonist 5-HT receptor 1B/1D subtype
Action  Exerts action at 2 main sites:
 TMV system
 Prevents release of CGRP
 Vasodilation
 Neurogenic inflammation
 Peripheral sensitization
 Cranial vasculature
 Causes vasoconstriction

Lexi-Comp Online
Image: https://step1.medbullets.com/neurology/113066/sumatriptan
 Almotriptan (Axert)

Eletriptan (Relpax)

Frovatriptan (Frova)

Triptans Naratriptan (Amerge)

Rizatriptan (Maxalt, Maxalt-ODT)

Sumatriptan (Imitrex, Onzetra Xsail, Zembrace)

Zolmitriptan (Zomig, Zomig-ZMT)

 Drug Route Initial Dose Max Dose

Almotriptan 6.25-12.5 mg, can repeat x1 after

(Axert) Tablet 2 hr 25 mg/day

Eletriptal (Relpax) Tablet 20-40 mg, can repeat x1 after 2 hr 80 mg/day

Frovatriptan Tablet 2.5 mg, can repeat x1 after 2 hr 7.5 mg/day

(Frova)

Drugs & Dosing Naratriptan

(Amerge) Tablet 1-2.5 mg, can repeat x1 after 4 hr 5 mg/day

Rizatriptan
(Maxalt, Maxalt- Tablet 5-10 mg, can repeat x1 after 2 hr 30 mg/day
MLT) ODT

Tablet
Zolmitriptan ODT 1.25-5 mg, can repeat x1 after 2 hr 10 mg/day
(Zomig, Zomig-
ZMT) Nasal spray 2.5-5 mg, can repeat x1 after 2 hr 10 mg/day

Lexi-Comp Online
 Drug Route Initial Dose Max Dose

Tablet 25, 50, or 100 mg, can repeat x1 200 mg/day

after 2 hr

Imitrex: 4 or 6 mg, can repeat x1

SubQ after 1 hr 12 mg/day
Sumatriptan Zembrace: 3 mg, can repeat up
Drugs & Dosing (Imitrex, Imitrex
STATdose, Onzetra
to 4x per day (1 hr in between)
Xsail, Zembrace
SymTouch)
Nasal spray 5, 10, or 20 mg in one nostril, 40 mg/day
can repeat x1 in 2 hr

Nasal 11 mg in each nostril, can repeat 44 mg/day

powder x1 after 2 hr

Lexi-Comp Online
 Warnings/
Side Effects Contraindication
Precautions

IHD, stroke, TIA,

Tingling, Risk of increased
peripheral
numbness blood pressure
vascular disease
Side Effects &
Warnings Cardiac and
Dizziness, cerebrovascular Uncontrolled
nausea events, HTN
arrhythmias

Use of ergot
“triptan Serotonin derivatives or
sensation” syndrome other triptan
within 24 hours

Lexi-Comp Online
  ODTs, nasal spray, injections  consider if nausea present
 Nasal sprays and injections work faster
 Sumatriptan injections
 Preferred site  lateral thigh or upper arm
 Available as prefilled syringe (Imitrex) and prefilled auto-injector
(Zembrace)
 Frovatriptan and naratriptan are considered long-acting 
Clinical Pearls consider if headache recurs after dosing or lasts long period
 Following have shorter half-life  fast onset
 Almotriptan, eletriptan, rizatriptan, sumatriptan, zolmitriptan
 Pediatrics
 Approved for ≥ 12 year-old  almotriptan tablets and zolmitriptan
nasal spray
 Approved for ≥ 6 year-old  rizatriptan

Lexi-Comp Online
  CGRP antagonists are available for prevention and treatment
 Few side effects
 Expensive, but discount cards available

Conclusion  Triptans are all equally effective at migraine treatment

 More side effects and warnings
 Take into consideration:
 PK profile
 Route of administration
Questions?
Email:
Hannah.Cooper@deaconess.com

Image: http://womenshelathmag.org
  The American Headache Society Position Statement On Integrating New
Migraine Treatments Into Clinical Practice. Headache. 2019;59(1):1-18.
 Russo AF. Calcitonin gene-related peptide (CGRP): a new target for migraine.
Annu Rev Pharmacol Toxicol. 2015;55:533-52.
 Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update:
pharmacologic treatment for episodic migraine prevention in adults: report of
the Quality Standards Subcommittee of the American Academy of Neurology
and the American Headache Society. Neurology. 2012;78(17):1337-45.
 Lexi-Drugs. Lexi-Comp Online. Lexi-Comp, Inc. Hudson, OH. Available at:
References http://online.lexi.com/crlonline. Accessed March 26, 2020.
 Novartis. Paying for Aimovig. https://www.aimovig.com/paying-for-aimovig/.
Accessed March 26, 2020.
 Teva. Ajovy. https://www.ajovy.com/why-ajovy. Accessed March 26, 2020.
 Lilly. Emgality. https://www.lillypricinginfo.com/emgality. Accessed March 26,
2020.
 Biohaven. Nurtec. https://www.nurtec.com/savings-support. Accessed March 26,
2020.
 Allegran. Ubrelvy. https://www.ubrelvy.com/. Accessed March 26, 2020.