Subject: 5-HT1 Agonist Limit 2-H P06-2024 v2

Drug

5-HT1 Agonists, Combinations (All Dosage Forms)

almotriptan (all brands)  (almotriptan )

FROVA  (frovatriptan)

IMITREX  (sumatriptan)

MAXALT/MAXALT-MLT  (rizatriptan)

naratriptan (all brands)  (naratriptan)

ONEZTRA XSAIL  (sumatriptan)

RELPAX  (eletriptan)

RIZAFILM  (rizatriptan)

SYMBRAVO  (meloxicam/rizatriptan)

TOSYMRA  (sumatriptan)

TREXIMET  (sumatriptan/naproxen)

ZEMBRACE SYMTOUCH  (sumatriptan)

ZOMIG  (zolmitriptan)

zolmitriptan (all other brands)  (zolmitriptan)

Policy:

Indications

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.

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.

Naratriptan

Naratriptan 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 has been established. If a patient has no response to the first migraine attack treated with naratriptan tablets reconsider the diagnosis of migraine before naratriptan tablets are administered to treat any subsequent attacks. Naratriptan tablets are not indicated for the prevention of migraine attacks. Safety and effectiveness of naratriptan tablets have not been established for cluster headaches.

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.

Symbravo

Symbravo is indicated for the acute treatment of migraine with or without aura in adults.

Limitations of Use

Symbravo 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 Symbravo, the diagnosis of migraine should be reconsidered before Symbravo is administered to treat any subsequent attacks. Symbravo is not indicated for the preventive treatment of migraine attacks. Symbravo is not indicated for the treatment of 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.

Zolmitriptan ODT

Zolmitriptan orally disintegrating tablets are indicated for the acute treatment of migraine with or without aura in adults.

Limitations of Use

Only use zolmitriptan if a clear diagnosis of migraine has been established. If a patient has no response to zolmitriptan treatment for the first migraine attack, reconsider the diagnosis of migraine before zolmitriptan is administered to treat any subsequent attacks. Zolmitriptan orally disintegrating tablets are not indicated for the prevention of migraine attacks. Safety and effectiveness of zolmitriptan have not been established for cluster headache.

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

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.

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.

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
almotriptan	12.5 mg	1-2 tablets	2 tablets 25 mg	6 tablets 12 tablets	12 tablets / 25 days   36 tablets / 75 days
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   0.5 mL each	12 vials (6 mL) / 25 days   40 vials (20 mL) / 75 days
Imitrex Injection  (sumatriptan) syringes   STATdose / Refill	4 mg	1-2 injections	3 injections   12 mg	2 prefilled syringes   0.5 mL each	18 syringes (9 mL) / 25 days   54 syringes (27 mL) / 75 days
Imitrex Injection (sumatriptan) syringes   STATdose / Refill	6 mg	1-2 injections	2 injections   12 mg	2 prefilled syringes   0.5 mL each	12 syringes (6 mL) / 25 days   36 syringes (18 mL) / 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
Imitrex Nasal Spray (sumatriptan)	20 mg	1-2 sprays	2 sprays 40 mg	6 nasal spray units	12 units / 25 days   36 units / 75 days
Imitrex Tablets (sumatriptan)	25 mg, 50 mg	1-2 tablets	2 tablets	9 tablets (brand and   generic) 27, 36, 90, 100   tablets (generic)	12 tablets / 25 days   36 tablets / 75 days
Imitrex Tablets (sumatriptan)	100 mg	1-2 tablets	2 tablets 200 mg	9 tablets (brand and   generic) 27, 36, 90, 100   tablets (generic)	12 tablets / 25 days   36 tablets / 75 days
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
Maxalt Maxalt-MLT (rizatriptan)	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)	18 tablets / 25 days   54 tablets / 75 days
naratriptan	1 mg	1-2 tablets	2 tablets	9 tablets	12 tablets / 25 days   36 tablets / 75 days
naratriptan	2.5 mg	1-2 tablets	2 tablets 5 mg	9 tablets	12 tablets / 25 days   36 tablets / 75 days
Onzetra Xsail (sumatriptan)	11 mg	2 nosepieces	4 nosepieces   44 mg	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
Relpax (eletriptan)	40 mg	1-2 tablets	2 tablets   80 mg	6 tablets   12 tablets	12 tablets / 25 days   36 tablets / 75 days
RizaFilm (rizatriptan)	10 mg	1-3 oral films	3 oral films   30 mg	6, 12, or 18 individually   packaged films	18 films / 25 days   54 films / 75 days
Symbravo (meloxicam/rizatriptan)	20 mg/10 mg	1 tablet	1 tablet   20 mg/10 mg	9 tablets dispense in   original container	9 tablets / 25 days   27 tablets / 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)	85 mg/500 mg	1-2 tablets	1-2 tablets 170   mg/1000 mg	9 tablets   dispense in   original container	9 tablets / 25 days   36 tablets / 75 days
Zembrace SymTouch (sumatriptan)	3 mg	1-4 injections	4 injections 12 mg	4 autoinjectors   0.5 mL each	24 injectors (12 mL) / 25 days   72 injectors (36 mL) / 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
Zomig Nasal Spray (zolmitriptan)	5 mg	1-2 sprays	2 sprays 10 mg	6 nasal spray units	12 units / 25 days   36 units / 75 days
Zomig Tablets (zolmitriptan)   zolmitriptan ODT	2.5 mg	1/2-2 tablets	2 tablets	6 tablets	12 tablets / 25 days   36 tablets / 75 days
Zomig Tablets (zolmitriptan)   zolmitriptan ODT	5 mg	1-2 tablets	2 tablets 10 mg	3 tablets	12 tablets / 25 days   36 tablets / 75 days

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. Frova [package insert]. Malvern, PA: Endo Pharmaceuticals Inc.; August 2018.
3. Imitrex Injection [package insert]. Research Triangle Park, NC: GlaxoSmithKline; February 2023.
4. Imitrex Nasal Spray [package insert]. Research Triangle Park, NC: GlaxoSmithKline; March 2024.
5. Imitrex Tablets [package insert]. Research Triangle Park, NC: GlaxoSmithKline; February 2024.
6. Maxalt and Maxalt-MLT [package insert]. Jersey City, NJ: Organon LLC; June 2021.
7. Naratriptan [package insert]. East Brunswick, NJ: Avet Pharmaceuticals Inc.; August 2023.
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.; December 2023.
11. Symbravo [package insert]. New York, NY: Axsome Therapeutics, Inc.; January 2025.
12. Tosymra [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC; February 2021.
13. Treximet [package insert]. Morristown, NJ: Currax Therapeutics, LLC; February 2024.
14. Zembrace SymTouch [package insert]. Maple Grove, MN: Upsher-Smith Laboratories LLC; February 2021.
15. Zolmitriptan ODT [package insert]. Pennington, NJ: Zydus Pharmaceuticals (USA) Inc.; November 2023.
16. Zomig Nasal Spray [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; May 2019.
17. Zomig [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; March 2023.
18. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Waltham, MA: UpToDate, Inc.; 2024. https://online.lexi.com. Accessed April 15, 2024.
19. Micromedex® (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com/ (cited: 04/15/2024).

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.

March 23, 2025