Sumatriptan

Pronunciation

Pronunciation: SOO-ma-TRIP-tan
Class: Selective 5-HT 1 receptor agonist

Trade Names

Imitrex
- Injection, solution 4 mg per 0.5 mL (as succinate)
- Injection, solution 6 mg per 0.5 mL (as succinate)
- Spray, nasal 5 mg
- Spray, nasal 20 mg
- Tablets 25 mg (as succinate)
- Tablets 50 mg (as succinate)
- Tablets 100 mg (as succinate)

Sumavel
- Injection, needle-free delivery system 6 mg per 0.5 mL (as succinate)

Apo-Sumatriptan (Canada)
CO Sumatriptan (Canada)
Gen-Sumatriptan (Canada)
Imitrex DF (Canada)
Novo-Sumatriptan (Canada)
Novo-Sumatriptan DF (Canada)
PMS-Sumatriptan (Canada)
ratio-Sumatriptan (Canada)
Sandoz Sumatriptan (Canada)

Pharmacology

Selective agonist for vascular serotonin (5-HT 1 ) receptor subtype, causing vasoconstriction of cranial arteries.

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Pharmacokinetics

Absorption

T max for subcutaneous, oral, and intranasal administration is 0.2, 2, and 1.5 h, respectively. C max for subcutaneous, oral, and intranasal administration is 72, 51, and 13 mg/L, respectively. Bioavailability for subcutaneous, oral, and intranasal administration is 97%, 15%, and 15.8%, respectively.

Distribution

Protein binding is 14% to 21%. Vd is 2.4 L/kg (oral).

Metabolism

Metabolized by MAO-A.

Elimination

Sumatriptan half-life is approximately 2.5 h.

Special Populations

Renal Function Impairment

The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined, but little clinical effect would be expected because sumatriptan is largely metabolized to an inactive substance.

Hepatic Function Impairment

Bioavailability following oral administration may be markedly increased in patients with liver disease. There were no statistically significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in patients with hepatic function impairment compared with healthy controls. The intranasal dosage form has not been studied.

Elderly

The pharmacokinetics of sumatriptan in the elderly were similar to those in healthy patients.

Gender

No apparent difference in pharmacokinetics based on gender.

Race

No apparent difference in pharmacokinetics based on race.

Indications and Usage

Acute treatment of migraine attacks with or without aura; treatment of acute cluster headaches (injection only).

Unlabeled Uses

Migraines in children/adolescents, postdural puncture headache.

Contraindications

IV use (causes coronary vasospasm); patients with history, signs, or symptoms of ischemic heart disease (eg, angina, including Prinzmetal variant; MI; silent myocardial ischemia, ischemic heart disease, coronary artery vasospasm); cerebrovascular syndromes (eg, strokes of any type, TIA) or peripheral vascular syndromes (eg, ischemic bowel disease); other significant underlying CV diseases; uncontrolled hypertension; concurrent use or use within 24 h of ergotamine-containing preparations (eg, dihydroergotamine, methysergide); concurrent use within 24 h of another 5-HT 1 agonist (eg, triptan); concurrent use or within 2 wk of using an MAO-A inhibitor (oral and intranasal only); hemiplegic or basilar migraine; severe hepatic impairment; hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO Initially, single dose of 25, 50, or 100 mg. Doses of 100 mg have not been proven to provide a greater effect than 50 mg. If headache returns or the patient has a partial response to the initial dose, a single additional dose may be taken after 2 h up to a max of 200 mg/day. If headache returns following an initial dose with the injection, additional doses of single tablets (up to 100 mg/day) may be given with an interval of at least 2 h between tablet doses.

Subcutaneous 6 mg initially. May repeat once after 1 h (max, 6 mg per single dose or 12 mg/day).

Intranasal Administer a single dose of 5, 10, or 20 mg in one nostril. The dose may be repeated once after 2 h (max, 40 mg/day).

Hepatic Function Impairment

Max single dose is 50 mg. Contraindicated in patients with severe hepatic impairment.

General Advice

Oral
  • Instruct patient to take with or without food.
Intranasal
  • For intranasal use only.
  • A 10 mg dose can be achieved by the administration of a single 5 mg dose in each nostril.
Injection
  • For subcutaneous use only. Do not administer IM or IV.
  • In patients receiving doses other than 4 or 6 mg, only the 6 mg single-dose vials should be used.
  • An autoinjection device is available for use with the 4 or 6 mg prefilled syringe cartridges. With this device, the needle penetrates approximately one-fourth of an inch (5 to 6 mm). Administration sites should have an adequate skin and subcutaneous thickness to accommodate the length of the needle.
  • A needle-free injection is available for use with a 6 mg prefilled system. Administration sites should be on the abdomen or thigh with an adequate subcutaneous thickness to accommodate penetration of sumatriptan into the subcutaneous space. Administration should not be made within 2 inches of the navel. Do not administer to other areas of the body, including the arm.
  • Do not use sumatriptan needle-free injection if the tip of the device is tilted or broken off upon removal from packaging.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

Storage/Stability

Store tablets and nasal spray at 36° to 86°F. Store injection vials and cartridges at 36° to 86°F. Store needle-free injection at 59° to 86°F. Protect nasal spray and injection from light. Sumatriptan prefilled injection is for single-use only. Discard after use.

Drug Interactions

5-HT 1 agonists (eg, naratriptan)

Increased risk of vasospastic reactions; therefore, coadministration of two 5-HT1 agonists within 24 h of each other is contraindicated.

Ergot-containing drugs

May cause additive prolonged vasospastic reactions. Avoid use within 24 h of each other.

MAOIs

MAO-A inhibitors reduce sumatriptan clearance, increasing systemic exposure. Use of oral or intranasal forms of sumatriptan concomitantly with or within 2 wk following discontinuation of an MAOI is contraindicated. Concomitant use of injectable sumatriptan and an MAOI is not recommended. If the clinical situation warrants the combined use, give a reduced dose of sumatriptan and carefully monitor the patient.

Sibutramine

Serotonin syndrome, including altered consciousness, CNS irritability, motor weakness, myoclonus, and shivering, may occur. Coadministration is not recommended. If concurrent use cannot be avoided, monitor the patient for adverse reactions. Serotonin syndrome requires immediate medical attention.

SNRIs (eg, duloxetine), SSRIs (eg, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

There have been reports of life-threatening serotonin syndrome (eg, hyperreflexia, incoordination, weakness) with combined use of sumatriptan and an SNRI or SSRI. If coadministration is warranted, observe the patient carefully. Serotonin syndrome requires immediate medical attention.

Adverse Reactions

Cardiovascular

Flushing (7%); decreased or increased BP, palpitation, syncope (at least 1%); atrial fibrillation, cardiac arrest, cardiomyopathy, coronary artery vasospasm, MI, Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis, transient ischemia, ventricular fibrillation, ventricular tachycardia (postmarketing).

CNS

Dizziness/vertigo (12%); paresthesia (5%); drowsiness/sedation, malaise, or fatigue (3%); headache (2%); anxiety, migraine (at least 1%); cerebrovascular accident, dysphasia, panic disorder, serotonin syndrome, subarachnoid hemorrhage, vasculitis (postmarketing).

Dermatologic

Sweating (2%); exacerbation of sunburn, photosensitivity (postmarketing).

EENT

Unusual taste (25%); discomfort in nasal cavity or sinuses (4%); neck/throat/jaw discomfort, throat discomfort (3%); visual alterations (at least 1%); allergic rhinitis, ear, nose, and throat hemorrhage, external otitis, hearing loss, hyposalivation, nasal inflammation, phonophobia, photophobia, sensitivity to noise, sinusitis, tinnitus, upper respiratory inflammation (at least 1%); deafness, ischemic optic neuropathy, loss of vision, retinal artery occlusion, retinal vein thrombosis (postmarketing).

GI

Nausea, vomiting (14%); abdominal discomfort, diarrhea, dysphagia, gastric symptoms (at least 1%); colonic ischemia, ischemic colitis with rectal bleeding, xerostomia (postmarketing).

Hematologic

Hemolytic anemia, pancytopenia, thrombocytopenia (postmarketing).

Hypersensitivity

Hypersensitivity (at least 1%); allergic vasculitis, anaphylaxis/anaphylactoid reactions, angioneurotic edema, erythema, pruritus, rash, shortness of breath, urticaria (postmarketing).

Local

Injection-site reaction (59%); administration-site pain (2%); contusion, induration, lipoatrophy, lipohypertrophy, pain, redness, stinging, subcutaneous bleeding and swelling after subcutaneous administration (postmarketing).

Musculoskeletal

Neck pain or stiffness, weakness (5%); myalgia (2%); muscle cramps (at least 1%).

Respiratory

Dyspnea (at least 1%); bronchospasm (1%).

Miscellaneous

Atypical sensations (42%); tingling (14%); warm/hot sensation (11%); pain and other pressure sensations (8%); burning sensation, feeling of heaviness or pressure (7%); chest discomfort, feeling of tightness, numbness (5%); tightness in chest (3%); feeling strange, head tightness, pressure in chest (2%); acute renal failure, cyanosis, elevated LFTs, temporal arteritis (postmarketing).

Precautions

Monitor

Obtain ECG on the first use during the initial interval following administration in patients with risk factors for cardiac ischemia. Evaluate patients who experience signs or symptoms suggestive of angina following sumatriptan for the presence of coronary artery disease or a predisposition to Prinzmetal variant angina before administering additional doses of sumatriptan; monitor by ECG if dosing is resumed and similar symptoms recur. Periodically evaluate CV function in patients on long-term therapy. Evaluate patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud syndrome, following sumatriptan for atherosclerosis or predisposition to vasospasm.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Use is not recommended because elderly patients are more likely to have decreased hepatic function, are at a higher risk of coronary artery disease, and BP increases may be more pronounced.

Hypersensitivity

Life-threatening and fatal hypersensitivity reactions (eg, anaphylaxis or anaphylactoid) have been reported.

Renal Function

Use caution.

Hepatic Function

Use caution. Contraindicated in severe hepatic impairment.

Special Risk Patients

Use with caution in patients with diseases that may alter absorption, metabolism, or excretion of drugs (eg, hepatic or renal impairment); use with caution in patients with a history of epilepsy or conditions associated with lowered seizure thresholds.

Cardiac events/vasoconstriction

Serious coronary events, some resulting in death, can occur after use. Administer first dose in health care provider's office to patients at possible risk of unrecognized coronary disease. If symptoms consistent with angina occur, conduct ECG evaluation for ischemic changes. May cause coronary vasospasm in patients with a history of coronary heart disease. Rare reports of MI, major arrhythmias, angina symptoms, and death.

Cerebrovascular events

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported.

Chest, jaw, or neck tightness

Chest, jaw, or neck tightness is relatively common after administration. Only rarely have these symptoms been associated with ischemic ECG changes.

Diagnosis

Only use when a clear diagnosis has been established. Exclude other potentially serious neurologic conditions before treating patients not previously diagnosed with migraine or cluster headache or who experience a headache that is atypical for them. If a patient does not respond to the first dose, reconsider the diagnosis before administration of a second dose.

Hypertension

Elevation in BP, including hypertensive crisis, has been reported. Use with caution in patients with controlled hypertension.

Melanin binding

Because sumatriptan binds to melanin, it may accumulate in melanin-rich tissues (eg, eye), possibly causing toxicity after extended use.

Other vasospastic events

Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported. Transient and permanent blindness and partial vision loss have also been reported.

Overuse

Overuse has been associated with the exacerbation of headache; withdrawal of treatment may be necessary.

Serotonin syndrome

Life-threatening serotonin syndrome may occur, particularly when combined with serotonin reuptake inhibitors.

Overdosage

Symptoms

Ataxia, cyanosis, erythema of extremities, inactivity, injection-site reactions (eg, desquamation, hair loss, scab formation), mydriasis, paralysis, reduced respiratory rate, seizures, tremor.

Patient Information

  • Advise patient to read patient information leaflet before starting therapy and again with each refill.
  • Explain that drug is to be used only during migraine (or cluster headache if using injection) and does not prevent or reduce the number of attacks. Emphasize that drug is used only to treat actual migraine attack (or cluster headache if using injection) and should not be used to prevent headaches or treat headaches caused by other conditions.
  • Advise patient that drug is to be taken as soon as symptoms of migraine appear. A second dose may be taken if symptoms return, but no sooner than 2 h (1 h for injection) following the first dose. For a given attack, if there is no response to the first tablet, advise patient to not take a second dose without first consulting with health care provider.
  • Advise patient not to take more than 200 mg/day if using tablets, 40 mg/day if using nasal spray, or 12 mg/day if using injection.
  • Advise patient that safety of treating more than 4 headaches in a 30-day period has not been established and to inform health care provider if headaches are occurring more frequently.
  • Advise patient to immediately notify health care provider if any of the following occur after taking a dose of sumatriptan: severe chest pain or chest pain that does not go away; shortness of breath; sudden and/or severe stomach pain; swelling of the eyelids, face, or lips; wheezing.
  • Advise patient that if tightness, pain, pressure, or heaviness in the chest, throat, neck, or jaw occurs when using sumatriptan, to discuss these symptoms with health care provider before using again.
  • Advise patient to notify health care provider if feelings of tingling, heat, flushing, tiredness, dizziness, heaviness, or pressure occur after treatment.
  • Advise patient that drug may cause fatigue or dizziness and to use caution while driving or performing other activities requiring mental alertness.
  • Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
  • Instruct patient to continue taking prescribed migraine prophylactic medications daily as directed.
  • Advise patient not currently taking a migraine prophylactic drug to discuss the use of such drugs with health care provider.
  • Caution patients about the risk of serotonin syndrome, especially during combined use with SSRIs and SNRIs.
  • Injection
  • Ensure that patient or caregiver understands how to store, prepare, and administer the dose and dispose of used equipment and supplies.

Copyright © 2009 Wolters Kluwer Health.

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