Effective Date

Date of Origin   

07-01-2025           

Elyxyb®

(celecoxib)

Oral solution

Acute treatment of migraine headaches with or without aura in adults

Limitations of Use: Elyxyb is not indicated for the preventive treatment of migraine. 

12

MIGRANAL®

(dihydroergotamine mesylate)*

Nasal Spray

Acute treatment of migraine headaches with or without aura

MIGRANAL Nasal Spray is not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine.

*generic available

1

REYVOW®

(lasmiditan)

Tablet

Acute treatment of migraine with or without aura in adults

Limitations of Use: REYVOW is not indicated for the preventive treatment of migraine. 

2

Trudhesa®

(dihydroergotamine mesylate)

Nasal spray

Acute treatment of migraine with or without aura in adults

Limitations of Use: Trudhesa is not indicated for the preventive treatment of migraine or for the management of hemiplegic or basilar migraine.

10

Migraine and Cluster Headache Management

Migraine is a common disabling primary headache disorder with high prevalence, ranking second globally in terms of years lost to disability.(13) Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia. Migraines can present with or without aura, unilateral fully reversible visual, sensory, or other central nervous system symptoms that usually develop gradually and are most-often followed by headache and associated migraine symptoms.(5)

The International Classification of Headache Disorders 3rd Edition (ICHD-3) Diagnostic Criteria:(5)

Migraine Prevention:

The American Headache Society (AHS) position statement update (2024) states that based on ICDH-3, for those with episodic migraine (4-14 monthly migraine days) or chronic migraine (greater than or equal to 15 headache days/month), CGRP-targeting therapies should be considered a first-line migraine prevention treatment option. The guideline states that initiation of CGRP-targeting therapies should not require the prior failure of other migraine preventative drug classes. CGRP-targeting therapies are "migraine-specific" compared to other established preventative therapies. Cumulative evidence supports better efficacy, safety, and tolerability compared to any established first-line migraine prevention therapy. In addition, most CGRP-targeting therapies are labeled for episodic and chronic migraine which aids in decision making if patients spontaneously fluctuate from episodic to chronic migraine.(3) Injectable treatments (i.e., onabotulinumtoxin A, CGRP) should be evaluated at 4, 8, and 12 weeks after treatment initiation. There is data to support continued improvement beyond 3 months. An adequate trial should be assessed at 3 months for monthly administered CGRPs and 6 months for quarterly treatments. Oral treatments should be used for a minimum of 8 weeks and cumulative benefits should occur within 6-12 months of continued use.(13)

AHS Guidelines:(3)

The European Headache Federation and WHO consensus article (2019) states the following for episodic migraine prophylaxis:(8)

• Indication for migraine prophylaxis include:
  • Attacks cause disability on two or more days per month, and
  • Acute therapy has been optimized but does not prevent this, or is poorly tolerated, or there is a risk of over-frequent use of acute therapy, even when it is effective, and
  • Patient is willing to take daily medication
  • Failure of acute therapy is an indication for migraine prophylaxis
  • For children, frequent absence from school is an additional indication for prophylaxis
• Migraine prophylaxis agents may take 2-3 months to show efficacy
• Onabotulinumtoxin A is not effective in episodic migraine and not recommended
• When prophylaxis therapy fails:
  • May be due to subtherapeutic dosage or duration of therapy
  • Failure of one therapy does not predict the failure of another therapy in a different class
  • Review of the following are recommended:
    • Diagnosis
    • Adherence
    • Other medications, especially for MOH causes
  • The prophylaxis therapy should be discontinued if it fails to show clear benefit
  • If all prophylaxis therapies fail, a specialist should be referred

Acute Migraine Treatment:

The AHS guidelines recommend the following indications for initiating treatment acute treatment with gepants and ditans agents:(13)

• Prescribed by a licensed clinician
• Patient is at least 18 years of age
• Diagnosis of ICHD-3 migraine with aura, migraine without aura, or chronic migraine
• Either of the following: 
  • Contraindication to or inability to tolerate triptans
  • Inadequate response to two or more oral triptans, as determined by either of the following: 
    • Validated acute treatment patient-reported outcoming questionnaire:
      • Migraine Functional Impact Questionnaire (mTOQ)
      • Migraine Assessment of Current Therapy (Migraine-ACT)
      • Patient Perception of Migraine Questionnaire-Revised (PPMQ-R)
      • Functional Impairment Scale (FIS)
      • Patient Global Impression of Change (PGIC)
    • Clinician attestation
• At least three attacks should be treated to evaluate response and assess clinical improvement

The European Headache Federation and WHO consensus article (2019) states the following regarding the treatment of acute migraine headaches:(8)

• Treatment should be approached in a step wise manner and should treat three attacks at each step before moving to the next step if needed:
  • Step 1:
    • Use non-opioid analgesics, plus an antiemetic when needed
  • Step 2 for adults:
    • Use triptan products
    • Triptans should not be used regularly for 10 or more days per month to avoid the risk of MOH
    • Triptan efficacy is highly variable between individuals, so patients should try different triptans and formulations. Sumatriptan subcutaneous injection should be considered when all other triptans are ineffective.
    • When vomiting is present, zolmitriptan nasal spray or sumatriptan subcutaneous injection may be preferred
  • Step 2 for children and adolescents:
    • Failure of Step 1 in children should lead to specialist referral. No specific anti-migraine drugs have shown efficacy in children under 12 years of age.
    • Failure of Step 2 in adolescents (12-17 years of age), the following have shown efficacy and are approved:
      • Sumatriptan nasal spray
      • Zolmitriptan nasal spray

The Medical Letter Treatment Guidelines (2023) state that a triptan is the drug of choice for moderate to severe migraine. The short-acting oral serotonin (5-HT1B/1D) receptor agonists (triptans) sumatriptan (IMITREX, and others), almotriptan (Axert, and generics), eletriptan (RELPAX), rizatriptan (Maxalt, and generics), and zolmitriptan (Zomig, and generics) are similar in efficacy. Onset of pain relief generally occurs 30-60 minutes after administration. The longer-acting oral triptans naratriptan (Amerge, and generics) and frovatriptan (Frova, and generics) have a slower onset of action and lower initial response rate than other triptans, but they are better tolerated. Patients with migraine who have nausea or vomiting may not be able to take an oral triptan. Intranasal triptan formulations have a more rapid onset of action than oral tablets, but their efficacy is partially dependent on GI absorption of the portion of the dose that is swallowed. Use of sumatriptan nasal powder (ONZETRA Xsail) results in a faster rise in sumatriptan plasma concentrations and higher peak concentrations than use of a similar dose of sumatriptan nasal spray, suggesting that a larger portion of the dose is absorbed intranasally with the powder. Subcutaneously administered sumatriptan relieves pain faster (in about 10 minutes) and more effectively than other triptan formulations, but it causes more adverse effects.(15)

AHS (2018, updated 2021): Triptans are effective (Level A) and considered by AHS guidelines to be the gold standard for acute treatment of moderate to severe migraine headaches. Dihydroergotamine is recommended for use as a second- or third-line therapy for select patients or for those with refractory migraine. Intranasal dihydroergotamine has strong evidence of effectiveness but more adverse effects than triptans because of its decreased receptor specificity. An assessment of new migraine treatments by the AHS lists triptans, dihydroergotamine, the oral gepants (Nurtec ODT [rimegepant] and UBRELVY [ubrogepant]), and REYVOW (lasmiditan) as effective treatment of moderate or severe acute attacks and mild to moderate attacks that respond poorly to non-specific nonsteroidal anti-inflammatory drugs (NSAIDs), non-opioid analgesics, acetaminophen, or caffeinated combinations (e.g., aspirin/acetaminophen/caffeine).(13)

Cluster Headache:

Cluster headache (CH) is the most common primary headache disorder and considered the most severe due to extreme pain, autonomic symptoms and high frequency of attacks.(18) The International Headache Society (IHS) notes that cluster periods usually last between 2 weeks and 3 months.(5)

The American Academy of Neurology (AAN) Guidelines (2010, re-reviewed 2016): For acute treatment, sumatriptan subcutaneous, zolmitriptan nasal spray, and high flow oxygen remain the treatments with a Level A recommendation. For transitional and prophylactic therapy, suboccipital steroid injections is the only treatment with a Level A recommendation. Verapamil is the prophylactic therapy of choice, and because suboccipital corticosteroid injections are typically used for transitional prophylaxis, lithium and verapamil have the highest evidence among preventative therapies. Oral corticosteroids are commonly used for transitional prophylaxis and considered first or second line. Melatonin is another prophylactic treatment with favorable adverse effect profile.(18) 

The European Academy of Neurology Guidelines (2023): For the acute treatment of CH attacks, high flow oxygen and 6mg subcutaneous sumatriptan are still highly recommended. For prophylaxis of CH, verapamil at a daily dose of at least 240 mg (or maximum dose based on efficacy and tolerability) is recommended. Corticosteroids show efficacy for cluster headache while lithium, topiramate, and galcanezumab (only for episodic cluster headache) are recommended as alternative treatment options.(4)

The European Headache Federation and WHO consensus article (2019) states the following for CH management:(8)

• Cluster Headache management: 
  • Acute therapies include: 
    • Triptans: 
      • Sumatriptan subcutaneous injection
      • Sumatriptan nasal spray
      • Zolmitriptan nasal spray
    • Oxygen
  • Transition and maintenance therapies include: 
    • Prednisone
    • Greater occipital nerve blockade
    • Verapamil
    • Lithium carbonate
    • Topiramate 
  • Neuromodulation is another treatment option
  • Failure of one prophylactic therapy does not predict the failure of other therapies
  • Combination prophylaxis therapy can be considered though the potential for toxicity is high
  • Long-term prophylaxis therapy may need to be continued

Combination of therapies: 

• Migraine Prophylaxis Therapies: 
  • The European Headache Federation guideline states the following on combining migraine prophylaxis therapy:(9)
    • In episodic migraine, guidelines suggest to stop oral prophylaxis migraine agents before starting CGRPs, unless the patient previously had chronic migraine prior to prophylaxis. In such patients, the suggestion is to add CGRP to the ongoing oral prophylaxis therapy
    • In chronic migraine, guidelines suggest to add CGRP to ongoing oral prophylaxis therapy
    • In chronic migraine patients on onabotulinumtoxin A therapy and are receiving inadequate treatment response, guidelines suggest to stop onabotulinumtoxin A therapy before starting CGRPs
    • In patients with chronic migraine who are on treatment with CGRP and may benefit from additional prevention, guidelines suggest to add on oral preventative agents
    • In patients with medication overuse, guidelines suggest to use CGRPs before or after withdrawal of acute medications
  • The clinical trials referenced in FDA labeled package inserts for the preventative CGRP agents excluded patients that had received botulinum toxin within 4 months prior to receiving the CGRP agent.(19,20,21) However, the 2021 AHS consensus statement states that CGRP monoclonal antibody treatment (e.g., eptinezumab-jjmr, erenumab, fremanezumab, galcanezumab) may be added to greater than or equal to one established preventative treatment, based on clinical judgement, in adults who meet the ICHD-3 criteria for migraines.(5,13)
• Acute Use Therapies: 
  • Literature supports the use of gepants and triptans in combination for acute migraine therapy. All studies showed co-administration of these medications were well tolerated with a favorable safety profile.
    • Ubrogepant when co-administered with sumatriptan showed healthy patients tolerated these medications well and the slight alterations in pharmacokinetic parameters had minimal clinical relevance. Pooled Phase 3 ACHIEVE trials safety assessment supported use of optional second dose of a rescue medication for the treatment of moderate to severe headache starting 2-48 hours after initial dose of study medication. Rescue medication included triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Overall frequency of treatment-related adverse effects was similar among patients that took ubrogepant along with patients that took ubrogepant and a triptan rescue medication.(22)
    • Concomitant administration of oral rimegepant and subcutaneous sumatriptan in healthy adults showed no hemodynamic or pharmacokinetic interactions suggesting it is safe and well tolerated.(6)
    • The pharmacokinetic and pharmacodynamic interactions between zavegepant and triptans in healthy adults showed no statistically significant difference when co-administered compared to sumatriptan alone.(7)
  • Lasmiditan with a triptan or gepant used in combination is not recommended(13,15)
  • Triptans and ergots used in combination is contraindicated(15)
  • The safety, tolerability, and efficacy of co-administering of the following agents has not been assessed or supported in literature:
    • Two acute use CGRPs
    • Acute use CGRP with ergotamine

Medication overuse headache (MOH)

 The European Headache Federation and WHO consensus article (2019) states the following:(8)

• • In adults and children, regular high frequency use (greater than 2 day/week) of acute medication risks the development of MOH
  • Prevention is preferred
  • The four objectives of management are:
    • Stop the overused medication
    • Recovery from MOH
    • Review and reassess the underlying headache disorder
    • Prevent relapse while allowing acceptable use of medications
  • Comorbidities may require management

Safety

Elyxyb has the following boxed warnings:(12)

• Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use
• Elyxyb is contraindicated in the setting of coronary artery bypass graft (CABG) surgery
• NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events

Elyxyb is contraindicated in the following:(12)

• Patients with known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to celecoxib, any components of the drug product
• Patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. 
• In the setting of CABG surgery
• Patients who have demonstrated allergic-type reactions to sulfonamides

MIGRANAL has the following boxed warning:(1)

• Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.

MIGRANAL is contraindicated in the following:(1)        

• Patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina
• Patients with uncontrolled hypertension
• Use within 24 hours of 5-HT1 agonists (e.g., sumatriptan), ergotamine-containing or ergot-type medications, or methysergide
• Patients with hemiplegic or basilar migraine
• Patients with known peripheral arterial disease, sepsis, following vascular surgery, and severely impaired hepatic or renal function
• Pregnant women
• Patients who have previously shown hypersensitivity to ergot alkaloids
• Use with peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure

REYVOW has no FDA labeled contraindications for use.(2)

Trudhesa has the following boxed warning:(10)

• Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors. Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of Trudhesa with strong CYP 3A4 inhibitors is contraindicated.

Trudhesa is contraindicated in the following:(10)

• Concomitant use of strong CYP 3A4 inhibitors
• Patients with ischemic heart disease or coronary artery vasospasm
• Patients with uncontrolled hypertension, peripheral arterial diseases, sepsis, following vascular surgery, or severe hepatic or renal impairment
• Patients with hypersensitivity to ergot alkaloids
• Concomitant use of other 5-HT1 agonists (e.g., sumatriptan) or ergotamine-containing or ergot-type medications within 24 hours
• Concomitant use of peripheral and central vasoconstrictors

1

MIGRANAL prescribing information. Bausch Health US, LLC. September 2022.

2

REYVOW prescribing information. Eli Lilly and Company. September 2022.

3

Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey A. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update. Headache the Journal of Head and Face Pain. 2024;64(4):333-341. doi:10.1111/head.14692

4

May A, Evers S, Goadsby PJ, et al. European Academy of Neurology guidelines on the treatment of cluster headache. European Journal of Neurology. 2023;30(10):2955-2979. doi:10.1111/ene.15956

5

Gobel H. The International Classification of Headache Disorders - ICHD-3. ICHD-3. https://ichd-3.org/

6

Croop R, Ivans A, Anderson MS, et al. A phase 1 randomized study of hemodynamic effects and pharmacokinetic interactions during concomitant use of rimegepant and sumatriptan in healthy adults. Cephalalgia Reports. 2021;4:251581632110079. doi:10.1177/25158163211007922

7

Bhardwaj R, Donohue MK, Madonia J, et al. Assessment of pharmacokinetic and pharmacodynamic interactions between zavegepant and sumatriptan: A phase 1, randomized, placebo-controlled study in healthy adults. Headache the Journal of Head and Face Pain. Published online October 4, 2024. doi:10.1111/head.14853

8

Steiner TJ, Jensen R, Katsarava Z, et al. Aids to management of headache disorders in primary care (2nd edition). The Journal of Headache and Pain. 2019;20(1). doi:10.1186/s10194-018-0899-2

9

Sacco S, Bendtsen L, Ashina M, et al. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. The Journal of Headache and Pain. 2019; 20:6. https://doi.org/10.1186/s10194-018-0955-y

10

Trudhesa prescribing information. Impel Pharmaceuticals Inc. August 2023.

11

Reference no longer used.

12

Elyxyb prescribing information. BioDelivery Sciences International Inc. September 2021.

13

Ailani J, Burch RC, Robbins MS; the Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021; 61: 1021-1039. https://doi.org/10.1111/head.14153

14

Reference no longer used.

15

Drugs for Migraine. Med Lett Drugs Ther. 2023 Jun 12; 65(1678):89-96. doi:10.58347/tml.2023.1678a

16

Reference no longer used.

17

Beithon J, Gallenberg M, Johnson K, Kildahl P, Krenik J, Liebow M, Linbo L, Myers C, Peterson S, Schmidt J, Swanson J. Institute for Clinical Systems Improvement. Diagnosis and Treatment of Headache. ICSI. Updated January 2013. https://www.icsi.org/wp-content/uploads/2019/01/Headache.pdf.

18

Robbins MS, Starling AJ, Pringsheim TM, Becker WJ, Schwedt TJ. Treatment of Cluster Headache: The American Headache Society Evidence‐Based Guidelines. Headache the Journal of Head and Face Pain. 2016;56(7):1093-1106. doi:10.1111/head.12866

19

Tepper S, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomized, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jun; 16(6): 425-434. doi: 10.1016/S1474-4422(17)30083-2

20

Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018 Dec 11; 91(24): e2211-e2221. doi: 10.1212/WNL.0000000000006640

21

Lipton RB, Cohen JM, Gandhi SK, Yang R, Yeung PP, Buse DC. Effect of fremanezumab on quality of life and productivity in patients with chronic migraine. Neurology. 2020 Aug 18; 95(7): e878-e888. doi: 10.1212/WNL.0000000000010000

22

Jakate A, Boinpally R, Butler M, Lu K, McGeeney D, Periclou A. Evaluation of the pharmacokinetic interaction of ubrogepant coadministered with sumatriptan and of the safety of ubrogepant with triptans. Headache the Journal of Head and Face Pain. 2020;60(7):1340-1350. doi:10.1111/head.13862

Elyxyb

celecoxib oral soln

120 MG/4.8ML

M ; N ; O ; Y

N

Trudhesa

dihydroergotamine mesylate hfa nasal aerosol

0.725 MG/ACT

M ; N ; O ; Y

N

Migranal

Dihydroergotamine Mesylate Nasal Spray 4 MG/ML

4 MG/ML

M ; N ; O ; Y

O ; Y

Reyvow

lasmiditan succinate tab

100 MG ; 50 MG

M ; N ; O ; Y

N

Elyxyb

Celecoxib Oral Soln

120 MG/4.8ML

6

Bottles

30

DAYS

Migranal

Dihydroergotamine Mesylate Nasal Spray 4 MG/ML

4 MG/ML

8

mLs

28

DAYS

Reyvow

Lasmiditan Succinate Tab 100 MG

100 MG

8

Tablets

30

DAYS

Reyvow

Lasmiditan Succinate Tab 50 MG

50 MG

8

Tablets

30

DAYS

Trudhesa

Dihydroergotamine Mesylate HFA Nasal Aerosol

0.725 MG/ACT

12

mLs

28

DAYS

Elyxyb

celecoxib oral soln

120 MG/4.8ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Migranal

Dihydroergotamine Mesylate Nasal Spray 4 MG/ML

4 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Reyvow

lasmiditan succinate tab

100 MG ; 50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Trudhesa

dihydroergotamine mesylate hfa nasal aerosol

0.725 MG/ACT

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Elyxyb

Celecoxib Oral Soln

120 MG/4.8ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Migranal

Dihydroergotamine Mesylate Nasal Spray 4 MG/ML

4 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Reyvow

Lasmiditan Succinate Tab 100 MG

100 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Reyvow

Lasmiditan Succinate Tab 50 MG

50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Trudhesa

Dihydroergotamine Mesylate HFA Nasal Aerosol

0.725 MG/ACT

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is being used for acute migraine treatment AND ALL of the following:
      1. ONE of the following:
         1. The patient has ONE of the following:
            1. Has tried and had an inadequate response to ONE prerequisite agent OR
            2. Has an intolerance or hypersensitivity to ONE prerequisite agent OR
         2. The patient has an FDA labeled contraindication to ALL prerequisite agent(s) AND
      2. ONE of the following:
         1. The requested agent is NOT REYVOW OR
         2. The requested agent is REYVOW AND the patient will NOT be using the requested agent in combination with another acute migraine therapy (i.e., 5HT-1F, acute use CGRP, ergotamine, triptan) AND
      3. Medication overuse headache has been ruled out OR
   2. The patient has another FDA labeled indication for the requested agent and route of administration OR
   3. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been approved for the requested agent previously through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. ONE of the following:
   1. The requested agent is being used for acute migraine treatment AND ALL of the following:
      1. The patient has had clinical benefit with the requested agent AND
      2. ONE of the following:
         1. The requested agent is NOT REYVOW OR
         2. The requested agent is REYVOW AND the patient will NOT be using the requested agent in combination with another acute migraine therapy (i.e., 5HT-1F, acute use CGRP, ergotamine, triptan) AND
      3. Medication overuse headache has been ruled out OR
   2. The patient has a diagnosis other than acute migraine treatment AND has had clinical benefit with the requested agent AND
3. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
3. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
   3. The patient has greater than 4 migraine headaches per month AND ONE of the following:
      1. The patient is currently being treated with a migraine prophylactic medication (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], tricyclic antidepressants [i.e., amitriptyline, nortriptyline], SNRIs [i.e., venlafaxine, duloxetine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec ODT, QULIPTA, Vyepti], or onabotulinumtoxin A [BOTOX]) OR
      2. The patient has an intolerance or hypersensitivity to therapy with migraine prophylactic medication (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], tricyclic antidepressants [i.e., amitriptyline, nortriptyline], SNRIs [i.e., venlafaxine, duloxetine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec ODT, QULIPTA, Vyepti], onabotulinumtoxin A [BOTOX]) OR
      3. The patient has an FDA labeled contraindication to ALL migraine prophylactic medications (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], tricyclic antidepressants [i.e., amitriptyline, nortriptyline], SNRIs [i.e., venlafaxine, duloxetine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec ODT, QULIPTA, Vyepti], AND onabotulinumtoxin A [BOTOX]) OR
      4. There is support that the patient’s migraines are manageable with acute therapy alone AND
   4. There is support of therapy with a higher dose for the requested indication

Length of Approval: up to 12 months