Acute Migraine Treatment in Adults

PL Detail-Document #301104 This PL Detail-Document gives subscribers additional insight related the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER November 2014 Acute Migraine Treatment in Adults Treatment of patients with migraine is challenging because it is a complex condition. 1,2 Experts suggest several goals for the successful treatment of acute migraine. These goals include prompt treatment at the onset of sympms, resration of the patient s ability function, and minimization of the need for backup and rescue medications. Since patient response is unpredictable, treatment must be individualized. 1 The choice of treatment should be based on the frequency and severity of attacks, the presence and degree of temporary disability, and whether sympms such as nausea and vomiting are present. 1,2 Finally, patients must be counseled regarding appropriate use of medications avoid medication overuse headaches. 1 The table below compares the role in therapy of drugs used for acute migraine treatment in adults. For information about prevention of migraines, see our PL Charts, Drugs Prevent Migraine in Adults and Pediatric Migraine Prevention. DRUG/ DRUG CLASS Acetaminophen ROLE IN THERAPY be useful first choice drug for acute migraine in those with mild moderate attacks or in those with contraindications, or who cannot lerate, NSAIDs or aspirin. 3 CONSIDERATIONS FOR USE Acetaminophen, with or without caffeine, in doses of 1000 mg, is effective in the treatment of acute migraine. 1,3 (Max dose 4000 mg in 24 hours.) 1 Pain-free response at two hours is inferior other commonly used analgesics such as NSAIDs and aspirin. 3 Addition of 10 mg meclopramide may improve efficacy. 1,3 Safe. Adverse events similar placebo. 3 Barbiturate-containing products (e.g. butalbitalcontaining products such as Fiorinal, others) Corticosteroids Avoid. 1 Limited evidence of efficacy. 1 be beneficial in refracry migraine attack that has failed respond the patient s usual acute medication. 1 Potential for abuse or dependence. 1 Withdrawal syndrome may occur with discontinuation. 1 High risk of medication overuse headaches with butalbital. 9 Lack of randomized controlled trials support use. 1 Examples of regimens include prednisone 50 mg 60 mg on the first day and tapering over two or three additional days, or dexamethasone 8 mg on the first day, and tapering over two or three days. 1 When added standard therapy in the emergency room, a single parenteral dose of dexamethasone is associated with a reduction in headache. 1 Monotherapy with intravenous dexamethasone may be effective. 1 Copyright 2014 by Therapeutic Research Center

(PL Detail-Document #301104: Page 2 of 4) DRUG/ DRUG CLASS Ergotamine ROLE IN THERAPY First-line option for patients who don t respond, or can t use a triptan. 1 CONSIDERATIONS FOR USE Intranasal dihydroamine (e.g., Migranal) effective for migraines, but less effective than intranasal or subcutaneous sumatriptan. 1 Subcutaneous dihydroamine (DHE) similarly effective subcutaneous sumatriptan, but onset is slower. 1 Evidence does not support efficacy of intravenous DHE. 2 Evidence inconsistent support efficacy of oral amine or amine caffeine, and frequently associated with adverse events. 2 use 24 hours of triptan agent. 4 Ergotamine preparations associated with CYP3A4 drug interactions Meclopramide (and domperidone in Canada) Adjunct, treat or prevent nausea and vomiting. 1,2 Improves gastroparesis associated with migraines, which helps improve absorption of oral migraine medications. Also treats the nausea/vomiting associated with migraines. improve efficacy of NSAIDs or oral triptans. 1 Most commonly studied doses are meclopramide 10 mg orally and domperidone 10 mg orally (Canada only). 1 NSAIDs, including aspirin First-line treatment for mild moderate migraine attacks due efficacy and lerability, especially in migraines that have responded NSAIDs in the past. 2 Most consistent evidence with aspirin, ibuprofen, naproxen sodium. 2 Aspirin 1000 mg, with or without caffeine, similarly effective sumatriptan 50 mg or 100 mg. 5 Addition of meclopramide 10 mg aspirin improves nausea/vomiting and gastroparesis. 1,5 Ibuprofen effective in about half of patients. Doses of 400 mg provide better pain relief than 200 mg. 1,6 Soluble formulations of NSAIDs may provide more rapid relief. 1 Naproxen sodium (500 mg or 550 mg; up 82, as needed and lerated) immediate-release formulations have been shown be effective. 1 However, a recent meta-analysis suggests naproxen may be less effective than other NSAIDs. 7 Copyright 2014 by Therapeutic Research Center

(PL Detail-Document #301104: Page 3 of 4) DRUG/ DRUG CLASS Opioids ROLE IN THERAPY Avoid, if possible. Use only when other medications cannot be used, when sedation effects are not a concern, and when the risk for abuse has been addressed. 2 CONSIDERATIONS FOR USE Most evidence with burphanol nasal spray (formerly brand Stadol) but concerns exist about abuse and dependence. 1,2 High risk of causing medication overuse headaches. 9 Phenothiazines Adjunct, treat or prevent nausea and vomiting. 1 Monotherapy more effective than placebo in treatment of migraines. 8 Prochlorperazine has been used, orally (10 mg) and rectally (10 mg 2) for nausea and vomiting, but less evidence support use vs meclopramide. 1 cause extrapyramidal side effects. 1 Tramadol Avoid. 1 There is insufficient evidence support the use of tramadol alone or with acetaminophen. 1 Potential for abuse or dependence. 1 Withdrawal syndrome may occur with discontinuation. 1 Triptans First-line therapy in moderate severe migraine attacks. 1 Injectable or intranasal triptans may provide faster onset and be useful in patients with vomiting Triptans eletriptan (Relpax) and frovatriptan (Frova) may be beneficial for patients who suffer from recurrent headaches. 1 Patients who do not respond one triptan may respond a different triptan. 1 Addition of an NSAID may improve triptan efficacy and reduce headache recurrence. 1 For help choosing between the triptans see our PL Chart, Comparison of Triptans (U.S. subscribers; Canadian subscribers). Copyright 2014 by Therapeutic Research Center

(PL Detail-Document #301104: Page 4 of 4) Users of this PL Detail-Document are cautioned use their own professional judgment and consult any other necessary or appropriate sources prior making clinical judgments based on the content of this document. Our edirs have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Project Leader in preparation of this PL Detail- Document: Neeta Bahal O Mara, Pharm.D., BCPS, Drug Information Consultant References 1. Worthingn I, Pringsheim T, Gawel MJ, et al. Canadian Headache Society Guideline: acute drug therapy for migraine headache. Can J Neurol Sci 2013;40 (suppl 3):S1-S80. 2. Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med 2002;137:840-9. 3. Derry S, Moore RA. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(4):CD008040. 4. Pringsheim T, Becker WJ. Triptans for sympmatic migraine headache. BMJ 2014;348:g2285. Doi: 10.1136/bmj.g2285. 5. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(4):CD008041. 6. Rabbie R, Derry S, Moore RA. Ibuprofen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(4):CD008039. 7. Law S, Derry S, Moore RA. Naproxen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(10):CD009455. 8. Kelly AM, Walcynski T, Gunn B. The relative efficacy of phenothiazines for the treatment of acute migraine: a meta-analysis. Headache 2009;49:1324-32. 9. PL Detail-Document, Medication Overuse Headache. Pharmacist s Letter/Prescriber s Letter. April 2013. Cite this document as follows: PL Detail-Document, Acute Migraine Treatment in Adults. Pharmacist s Letter/Prescriber s Letter. November 2014. Evidence and Recommendations You Can Trust 3120 West March Lane, Sckn, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2014 by Therapeutic Research Center Subscribers the Letter can get PL Detail-Documents, like this one, on any pic covered in any issue by going www.pharmacistsletter.com, www.prescribersletter.com, or www.pharmacytechniciansletter.com

PL Detail-Document #291126 This PL Detail-Document gives subscribers additional insight related the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER November 2013 Comparison of Triptans Triptans are appropriate for moderate severe migraines. Many patients prefer oral options (Imitrex DF, Maxalt, etc), but injectable (Imitrex, etc) and intranasal (Imitrex Nasal, Zomig) options are more effective and have a faster onset. Suggest an injectable for migraines that build rapidly, occur upon awakening, or are accompanied by early vomiting. Lean ward a nasal formulation for those who usually vomit later in the attack; intranasal triptans are partially absorbed through the nasal mucosa. An oral triptan can be used for patients with mild nausea. ly disintegrating tablets (Maxalt RPD, Zomig Rapimelt, etc) don t have a faster onset, but are more convenient take and may be a good choice if oral liquids worsen nausea. The chart below provides dosing, pharmacokinetics, adverse effects, contraindications, and cost information for the triptans available in Canada. --Information from Canadian product monographs a unless otherwise noted-- Drug Route Dose Supplied Max Dose Amerge (naratriptan) Glaxo SmithKline Generic available 1 mg or after 4 hr 1 mg of 8) of 2, 6, or 8) Onset Tmax Half- Life (24 hr) 1 hr 2 hr 5 hr 74% 3 hr 1 3 hr 1 8 hr 1 (females) 63% (males) 1 Adverse Effects b,e : nausea 6.3%, 2.2%, 2.4%, 2.1%, 1.7%, paresthesia 1.5% Bioavailability Contraindicated Drugs c 24 hr of other triptans or Comments c Not contraindicated with MAOIs. Potential for reaction in sulfonamide -allergic patients. Cost d 1 mg $11.24 $6.64

(PL Detail-Document #291126: Page 2 of 8) Drug Route Dose Supplied Max Dose Axert (almotriptan) McNeil Consumer Healthcare Generic available 6.2 or 1 after 2 hr 6.2 of 6) 1 of 6) (24 hr) 2 0.5 hr 2 hr 1 Onset Tmax Half- Life 1 hr 3 hr 70% 1 3 hr 1 4 hr 1 Adverse Effects b,e 1: 5%, 3%, nausea 3%, paresthesia 1%, dry mouth 1%, <1% Bioavailability Contraindicated Drugs c 24 hrs of other Comments c Not contraindicated with MAOIs. Contains a sulfonyl group. Allergy risk in sulfonamide -allergic patients has not been evaluated. Cost d 6.2 $7.61 1 $7.61 Frova (frovatriptan) Teva Canada after 4 hr of 7) 2 hr 2 hr 3 hr 2 4 hr 1 Food delays peak by 1 hr. About 30% 26 hr 1 (females) 20% (males) 1 : 8%, 5%, paresthesia 4%, dry mouth 3%, 2% Not contraindicated with MAOIs. No sulfa allergy precaution. $14.87

(PL Detail-Document #291126: Page 3 of 8) Drug Route Dose Supplied Max Dose Imitrex DF (sumatriptan) Glaxo SmithKline Generic available Imitrex (sumatriptan) Glaxo SmithKline Nasal spray 50 mg or 100 mg after 2 hr 50 mg & 100 mg have similar efficacy. Some patients may respond 2. 3 or 20 mg after 2 hr 2 of 6) 50 mg of 6) 100 mg of 6) (two singledose spray devices per box) 20 mg (two singledose spray devices per box) Onset Tmax Half- Life Adverse Effects b,e (24 hr) 200 mg 0.5 hr 1 2.5 hr 1 2 hr 1 14% 1 100 mg: nausea 11%, 9.5%, 6.2%,, 5.2%, vomiting 4.4%, 2.1% 40 mg 0.25 hr 1 1 hr 2 hr 1 1.5 hr 1 16% 1 20 mg: odor/taste disturbance 20%, nausea 8.3%, vomiting 6.8%, 2.3%, nasal sympms 1.8%, 1.5% Bioavailability Contraindicated Drugs c use with, or 2 weeks of spping, an MAOI. use with, or 2 weeks of spping, an MAOI. Comments c Swallow tablet whole; do not chew, crush, or split. Potential for crossreaction in sulfonamide -allergic patients. prime device prior use. Administer in one nostril only. Potential for reaction in sulfonamide -allergic patients. Cost d 2 $7.43 50 mg $7.71 100 mg $8.49 $15.77 20 mg $16.23

(PL Detail-Document #291126: Page 4 of 8) Drug Route Dose Supplied Max Dose Imitrex (sumatriptan) Glaxo SmithKline Generic available SQ inj 6 mg To outside of thigh or upper arm using auinjecr. after 1 hr 6 mg syringe of 2, with or without auinjecr) 6 mg vial (5 vials per carn) (24 hr) 12 mg 10 min 15 min 1 Onset Tmax Half- Life 15 2 hr 1 min 1 Adverse Effects b,e 96% 1 6 mg: injection site reactions 24.7%, 12%, nausea 9.4%, 7.9%, 4.7%, 2.9%, Bioavailability Contraindicated Drugs c use with, or 2 weeks of spping, an MAOI. Comments c Only injectable triptan available. load auinjecr until ready give an injection. Potential for reaction in sulfonamide -allergic patients. Cost d 6 mg $33.33 Maxalt, Maxalt RPD (rizatriptan) Merck Generic available Continued or 10 mg after 2 hr of 6 or 12) 10 mg of 6 or 12) 20 mg 0.5 hr 1 hr 1 1 hr 1.5 hr for tabs 1 1.6 hr 2.5 hr for wafer (RPD) 1 Food delays peak by 1 hr. 2 hr 45% 1 3 hr 1 10 mg tab: 8.9%, 8.4%, 6.9%, nausea 5.7%, 3.1%, dry mouth 3%, paresthesia 2.9%, vomiting use with, or 2 weeks of spping, an MAOI. Maxalt RPD may be taken without water. Maxalt RPD absorption slower than tablets. Keep wafer in foil until ready use. tab $5.29 10 mg tab $5.29 RPD $5.56 10 mg RPD $5.56

(PL Detail-Document #291126: Page 5 of 8) Drug Route Dose Supplied Max Dose Rizatriptan, continued (24 hr) Onset Tmax Half- Life Adverse Effects b,e 2.3%, bad taste 2.3% (wafer) Bioavailability Contraindicated Drugs c Comments c Maxalt RPD contains aspartame. Caution phenylkenurics. Cost d No sulfa allergy precaution. Relpax (eletriptan) Pfizer 20 mg or 40 mg 20 mg dose after 2 hr 20 mg of 6) 40 mg of 6) 40 mg 0.5 hr 1 hr 1 1 hr 3.8 hr 1 2 hr 1 50% 1 Increased with a high fat meal. 40 mg: nausea 6.9%, 5.1%, 4.9%, 4.5%, vomiting 3%, cardiaclike 2.2% 72 hr of a potent CYP3A4 inhibir. Not contraindicated with MAOIs. No sulfa allergy precaution. 20 mg $10.89 40 mg $10.89

(PL Detail-Document #291126: Page 6 of 8) Drug Route Dose Supplied Max Dose Zomig, Zomig- Rapimelt (zolmitriptan) AstraZeneca Zomig Nasal Spray (zolmitriptan) AstraZeneca Nasal spray after 2 hr or after 2 hr tab of 3 or 6) Rapimelt of 2 or 6) (two singledose spray devices per box) (six singledose spray devices per box) Onset Tmax Half- Life (24 hr) 10 mg 45 2 hr 1 min. 1 10 mg 10 min 15 min 1 2.5 hr 3 hr 1 2 hr 1 2.5 hr 3 hr 1 Adverse Effects b,e 40% 1 tab: 10.9%, 9.5%, 8.8%, 7.7%, nausea 6.2%, dry mouth 3.2%, vomiting 1.5% 41% 1 : unusual taste 16.9%, paresthesia 5.9%, 2.1%, 2.1%, 1.7%, nausea 1.7%, dry mouth 1.3%, nasal discomfort 1.3% Bioavailability Contraindicated Drugs c use with, or 2 weeks of spping, an MAOI. use with, or 2 weeks of spping, an MAOI. Comments c Zomig- Rapimelt may be taken without water. split Rapimelt tab. No sulfa allergy precaution. prime device prior use. Administer in one nostril only. No sulfa allergy precaution. Cost d tab $5.04 Rapimelt $5.04 $15.13 $15.13

(PL Detail-Document #291126: Page 7 of 8) a. Canadian product monographs used in the preparation of this document: Amerge (September 2013), Axert (November 2012), Frova (December 2012), Imitrex DF/Imitrex injection/imitrex nasal spray (January 2013), Maxalt/Maxalt RPD ( 2013), Relpax (March 2012), Zomig/Zomig Rapimelt/Zomig nasal spray (November 2012). b. Selected adverse effects that are common or that may be of most interest when choosing among products. Due differences in study design among clinical trials, and differences between study populations and populations seen in clinical practice, use caution when using this information choose among triptans. c. All the triptans described in this chart share the following features: Indication: Treatment of acute migraine with or without aura in adults (Axert [almotriptan] also approved for adolescents 12 17 years of age with migraine usually lasting at least four hours); Safety in pregnancy: should only be used if potential benefits justify potential risk; Contraindications: signs, sympms, or hisry of cardiovascular disease, uncontrolled HTN, or hemiplegic, ophthalmoplegic, or basilar migraines. Amerge (naratriptan), Frova (frovatriptan), Imitrex (sumatriptan), Maxalt (rizatriptan), and Relpax (eletriptan) contraindicated in severe hepatic impairment. Amerge contraindicated if CrCl <15 ml/min. d. Wholesale cost per dose of generic, if available. e. Cases of seronin syndrome associated with combined use of triptans and SSRIs or SNRIs. 4 Users of this PL Detail-Document are cautioned use their own professional judgment and consult any other necessary or appropriate sources prior making clinical judgments based on the content of this document. Our edirs have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication.

(PL Detail-Document #291126: Page 8 of 8) Project Leader in preparation of this PL Detail- Document: Melanie Cupp, Pharm.D., BCPS References 1. Worthingn I, Pringsheim T, Gawel MJ, et al. Canadian Headache Society guideline. Acute drug therapy for migraine headache. Can J Neurol Sci 2013;40(Suppl 3):S1-80. 2. Fidler BD. Review of almotriptan: a 5-HT 1B/1D agonist. P&T 2002;27:83-4, 88, 93-4. 3. Product monograph for Dom-sumatriptan. Montreal, QC H4P 2T4. April 2013. 4. PL Detail-Document, Facts About Seronin Syndrome. Pharmacist s Letter/Prescriber s Letter. Ocber 2009. Cite this document as follows: PL Detail-Document, Comparison of Triptans. Pharmacist s Letter/Prescriber s Letter. November 2013. Evidence and Recommendations You Can Trust 3120 West March Lane, Sckn, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Subscribers the Letter can get PL Detail-Documents, like this one, on any pic covered in any issue by going www.pharmacistsletter.com, www.prescribersletter.com, or www.pharmacytechniciansletter.com