FDA approved a REMS for sumatriptan to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of sumatriptan and consists of the following: medication guide. See the FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).
Administer orally, intranasally, or by sub-Q injection. Do not administer IM or IV; IV administration may induce coronary vasospasm.
To achieve maximum relief, initiate therapy as soon as possible after onset of migraine attack.
Oral Administration
Administer orally with fluids; swallow tablet whole.
Intranasal Administration
Administer intranasally as a single spray into 1 nostril.
Nasal solution unit contains only 1 spray; do not test before use.
To administer, remove unit from package just before use. While sitting down, gently blow nose to clear nasal passages. Keep head in upright position and gently close 1 nostril with index finger; exhale gently through mouth. With other hand, hold unit with thumb supporting at bottom and index and middle fingers on either side of nozzle. Insert nozzle into open nostril about ½ inch. While gently inhaling through nose (with closed mouth), release spray by firmly pressing plunger. 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. Consult administration instructions provided by manufacturer before use.
Sub-Q Administration
Administer only by sub-Q injection, preferably into lateral aspect of thigh or deltoid.
Do not administer IM or IV; IV administration may induce coronary vasospasm.
Autoinjection device available for use with prefilled syringes (each containing a 4- or 6-mg dose) to facilitate self-administration. Needles with this device penetrate approximately 5–6 mm (¼ inch); use injection sites with an adequate skin and subcutaneous thickness to accommodate needle length.
Dosage
Available as sumatriptan (nasal solution) and sumatriptan succinate (tablets and injection); dosage expressed in terms of sumatriptan.
Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.
Adults
Vascular Headaches
Migraine
Oral
25, 50, or 100 mg as a single dose. 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.
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.
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.
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. Doses >20 mg provide no additional benefit.
To achieve a 10-mg dose, administer a single 5-mg dose into each nostril.
If headache recurs, dose may be repeated once after 2 hours, up to a maximum dosage of 40 mg daily.
Sub-Q
≤6 mg as a single dose. If dose-limiting adverse effects occur with 6-mg dose, lower doses (e.g., 4 mg) may be given. 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.
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.
If patient does not respond to first 6-mg dose, additional doses are unlikely to provide benefit.
Cluster Headache
Sub-Q
≤6 mg as a single dose. If dose-limiting adverse effects occur with 6-mg dose, lower doses may be administered using only single-dose vials; use autoinjection device only with prefilled, unit-of-use syringes containing 6 mg.
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.
If patient does not respond to first 6-mg dose, additional doses are unlikely to provide benefit.
Prescribing Limits
Adults
Vascular Headaches
Migraine
Oral
Maximum 200 mg daily; do not exceed 100 mg daily if following an initial sub-Q dose.
Safety of treating an average of >4 headaches per 30-day period has not been established.
Intranasal
Maximum 40 mg daily.
Safety of treating an average of >4 headaches per 30-day period has not been established.
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.
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.
Special Populations
Hepatic Impairment
Contraindicated in patients with severe hepatic impairment. Unpredictable increases in bioavailability following oraladministration in patients with hepatic impairment. If oral therapy is deemed advisable in these patients, do not exceed 50 mg as a single dose.
Patients Receiving MAO-A Inhibitors
Concurrent or recent (within 2 weeks) use of MAO-A inhibitor and oral or intranasal sumatriptan is contraindicated; sub-Qsumatriptan is not generally recommended, but if concomitant use is clinically warranted, decrease sumatriptan sub-Q dosage and administer under careful medical supervision.
Cautions
Contraindications
Known or suspected ischemic heart disease (e.g., angina pectoris, MI, silent ischemia).
Treatment within previous 24 hours with another 5-HT1 receptor agonist or an ergot alkaloid. (See Specific Drugs under Interactions.)
Concurrent or recent (within 2 weeks) treatment with an MAO-A inhibitor (oral and nasalsumatriptan formulations).
Severe hepatic impairment.
Known hypersensitivity to sumatriptan or any ingredient in the formulation.
Warnings/Precautions
Warnings
Use oral or intranasal sumatriptan only in patients in whom a clear diagnosis of migraine has been established. Use sub-Q sumatriptan only in patients in whom a clear diagnosis of migraine or cluster headache has been established.
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.
Cardiac Effects
Risk of myocardial ischemia and/or infarction, coronary vasospasm, life-threatening cardiac rhythm disturbances, and death.
Use not recommended in patients with known or suspected ischemic or vasospastic heart disease or in patients in whom unrecognized CAD is likely (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of CAD) unless there is satisfactory evidence from prior cardiovascular evaluation that patient does not have CAD, ischemic heart disease, or other underlying cardiovascular disease.
Administer initial dose to patients with risk factors for CAD who have completed satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician’s office, possibly followed by ECG) unless patient previously received the drug.
Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy, including patients with cluster headache (predominantly males >40 years of age).
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; if administration resumed and such signs or symptoms recur, ECG evaluation recommended.
Cerebrovascular Events
Possible cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, sometimes fatal.
Risk of certain cerebrovascular events (e.g., stroke, TIA) may be increased in patients with migraine.
Other Cardiovascular or Vasospastic Effects
Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported. Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic bowel syndrome, Raynaud’s syndrome) occur following administration.
Substantial increases in BP, including hypertensive crises, reported rarely in patients with or without history of hypertension; administer with caution in patients with controlled hypertension as transient increases in BP and peripheral vascular resistance are possible. (See Contraindications under Cautions.)
Serotonin Syndrome
Potentially life-threatening serotonin syndrome reported during concurrent therapy with 5-HT1 receptor agonists (“triptans”) and SSRIs or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs). 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).
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. Effects of extended and repeated use on nasal and/or respiratory mucosa not systematically evaluated.
Sensitivity Reactions
Hypersensitivity
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.
General Precautions
Seizures
Seizures reported rarely; use with caution in patients with a history of seizures or with conditions associated with a lowered seizure threshold.
Ocular Effects
Possible accumulation of sumatriptan and/or its metabolites in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.
Corneal opacities and corneal epithelial defects reported in dogs. No specific recommendations for monitoring.
Specific Populations
Pregnancy
Category C. Sumatriptan Pregnancy Registry at 800-336-2176.
Lactation
Distributed into human milk. The manufacturer recommends avoiding breast-feeding for 12 hours after receiving sumatriptan oral tablets, sub-Q injection, or nasal spray.
Pediatric Use
Safety and efficacy not established in children <18 years of age; use not recommended.
Geriatric Use
Use not recommended due to possible decreased hepatic function, potential for more pronounced increases in BP, and increased risk for CAD in geriatric patients.
Hepatic Impairment
Contraindicated in patients with severe hepatic impairment. 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. (See Special Populations under Dosage and Administration.)
Common Adverse Effects
With oral therapy, pain/pressure sensations in chest/neck/throat/jaw, paresthesia, warm or cold sensation, malaise/fatigue, vertigo.
With intranasal therapy, taste disturbances, nausea, vomiting, disorder/discomfort of nasal cavity or sinuses.
With sub-Q therapy, injection site reaction, atypical sensations (e.g., tingling, warm/hot sensation, burning, feeling of heaviness, pressure, tightness, numbness), dizziness/vertigo, flushing, mouth/tongue discomfort, weakness, neck pain/stiffness, chest discomfort.
Interactions
Metabolized principally by MAO-A isoenzyme in vitro.
Protein-bound Drugs
Effect on protein binding of other drugs has not been evaluated, but expected to be minor due to low-level protein binding of sumatriptan.
MAO-A inhibitors decrease sumatriptan clearance, resulting in substantially increased systemic exposure; no substantial effect on sumatriptan metabolism seen with an MAO-B inhibitor
Use of nasal or oralsumatriptan within 2 weeks of MAO-A inhibitor contraindicated; although not generally recommended, if clinically warranted, sub-Q sumatriptan may be used concurrently with MAO-A inhibitors with appropriate dosage adjustment and careful monitoring
Concomitant use did not affect sumatriptan efficacy; pretreatment with propranolol did not alter pharmacokinetics or pharmacodynamics of oral sumatriptan
Concomitant use did not affect sumatriptan efficacy
Xylometazoline
Topical application of xylometazoline to nasal mucosa 15 minutes prior to intranasal sumatriptan did not affect sumatriptan pharmacokinetics
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. Bioavailability after sub-Q administration averages 97% of that obtained with IV administration; 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.
Oral absorption is not appreciably affected by gastric stasis that may occur during migraine attack, but time to peak concentration is prolonged by about 30 minutes; pharmacokinetics after sub-Q injection appear to be similar during migraine attacks and pain-free periods.
Special Populations
In patients with hepatic impairment, bioavailability after oral administration may be markedly increased. 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.
Onset
After oral administration, onset of relief of migraine symptoms generally occurs within 1–3 hours after single doses (25–100 mg), with maximum pain relief attained within 3–6 hours.
After intranasal administration, onset of headache relief occurs within 30 minutes following a 10-, 20-, or 40-mg dose.
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; onset of pain relief generally occurs within 4–7 minutes in patients with cluster headache, with headache resolution shortly thereafter.
Food
Food does not appreciably affect oral bioavailability, but prolongs time to peak concentration.
Distribution
Extent
Rapidly and widely distributed into body tissues after sub-Q administration.
Distributed into human milk; only small amounts cross placenta by passive transport in vitro.
Plasma Protein Binding
Approximately 14–21%.
Elimination
Metabolism
Metabolized in the liver and possibly in the GI tract principally to inactive indole acetic acid metabolite and other minor metabolites; metabolized principally by MAO-A isoenzyme in vitro.
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. After sub-Q administration, approximately 22 or 38–53% of dose is excreted in urine unchanged or as indole acetic acid metabolite, respectively; 0.6 and 3.3% of dose is excreted in feces as unchanged drug and indole acetic acid metabolite, respectively.
Half-life
1.5–2.6 hours.
Special Populations
In patients with renal impairment, pharmacokinetics not evaluated, but little clinical effect expected since drug is largely metabolized to an inactive metabolite.
Stability
Storage
Oral
Tablets
2–30°C.
Intranasal
Solution
2–30°C; protect from light.
Parenteral
Injection
2–30°C; protect from light.
Actions
Binds with high affinity to 5-HT type 1-like receptors, probably 5-HT1B and 5-HT1D subtypes.
Precise mechanism of action not established; 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.
Advice to Patients
Importance of immediately informing a clinician of any tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck, as well as sudden and/or severe abdominal pain, shortness of breath, wheezing, heart throbbing, facial swelling (e.g., eyelids, face, lips), rash, or hives after taking sumatriptan and of not taking sumatriptan again until evaluated by a clinician.
Importance of taking sumatriptan exactly as prescribed.
Importance of providing patient a copy of manufacturer’s patient information. Importance of clinician providing adequate instructions, as well as the written administration instructions supplied with the autoinjection device or nasal spray, before first use.
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).
Importance of informing patients of risk of serotonin syndrome with concurrent use of sumatriptan and an SSRI or SNRI. Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Imitrex® (available in 0.5-mL [4-mg] unit-of-use syringes)
GlaxoSmithKline
6 mg/0.5 mL (of sumatriptan)
Imitrex® (available in 0.5-mL [6-mg] unit-of-use syringes and as 0.5 mL [6-mg] single-dose vials)
GlaxoSmithKline
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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