Migraine Headache Drug Summary

ACUTE ATTACK TREATMENTS

Drug	Dosage	Remarks
Paracetamol (Acetaminophen)	Oral: 500-1,000 mg PO 4-6 hourly Max dose: 4 g/day Rectal: 500-1,000 mg 4-6 hourly Max dose: 4 g/day	Adverse Reactions Dermatologic effects (hypersensitivity reactions, rashes, urticaria, erythema); GI effects (nausea/vomiting, constipation, GI disturbance); CNS effect (headache) Potentially fatal effects: Hepatotoxicity, acute renal tubular necrosis Special Instructions Contraindicated in patients with severe hepatic impairment Use with caution in patients with renal, hepatic, cardiac, and respiratory impairment, known glucose-6-phosphate dehydrogenase (G6PD) deficiency Not for long-term use
*Combinations with various non-opioid analgesics are available. Please see the latest MIMS for specific formulations and prescribing information.

ACUTE ATTACK TREATMENTS

Drug	Dosage	Remarks
Rimegepant	75 mg PO 24 hourly Max dose: 75 mg/day	Adverse Reactions GI effect (nausea); Other effects (skin rash, hypersensitivity reaction, dyspnea) Special Instructions Contraindicated in patients with severe hepatic impairment or end-stage renal disease
Ubrogepant	Initial dose: 50-100 mg PO 24 hourly, may repeat after ≥2 hours based on response or tolerability Max dose: 200 mg/day	Adverse Reactions GI effects (nausea, xerostomia); CNS effect (drowsiness) Special Instructions Contraindicated in patients with end-stage renal disease Reduce dose in patients with severe hepatic or renal impairment Use with caution in patients who are taking strong CYP3A4 inhibitors
Zavegepant	10 mg intranasally in 1 nostril as needed Max dose: 10 mg/day	Adverse Reactions GI effects (nausea/vomiting, taste disorders); Other effects (hypersensitivity reactions, nasal discomfort) Special Instructions Avoid coadministration with intranasal decongestants Intranasal decongestants must be given at least 1 hour after administration Avoid in patients with creatinine clearance (CrCl) <30 mL/min and in patients with severe hepatic failure Safety of treating >8 attacks/month has not been established

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Oral
Atogepant	10, 30 or 60 mg PO 24 hourly Max dose: 60 mg/day	Adverse Reactions GI effects (constipation, decreased appetite, nausea); Other effects (weight loss, drowsiness, fatigue) Special Instructions Rimegepant: Contraindicated in patients with severe hepatic impairment or end-stage renal disease Use with caution in patients with hepatic and renal impairment
Rimegepant	75 mg PO every other day Max dose: 75 mg/day
Parenteral
Eptinezumab	100 mg IV infusion over 30 minutes every 3 months May be administered as 300 mg IV infusion every 3 months	Adverse Reactions Injection site reactions (pain, erythema, pruritus) Less common reactions: Immunogenicity, antibody reaction, hypersensitivity reactions Eptinezumab: Nasopharyngitis, hypersensitivity Erenumab: Constipation, muscle cramps Special Instructions Prior to injection, allow to sit at room temperature for 30 minutes protected from sunlight; do not warm using a heat source and do not shake Administer subcutaneously in the abdomen, thigh or upper arm Contraindicated in pregnancy and lactating women
Erenumab	70 mg SC once monthly
Fremanezumab	225 mg SC once monthly or 675 mg SC every 3 months
Galcanezumab	Loading dose: 240 mg SC given as 2 consecutive doses of 120 mg SC each Maintenance dose: 120 mg SC once monthly

ACUTE ATTACK TREATMENTS

Drug	Dosage	Remarks
Dihydroergotamine mesylate (Dihydroergotamine methanesulphonate, Co-dergocrine mesylate, DHE)	Oral: 10 mg PO in divided doses IM/SC: 1 mg at onset of HA, may repeat after 1 hour Max dose: 3 mg/day, 6 mg/wk IV: 1 mg at onset of HA, may repeat after 1 hour Max dose: 2 mg/day, 6 mg/wk Nasal: Spray 0.5 mg into each nostril as 0.4% solution, may repeat after 15 minutes Max dose: 2 mg/day, 4 mg/wk	Adverse Reactions GI effects (abdominal pain, nausea/vomiting though may be less with DHE); Other effects (weakness, muscle pain, numbness and tingling of the fingers and toes, localized edema and itching in hypersensitive patients) Acute overdosage may occur in susceptible patients (eg hepatic, renal impairment) signs of which are: Hypotension, nausea/vomiting, diarrhea, thirst, coldness, tingling and itchiness of skin, shock Special Instructions Stop treatment if signs of vasoconstriction occur Contraindicated in patients with uncontrolled hypertension, coronary heart disease (CHD), history of MI, coronary vasospasm, peripheral vascular disease, or previous cerebrobrovascular accident (CVA) or transient ischemic attack (TIA), severe or persistent sepsis, hyperthyroidism, impaired hepatic or renal function
Ergotamine1	Oral: 2 mg SL at the onset of HA, may repeat after 30 min Max dose: 6 mg/day, 10 mg/wk Inhalation: Single dose (360 mcg) at onset, may repeat at 5-miniute intervals Max dose: 6 inhalations/24 hr; 15 inhalations/wk
1Many products including oral and suppository dosage forms that combine Ergotamine with Caffeine, Belladonna, Phenobarbital, etc are available. Please see the latest MIMS for specific formulations and prescribing information.

ACUTE ATTACK TREATMENTS

Drug	Dosage	Remarks
Isometheptene/Paracetamol/Caffeine	Isometheptene 65 mg/Paracetamol 325 mg/Caffeine 20 mg: 2 tab PO initially followed by 1 tab PO 1 hourly until relief Max dose: 5 tab/12 hr	Adverse Reactions Hypertension, dizziness, rash, hypersensitivity Special Instructions Contraindicated in patients with severe renal, hepatic or organic heart disease, severe hypertension, glaucoma, porphyria, on concurrent monoamine oxidase inhibitors (MAOIs), G6PD deficiency Use with caution in patients with CV disease, DM, hyperthyroidism, impaired renal or hepatic function Dichloralphenazone: May impair physical and mental abilities (eg operating machinery or driving)
Isometheptene/ Paracetamol/Dichloral- phenazone	Isometheptene 65 mg/Paracetamol 325 mg/Dichloralphenazone 100 mg: 2 cap PO initially followed by 1 cap PO 1 hourly until relief Max dose: 5 cap/12 hr

ACUTE ATTACK TREATMENTS

Drug	Dosage	Remarks
Aspirin	300-900 mg PO 4-6 hourly Max dose: 4 g/day Extended-release: 650-1,300 mg PO 8 hourly Max dose: 3.9 g/day PO or 500 mg PO as a single dose Combined with 130 mg caffeine	Adverse Reactions GI effects (nausea/vomiting, GI discomfort, risk of GI ulcers); Hematologic effect (inhibition of platelet aggregation); Dermatologic effects (urticaria, angioedema); Other effects (tinnitus, rhinitis, bronchospasm); Hepatotoxicity, nephrotoxicity if used long-term Special Instructions Should be taken with food Contraindicated in patients with hypersensitivity (attacks of asthma, angioedema, urticaria, or rhinitis), peptic ulcer, hemophilia, hemorrhagic disorders, gout, severe hepatic or renal impairment Use with caution in patients with history of peptic ulcer, prone to dyspepsia, asthma or allergic diseases, dehydrated patients, uncontrolled hypertension, impaired renal or hepatic function, G6PD deficiency
Diclofenac	Oral1: Initially 50 mg PO followed by 50 mg in 2 hours and 4-6 hours later if needed Max dose: 200 mg/day Rectal: 75-150 mg/day in divided doses Max dose: 150 mg/day Parenteral: 75 mg IM followed by 100 mg suppository if necessary Max dose: 150 mg/day Note: Parenteral use should not exceed >2 days	Adverse Reactions CNS effect (dizziness); GI effects (nausea/vomiting, risk of GI ulcers, diarrhea, abdominal pain); Hematologic effect (inhibition of platelet aggregation which is reversible); Other effects (tinnitus, heartburn, edema, fluid retention); Hepatotoxicity, nephrotoxicity if used long-term Special Instructions Take with food Paracetamol: May be taken with or without food Contraindicated in patients with active or peptic ulcer, active bleeding, hypersensitivity Use with caution in patients with asthma, renal or hepatic disorders, bleeding diseases, CV disease
Ibuprofen	1.2-1.8 g/day PO in 3-4 divided doses Maintenance dose: 600-1,200 mg/day in divided doses or 200-400 mg PO initially, may repeat dose 4-6 hourly as needed Max dose: 3.2 g/day
Mefenamic acid	500 mg PO 8 hourly or 500 mg PO initially then 250 mg 6 hourly
Naproxen Na	825 mg at onset of HA, followed by 275-550 mg 30 minutes after the initial dose Max dose: 1,375 mg/day (Naproxen 250 mg = Naproxen Na 275 mg)
Phenazone	1,000 mg PO 4-8 hourly Max dose: 4 g/day
Tolfenamic acid	200 mg PO at onset of HA, may repeat once after 1-2 hours
*Many analgesic combination products are available. Please see the latest MIMS for specific formulations and prescribing information. 1Also available in powder for oral solution. Please see the latest MIMS for specific formulations and prescribing information.

ACUTE ATTACK TREATMENTS

Drug	Dosage	Remarks
Lasmiditan	50 mg, 100 mg or 200 mg PO 24 hourly Max dose: 200 mg/day	Adverse Reactions CNS effects (dizziness, fatigue, paresthesia, sedation); Other effects (palpitations, nausea/vomiting) Special Instructions Patients are advised not to drive or operate machinery until at least 8 hours after taking each dose of Lasmiditan Avoid in patients with severe hepatic impairment or concomitant use with P-gp and breast cancer resistant protein (BCRP) substrates Use with caution if used in combination with alcohol or other CNS depressants May further lower heart rate when given with heart rate-lowering drugs Discontinue use if serotonin syndrome symptoms occur

ACUTE ATTACK TREATMENTS

Drug	Dosage	Remarks
Almotriptan	6.25-12.5 mg PO in single dose, may repeat in ≥2 hours Max dose: 2 doses/day (25 mg/day)	Adverse Reactions CV effects (hypotension, bradycardia/tachycardia, palpitations); CNS effects (dizziness, flushing, weakness, headache, drowsiness, fatigue, visual disturbance); GI effects (nausea/vomiting); Other effects (pain, tingling, heaviness, heat, pressure or tightness in any part of the body, Raynaud’s syndrome, ischemic colitis); Vasospasm which has rarely caused CV event SC Sumatriptan: Stinging at injection site Toxic epidermal necrolysis has occurred with Rizatriptan Special Instructions Contraindicated in patients with uncontrolled hypertension, CHD, history of MI, coronary vasospasm (including Prinzmetal’s angina), peripheral vascular disease, or previous CVA or TIA, patients with basilar, hemiplegic or ophthalmoplegic migraine Unrecognized CV disease should be excluded before administering triptans Do not use within 24 hours of treatment with another serotonin agonist, ergotamine derivatives and/or ergotamine-containing drugs (eg DHE, Ergotamine) Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan: If first dose does not relieve pain, second dose should not be taken for same HA but may be taken if HA recurs Eletriptan: Do not use within 72 hours of treatment with strong CYP3A4 inhibitors (eg Ketoconazole, Itraconazole, Erythromycin, Clarithromycin, Amprenavir, Ritonavir, Indinavir, Saquinavir, Nelfinavir and Nefazodone) Frovatriptan, Naratriptan: Contraindicated in patients with cardiac arrhythmias, valvular heart disease, atherosclerotic disease Almotriptan, Naratriptan, Sumatriptan: Use with caution in patients with sulfonamide hypersensitivity Almotriptan, Sumatriptan: Use with caution in patients with history of seizures Rizatriptan: Halve the dose in patients taking Propranolol Avoid taking Rizatriptan within 2 hours of Propranolol dose and within 24 hours after taking ergot-containing drug Zolmitriptan: Avoid in patients with Wolf-Parkinson-White syndrome or arrhythmias associated with accessory cardiac conduction pathways Almotriptan, Rizatriptan, Sumatriptan, Zolmitriptan: Do not use within 2 weeks of discontinuing MAOI
Eletriptan	20-40 mg PO single dose May repeat in ≥2 hours Max dose: 160 mg/day
Frovatriptan	2.5 mg PO single dose May repeat in ≥2 hours Max dose: 5 mg/day
Naratriptan	1-2.5 mg PO single dose May repeat in ≥4 hours Max dose: 5 mg/day
Rizatriptan	5-10 mg PO single dose May repeat in ≥2 hours Max dose: 20-30 mg/day
Sumatriptan	Oral: 50-100 mg PO as single dose May repeat after 24 hours Max dose: 300 mg/day PO Parenteral: 6 mg SC single dose May repeat in ≥1 hour Max dose: 12 mg/day SC Nasal: 5, 10 or 20 mg into 1 nostril at onset of HA, may repeat in ≥2 hours Max dose: 40 mg/day
Zolmitriptan	Oral: 2.5 mg PO single dose May repeat in ≥2 hours If 2.5 mg dose does not provide relief, subsequent attacks can be treated with 5 mg dose Max dose: 10 mg/day Nasal: 1 spray (5 mg) into 1 nostril at onset of HA May may repeat in ≥2 hours Max dose: 10 mg/day

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Clonidine	0.050 mg PO 12 hourly May be increased after 2 weeks to 0.075 mg PO 12 hourly if necessary	Adverse Reactions GI effects (constipation, dry mouth, nausea, anorexia); CNS effects (dizziness which may subside with continued use, anxiety, fatigue, sleep disturbances, drowsiness, may aggravate depression and insomnia); Other effects (impotence, decreased libido) Special Instructions Use with caution in patients with cerebrovascular disease, ischemic heart disease, MI, renal impairment, peripheral vascular disorders, history of depression

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Candesartan	16 mg PO 24 hourly	Adverse Reactions Usually mild and transient: CNS effects (dizziness, headache); CV effect (dose-related orthostatic hypotension which may occur particularly in patients with volume depletion); Renal impairment Rare effects: Rash, angioedema, elevated LFTs, myalgia Special Instructions Use with caution in patients with renal artery, aortic or mitral valve stenosis, renal or hepatic impairment Serum K should be monitored especially in the elderly, patients with renal impairment, and K-sparing diuretics should be avoided

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Fatty Acid Derivatives
Valproate semisodium (Divalproex sodium)	Extended-release: 500 mg PO 24 hourly for 1 week then may increase to 1 g PO 24 hourly	Adverse Reactions CNS effects (headache, somnolence, behavioral changes, asthenia, tremor); GI effects (abdominal cramps, nausea/vomiting, indigestion, anorexia); Other effect (hair loss); Less commonly thrombocytopenia, leukopenia; liver dysfunction has been reported Special Instructions Contraindicated in patients with hepatic or significant impairment and urea cycle disorders Increased risk of hyperammonemic encephalopathy in patients with urea cycle disorders Use with caution in patients with congenital metabolic disorders, organic brain disease, severe seizure disorder, HIV and renal dysfunction Monitor liver function test (LFT) before and during first 6 months of therapy Watch out for signs of pancreatitis
Valproic acid (Sodium valproate)	250 mg PO 12 hourly May increase up to 1 g/day
Other Anticonvulsant
Topiramate	Initial dose: 25 mg PO 24 hourly at night for 1 week May increase dose by 25 mg/day at 1-week interval Usual dose: 100 mg/day PO divided 12 hourly	Adverse Reactions CNS effects (fatigue, confusion, paresthesia, somnolence, difficulty with concentration, ataxia, mood changes); GI effects (weight loss, nausea, anorexia, diarrhea, taste perversion); Other effects (abnormal vision, hyperthermia, risk of renal stone formation) Special Instructions Use with caution in patients with hepatic or renal impairment Maintain adequate hydration to reduce the risk of renal calculi and when exposed to warm temperatures May impair ability to drive or operate machinery

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Selective Serotonin Reuptake Inhibitors (SSRIs)
Fluoxetine	20 mg PO every other day up to 40 mg PO 24 hourly	Adverse Reactions Dose-related: Nervousness and anxiety, insomnia CNS effects (headache, drowsiness, fatigue, tremor, mania); GI effects (nausea, diarrhea, anorexia); Other effects (blurred vision, sexual dysfunction, hyponatremia, increased liver enzymes) Special Instructions If discontinued after long-term use, taper dose over several weeks Contraindicated in patients with severe renal or hepatic failure and in those taking MAOIs or within 2 weeks of MAOI withdrawal Use with caution in patients with hepatic or renal dysfunction, seizure disorders, cardiac disease, bleeding disorders and closed-angle glaucoma Monitor behavioral changes during the first few months of therapy or during dose changes
Venlafaxine	37.5 mg PO 24 hourly x 3 days, then 75 mg PO 24 hourly x 3 days, followed by 150 mg PO 24 hourly
Tricyclic Antidepressant (TCA)
Amitriptyline	Initial dose: 10-25 mg PO at bedtime Maintenance dose: 50-150 mg PO at bedtime Max dose: 150 mg PO at bedtime	Adverse Reactions Side effects are mostly due to antimuscarinic actions and may be decreased if started at low dose and increased gradually CNS effects (drowsiness, nervousness, insomnia, headache, ataxia, tremor, confusion/delirium can occur especially in older patients); GI effects (dry mouth, nausea/vomiting, weight gain, gastric irritation, constipation may lead to paralytic ileus); CV effects (hyperthermia, hypotension, tachycardia, sweating); Other effects (blurred vision, peripheral neuropathy, increased IOP, urinary retention, urticaria, angioedema) Special Instructions Do not stop medication abruptly; taper dose over several weeks Contraindicated in patients with concomitant use of Cisapride and MAOI within the last 14 days, acute recovery phase following MI Use with caution in patients with urinary retention, prostatic hyperplasia, chronic constipation, untreated angle-closure glaucoma, CV disease, DM, impaired hepatic function, thyroid dysfunction, history of epilepsy Elderly patients may be sensitive to side effects; lower dose should be used

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Metoprolol	100-200 mg PO 24 hourly or divided 12 hourly	Adverse Reactions CV effects (bradycardia, hypotension, heart block and heart failure in patients with pre-existing CV disorders); CNS effects (fatigue, depression, headache, confusion, dizziness, sleep disturbances); GI effects (diarrhea, nausea/vomiting, abdominal discomfort); Other effects (bronchospasm, reduced sexual activity, edema, cold extremities, thrombocytopenia, leukopenia, rashes) May interfere with carbohydrate and lipid metabolism Special Instructions Contraindicated in patients with sinus bradycardia, uncompensated heart failure, bronchospasm, COPD, asthma, sinus node dysfunction, 2nd- and 3rd-degree AV block except those with pacemaker Use with caution in patients with DM, heart disease, history of MI, coronary vasospasm, peripheral vascular disease, or previous CVA or TIA, severe or persistent sepsis, hyperthyroidism, impaired hepatic or renal function
Propranolol	40 mg PO 8-12 hourly, increased in 40-mg increments at weekly intervals according to response Usual dose range: 80-160 mg/day Max dose: 240 mg/day
Timolol	Initial dose: 10 mg PO 12-24 hourly Maintenance dose: 20 mg PO 24 hourly Max dose: 30 mg/day in divided doses

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Calcium Antagonists
Cinnarizine	25-50 mg PO 8 hourly	Adverse Reactions CNS effects (drowsiness, lassitude, blurred vision, dizziness, insomnia, headache, psychomotor impairment); GI effects (constipation, gastric reflux, nausea/vomiting, diarrhea, increased appetite, weight gain, dry mouth); Other effects (thickened respiratory secretions, galactorrhea, urinary retention); Extrapyramidal symptoms (EPS) associated with depressive feelings have been reported Special Instructions Contraindicated in patients with GI or urinary obstruction, acute porphyria, acute asthmatic attack Flunarizine: Contraindicated in patients with history of depression, Parkinson’s disease and other extrapyramidal disorders Use with caution in patients with angle-closure glaucoma, urinary retention, prostatic hyperplasia, renal & hepatic impairment May impair ability to drive or operate machinery
Flunarizine	5-10 mg PO 24 hourly at bedtime Max dose: 10 mg/day

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Onabotulinumtoxin A (Botulinum toxin A)	5 u IM/injection site every 12 weeks Total dose: 155-195 u IM	Adverse Reactions Injection site reactions (pain, tenderness and/or bruising); Other effects (fever, flu, facial paresis, neck pain); Dermatologic effects (rarely skin rash, pruritus) Special Instructions Contraindicated in patients with myasthenia gravis or Eaton-Lambert syndrome Use with caution in patients at risk of angle-closure glaucoma, amyotrophic lateral sclerosis, pregnant, children <12 years old and elderly Injection should be divided in seven specific head/neck muscle areas

PROPHYLACTIC TREATMENTS

Drug	Dosage	Remarks
Cyproheptadine	Initially 4 mg PO May repeat 30 minutes later Maintenance dose: 4 mg PO 4-6 hourly Max dose: 8 mg/4-6 hours period	Adverse Reactions CNS effects (drowsiness, lassitude, dizziness, psychomotor impairment, fatigue, impaired alertness, blurred vision); GI effects (dry mouth, constipation, gastric reflux, nausea/vomiting, diarrhea, increased appetite, weight gain); Other effects (thickened respiratory secretions, urinary retention) Special Instructions Contraindicated in patients with narrow-angle glaucoma, acute asthmatic attack, bladder neck obstruction, stenosing peptic ulcer, GI tract obstruction, MAOI therapy Use with caution in patients with CV disease (eg hypertension, ischemic heart disease), increased IOP, asthma or other chronic breathing disorders, thyroid dysfunction
Methysergide	4-8 mg PO in divided doses	Adverse Reactions During initial treatment: Drowsiness, dizziness, GI disturbances CV effects (postural hypotension, tachycardia, arterial spasm including coronary artery spasm with potential MI); GI effect (weight gain); Other effects (mental and behavioral disturbances, paresthesia of extremities, alopecia) Rarely after long-term use, retroperitoneal fibrosis and fibrosis of endocardial tissue Special Instructions Administer under hospital supervision After 6 months of therapy, withdraw gradually, stop for 4 weeks and re-assess the need to continue Avoid in patients with CV or pulmonary disease, renal or hepatic impairment, severe hypertension, collagen disease, urinary tract disorders Use with caution in patients with history of peptic ulcer
Pizotifen	Initially 0.5 mg PO 24 hourly then increase gradually as required to Maintenance dose: 1.5 mg/day PO at bedtime or in 3 divided doses Max dose: 4.5 mg/day	Adverse Reactions Same as Cyproheptadine Special Instructions Contraindications same as Cyproheptadine Use with caution in patients with urinary retention, symptomatic prostatic hyperplasia, renal and hepatic impairment, epilepsy, alcoholism

All dosage recommendations are for non-pregnant and non-breastfeeding women, and non-elderly adults with normal renal and hepatic function unless otherwise stated.  
Not all products are available or approved for above use in all countries.  
Products listed in the Drug Summary are based on indications stated in the locally approved product monographs.   
Please refer to local product monographs in Related MIMS Drugs for country-specific prescribing information.