Sumatriptan

Class: Selective Serotonin Agonists
- Antimigraine Agents
- Selective Vascular Serotonin Type 1-Like Receptor Agonists
- 5-HT1 Agonists
VA Class: CN105
Chemical Name: C14H21N3O2S
Molecular Formula: C₁₄H₂₁N₃O₂S•C₄H₆O₄
CAS Number: 103628-46-2
Brands: Alsuma, Imitrex, Sumavel

Medically reviewed on Nov 20, 2017

Introduction

Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ²²³ ²²⁴ ²⁶⁸

Uses for Sumatriptan

Vascular Headaches

Acute treatment of migraine attacks with or without aura.¹ ² ³ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹³ ⁴⁸ ⁸⁰ ¹⁴⁵ ¹⁴⁸ ¹⁸⁴ ¹⁹⁵ ²¹⁴ ²¹⁷ ²²⁵ ²⁴⁹ ²⁷⁹ ²⁸⁰

Sub-Q for acute treatment of cluster headache episodes.¹ ² ⁴⁹ ⁷⁵ ¹⁸³ ¹⁸⁴ ¹⁸⁵ ²¹⁰ ²¹⁴ ²⁷⁹ ²⁸⁰ Safety and efficacy of oral or intranasal sumatriptan for this use not established.¹⁴⁸ ²⁴⁹

Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine or cluster headache.¹ ⁷ ¹¹⁴ ¹⁵⁸

Sumatriptan Dosage and Administration

Administration

Administer orally, intranasally, or by sub-Q injection.¹ ¹² ¹⁴⁸ ²⁴⁹ Do not administer IM or IV; IV administration may induce coronary vasospasm.¹ ¹³ ⁴⁰ ⁹⁰ ²³⁶ ²³⁷ ²⁷⁹ ²⁸⁰ Has been administered as an iontophoretic transdermal system; however, marketing was suspended because of serious application site reactions.²⁸⁶ ²⁸⁷ (See Local Effects under Cautions.)

To achieve maximum relief, initiate therapy as soon as possible after onset of migraine attack.⁵⁰ ⁹² ¹⁰⁸ ¹²⁴ ¹⁴⁸ ¹⁸⁰ ²³⁷

Oral Administration

Administer sumatriptan tablets orally with fluids; swallow tablet whole.¹⁴⁸

Administer sumatriptan/naproxen fixed-combination tablets with or without food; do not split, crush, or chew.²⁸¹

Intranasal Administration

Administer intranasally as a single spray into 1 nostril.²⁴⁹

Nasal solution unit contains only 1 spray; do not test before use.²⁴⁹

To administer, remove unit from package just before use.²⁴⁹ While sitting down, gently blow nose to clear nasal passages.²⁴⁹ Keep head in upright position and gently close 1 nostril with index finger; exhale gently through mouth.²⁴⁹ With other hand, hold unit with thumb supporting at bottom and index and middle fingers on either side of nozzle.²⁴⁹ Insert nozzle into open nostril about ½ inch.²⁴⁹ While gently inhaling through nose (with closed mouth), release spray by firmly pressing plunger.²⁴⁹ Remove nozzle from nostril while keeping head level for 10–20 seconds and gently inhaling through nose and exhaling through mouth; do not inhale deeply.²⁴⁹ Consult administration instructions provided by manufacturer before use.²⁴⁹

Sub-Q Administration

Administer only by sub-Q injection.¹ ²⁷⁹ ²⁸⁰

Do not administer IM or IV; IV administration may induce coronary vasospasm.¹ ¹³ ⁴⁰ ⁹⁰ ²³⁶ ²³⁷ ²⁷⁹ ²⁸⁰

Autoinjection devices are available to facilitate self-administration of 4- or 6-mg dose.¹ ²⁷⁹ ²⁸⁰

Injection pen for use with prefilled cartridges (each containing a 4- or 6-mg dose): Needle penetrates approximately 5–6 mm (¼ inch); use injection sites with an adequate skin and subcutaneous thickness to accommodate needle length (e.g., lateral thigh, upper arm).¹ ²⁸⁴

Prefilled injection pen (containing 6-mg dose): Needle projects ¼ inch following activation of device; use injection sites with an adequate skin and subcutaneous thickness to accommodate needle length (e.g., lateral thigh, upper arm).²⁷⁹

Prefilled needleless injection device (containing 6-mg dose): Use administration sites on abdomen (avoiding 2-inch area around the umbilicus) or thigh with an adequate subcutaneous thickness to accommodate penetration of the solution into the subcutaneous space.²⁸⁰ Avoid using administration sites on upper arm, since delivered dose may be suboptimal.²⁸⁰

In patients receiving doses other than 4 or 6 mg, only the single-dose vials containing 6 mg/0.5 mL should be used to provide the desired dose.¹

Dosage

Available as sumatriptan (nasal solution) and sumatriptan succinate (tablets and injection); dosage expressed in terms of sumatriptan.¹ ¹⁴⁸ ²⁴⁹

Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.¹ ¹⁴⁸ ²⁴⁹

Adults

Vascular Headaches

Migraine

Oral (Sumatriptan)

25, 50, or 100 mg as a single dose.¹⁴⁸ Individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 50- or 100-mg dose; 100-mg dose may not provide substantially greater effect than 50-mg dose.¹⁴⁸

If headache recurs or partial response occurs after initial dose, additional oral doses may be administered at intervals of ≥2 hours, up to a maximum oral dosage of 200 mg daily.¹⁴⁸

If headache recurs after an initial sub-Q dose, additional oral doses may be administered at intervals ≥2 hours, up to a maximum oral dosage of 100 mg daily.¹⁴⁸

Oral (Sumatriptan/Naproxen)

Sumatriptan 85 mg (with naproxen sodium 500 mg) as a single dose.²⁸¹

Efficacy of >1 dose not established.²⁸¹ If a second dose is administered, allow ≥2 hours to elapse between the first and second doses.²⁸¹

Intranasal

5, 10, or 20 mg as a single dose; individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 20-mg dose.²⁴⁹ Doses >20 mg provide no additional benefit.²⁴⁹

To achieve a 10-mg dose, administer a single 5-mg dose into each nostril.²⁴⁹

If headache recurs, dose may be repeated once after 2 hours, up to a maximum dosage of 40 mg daily.²⁴⁹

Sub-Q

≤6 mg as a single dose.¹ If dose-limiting adverse effects occur with 6-mg dose, lower doses (e.g., 1–5 mg) may be given.

If headache recurs, a 6-mg sub-Q dose may be repeated once after ≥1 hour or additional oral doses may be administered at intervals ≥2 hours, up to a maximum oral dosage of 100 mg daily.¹ ¹⁴⁸

If patient does not respond to first 6-mg dose, additional doses are unlikely to provide benefit.² ³ ⁶ ⁷ ⁸ ⁹ ¹⁷⁴ ¹⁷⁶ ¹⁸¹ ²³⁶ ²³⁷

Cluster Headache

Sub-Q

≤6 mg as a single dose.¹ Manufacturers state that efficacy of doses <6 mg not established;¹ however, some patients may derive benefit from such lower doses (e.g., 3 mg).¹³ ²¹⁰ ²⁸⁵

If headache recurs, 6-mg dose may be repeated once after ≥1 hour, up to a maximum dosage of 12 mg in any 24-hour period.¹

If patient does not respond to first 6-mg dose, additional doses are unlikely to provide benefit.¹ ² ³ ⁶ ⁷ ⁸ ⁹ ¹⁷⁴ ¹⁷⁶ ¹⁸¹ ²³⁶ ²³⁷

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral (Sumatriptan)

Maximum 200 mg daily; do not exceed 100 mg daily if following an initial sub-Q dose.¹⁴⁸

Safety of treating an average of >4 headaches per 30-day period has not been established.¹⁴⁸

Oral (Sumatriptan/Naproxen)

Maximum 2 doses (total sumatriptan dosage of 170 mg) in any 24-hour period.²⁸¹

Safety of treating an average of >5 headaches per 30-day period has not been established.²⁸¹

Intranasal

Maximum 40 mg daily.²⁴⁹

Safety of treating an average of >4 headaches per 30-day period has not been established.²⁴⁹

Sub-Q

Maximum 6 mg as a single dose; do not exceed 12 mg (i.e., two 6-mg doses given ≥1 hour apart) in any 24-hour period.¹

Cluster Headache

Sub-Q

Maximum 6 mg as a single dose; do not exceed 12 mg (i.e., two 6-mg doses given ≥1 hour apart) in any 24-hour period.¹

Special Populations

Hepatic Impairment

Contraindicated in patients with severe hepatic impairment.¹ ¹⁴⁸ ²⁴⁹

Unpredictable increases in bioavailability following oral administration in patients with hepatic impairment.¹⁴⁸ If oral therapy is deemed advisable in these patients, do not exceed 50 mg as a single dose.¹⁴⁸ Avoid use of fixed-combination tablets containing sumatriptan 85 mg and naproxen sodium 500 mg, since sumatriptan dosage cannot be appropriately adjusted.²⁸¹

Geriatric Patients

Select dosage with caution, usually starting at the low end of the dosage range.¹

Cautions for Sumatriptan

Contraindications

Ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).¹ ¹⁴⁸ ²⁴⁹
Coronary artery vasospasm (e.g., Prinzmetal variant angina).¹ ¹⁴⁸ ²⁴⁹
Wolff-Parkinson-White syndrome or cardiac arrhythmias associated with other accessory pathway conduction disorders.¹
Uncontrolled hypertension.¹ ¹⁴⁸ ²⁴⁹
Other serious underlying cardiovascular disease.¹⁴⁸ ²⁴⁹
History of stroke or TIA.¹ ¹⁴⁸ ²⁴⁹
Peripheral vascular disease or ischemic bowel disease.¹ ¹⁴⁸ ²⁴⁹
Hemiplegic or basilar migraine.¹ ¹⁴⁸ ²⁴⁹
Treatment within previous 24 hours with another 5-HT₁ receptor agonist or an ergot alkaloid.¹ ¹⁴⁸ ²⁴⁹ (See Specific Drugs under Interactions.)
Concurrent or recent (within 2 weeks) treatment with an MAO-A inhibitor.¹ ¹⁴⁸ ²⁴⁹
Severe hepatic impairment.¹ ¹⁴⁸ ²⁴⁹
Known hypersensitivity to sumatriptan or any ingredient in the formulation.¹ ¹⁴⁸ ²⁴⁹

Warnings/Precautions

Careful Diagnosis of Migraine

Use oral or intranasal sumatriptan only in patients in whom a clear diagnosis of migraine has been established.¹⁴⁸ ²⁴⁹ Use sub-Q sumatriptan only in patients in whom a clear diagnosis of migraine or cluster headache has been established.¹

If first migraine attack treated with sumatriptan fails to respond to the drug, reconsider diagnosis before administering sumatriptan to treat subsequent attacks.¹

Exclude other potentially serious neurologic disorders before administering sumatriptan to patients not previously diagnosed with migraine or cluster headache or to those with atypical symptoms.¹ ⁶¹ ¹⁴⁸ ²³⁶ ²³⁷ ²⁴⁹

Cardiac Effects

Possible myocardial ischemia and/or infarction and coronary vasospasm, even in patients without a history of CAD.¹ ¹⁴⁸ ²⁴⁹ Contraindicated in patients with ischemic or vasospastic heart disease.¹ ¹⁴⁸ ²⁴⁹

Possible fatal or life-threatening cardiac rhythm disturbances (e.g., ventricular tachycardia or fibrillation).¹ ¹⁴⁸ ²⁴⁹ Discontinue if such disturbances occur.¹

Contraindicated in patients with Wolff-Parkinson-White syndrome or cardiac arrhythmias associated with other accessory pathway conduction disorders.¹

Tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw occur frequently but usually are noncardiac in origin.¹ ¹⁴⁸ ²⁴⁹ Manufacturer states that cardiovascular evaluation should be performed if patient is at high cardiac risk.¹

Patients with symptoms suggestive of angina after receiving sumatriptan should be evaluated for presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses;¹ ¹⁴⁸ ²⁴⁹ if administration resumed and such signs or symptoms recur, ECG evaluation recommended.¹⁴⁸ ²⁴⁹

Patients at Risk for CAD

Perform cardiovascular evaluation prior to initiating therapy in patients with multiple cardiovascular risk factors (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history of CAD) who have not previously received 5-HT₁ receptor agonist therapy.¹ ³⁴ ¹⁴⁸ ¹⁶⁴ ²⁴⁹

If evaluation provides evidence of CAD or coronary vasospasm, do not administer the drug.¹ ¹⁴⁸ ²⁴⁹

If results of evaluation are satisfactory, consider administering the initial dose in a medically supervised setting followed immediately by an ECG.¹ ⁴⁰ ¹⁴⁸ ²³⁶ ²³⁷ ²⁴⁹

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.¹ ¹⁴⁸ ²³⁶ ²³⁷ ²⁴⁹

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage and stroke, sometimes fatal.¹ ¹⁴⁸ ²⁴⁹ (See Careful Diagnosis of Migraine under Cautions.) Discontinue therapy if a cerebrovascular event occurs.¹

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.¹ ¹⁴⁸ ²⁴⁹

Other Vasospastic Effects

Possible noncoronary vasospastic reactions (e.g., peripheral vascular ischemia, GI ischemia and infarction with abdominal pain and bloody diarrhea, splenic infarction, Raynaud’s syndrome); transient or permanent blindness and partial vision loss reported very rarely in patients receiving 5-HT₁ receptor agonists.¹ ¹⁴⁸ ²⁴⁹

If signs or symptoms suggestive of vasospasm occur following administration, evaluate patient to rule out vasospastic reaction before administering additional doses.¹ ⁶ ⁸ ¹⁴⁸ ²⁴⁹

Hypertensive Effects

Substantial increases in BP, including hypertensive crisis with acute impairment of organ systems, reported rarely in patients with or without history of hypertension.¹ ¹⁴⁸ ²⁴⁹

Administer with caution in patients with controlled hypertension as transient increases in BP and peripheral vascular resistance are possible.³ ¹¹ ¹⁴⁸ ²⁴⁹ (See Contraindications under Cautions.)

Monitor BP in all patients receiving the drug.¹

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported in patients receiving 5-HT₁ receptor agonists, particularly in those receiving SSRIs or SNRIs concomitantly.¹ ¹⁴⁸ ²⁴⁹ ²⁷² (See Specific Drugs under Interactions.) Also may occur in patients receiving MAO inhibitors or tricyclic antidepressants concomitantly.¹

Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).¹ ¹⁴⁸ ²⁴⁹ ²⁷²

If manifestations of serotonin syndrome occur, discontinue sumatriptan and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.¹ ¹⁴⁸ ²⁴⁹ ²⁷⁸

Medication Overuse Headache

Overuse of drugs indicated for management of acute migraine attacks (e.g., use of 5-HT₁ receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for ≥10 days per month) may result in migraine-like daily headaches or a marked increase in frequency of migraine attacks.¹ ¹⁴⁸ ²⁴⁹ ²⁷⁶ ²⁷⁷

Detoxification, including withdrawal of overused drugs; treatment of withdrawal symptoms (e.g., transient worsening of headaches); and consideration of prophylactic migraine therapy may be necessary.¹ ¹⁴⁸ ²⁴⁹ ²⁷⁶ ²⁷⁷

Local Effects

Possible transient irritation in nose and throat (e.g., burning, numbness, paresthesia, discharge, pain/soreness), sometimes severe, after intranasal administration; symptoms usually resolve in <2 hours.²⁴⁹ Effects of extended and repeated use on nasal and/or respiratory mucosa not systematically evaluated.²⁴⁹

Burns and scarring reported at application site of sumatriptan iontophoretic transdermal system (Zecuity).²⁸⁶ ²⁸⁷ Reactions included severe erythema, cracked skin, blistering or welts, burns or scars, skin discoloration, severe pain, pruritus, and burning sensation.²⁸⁶ ²⁸⁷ Many cases resolved within hours to weeks, but some reactions, typically skin discoloration, were unresolved after several months.²⁸⁶ Manufacturer voluntarily suspended marketing of the formulation.²⁸⁶ ²⁸⁷

Sensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis/anaphylactoid reactions), possibly life-threatening or fatal, reported rarely; increased risk in patients with history of sensitivity to multiple allergens.¹ ¹⁴⁸ ²⁴⁹

Seizures

Seizures reported rarely; use with caution in patients with a history of seizures or with conditions associated with a lowered seizure threshold.¹ ¹⁴⁸ ²⁴⁹

Ocular Effects

Corneal opacities and corneal epithelial defects reported in dogs.¹ ¹⁴⁸ ²⁴⁹

Use of Fixed Combinations

When used in fixed combination with naproxen, consider the cautions, precautions, and contraindications associated with naproxen.²⁸¹

Specific Populations

Pregnancy

Category C.¹ ¹⁴⁸ ²⁴⁹

Lactation

Distributed into human milk.¹⁴ ⁴⁰ ¹⁴⁸ ²⁴² ²⁴⁹ ²⁷⁹ ²⁸⁰ ²⁸³ Caution advised if sumatriptan is used.²⁷⁹ ²⁸⁰ Expressing and discarding all milk for 8 hours after receiving a sub-Q dose may minimize exposure to the limited amount of drug distributed into milk.²⁴² ²⁸³ The manufacturers recommend avoiding breast-feeding for 12 hours after receiving sumatriptan oral tablets or nasal spray.¹⁴⁸ ²⁴⁹

Pediatric Use

Safety and efficacy not established in children <18 years of age;¹ ¹² ¹⁴⁸ ²³⁶ ²³⁷ ²⁴⁹ use not recommended.¹ ¹⁴⁸ ²⁴⁹ Serious adverse events reported in children receiving sumatriptan.¹ ¹⁴⁸ ²⁴⁹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Potential for more pronounced increases in BP; consider increased risk for CAD in geriatric patients.¹ ¹⁴⁸ ²⁴⁹ (See Cardiac Effects under Cautions.)

Select dosage with caution.¹ Consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.¹

Hepatic Impairment

Contraindicated in patients with severe hepatic impairment.¹ ¹⁴⁸ ²⁴⁹

Due to important role of the liver in presystemic clearance of oral sumatriptan, dosage adjustment recommended if oral therapy is deemed advisable in patients with hepatic impairment.¹⁴⁸ (See Hepatic Impairment under Dosage and Administration.)

Pharmacokinetics of sub-Q sumatriptan not substantially altered in patients with moderate hepatic impairment.¹

Common Adverse Effects

With oral therapy, pain/pressure sensations in chest/neck/throat/jaw, paresthesia, warm or cold sensation, malaise/fatigue, vertigo.¹⁴⁸

With intranasal therapy, taste disturbances, nausea, vomiting, disorder/discomfort of nasal cavity or sinuses.²⁴⁹

With sub-Q therapy, injection site reaction; atypical sensations (e.g., tingling, warm/hot sensation, burning, feeling of heaviness, pressure, tightness, numbness, paresthesia); dizziness/vertigo; flushing; discomfort of throat, jaw, sinuses, or nasal cavity; weakness, neck pain/stiffness, myalgia; drowsiness/sedation; headache; sweating; chest discomfort (tightness, pressure); nausea and vomiting.¹

Interactions for Sumatriptan

Metabolized principally by MAO-A isoenzyme in vitro.¹⁴⁸

Protein-bound Drugs

Effect on protein binding of other drugs has not been evaluated,¹ but expected to be minor due to low-level protein binding of sumatriptan.¹⁴⁸ ²⁴⁹

Specific Drugs

Drug	Interaction	Comments
Acetaminophen	Pretreatment with oral sumatriptan followed by acetaminophen affected rate, but not extent of acetaminophen absorption over 8 hours¹⁸⁷
Alcohol	Administration of alcohol 30 minutes prior to oral sumatriptan did not affect sumatriptan pharmacokinetics⁴⁴ ⁴⁵ ¹⁴⁸ ²³⁶
Amitriptyline	Concomitant use did not affect sumatriptan efficacy⁴⁰ ⁶²
Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine)	Potentially life-threatening serotonin syndrome¹ ¹⁴⁸ ²⁴⁹ ²⁷²	Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated²⁷²
Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide [no longer commercially available in the US])	Additive vasospastic effects¹ ¹⁴⁸ ²⁴⁹	Use within 24 hours contraindicated¹ ¹⁴⁸ ²⁴⁹
5-HT₁receptor agonists	Additive vasospastic effects¹ ¹⁴⁸ ²⁴⁹	Use within 24 hours contraindicated¹ ¹⁴⁸ ²⁴⁹
MAO inhibitors	MAO-A inhibitors decrease sumatriptan clearance, resulting in substantially increased systemic exposure; no substantial effect on sumatriptan metabolism seen with an MAO-B inhibitor¹ ¹⁴⁸ ²⁴⁹	Use within 2 weeks of MAO-A inhibitor contraindicated¹ ²⁶ ³⁷ ¹⁴⁸ ¹⁵⁷ ²³⁶ ²⁴⁹
Propranolol	Concomitant use did not affect sumatriptan efficacy;⁴⁰ ⁶² pretreatment with propranolol did not alter pharmacokinetics or pharmacodynamics of oral sumatriptan⁶²
Verapamil	Concomitant use did not affect sumatriptan efficacy⁴⁰ ⁶²
Xylometazoline	Topical application of xylometazoline to nasal mucosa 15 minutes prior to intranasal sumatriptan did not affect sumatriptan pharmacokinetics²⁴⁹

Sumatriptan Pharmacokinetics

Absorption

Bioavailability

Absorbed rapidly after oral, intranasal, or sub-Q administration, with peak plasma concentrations attained within approximately 0.5–5 hours, 0.8–1.8 hours, or 5–20 minutes, respectively.¹ ² ³ ¹³ ⁴⁵ ⁶¹ ⁷⁸ ⁷⁹ ⁸⁹ ⁹⁶ ¹²³ ¹⁴⁶ ¹⁴⁸ ¹⁶⁶ ¹⁶⁸ ²³⁶ ²⁸⁰

Bioavailability after sub-Q administration averages 97% of that obtained with IV administration;¹ ⁴⁴ bioavailability after oral or intranasal administration averages only about 15 or 17%, respectively, principally due to presystemic metabolism and in part due to incomplete absorption.² ¹³ ¹⁴ ⁴⁴ ⁴⁵ ⁶¹ ⁸⁹ ¹⁴⁶ ¹⁴⁸ ¹⁶⁶ ¹⁶⁸ ²⁴⁹

Oral absorption is not appreciably affected by gastric stasis that may occur during migraine attack,³ ¹³ ⁴⁵ ¹⁴⁶ but time to peak concentration is prolonged by about 30 minutes;³ ¹³ ⁴⁵ ⁹⁶ ¹⁴⁶ ¹⁴⁸ pharmacokinetics after sub-Q injection or after oral administration in fixed combination with naproxen sodium appear to be similar during migraine attacks and pain-free periods.¹ ²⁸¹

Oral administration of sumatriptan 85 mg/naproxen sodium 500 mg (as fixed combination) or sumatriptan 100 mg alone resulted in similar peak concentrations and AUCs of sumatriptan; time to peak concentration was about 30 minutes shorter when administered as the fixed combination.²⁸¹

Following sub-Q injection via injection pen or manually in deltoid area or thigh, time to peak concentration and amount of drug absorbed was not affected by injection site or technique.¹ ²⁷⁹

Following sub-Q administration via needleless device at sites on the abdomen or thigh, peak concentrations and time to peak concentrations were similar; administration using this technique at sites on the upper arm may result in delivery of a suboptimal dose.²⁸⁰

Special Populations

In patients with hepatic impairment, bioavailability after oral administration may be markedly increased.¹⁴⁸ In a small study, AUC and peak plasma concentrations increased approximately 70% and time to peak plasma concentrations occurred 40 minutes earlier after oral administration compared with such values in healthy adults.¹³ ⁴⁴ ¹⁴⁸ ²³⁶

Moderate hepatic impairment did not alter pharmacokinetics of sub-Q sumatriptan.¹ Effect of severe hepatic impairment on pharmacokinetics of sub-Q sumatriptan not established.¹

Onset

After oral administration, onset of relief of migraine symptoms generally occurs within 1–3 hours after single doses (25–100 mg),⁹² ¹⁴⁸ ¹⁶² ¹⁷⁸ ¹⁹¹ with maximum pain relief attained within 3–6 hours.¹⁴⁸ ¹⁷⁸ ¹⁹¹

After intranasal administration, onset of headache relief occurs within 30 minutes following a 10-, 20-, or 40-mg dose.¹²³ ²⁴³

After sub-Q administration, onset of pain relief usually occurs within 10–34 minutes in patients with moderate to severe migraine headache pain, with maximum relief attained within 1–2 hours;¹ ⁸ ⁹ ¹³ ⁴⁷ ⁵⁶ ¹⁶² ¹⁷⁶ ¹⁸¹ onset of pain relief generally occurs within 4–7 minutes in patients with cluster headache, with headache resolution shortly thereafter.⁴⁰ ⁴⁹ ⁷⁵ ¹⁸⁴

Food

Food does not appreciably affect oral bioavailability, but prolongs time to peak concentration.² ¹³ ⁴⁴ ¹⁴⁸ ²⁸¹

Distribution

Extent

Rapidly and widely distributed into body tissues after sub-Q administration.¹ ¹⁴ ¹⁴⁶ ¹⁴⁸ ¹⁶⁸

Distributed into human milk;¹ ¹⁴⁸ only small amounts cross placenta by passive transport in vitro.²³⁵

Plasma Protein Binding

Approximately 14–21%.¹ ¹⁴ ⁴⁵ ¹⁴⁸

Elimination

Metabolism

Metabolized in the liver and possibly in the GI tract principally to inactive indole acetic acid metabolite and other minor metabolites;¹ ² ³ ¹³ ¹⁴ ¹⁰⁴ ¹⁴⁸ ¹⁶⁶ metabolized principally by MAO-A isoenzyme in vitro.¹ ³⁷ ⁴⁸ ¹⁴⁸

Elimination Route

After oral administration, excreted in urine (57–60%) and feces (37–40%); only 3 and 9% of dose is excreted as unchanged drug in urine and feces, respectively.¹⁴ ⁴⁵ ¹⁴⁸ ¹³ ⁴⁵ ¹⁴⁸ ¹⁶⁶ ¹⁶⁸ After sub-Q administration, approximately 22 or 38–53% of dose is excreted in urine unchanged or as indole acetic acid metabolite, respectively;¹ ⁴⁵ ¹⁶⁸ 0.6 and 3.3% of dose is excreted in feces as unchanged drug and indole acetic acid metabolite, respectively.² ¹³ ¹⁴ ⁴⁵

Half-life

1.5–2.6 hours.¹ ⁶ ⁴⁴ ⁴⁵ ⁷⁸ ⁷⁹ ⁸⁹ ⁹¹ ¹⁴⁸ ¹⁶⁶ ¹⁶⁸ ²⁴⁹ ²⁸⁰ ²⁸¹

Special Populations

In patients with renal impairment, pharmacokinetics not evaluated, but little clinical effect expected since drug is largely metabolized to an inactive metabolite.¹ ¹⁴⁸ ²⁴⁹

Stability

Storage

Oral

Tablets

Sumatriptan: 2–30°C.¹⁴⁸

Sumatriptan/naproxen: 25°C (may be exposed to 15–30°C).²⁸¹ Store in original container with desiccant packet; do not repackage.²⁸¹

Intranasal

Solution

2–30°C; protect from light.²⁴⁹

Parenteral

Injection

Cartridge, vial: 2–30°C; protect from light.¹

Prefilled injection pen: 25°C (may be exposed to 15–30°C); protect from light; do not refrigerate.²⁷⁹

Prefilled needleless device: 20–25°C (may be exposed to 15–30°C); do not freeze.²⁸⁰

Actions

Binds with high affinity to 5-HT type 1-like receptors, probably 5-HT_1B and 5-HT_1D subtypes.¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ²²³ ²²⁴
Precise mechanism of action not established;⁴ ⁶ ⁹ ¹³ ⁷⁷ ⁸⁷ may ameliorate migraine and cluster headache through selective constriction of certain large cranial blood vessels and/or inhibition of neurogenic inflammatory processes in the CNS.¹ ² ³ ⁶ ⁷ ⁹ ¹⁰ ¹³ ⁴⁷ ⁶⁶ ⁷³ ⁷⁷ ⁸⁸ ¹¹⁰ ¹¹⁹ ¹³¹ ¹⁷⁷ ¹⁸⁴ ¹⁸⁶ ²¹⁷ ²³⁶ ²³⁷

Advice to Patients

Risk of serious cardiovascular or cerebrovascular events (e.g., MI, stroke) or other vasospastic reactions.¹ ¹⁴⁸ ²⁴⁹ Importance of seeking medical care if symptoms of such reactions (e.g., shortness of breath, weakness, slurring of speech, sudden or severe abdominal pain, difficulty in seeing, or tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck) occur and of not taking sumatriptan again until evaluated by a clinician.¹ ¹⁴⁸ ²⁴⁹
Risk of somnolence or dizziness; advise patient to avoid performing hazardous activities that require mental alertness (e.g., driving, operating machinery) if such effects occur.¹ ¹⁴⁸ ²⁴⁹
Importance of contacting clinician immediately if symptoms suggestive of hypersensitivity (e.g., shortness of breath, wheezing, palpitations, rash, urticaria, swelling of mouth, tongue, or throat) occur.¹ ¹⁴⁸ ²⁴⁹
Importance of taking sumatriptan exactly as prescribed.¹ ¹⁴⁸ ²⁴⁹
Importance of providing patient a copy of manufacturer’s patient information.¹ ¹⁴⁸ ²⁴⁹ Importance of clinician providing adequate instructions, as well as the written administration instructions supplied with the autoinjection device or nasal spray, before first use.¹ ¹⁷¹ ²⁴⁹ ²⁷⁹ ²⁸⁰
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).¹ ¹⁴⁸ ²⁴⁹
Importance of informing patients of risk of serotonin syndrome, particularly with concurrent use of sumatriptan and an SSRI, SNRI, MAO inhibitor, or tricyclic antidepressant.¹ ¹⁴⁸ ²⁴⁹ ²⁷² Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.¹ ¹⁴⁸ ²⁴⁹ ²⁷²
Overuse of drugs indicated for the management of acute migraine attacks may exacerbate headaches; importance of recording headache frequency and drug use to monitor effectiveness of treatment.¹ ¹⁴⁸ ²⁴⁹ ²⁷⁶
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ ¹⁴⁸ ²⁴⁹
Importance of informing patients of other important precautionary information.¹ ¹⁴⁸ ²⁴⁹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

SUMAtriptan
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Nasal	Solution	5 mg/0.1 mL*	Imitrex Nasal Spray	GlaxoSmithKline
			SUMAtriptan Nasal Spray
		20 mg/0.1 mL*	Imitrex Nasal Spray	GlaxoSmithKline
			SUMAtriptan Nasal Spray

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

SUMAtriptan Succinate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	25 mg (of sumatriptan)*	Imitrex	GlaxoSmithKline
			SUMAtriptan Succinate Tablets
		50 mg (of sumatriptan)*	Imitrex	GlaxoSmithKline
			SUMAtriptan Succinate Tablets
		100 mg (of sumatriptan)*	Imitrex	GlaxoSmithKline
			SUMAtriptan Succinate Tablets
Parenteral	Injection, for subcutaneous use only	4 mg (of sumatriptan) per 0.5 mL*	Imitrex (available in 0.5-mL unit-of-use injection-pen cartridges)	GlaxoSmithKline
			SUMAtriptan Succinate Injection (available in 0.5-mL unit-of-use injection-pen cartridges)
		6 mg (of sumatriptan) per 0.5 mL*	Alsuma (available in prefilled disposable single-use 0.5-mL injection pen)	Pfizer
			Imitrex (available in 0.5-mL unit-of-use injection-pen cartridges and as 0.5-mL single-dose vials)	GlaxoSmithKline
			SUMAtriptan Succinate Injection (available in 0.5-mL unit-of-use injection-pen cartridges and as 0.5-mL single-dose vials)
			Sumavel (available in prefilled disposable single-use 0.5-mL needleless delivery device)	Zogenix

SUMAtriptan Succinate Combinations
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	85 mg (of sumatriptan) with 500 mg Naproxen Sodium	Treximet	GlaxoSmithKline

References

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264. Zeneca Pharmaceuticals. Zomig (zolmitriptan) tablets prescribing information. Wilmington, DE; 1997 Dec 1.

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