Subject: 5-HT1 Agonist Limit Policy 2-H 06-2023

Drug

5-HT1 AGONISTS, COMBINATIONS (ALL DOSAGE FORMS)

almotriptan

AMERGE  (naratriptan)

FROVA  (frovatriptan)

IMITREX  (sumatriptan)

MAXALT/MAXALT-MLT  (rizatriptan)

ONZETRA XSAIL  (sumatriptan)

RELPAX  (eletriptan)

RIZAFILM  (rizatriptan)

TOSYMRA  (sumatriptan)

TREXIMET  (sumatriptan/naproxen)

ZEMBRACE SYMTOUCH  (sumatriptan)

ZOMIG / ZOMIG-ZMT  (zolmitriptan)

Policy:

FDA-APPROVED INDICATIONS
Almotriptan
Adults: Almotriptan tablets are indicated for the acute treatment of migraine attacks in patients with a history of migraine with or without aura.
Adolescents Age 12 to 17 Years: Almotriptan tablets are indicated for the acute treatment of migraine headache pain in patients with a history of migraine attacks with or without aura usually lasting 4 hours or more (when untreated).
Limitations of Use:
Almotriptan tablets should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with almotriptan tablets, the diagnosis of migraine should be reconsidered before almotriptan tablets are administered to treat any subsequent attacks. In adolescents age 12 to 17 years, efficacy of almotriptan tablets on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. Almotriptan tablets are not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness of almotriptan tablets have not been established for cluster headache which is present in an older, predominantly male population.

Amerge
Amerge is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use:
Use only if a clear diagnosis of migraine has been established. If a patient has no response to the first migraine attack treated with Amerge, reconsider the diagnosis of migraine before Amerge is administered to treat any subsequent attacks. Amerge is not indicated for the prevention of migraine attacks. Safety and effectiveness of Amerge have not been established for cluster headache.

Frova
Frova is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use:
Use only if a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with Frova, reconsider the diagnosis of migraine before Frova is administered to treat any subsequent attacks. Frova is not indicated for the prevention of migraine attacks. Safety and effectiveness of Frova have not been established for cluster headache.

Imitrex Injection
Imitrex injection is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache.
Limitations of Use:
Use only if a clear diagnosis of migraine or cluster headache has been established. If a patient has no response to the first migraine or cluster headache attack treated with Imitrex injection, reconsider the diagnosis before Imitrex injection is administered to treat any subsequent attacks. Imitrex injection is not indicated for the prevention of migraine or cluster headache attacks.

Imitrex Nasal Spray and Imitrex Tablets
Imitrex nasal spray and Imitrex tablets are indicated for the 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. If a patient has no response to the first migraine attack treated with Imitrex, reconsider the diagnosis of migraine before Imitrex is administered to treat any subsequent attacks. Imitrex is not indicated for the prevention of migraine attacks. Safety and effectiveness of Imitrex nasal spray and Imitrex tablets have not been established for cluster headache.

Maxalt and Maxalt-MLT
Maxalt and Maxalt-MLT are indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old.
Limitations of Use:
Maxalt should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with Maxalt, the diagnosis of migraine should be reconsidered before Maxalt is administered to treat any subsequent attacks. Maxalt is not indicated for use in the management of hemiplegic or basilar migraine. Maxalt is not indicated for the prevention of migraine attacks. Safety and effectiveness of Maxalt have not been established for cluster headache.

Onzetra Xsail
Onzetra Xsail is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use:
Use only if a clear diagnosis of migraine has been established. If a patient has no response to the first migraine attack treated with Onzetra Xsail, reconsider the diagnosis of migraine before treatment of subsequent attacks with Onzetra Xsail. Onzetra Xsail is not indicated for the prevention of migraine attacks. Safety and effectiveness of Onzetra Xsail have not been established for the treatment of cluster headache.

Relpax
Relpax is indicated for the 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. If a patient has no response to the first migraine attack treated with Relpax, reconsider the diagnosis of migraine before Relpax is administered to treat any subsequent attacks. Relpax is not indicated for the prevention of migraine attacks. Safety and effectiveness of Relpax have not been established for the treatment of cluster headache.

RizaFilm
RizaFilm is indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 12 to 17 years of age weighing 40 kg or more.
Limitations of Use:
RizaFilm should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with RizaFilm, the diagnosis of migraine should be reconsidered before RizaFilm is administered to treat any subsequent attacks. RizaFilm is not indicated for the preventive treatment of migraine. Safety and effectiveness of RizaFilm have not been established for cluster headache.

Tosymra
Tosymra is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use:
Use only if a clear diagnosis of migraine has been established. If a patient has no response to the first migraine attack treated with Tosymra, reconsider the diagnosis before Tosymra is administered to treat any subsequent attacks. Tosymra is not indicated for the preventive treatment of migraine. Tosymra is not indicated for the treatment of cluster headache.

Treximet
Treximet is indicated for the 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 headache has been established. If a patient has no response to the first migraine attack treated with Treximet, reconsider the diagnosis of migraine before Treximet is administered to treat any subsequent attacks. Treximet is not indicated for the prevention of migraine attacks. Safety and effectiveness of Treximet have not been established for cluster headache.

Zembrace SymTouch
Zembrace SymTouch is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use:
Use only if a clear diagnosis of migraine has been established. If a patient has no response to the first migraine attack treated with Zembrace SymTouch, reconsider the diagnosis before Zembrace SymTouch is administered to treat any subsequent attacks. Zembrace SymTouch injection is not indicated for the prevention of migraine attacks.

Zomig Nasal Spray
Zomig nasal spray is indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older.
Limitations of Use:
Only use Zomig if a clear diagnosis of migraine has been established. If a patient has no response to Zomig treatment for the first migraine attack, reconsider the diagnosis of migraine before Zomig is administered to treat any subsequent attacks. Zomig is not indicated for the prevention of migraine attacks. Safety and effectiveness of Zomig have not been established for cluster headache. Not recommended in patients with moderate or severe hepatic impairment.

Zomig Tablets and Zomig-ZMT
Zomig is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use:
Only use Zomig if a clear diagnosis of migraine has been established. If a patient has no response to Zomig treatment for the first migraine attack, reconsider the diagnosis of migraine before Zomig is administered to treat any subsequent attacks. Zomig is not indicated for the prevention of migraine attacks. Safety and effectiveness of Zomig have not been established for cluster headache.

INITIAL LIMIT QUANTITY         The intent is for the patient to receive only one drug from this drug class at a time.      PLEASE NOTE: Since manufacturer package sizes may vary, it is the discretion of the dispensing pharmacy to fill      quantities per package size up to these quantity limits. In such cases the filling limit and day supply may be less than      what is indicated.
Medication	Strength	Dose per headache	Maximum dose per 24 hours	Package Size	1 Month Limit * 3 Months Limit *
almotriptan	6.25 mg	1-2 tablets	2 tablets**	6 tablets	12 tablets / 25 days 36 tablets / 75 days
	12.5 mg	1-2 tablets	2 tablets   25 mg	6 tablets   12 tablets
Amerge   (naratriptan)	1 mg	1-2 tablets	2 tablets**	9 tablets	12 tablets / 25 days                  36 tablets / 75 days
	2.5 mg	1-2 tablets	2 tablets   5 mg
Frova   (frovatriptan)	2.5 mg	1-2 tablets	3 tablets   7.5 mg	9 tablets	18 tablets / 25 days                  54 tablets / 75 days
Imitrex Injection   (sumatriptan) vials	6 mg	1-2   injections	2 injections   12 mg	5 single dose vials 0.5mL each	12 vials (6mL) / 25 days 40 vials (20mL) / 75 days
Imitrex Injection   (sumatriptan) syringes   STATdose / Refill	4 mg	1-2  injections	3 injections   12 mg	2 prefilled syringes 0.5mL each	18 syringes (9mL) / 25 days 54 syringes (27mL) / 75 days
	6 mg	1-2  injections	2 injections   12 mg		12 syringes (6mL) / 25 days 36 syringes (18mL) / 75 days
Imitrex Nasal Spray   (sumatriptan)	5 mg	1-4 sprays	4 sprays**	6 nasal spray units	24 units / 25 days 72 units / 75 days
	20 mg	1-2 sprays	2 sprays   40 mg		12 units / 25 days 36 units / 75 days
Imitrex Tablets   (sumatriptan)	25mg, 50mg	1-2 tablets	2 tablets**	9 tablets (brand and generic) 27, 36, 90, 100 tablets (generic)	12 tablets / 25 days 36 tablets / 75 days
	100 mg	1-2 tablets	2 tablets   200 mg
Maxalt   Maxalt-MLT   (rizatriptan)	5 mg	1-2 tablets	3 tablets**	12, 18 tablets (generic), 3, 9, 12, 18 orally disintegrating tablets (generic)	18 tablets / 25 days 54 tablets / 75 days
	10 mg	1-2 tablets	3 tablets   30 mg	18 tablets (brand and generic) 12 tablets (generic), 3 orally disintegrating tablets (brand and generic), 9, 12, 18 orally disintegrating tablets (generic)
Onzetra Xsail   (sumatriptan)	11mg	2 nosepieces	4 nosepieces   44mg	16 nosepieces – 2 nosepieces per pouch 8 pouches per kit	16 nosepieces / 25 days (1 kit, 8 pouches) 64 nosepieces / 75 days (4 kits, 32 pouches)
Relpax   (eletriptan)	20 mg	1-2 tablets	2 tablets**	6 tablets	12 tablets / 25 days 36 tablets / 75 days
	40 mg	1-2 tablets	2 tablets   80 mg	6 tablets   12 tablets
RizaFilm   (rizatriptan)	10mg	1-3 oral   films	3 oral films   30mg	6, 12, or 18 individually packaged films	18 films / 25 days 54 films / 75 days
Tosymra   (sumatriptan nasal)	10 mg	1-3 sprays	3 sprays   30 mg	6 nasal spray units	18 units / 25 days 54 units / 75 days
Treximet  (sumatriptan/naproxen)	85mg/500mg	1-2 tablets	1-2 tablets 170mg/1000mg	9 tablets dispense in original container	9 tablets / 25 days 36 tablets / 75 days
Zembrace SymTouch   (sumatriptan)	3 mg	1-4 injections	4 injections   12mg	4 autoinjectors   0.5mL each	24 injectors (12mL) / 25 days 72 injectors (36mL) / 75 days
Zomig Nasal Spray   (zolmitriptan)	2.5 mg	1-2 sprays	2 sprays**	6 nasal spray units	12 units / 25 days 36 units / 75 days
	5 mg	1-2 sprays	2 sprays   10 mg
Zomig Tablets   Zomig-ZMT   (zolmitriptan)	2.5 mg	1/2-2   tablets	2 tablets**	6 tablets	12 tablets / 25 days 36 tablets / 75 days
	5 mg	1-2 tablets	2 tablets   10 mg	3 tablets
* The duration of 25 days is used for a 30-day fill period and 75 days is used for a 90-day fill period to allow time for refill processing. **Utilize higher strength available.

 

Place of Service:

Outpatient

The above policy is based on the following references:

1. Almotriptan [package insert]. Bridgewater, NJ: Ajanta Pharma USA Inc. March 2023.
2. Amerge [package insert]. Research Triangle Park, NC: GlaxoSmithKline; October 2020.
3. Frova [package insert]. Malvern, PA: Endo Pharmaceuticals Inc.; August 2018.
4. Imitrex Injection [package insert]. Research Triangle Park, NC: GlaxoSmithKline; February 2023.
5. Imitrex Nasal Spray [package insert]. Research Triangle Park, NC: GlaxoSmithKline; December 2017.
6. Imitrex Tablets [package insert]. Research Triangle Park, NC: GlaxoSmithKline; December 2020.
7. Maxalt and Maxalt-MLT [package insert]. Jersey City, NJ: Organon LLC; June 2021.
8. Onzetra Xsail [package insert]. Morristown, NJ: Currax Pharmaceuticals LLC; December 2019.
9. Relpax [package insert]. New York, NY: Pfizer, Inc.; March 2020.
10. RizaFilm [package insert]. Saint-Laurent, Quebec: IntelGenx Corp.; April 2023.
11. Tosymra [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC; February 2021.
12. Treximet [package insert]. Morristown, NJ: Currax Therapeutics, LLC; October 2021.
13. Zembrace SymTouch [package insert]. Maple Grove, MN: Upsher-Smith Laboratories LLC; February 2021.
14. Zomig Nasal Spray [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; May 2019.
15. Zomig and Zomig-ZMT [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; May 2019.
16. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Waltham, MA: UpToDate, Inc.; 2023. https://online.lexi.com. Accessed April 27, 2023.
17. Micromedex (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com/ (cited: 04/27/2023).
18. American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache 2021;61:1021-1039.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

December 17, 2023