Subject: Anti-Migraine Agents, "Triptans"

Status	Drug	PR-B/D	PR	PR-QL	PR-AL	ST	M EX‡	TOC§
Ergotamines/dihydroergotamines:
C	ergotamine/caffeine
C	dihydroergotamine injection
NC	Cafergot®  (ergotamine/caffeine)						X
NC	DHE-45®  (dihydro-ergotamine injection)						X
NC	Ergomar®  (ergotamine)						X
NC	Migranal®  (dihydro-ergotamine nasal spray)			X			X
Triptans:
C	Amerge®  (naratriptan)			X
C	Imitrex®  (sumatriptan inj, nasal spray and tablets)			X
C	Maxalt®, Maxalt MLT®  (rizatriptan)			X
C	Relpax®  (eletriptan)			X
NC	Axert®  (almotriptan)			X			X
NC	Frova®  (frovatriptan)			X			X
NC	Zomig®, Zomig ZMT®  (zolmitriptan)			X			X

Policy:

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary, Amerge, Axert, Frova, Imitrex, Maxalt/Maxalt MLT, Migranal, Relpax and Zomig/Zomig ZMT are subject to precertification.  If precertification requirements apply Aetna considers Amerge, Axert, Frova, Imitrex, Maxalt/Maxalt MLT, Migranal, Relpax and Zomig/Zomig ZMT to be medically necessary for those members who meet the following precertification criteria:


According to the manufacturer, the safety of treating an average of more than the number of headaches listed below in a 30-day period has not been established. Clinical guidelines recommend two treatment days per week for abortive therapy. A quantity of each drug will be considered medically necessary as indicated in the table below

Drug	Maximum Daily Dose/ Dosing Interval	Dosage Strength	Quantity Limits
Amerge	Up to 4 headaches	1 mg, 2.5 mg	Up to 9 tablets in 30 days
Axert	Up to 4 headaches	6.25mg, 12.5mg	Up to 6 tablets 30 days
Frova	Up to 4 headaches	2.5 mg	Up to 9 tablets in 30 days
Imitrex	Up to 4 headaches	25mg, 50mg, 100mg	Up to 18 tablets in 30 days
Imitrex	Up to 4 headaches	Nasal spray	Up to 6 sprays in 30 days
Imitrex	Up to 4 headaches	Injection kits; refill syringes, 4mg/0.5ml; 6mg/0.5ml	Up to 4 kits (8 syringes) in 30 days
Imitrex	Up to 4 headaches	Injection, 6mg/0.5ml vials	Up to 10 vials (5ml) in 30 days
Maxalt, Maxalt MLT	Up to 4 headaches	5 mg, 10 mg	Up to 12 tablets in 30 days
Migranal	Up to 4 headaches	4 mg/ml nasal spray	Up to 2 boxes per 30 days
Relpax	Up to 3 headaches	20 mg	Up to 12 tablets in 30 days
Relpax	Up to 3 headaches	40 mg	Up to 6 tablets in 30 days
Zomig, Zomig ZMT	Up to 3 headaches	2.5 mg	Up to 12 tablets in 30 days
Zomig, Zomig ZMT	Up to 3 headaches	5 mg	Up to 6 tablets in 30 days
Zomig	Up to 3 headaches	Nasal spray	Up to 6 sprays in 30 days





For coverage of additional quantities, a member's treating physician must request prior authorization through the Aetna Pharmacy Management Precertification Unit. Additional quantities of these anti-migraine agents will be considered medically necessary for those members who meet ANY of the following criteria:

• Documented diagnosis of migraine AND member is receiving prophylactic* migraine therapy (may approve up to 2 times the set qty limit) OR
• Documented diagnosis of migraine AND member is being treated by a headache clinic or specialist(may approve up to 2 times the set qty limit) OR
• Documented diagnosis of  cluster headaches AND member is being treated by a headache clinic or specialist (may approve up to 3 times the set qty limit for indefinite period of time) OR
• Documented diagnosis of migraine AND member is being treated by a headache clinic or specialist AND member has been titrated up to 2 boxes/ 30 days and requires additional/higher dosing (one additional box is approvable)-Migranal-only OR
• Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose.
  
  



2. Medical Exception Criteria

Axert, Cafergot, DHE-45, Ergomar, Frova, Migranal, Zomig and Zomig-ZMT are currently Not Covered Part D drugs under the Aetna Medicare Prescription Drug Plan.*  Therefore, they are excluded from coverage for members enrolled in prescription drug benefit plans that use a closed formulary, unless a medical exception is granted.  Aetna considers Axert, Cafergot, DHE-45, Ergomar, Frova, Migranal, Zomig and Zomig-ZMT to be medically necessary for those members who meet the following criteria:

Cafergot, DHE-45, Ergomar and Migranal

A documented:

• Contraindication to one covered anti-migraine "triptan" alternative OR
• Intolerance to one covered anti-migraine "triptan" alternative OR
• Allergy to one covered anti-migraine "triptan" alternative OR
• Failure of an adequate trial of one day of one covered anti-migraine "triptan" alternative.

OR

B. Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for non-migraine medical use.

Axert, Frova, Zomig and Zomig-ZMT

A.   A documented:

• Contraindication to one covered anti-migraine "triptan" alternative OR
• Intolerance to one covered anti-migraine "triptan" alternative OR
• Allergy to one covered anti-migraine "triptan" alternative OR
• Failure of an adequate trial of one day of one covered anti-migraine "triptan" alternative
  

Special Notes:

According to the manufactures, Triptans are not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness of these agents have not been established for cluster headache, which is present in an older, predominantly male population.

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and any of these anti-migraine agents within 24 hours is contraindicated. Because their vasospastic effects may be additive, coadministration of more than one of these anti-migraine agents (5-HT₁ agonists) within 24 hours of each other is not recommended

Place of Service:

Outpatient

The above policy is based on the following references:

1. Anon. Drugs for migraine. Med Lett 1995; 37: 17-20.
2. Ferrari MD. Migraine. Lancet 1998; 351: 1043-1051.
3. Dahlof C, Winter P, Whitehouse H, and Hassani H. Randomized, double-blind placebo-controlled comparison of oral naratriptan and oral sumatriptan in the acute treatment of migraine [abstract]. Neurology 199748:A85.
4. Klassen A, Elkind A, Asghamejad M, et al Naratriptan is effective and well tolerated in the acute treatment of migraine: Results of a double-blind, placebo-controlled, crossover study. Headache 1997;37(10):640-5.
5. Mathew NT, Asgharnejad M, Peykamian M, et al. Naratriptan is effective and well tolerated in the acute treatment of migraine: Results of a double-blind, placebo-controlled, crossover study. Neurology 1997;49: 1485-90.
6. Bomhof M, Paz J, Legg N, et al. Comparison of rizatriptan 10 mg vs. naratriptan 2.5 mg in migraine. Neurology 1999;423:173-9.
7. Lipton RB. Methodologic issues in acute migraine clinical trials. Neurology 2000;55(Suppl 2):S1-7.
8. Goadsby PJ and Hargreaves RJ. Mechanisms of action of serotonin 5HT _1B/1D agonists: Insights into migraine pathophysiology using rizatriptan. Neurology 2000;55(Suppl 2):S8-14.
9. Silberstein SD, Goadsby PJ, and Lipton RB. Management of migraine: An algorithmic approach. Neurology 2000;55(Suppl 2):S46-52.
10. 5-HT Agonist Comparisons: Clinical. BMMA. 1999;3(2):89.
11. Jamieson DG. The safety of triptans in the treatment of patients with migraine. Am J Med. 2002;112:135-40.
12. Jhee SS, Shiovitz T, Crawford AW, Cutler NR. Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents. Clin Pharmacokinet 2001;40:189-205.
13. Tepper SJ. Safety and rational use of the triptans. Med Clin North Am. 2001;85:959-70.
14. Salonen R. Drug comparisons: why are they so difficult? Cephalalgia. 2000;29(Suppl 2):25-32.
15. Rapoport AM, Tepper SJ. All triptans are not the same. J Headache Pain. 2001;2:S87-S92.
16. Marcus DA. Establishing a standard of speed for assessing the efficacy of the serotonin _1B/1D agonists (triptans). Arch Neurol. 2001;58:1056-8.
17. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT _1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001;358:1668-75.
18. Ryan Jr RE. Patient treatment preferences and the 5-HT _1B/1D agonists. Arch Intern Med. 2001;161:2545-53.
19. Pascual J. Clinical benefits of early triptan therapy for migraine. Headache 2002;42(Suppl 1):S10-7.
20. Goadsby PJ, Lipton RB, Ferrari MD. Migraine - Current understanding and treatment. N Engl J Med. 2002;346:257-70.
21. Pascual J, Falk RM, Piessens F, et al. Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study. Cephalalgia 2000;20:588-96.
22. Gras J, Cardelus I, Llenas J, Palacios JM. Cardiovascular safety profile of almotriptan, a new indolic derivative for the treatment of migraine. Eur J Pharmacol. 2000;410:53-9.
23. Goldstein J, Keywood, and Hutchison J. Low 24-hour migraine recurrence during treatment with frovatriptan. Presented at Ninth Congress of the International Headache Society, Barcelona, Spain. June 22-26, 1999.
24. Spierings ELH, Keywood C on behalf of the VML 251/96/08 investigators. Consistent migraine relief with frovatriptan, a novel 5-HT _1B/1D agonists. Present at the Ninth Congress of the International Headache Society, Barcelona, Spain. June 22-26, 1999.
25. Elkind A, McDaris HL, Satin L, Keywood C. The cardiovascular safety of frovatriptan in patients at high risk of or with known coronary artery disease during a migraine attack. Presented at the Ninth Congress of the International Headache Society, Barcelona, Spain. June 22-26, 1999.
26. Easthope SE and Goa KL. Frovatriptan. CNS Drugs 2001:15(12);969-76.

Property of 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.

September 18, 2007