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Home , Almotriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan

Steven Leber, M.D., Ph.D. TREATMENT OF

I. Avoidance of precipitants; regular sleep habits II. Sleep III. Abortive agents: home use. Most effective if used at onset of symptoms

Drug Usual dose (all p.r.n.) Adults: 650-1000 mg GI distress, bleeding Children: 10-15 mg/kg Risk of Reye’s syndrome Acetaminophen Adults: 650-1000 mg Overdose may cause hepatotoxicity Children: 10-15 mg/kg Ibuprofen Up to 400 mg TID-QID; also GI distress, ulceration, bleeding available as 50 mg rectal suppository Naproxen 5 mg/kg/dose up to BID Rash, prolonged bleeding time more common than in adults; GI symtoms and CNS symptoms (sedation, lightheadedness, dizziness, ) similar Fioricet (butalbital, caffeine, and 1-2 tablets q 4 hrs, up to 6/day Drowsiness acetaminophen); [Fiorinal - Dizziness same but w/ ASA] Dependency Midrin [isometheptene 2 tablets at onset of headache, then 1 Transient dizziness (sympathomimetic), q hr, up to 5 per 12 hr dichloralphenazone (mild (less in children) sedative), acetaminophen] If does not work in first 1-2 hrs, probably will not Migranal (Nasal Adolescents: 1 spray (0.5 mg) into Variable absorption dihyroergotamine) each nostril (total dose: 1 mg); , vomiting, diarrhea repeat if needed within 15 minutes Headache up to a total of 4 sprays (2 mg); maximum daily dose: 6 sprays (3 ? cerebral vasospasm mg)/24-hour period; Note: Do not Risk of ergotism (intense arterial vasospasm) exceed 8 sprays (4 mg)/week. Dependency and withdrawal Contraindicated in patients with peripheral vascular disease, severe , peptic ulcer disease, ischemic heart disease, and during and nursing 6 mg subcutaneously (adults) Rebound headache with SQ (Imitrex) Can repeat in 1 hr Chest tightness, warmth, flushing 25-100 mg p.o. (start with 25; may -site reaction give 25-100 mg 2 hours later; if HA Nausea recurs, can give additional doses q 2 Nasal stuffiness with oral Other (e.g.): hrs up to maximum 300 mg per day Nasal spray: throat irritation (Zomig) Nasal spray. Otherwise, rare and mild (Amerge) Contraindicated in hemiplegic and basilar (Maxalt, Maxalt Maxalt MLT 5 mg , ischemic heart disease, MLT—dissolving wafer) uncontrolled hypertension, or within 24 FDA: rizatriptan ≥6 years old; Effective even after headache is well hours of use of or 2 week of almotripan ≥12 years old established MAO inhibitors

10/13/17 IV. Abortive agents: status migrainosus.

Drug Usual dose Side effects (DHE) See Pediatric Neurology Clinical Nausea and vomiting Guidelines. Low risk of vasoconstriction Precede with (0.2 mg/kg/dose IV up to a maximum of 10 mg/dose) and (1 mg/kg/dose IV up to a maximum of 50 mg/dose). 30 min later, give DHE 0.015 mg/kg/dose IV up to a maximum of 1 mg/dose. May repeat q 8 hrs p.r.n. intractable up to 5 doses; see protocol. Sumatriptan 6 mg subcutaneously (adults) Rebound headache (Imitrex) Can repeat in 1 hr Chest tightness, warmth, flushing 25 mg p.o. Injection-site reaction Other triptans: Nasal spray Nausea Zolmitriptan (Zomig) Effective even after headache is well Nasal: throat irritation Naratriptan (Amerge) established Otherwise, rare and mild Rizatriptan (Maxalt) Not approved in kids Ketoralac IM 15-60 mg IM GI symptoms, headache, rash (Toradol) 0.1 mg/kg q 15 min x3; IV more Orthostatic hypotension (Thorazine) effective than IM or PR Dystonic reactions 7.5-15 gm/dose IV Orthostatic hypotension (Compazine) Dystonic reactions Steroids e.g., dexamethasone up to 20 Hypertension mg/day IV in divided doses, tapering Hyperglycemia over 2-3 days Mood changes Narcotics Sedation Respiratory suppression Abuse Dependence Constipation IV 10-20 mg/kg Behavioral changes, sedation GI side effects, weight gain Tremor Thrombocytopenia, leukopenia toxicity

Intranasal lidocaine??

2 V. Prophylactic agents Drug Usual dose Side effects Aspirin Adults: 650-1000 mg GI distress, bleeding Children: 10-15 mg/kg Risk of Reye’s syndrome Ibuprofen Adults: 400 mg q 4-6 hrs GI ulceration, bleeding Naproxen 5 mg/kg (275-375 mg)/dose given GI ulceration, bleeding, rash, sedation, BID dizziness Propanolol Adults: start at 80 mg/day ÷ BID, Bradycardia, fatigue advance slowly to effective dose Orthostatic hypotension (some other ß-blockers, (usually 160-240 mg/day ÷ TID) Bronchospasm generally those without partial Children: start at 1 mg/kg/day ÷ Mood changes, vivid dreams, insomnia activity, effective as TID, advance to 2-4 mg/kg/day ÷ Use with extreme caution in patients with well) TID cardiac failure, diabetes (masks hypoglycemia), asthma Metoprolol (selective ß1 2-6 mg/kg/day ÷ BID Similar to propanolol, but with less frequent antagonist) bronchospasm (selective ß1 1-2 mg/kg/day; single dose Similar to propanolol, but with less frequent antagonist) bronchospasm 2-4 mg/day ÷ BID Sedation Advance slowly as tolerated up to 8- Weight gain and increased appetite 16 mg/day if needed Dry mouth Start at 2 mg/day and gradually Retroperitoneal fibrosis with long-term use (USE WITH EXTREME increase to 6 mg/day ÷ TID Nausea and vomiting CAUTION) After 4-5 months, taper over 2-3 Insomnia wks and stop for 1 month Dizziness Vasospasm 25 mg qHS, increasing weekly by 25 Sedation mg/day; Dry mouth, urinary retension, constipation final dose generally 50-150 mg/day Postural hypotension Confusional episodes May take up to a month to work 15-40 mg/day ÷TID-QID Similar to amitriptyline, but less sedating 25 mg qHS, increasing weekly by 25 Similar to amitriptyline, but less sedating (Pamelor) mg/day to up to 75 mg qHS (but some suggestion that 10 mg advancing to 30 mg qHS may work as well); levels should be monitored for doses between 100 and 150 mg/day 80 mg/dose ÷ TID-QID Constipation May take up to 1-2 months to work Typically advance to 50 mg BID; Anorexia, anhydrosis, , renal alternatively, to 75 mg qHS stones, metabolic acidosis, confusion Valproate Gradually increase to 15-60 Behavioral changes, sedation mg/kd/day (??) GI side effects, weight gain Tremor Thrombocytopenia, leukopenia Liver toxicity Other (phenobarbital, phenytoin) have also been used.

VI. Behavioral treatment Biofeedback (temporal artery; thermal) Relaxation therapy Self-hypnosis

3 Triptans

Generic name Brand Sizes Adult Cost Comments name starting per dose; dose repeat (2005) time; max per 24 hours Axert 6.25, 12.5 12.5 mg/ $22-23 FDA approved for mg tabs 2 hr/ ≥12 years old. 25 mg Similar to oral sumatriptan in efficacy but may have fewer side effects. Relpax 20, 40 mg 40 mg $22-24 Higher dose (80 mg) tabs 2 hr/ may be as efficacious 80 mg as rizatriptan but high rate of side effects. Lowest NNT in one study Frova 2.5 mg tab 2.5 mg $24 Slow onset, long half- 2 hr time. Few side 7.5 mg effects. Naratriptan Amerge 1, 2.5 mg 2.5 mg/ $25-26 Slow onset, long half- tabs 4 hr/ time. Few side effects. 5 mg Lower recurrence risk. Useful prophylactically for menstrual migraine Rizatriptan Maxalt 5, 10 mg 10 mg/ $22-23 FDA approved for ≥6 tabs 2 hr/ years old. Greatest 30 mg early efficacy of oral triptans, but rebound more likely. Reduce dose if using propanolol. Rizatriptan Maxalt 5, 10 mg 10 mg/ $23 dissolvable MLT 2 hr/ tab 30 mg Sumatriptan Imitrex 25, 50, 50 mg/ $21-25 Gold standard 100 mg 2 hr/ tabs 200 mg Sumatriptan Imitrex 5, 20 mg 20 mg/ $32-33 Rapid onset but 2-hr nasal spray 2 hr/ efficacy similar to oral 40 mg zolmitriptan Sumatriptan Imitrex 6 mg 6 mg/ $79 Most rapid onset and 4 Injectable 1 hr/ greatest efficacy but 12 mg most side effects Zolmitriptan Zomig 2.5, 5 mg 2.5 mg/ $22-24 tabs 2 hrs/ 10 mg Zolmitriptan Zomig 2.5, 5 mg 2.5 mg/ $22-25 dissolvable 2 hrs/ tabs 10 mg Zolmitriptan Zomig 5 mg 5 mg $32 nasal spray 2 hrs 10 mg

Ranking:

Speed: Sumatriptan SQ > sumatriptan nasal spray = rizatriptan tab/wafer > zolmitriptan> sumatriptan oral = almotriptan > naratriptan

Early efficacy (1 and 2 hr) Sumatriptan SQ > rizatriptan tablet/wafer > sumatriptan nasal spray = zolmitriptan > sumatriptan oral = almotriptan > naratriptan

Tolerability Naratriptan = almotriptan > sumatriptan oral = zolmitriptan = rizatriptan > sumatriptan nasal spray > sumatriptan SQ

Recurrence Naratriptan = almotriptan < zolmitriptan = rizatriptan = sumatriptan SQ, oral, nasal spray

Formulations Sumatriptan > rizatriptan = zolmitriptan > naratriptan = almotriptan

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