Please be sure to list all therapies that have been previously tried on the request form so that your request can be processed in a timely manner.

Transcription

1 Drug Therapy Guidelines: Migraine Agents Axert (almotriptan), Relpax (eletriptan), Frova (frovatriptan), Amerge (naratriptan), Maxalt/MLT (rizatriptan), Imitrex (sumatriptan), Zomig/ZMT (zolmitriptan), Migranal (dihydroergotamine) Effective Date: 11/20/07 Committee Review Date: 8/29/06, 11/5/07 Policy Statements: Non-Formulary or Prior Authorization drugs will require an appropriate trial of a Formulary agent(s) based on clinical criteria. Members with a closed Formulary (2 Tier) prescription benefit are limited to use of Formulary agents only. A therapeutic trial of samples of a Non-Formulary or Prior Authorization agent will not be accepted as appropriate. Please be sure to list all therapies that have been previously tried on the request form so that your request can be processed in a timely manner. What it Does and How it is Used: Migraine agents are used to treat (not prevent) acute attacks of migraine headaches. Sumatriptan nasal and injection are faster acting agents that may be used to treat cluster headaches. These agents work by binding to specific serotonin receptors in the brain to constrict cerebral arteries. These serotonin agonists decrease the release of chemicals responsible for the vasodilation of cerebral blood vessels, decrease the activity of painsignaling neurons, and reduce inflammation. Patients who suffer migraines may experience 2 to 5 attacks per month. Each migraine may last from 3 to 72 hours. A dose of a triptan agent is taken at the onset of migraine and can be repeated within 2-4 hours (time may vary according to agent used). In some cases, patients use two to three tablets of a lower strength triptan to abort a migraine attack. The maximum daily dose should not be exceeded. A full dose (2mg/24hr) of dihydroergotamine nasal is taken at the onset of migraine. All of these agents have vasoconstrictive actions. Their vasoconstrictive actions make these agents contraindicated in conditions such as ischemic heart disease, uncontrolled hypertension, hemiplegic migraine (migraine associated with temporary paralysis) or basilar migraine (migraine associated with neurologic symptoms such as nausea, vomiting and vertigo). These agents are also contraindicated in the presence of specific antidepressant drugs known as MAO inhibitors (this does not pertain to Amerge, Frova, or Relpax ). Sumatriptan is available as an oral tablet, subcutaneous injection, and nasal. Zolmitriptan is available as an oral tablet, orally disintegrating tablet which can be administered without water, and as a nasal.

2 Naratriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan are available as oral tablets. Rizatriptan is also available as orally disintegrating tablets, which can be administered without water. Dihydroergotamine is available as a nasal. Migranal NS is available in a kit containing 4 ampules. Each ampule delivers 2 mg administered as one (0.5 mg) in each nostril followed by an additional 0.5 mg into each nostril 15 minutes later. Two ampules may be needed in any 24-hour period. Ampules are stable for up to 8 hours once opened. What it Costs: Table 1: Drug Cost Medication AWP/ unit Sumatriptan (Imitrex ) 25mg tab $ & 100mg tab $ ml S.D.V.(6mg/0.5ml) $74.39 Imitrex STATdose 6mg Pen $ (2 cartridges 6mg/0.5ml ea. & 1 pen) Imitrex STATdose 6mg Refill $ (2 cartridges 6mg/0.5ml ea.) Imitrex STATdose 4mg Cartridge $ (2 cartridges 4mg ea.) Imitrex STATdose 4mg Refill $ (2 cartridges 4mg ea.) 5 & 20mg Nasal Spray $31.84 Zolmitriptan (Zomig, Zomig-ZMT ) 2.5mg tab & ODT $ mg tab & ODT $ mg Nasal Spray $27.96 Rizatriptan (Maxalt ; Maxalt-MLT ) 5mg & 10mg tab & ODT $15.48 Naratriptan (Amerge ) 1 & 2.5 mg tab $23.03 Almotriptan (Axert ) 6 & 12.5mg tab $20.69 Frovatriptan (Frova ) 2.5mg tab $33.73 Eletriptan (Relpax ) 20 & 40 mg tab $19.08 Dihydroergotamine Nasal Spray (Migranal NS) 0.5mg/inh, 4ml $42.35/ ml Rationale for Prior Authorization: To reduce exposure to cost associated with uncovered uses such as use in the treatment of hemiplegic or basilar migraine and/or To limit coverage to an amount sufficient for up 4 treatment days per month and provide coverage for additional drug quantities through a coverage authorization process.

3 Form/ Strength Benefit Design: Coverage is provided immediately (without generating a prior authorization process), for a drug quantity sufficient for 4 treatment days per month. Requests for coverage of a greater drug quantity (e.g., that necessary to treat more frequent headaches) are determined through a prior authorization process. Prior Authorization Criteria: Coverage for migraine agents is provided in accord with the following: Coverage is provided for the treatment of acute migraine or for treatment of cluster headache (with Imitrex nasal and injection only). Benefit is not covered in the presence of any of the following: documented or suspected ischemic heart disease, uncontrolled hypertension, or hemiplegic or basilar migraine. Benefit is not covered in situations where there is use of more than one abortive agent simultaneously (e.g., use of a 5HT1 agonist with an ergotamine derivative or use of two different 5HT1 agonists within the same 24 hour period). Benefit is not covered in the presence of current or recent treatment (within the last 14 days) of monoamine oxidase inhibitor (MAOI) antidepressant therapy (excluding Amerge,Frova, and Relpax ). Coverage Duration: Coverage is provided immediately (without generating a coverage review process), for a drug quantity sufficient for 4 treatment days per month (based either on a total mg quantity of drug OR a total tablet quantity of drug) accommodating up to the maximum daily dose of the prescribed drug. per Table 2: Drug Quantity Limits Almotriptan (Axert ) MDD 25 mg orally per 12.5 mg tablet 100 mg or 8 tablets 300 mg or 24 tablets 8 tablets 24 tablets 6.25 mg tablet 100 mg or 12 tablets 300 mg or 36 tablets 12 tablets 36 tablets Tablets available as 6.25 or 12.5 mg in blister packs of 6 tablets each. Blisters may be split. Eletripan (Relpax ) MDD 80 mg orally per per 40 mg tablet 320 mg or 8 tablets 960 mg or 24 tablets 8 tablets 24 tablets 20 mg tablet 240 mg or 12 tablets 720 mg or 36 tablets 12 tablets 36 tablets Tablets available as 20 or 40 mg in blister packs of 6 tablets each. Frovatriptan (Frova ) MDD 7.5 mg orally per per 2.5 mg tablet 30 mg or 12 tablets 90 mg or 36 tablets 12 tablets 36 tablets Tablets available as 2.5 mg in blister packs of 9 tablets each Naratriptan (Amerge ) MDD 5 mg orally

4 per per 2.5 mg tablet 20 mg or 8 tablets 60 mg or 24 tablets 8 tablets 24 tablets 1 mg tablet 20 mg or 12 tablets 60 mg or 36 tablets 12 tablets 36 tablets Tablets available as 1 or 2.5 mg in blister packs of 9 tablets each Sumatriptan (Imitrex ) MDD 200 mg orally, 12 mg subcutaneously, or 40 mg intranasally per per per 100 mg tablet 800 mg or 9 tablets 2400 mg or 27 tablets 9 tablets 27 tablets 50 mg tablet 800 mg or 18 tablets 2400 mg or 54 tablets 18 tablets 36 tablets 25 mg tablet 800 mg or 36 tablets 2400 mg or tablets 36 tablets tablets 6 mg syringe or vial 8 syringes or vials/ 4 kits 24 syringes or vials/ 12 kits 8 syringes or vials/ 4 kits 24 syringes or vials/ 12 kits 4 mg cartridge 12 cartridges/6 stat 36 cartidges/18 stat 12 cartridges/6 stat 36 cartidges/18 stat 5 mg or 20 mg nasal 160 mg or 2 cartons 480 mg or 4 cartons 2 cartons nasal 4 cartons nasal Tablets available as 25, 50 or 100 mg in blister packs of 9 tablets each Injection available as 6 mg per syringe- 2 injections per kit Nasal supplied as 5 or 20 mg unit of use devices packaged as 6 devices per carton As per the manufacturer blister packs must be dispensed in multiples of 9 to ensure drug stability. Rizatriptan (Maxalt ; Maxalt-MLT ) MDD 30 mg per per per 10 mg tablet 120 mg or 12 tablets 360 mg or 36 tablets 12 tablets 36 tablets 5 mg tablet 120 mg or 24 tablets 360 mg or 72 tablets 12 tablets 36 tablets Tablets available as 5 or 10 mg in blister packs of 9 tablets each MLT-tablets available as 5 or 10 mg in three unit of use cases containing 3 tablets each (9 tablets per case) Zolmatriptan (Zomig, Zomig ZMT, Zomig Nasal Spray ) MDD 10 mg orally or intranasally per per per 5 mg tablet 40 mg or 8 tablets 120 mg or 24 tablets 8 tablets 24 tablets 2.5 mg tablet 40 mg or 16 tablets 120 mg or 48 tablets 12 tablets 36 tablets 5 mg nasal 40 mg or 2 cartons 120 mg or 4 cartons 2 cartons nasal 4 cartons nasal Tablets available as 2.5 mg (regular and ZMT tablets) in blister packs of 6 tablets each and as 5 mg (regular and ZMT tablets) in blister packs of 3 tablets each Nasal supplied as 5mg single dose unit packaged as 6 unit s per carton Blister packs have each tablet labeled with lot and expiration and may be split. Dihydroergotamine Nasal Spray (Migranal NS)

5 Existing quantity covered per 30-day period Existing Alternative quantity covered per 30 -day period Alternative quantity covered per 90 -day period 12 ampules 24 ampules 12 ampules 24 ampules Migranal NS is available in a kit containing 4 ampules. Each ampule delivers 2 mg administered as one (0.5 mg) in each nostril followed by an additional 0.5 mg in to each nostril 15 minutes later. Two ampules may be needed in any 24 hour period. Ampules are stable for up to 8 hours once opened. Requests for coverage of a greater drug quantity (e.g., that necessary to treat more frequent headaches) are determined through a coverage authorization process. Coverage is provided for a greater drug quantity in the following situations: a) Patient must be experiencing > 4 headaches per month. Requests for drug quantities beyond that needed to treat 12 headaches per month will be reviewed on a case by case basis AND b) Patient must be evaluated by a neurologist AND/OR c) Patient must be receiving preventative therapy, if eligible. Benefit approval duration: Coverage is provided for 12 months and may be renewed. Coverage MAY be provided for 6 months or 3 months for situations in which patients are eligible for preventative therapy but not receiving preventative therapy. References: 1. Dowson A. Eur Neurol 1996;36(suppl 2):28-31 (n=40) ~ 2 per month 2. Eur Neurol 1996;32(suppl 2):24-7 (n=606) ~ per month 3. Fletcher PE, et al. Headache Treatment: Trial Methodology and New Drugs. Lippincott- Raven Publishers, 1997 (n = 701) ~ 2.9 to 3.2 per month 4. Lipton RB et al. Prevalence and Burden of Migraine in the united States: Data from the American Migraine Study II. Headache 2001;41: Solomon GD, et al. Neurology 1997;49: (n=327) study ~3 +/ per month. 6. Visser WH, et al. Neurology 1996;46:522-6 (n = 84) ~ 3-4 per month 7. Product Information: Dihydroergotamine nasal (Migranal - Xcel Pharmaceuticals) Product Information: Naratriptan (Amerge - GlaxoSmithKline) Product Information: Rizatriptan (Maxalt, Maxalt-MLT - Merck) Product Information: Sumatriptan nasal (Imitrex NS -GlaxoSmithKline) Product Information: Sumatriptan tablets (Imitrex - GlaxoWellcome) Product Information: Sumatriptan injection (Imitrex Injection -GlaxoWellcome) Product Information: Zolmitriptan tablets (Zomig, Zomig-ZMT - AstraZeneca) Product Information: Zolmitriptan nasal (Zomig Nasal Spray AstraZeneca) Product Information: Almotriptan (Axert OrthoMcNeil) Product Information: Frovatriptan (Frova Elan) Product Information: Eletriptan (Relpax - Pfizer) Beckett B. Headache disorder, in Dipiro J (ed): Pharmacotherapy: a pathophysiologic approach. Stamford, Simon & Schuster, 1997; pp Consultation with Dr. Richard Lipton, Migraine Specialist, Department of Neurology, Montefiore Medical Center, Bronx, New York, Nov Diener HC, Limmroth V. A practical guide to the management and prevention of migraine. Drugs 1998;56:

6 21. Ferrari MD. Zomig:increasing the options for therapy with effective acute antimigraine 5HT1B/1D receptor agonists. Neurology 1997;48:s21-s Gaist D et al. Misuse of sumatriptan. Lancet 1994;344: Gaist D, Tsiropoulos I, Sindrup SH. Inappropriate use of sumatriptan:population based register and interview study. BMJ 1998;316: Gallagher RM. Acute treatment of migraine with dihydroergotamine nasal. Arch Neurol 1996;53: Gijsman H, Kramer MS, Sargent J, et al. Double-blind placebo-controlled, dose-finding study of rizatriptan (MK-462) in the acute treatment of migraine. Cephalalgia 1997:17: Goadsby PJ, Olesen J. Increasing the options for effective migraine management. Neurology 1997;48:s1-s Greiner DL et al. Sumatriptan use in a large group-model health maintenance organization. Am J Health Syst Pharm 1996;53: Honkasalo ML et al. A population-based survey of headache and migraine in 22,809 adults. Headache. 1993;33: Klassen A, Elkind A, Asgharnedjad M, et al. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind placebo-controlled, parallelgroup study. Headache 1997;37: Lipton RB, Stewart WF. Clinical applications of zolmitriptan. Cephalalgia 1997;18: Mathew N. Dosing and administration of ergotamine and dihydroergotamine. Headache 1997;37:s Mathew N, Asgharnejad M, Peykamian M, et al. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebocontrolled crossover study. Neurology 1997;49: Peroutka S. Drugs effective in the therapy of migraine, Hardman J, Goodman A, Gilman, Limbird L (eds): Goodman & Gilman s The pharmacological basis of therapeutics, New York, 1996, pp Rapport AM, Ramadan NM. Adelman JU. Optimizing the dose of zolmitriptan for the acute treatment of migraine. Neurology 1997;49: Salonen R, Ashford E, Dathlof C, et al. Intranasal sumatriptan for the acute treatment of migraine. Neurology 1994;241: Silberstein SD. Practice parameter: evidenced based guidelines for migraine headache (an evidenced- based review): Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2000;55(6): Solomon GD, Cady RK, Klapper JA. Clinical efficacy and tolerability of 2.5mg zolmitriptan for the acute treatment of migraine. Neurology 1997;49: Teall J, Tuchman M,. Cutler N, et al. Rizatriptan (Maxalt) for the acute treatment of migraine and migraine recurrence- a placebo controlled, outpatient study. Headache 1998;38: The Dihydroergotamine Nasal Spray Multicenter Investigators. Efficacy, safety, and tolerability of dihydroergotamine nasal as monotherapy in the treatment of acute migraine. Headache 1995;35: The Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group. A placebo-controlled study of intranasal sumtriptan for the acute treatment of migraine. Eur Neurol 1991;31: Touchon J, Bertin L, Pilgrim AJ et al. A comparison of subcutaneous sumatriptan and dihydrogergotamine nasal in the acute treatment of migraine. Neurology 1996;47: Visser WH, et al. Sumatriptan in clinical practice: a 2-year review of 453 migraine patients. Neurology 1996;47: Visser WH, Terwindt GM, Reines SA, et al. Rizatriptan vs sumatriptan in the acute treatment of migraine. Arch Neurol 1996;53:

7 44. Young WB. Appropriate use of ergotamine tartrate and dihydroergotamine in the treatment of migraine: current perspectives. Headache 1997;37:s42-s Zagami AS. Zomig:long-term efficacy and tolerability profile for the acute treatment of migraine. Neurology 1997;48:s25-s Ziegler D, Ford R, Kriegler J et al. Dihydroergotamine nasal for the acute treatment of migraine. Neurology 1994;44: