Effective Date

Date of Origin 

07-01-2025            

almotriptan

Tablet

Acute treatment of migraine attacks in adults with a history of migraine with or without aura

Acute treatment of migraine headache pain in adolescents age 12 to 17 years with a history of migraine with or without aura, and who have migraine attacks usually lasting 4 hours or more

Important limitations: 

• Use only after a clear diagnosis of migraine has been established
• In adolescents age 12 to 17 years, efficacy of almotriptan tablets on migraine-associated symptoms was not established
• Not intended for the prophylactic therapy of migraine
• Not indicated for the treatment of cluster headache

2

naratriptan

Tablet

Acute treatment of migraine attacks with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

*generic available

1

Frova®

(frovatriptan)*

Tablet

Acute treatment of migraine attacks with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

*generic available

3

IMITREX®

(sumatriptan)*

Nasal spray

Acute treatment of migraine with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine headache has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

*generic available

5

IMITREX®

(sumatriptan)*

Subcutaneous injection

Acute treatment of migraine with or without aura in adults

Acute treatment, cluster headache episodes in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine or cluster headache has been established
• Not indicated for the prophylactic therapy of migraine or cluster headache attacks

*generic available

4

IMITREX®

(sumatriptan)*

Tablet

Acute treatment of migraine with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine headache has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

*generic available

6

Maxalt® MLT/Maxalt®

(rizatriptan)*

Orally disintegrating tablet

Tablet

Acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years of age

Limitations of Use:

• Use only after clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine
• Not indicated for the treatment of cluster headache

*generic available

7

ONZETRA® Xsail®

(sumatriptan)

Nasal powder

Acute treatment of migraine with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

8

RELPAX®

(eletriptan)*

Tablet

Acute treatment of migraine with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

*generic available

9

Tosymra®

(sumatriptan)

Nasal spray

Acute treatment of migraine with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

11

Treximet®

(sumatriptan/naproxen sodium)*

Tablet

Acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

*generic available

12

Zembrace® SYMTOUCH®

(sumatriptan)

Subcutaneous injection

Acute treatment of migraine with or without aura in adults

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks

13

Zomig®

(zolmitriptan)*

Nasal spray

Acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache
• Not recommended in patients with moderate to severe hepatic impairment

*generic available

15

Zomig®/Zomig-ZMT®

(zolmitriptan)*

Tablet

Orally disintegrating tablet

Acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older

Limitations of Use:

• Use only if a clear diagnosis of migraine has been established
• Not indicated for the prophylactic therapy of migraine attacks
• Not indicated for the treatment of cluster headache

*generic available

14

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.(30) 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.(25)

The International Classification of Headache Disorders 3rd Edition (ICHD-3) Diagnostic Criteria:(25)

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.(17) 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.(30)

AHS Guidelines:(17)The European Headache Federation and WHO consensus article (2019) states the following for episodic migraine prophylaxis:(23)

The European Headache Federation and WHO consensus article (2019) states the following for episodic migraine prophylaxis:(23)

• 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:(30)

• 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:(23)

• 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.(19)

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).(30)

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.(21) The International Headache Society (IHS) notes that cluster periods usually last between 2 weeks and 3 months.(25)

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.(21) 

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.(18)

The European Headache Federation and WHO consensus article (2019) states the following for CH management:(23)

• 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:(24)
    • 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.(27,28,29) 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.(25,30)
• 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.(10)
    • Concomitant administration of oral rimegepant and subcutaneous sumatriptan in healthy adults showed no hemodynamic or pharmacokinetic interactions suggesting it is safe and well tolerated.(20)
    • The pharmacokinetic and pharmacodynamic interactions between zavegepant and triptans in healthy adults showed no statistically significant difference when co-administered compared to sumatriptan alone.(30)
  • Lasmiditan with a triptan or gepant used in combination is not recommended(19,30)
  • Triptans and ergots used in combination is contraindicated(19)
  • 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:(23)

• In adults and children, regular high frequency use (greater than 2 day/week)
• 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

Almotriptan has the following contraindications:(2)

• Ischemic heart disease, coronary artery vasospasm, or other significant underlying cardiovascular disease
• Cerebrovascular syndromes (e.g., history of stroke or TIA)
• Peripheral vascular disease (including ischemic bowel disease)
• Uncontrolled hypertension
• Do not use almotriptan tablets within 24 hours of an ergotamine-containing, or ergot-type medication, or of another 5-HT1 agonist, e.g., another triptan
• Hemiplegic or basilar migraine
• Known hypersensitivity to almotriptan tablets 

Eletriptan has the following contraindications:(9)

• History of coronary artery disease (CAD) or coronary artery vasospasm
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
• History of stroke, transient ischemic attack, or history or current evidence of hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Within 24 hours of treatment with another 5-HT1 agonist, or an ergotamine-containing medication
• Hypersensitivity to RELPAX (angioedema and anaphylaxis seen)
• Within at least 72 hours of treatment with the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, or nelfinavir

Frovatriptan has the following contraindications:(3)

• History of coronary artery disease or coronary artery vasospasm
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
• History of stroke, transient ischemic attack, or hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Recent (within 24 hours) use of treatment with another 5-HT1 agonist, or an ergotamine-containing medication
• Hypersensitivity to Frova (angioedema and anaphylaxis seen)

Naratriptan has the following contraindications:(1)

• History of coronary artery disease or coronary artery vasospasm
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
• History of stroke, transient ischemic attack, or hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another triptan) or an ergotamine-containing medication
• Hypersensitivity to naratriptan (angioedema and anaphylaxis seen)
• Severe renal or hepatic impairment

Rizatriptan has the following contraindications:(7)

• History of ischemic heart disease or coronary artery vasospasm
• History of stroke or transient ischemic attack
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another triptan), or of an ergotamine-containing medication
• Hemiplegic or basilar migraine
• MAO-A inhibitor used in the past 2 weeks
• Hypersensitivity to rizatriptan or any of the excipients

Sumatriptan subcutaneous injection, tablet, nasal spray, and nasal powder have the following contraindications:(4-6,8,11)

• History of coronary artery disease or coronary artery vasospasm
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
• History of stroke, transient ischemic attack, or hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Recent (within 24 hours) use of treatment with another 5-HT1 agonist (e.g., another triptan), or of an ergotamine-containing medication
• Concurrent or recent (past 2 weeks) use of monoamine oxidase-A inhibitor
• Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen)
• Severe hepatic impairment

Sumatriptan/naproxen sodium tablet has the following contraindications:(12)

• History of coronary artery disease or coronary vasospasm
• In the setting of CABG surgery
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
• History of stroke, transient ischemic attack, or hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another triptan) or of ergotamine-containing medication
• Concurrent or recent (past 2 weeks) use of monoamine oxidase-A inhibitor
• History of asthma, urticaria, other allergic type reactions, rhinitis, or nasal polyps syndrome after taking aspirin or other NSAID/analgesic drugs
• Known hypersensitivity to sumatriptan, naproxen, or any components of Treximet (angioedema and anaphylaxis seen)
• Severe hepatic impairment

Sumatriptan/naproxen sodium tablet has the following boxed warning:(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 treatment and may increase with duration of use.
• Treximet 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.

Zolmitriptan has the following contraindications:(14-15)

• History of coronary artery disease or coronary artery vasospasm
• Symptomatic Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
• History of stroke, transient ischemic attack, or hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Recent (within 24 hours) use of treatment with another 5-HT1 agonist, or an ergotamine-containing medication
• MAO-A inhibitor used in the past 2 weeks 
• Hypersensitivity to zolmitriptan

1

Naratriptan prescribing information. Bionpharma Inc. December 2023.

2

Almotriptan malate prescribing information. Ajanta Pharma USA Inc. March 2023.

3

Frova prescribing information. Endo USA, Inc. August 2018.

4

IMITREX Injection prescribing information. GlaxoSmithKline LLC. February 2023.

5

IMITREX Nasal Spray prescribing information. GlaxoSmithKline LLC. March 2024.

6

IMITREX Tablets prescribing information. GlaxoSmithKline LLC. February 2024.

7

Maxalt Tablets/Maxalt-MLT Tablets prescribing information. Organon LLC. June 2021.

8

ONZETRA Xsail prescribing information. Currax Pharmaceuticals LLC. January 2024.

9

RELPAX Tablets prescribing information. Roerig. March 2020.

10

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

11

Tosymra prescribing information. Promius Pharma, LLC. January 2019.

12

Treximet prescribing information. Currax Pharmaceuticals LLC. February 2024.

13

Zembrace SYMTOUCH prescribing information. Promius Pharma, LLC. June 2019.

14

Zomig Tablets/Zomig ZMT Tablets prescribing information. Amneal Pharmaceuticals. March 2022.

15

Zomig Nasal Spray prescribing information. Amneal Pharmaceuticals. May 2019.

16

Reference no longer used.

17

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

18

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

19

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

20

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

21

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

22

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

23

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

24

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.

25

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

26

Reference no longer used.

27

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

28

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

29

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. 

30

Ailani J, Burch RC, Robbins MS. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache the Journal of Head and Face Pain. 2021;61(7): 1021-1039. doi:10.1111/head.14153

1 MG ; 2.5 MG

M ; N ; O

Y

6 MG/0.5ML

M ; N ; O

Y

2.5 MG ; 5 MG

M ; N ; O

Y

almotriptan malate tab

12.5 MG ; 6.25 MG

M ; N ; O ; Y

Y

Frova

frovatriptan succinate tab

2.5 MG

M ; N ; O ; Y

O ; Y

Imitrex

100 MG ; 25 MG ; 50 MG

M ; N ; O

O ; Y

Imitrex ; Tosymra

10 MG/ACT ; 20 MG/ACT ; 5 MG/ACT

M ; N ; O

N ; O ; Y

Imitrex statdose refill ; Sumatriptan succinate ref

4 MG/0.5ML

M ; N ; O

M

Imitrex statdose refill ; Sumatriptan succinate ref

6 MG/0.5ML

M ; N ; O

M

Imitrex statdose system

4 MG/0.5ML

M ; N ; O

O ; Y

Imitrex statdose system

6 MG/0.5ML

M ; N ; O

O ; Y

Maxalt

10 MG ; 5 MG

M ; N ; O

O ; Y

Maxalt-mlt

10 MG ; 5 MG

M ; N ; O

O ; Y

Onzetra xsail

11 MG/NOSEPC

M ; N ; O

N

Relpax

20 MG ; 40 MG

M ; N ; O

O ; Y

Treximet

sumatriptan-naproxen sodium tab

85-500 MG

M ; N ; O ; Y

O ; Y

Zembrace symtouch

3 MG/0.5ML

M ; N ; O

N

Zolmitriptan ; Zomig

zolmitriptan nasal spray

2.5 MG ; 5 MG

M ; N ; O ; Y

M ; N ; O ; Y

Zomig

2.5 MG ; 5 MG

M ; N ; O

O ; Y

almotriptan malate tab

12.5 MG ; 6.25 MG

12

Tablets

30

DAYS

naratriptan hcl tab

1 MG ; 2.5 MG

18

Tablets

30

DAYS

Sumatriptan Succinate Inj 6 MG/0.5ML

6 MG/0.5ML

10

Vials

30

DAYS

zolmitriptan orally disintegrating tab

2.5 MG ; 5 MG

12

Tablets

30

DAYS

Frova

frovatriptan succinate tab

2.5 MG

18

Tablets

30

DAYS

Imitrex

sumatriptan succinate tab

100 MG ; 25 MG ; 50 MG

18

Tablets

30

DAYS

Imitrex ; Tosymra

sumatriptan nasal spray

10 MG/ACT ; 20 MG/ACT ; 5 MG/ACT

12

Inhalers

30

DAYS

Imitrex statdose refill ; Sumatriptan succinate ref

Sumatriptan Succinate Solution Cartridge 4 MG/0.5ML

4 MG/0.5ML

12

Doses

30

DAYS

Imitrex statdose refill ; Sumatriptan succinate ref

Sumatriptan Succinate Solution Cartridge 6 MG/0.5ML

6 MG/0.5ML

12

Doses

30

DAYS

Imitrex statdose system

Sumatriptan Succinate Solution Auto-injector 4 MG/0.5ML

4 MG/0.5ML

12

Doses

30

DAYS

Imitrex statdose system

Sumatriptan Succinate Solution Auto-injector 6 MG/0.5ML

6 MG/0.5ML

12

Doses

30

DAYS

Maxalt

rizatriptan benzoate tab

10 MG ; 5 MG

18

Tablets

30

DAYS

Maxalt-mlt

rizatriptan benzoate oral disintegrating tab

10 MG ; 5 MG

18

Tablets

30

DAYS

Onzetra xsail

Sumatriptan Succinate Exhaler Powder 11 MG/NOSEPIECE

11 MG/NOSEPC

2

Kits

30

DAYS

Relpax

eletriptan hydrobromide tab

20 MG ; 40 MG

12

Tablets

30

DAYS

Tosymra

Sumatriptan Nasal Spray 10 MG/ACT

10 MG/ACT

18

Doses

30

DAYS

Treximet

sumatriptan-naproxen sodium tab

85-500 MG

18

Tablets

30

DAYS

Zembrace symtouch

Sumatriptan Succinate Solution Auto-injector 3 MG/0.5ML

3 MG/0.5ML

24

Pens

30

DAYS

Zolmitriptan ; Zomig

zolmitriptan nasal spray

2.5 MG ; 5 MG

2

Boxes

30

DAYS

Zomig

zolmitriptan tab

2.5 MG ; 5 MG

12

Tablets

30

DAYS

6 MG/0.5ML

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

2.5 MG ; 5 MG

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

1 MG ; 2.5 MG

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

almotriptan malate tab

12.5 MG ; 6.25 MG

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

Frova

frovatriptan succinate tab

2.5 MG

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

Imitrex

100 MG ; 25 MG ; 50 MG

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

Imitrex ; Tosymra

10 MG/ACT ; 20 MG/ACT ; 5 MG/ACT

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

Imitrex statdose refill ; Sumatriptan succinate ref

6 MG/0.5ML

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

Imitrex statdose refill ; Sumatriptan succinate ref

4 MG/0.5ML

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

Imitrex statdose system

6 MG/0.5ML

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

Imitrex statdose system

4 MG/0.5ML

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

Maxalt

10 MG ; 5 MG

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

Maxalt-mlt

10 MG ; 5 MG

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

Onzetra xsail

11 MG/NOSEPC

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

Relpax

20 MG ; 40 MG

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

Treximet

sumatriptan-naproxen sodium tab

85-500 MG

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

Zembrace symtouch

3 MG/0.5ML

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

Zolmitriptan ; Zomig

zolmitriptan nasal spray

2.5 MG ; 5 MG

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

Zomig

2.5 MG ; 5 MG

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

almotriptan malate tab

12.5 MG ; 6.25 MG

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

naratriptan hcl tab

1 MG ; 2.5 MG

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

Sumatriptan Succinate Inj 6 MG/0.5ML

6 MG/0.5ML

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

zolmitriptan orally disintegrating tab

2.5 MG ; 5 MG

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

Frova

frovatriptan succinate tab

2.5 MG

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

Imitrex

sumatriptan succinate tab

100 MG ; 25 MG ; 50 MG

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

Imitrex ; Tosymra

sumatriptan nasal spray

10 MG/ACT ; 20 MG/ACT ; 5 MG/ACT

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

Imitrex statdose refill ; Sumatriptan succinate ref

Sumatriptan Succinate Solution Cartridge 4 MG/0.5ML

4 MG/0.5ML

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

Imitrex statdose refill ; Sumatriptan succinate ref

Sumatriptan Succinate Solution Cartridge 6 MG/0.5ML

6 MG/0.5ML

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

Imitrex statdose system

Sumatriptan Succinate Solution Auto-injector 4 MG/0.5ML

4 MG/0.5ML

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

Imitrex statdose system

Sumatriptan Succinate Solution Auto-injector 6 MG/0.5ML

6 MG/0.5ML

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

Maxalt

rizatriptan benzoate tab

10 MG ; 5 MG

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

Maxalt-mlt

rizatriptan benzoate oral disintegrating tab

10 MG ; 5 MG

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

Onzetra xsail

Sumatriptan Succinate Exhaler Powder 11 MG/NOSEPIECE

11 MG/NOSEPC

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

Relpax

eletriptan hydrobromide tab

20 MG ; 40 MG

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

Tosymra

Sumatriptan Nasal Spray 10 MG/ACT

10 MG/ACT

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

Treximet

sumatriptan-naproxen sodium tab

85-500 MG

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

Zembrace symtouch

Sumatriptan Succinate Solution Auto-injector 3 MG/0.5ML

3 MG/0.5ML

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

Zolmitriptan ; Zomig

zolmitriptan nasal spray

2.5 MG ; 5 MG

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

Zomig

zolmitriptan tab

2.5 MG ; 5 MG

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

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

1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
   2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
2. ONE of the following:
   1. The patient has ONE of the following:
      1. Has a medication history of use in the past 90 days to ONE prerequisite agent OR
      2. Has intolerance or hypersensitivity to ONE prerequisite agent OR
   2. The patient has an FDA labeled contraindication to ALL prerequisite agent(s)

Length of approval: 12 months

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

QL

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

1. ALL of the following:
   1. The patient has a diagnosis of migraine headache AND
   2. 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, 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, 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, QULIPTA, Vyepti], AND onabotulinumtoxin A [BOTOX]) AND
   3. Medication overuse headache has been ruled out AND
   4. The patient will NOT be using the requested agent in combination with another acute migraine therapy (i.e., triptan, 5HT-1F [REYVOW], ergotamine) AND
   5. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication OR
2. BOTH of the following:
   1. The patient has a diagnosis of cluster headache AND
   2. The requested agent is an injection or nasal spray 

Length of Approval: up to 12 months. NOTE: For a diagnosis of migraine, the quantity requested up to the FDA labeled maximum dose allowed per 24 hours will be approved.