Sumatriptan

Approved Indications:

• Acute Treatment of Migraine Attacks
  For the acute management of migraine with or without aura in adults.
• Acute Treatment of Cluster Headache
  Subcutaneous injection is approved for the acute treatment of cluster headaches.

Off-Label/Clinically Accepted Uses:

• Menstrual Migraine
  For short-term prevention of menstrual migraine (especially in women with predictable cycles).
• Migraine in Adolescents (12–17 years)
  Certain formulations (nasal spray, injection) are used off-label under clinical supervision.

Adults:

• Migraine (Oral):
  25 mg, 50 mg, or 100 mg as a single dose. If headache recurs, a second dose may be taken after at least 2 hours.
  Max: 200 mg/day.
• Migraine (Subcutaneous Injection):
  6 mg subcutaneously; may repeat after ≥1 hour if needed.
  Max: 12 mg/day.
• Migraine (Nasal Spray):
  5 mg, 10 mg, or 20 mg in one nostril; repeat once after ≥2 hours if needed.
  Max: 40 mg/day.
• Cluster Headache (Subcutaneous):
  6 mg subcutaneously once; may repeat after ≥1 hour.
  Max: 12 mg/day.

Pediatrics (Off-label):

• Ages 12–17 (Nasal Spray):
  5–20 mg intranasally as a single dose.
  Efficacy and safety to be assessed individually.

Elderly:

• Use with caution due to potential for decreased hepatic, renal, or cardiac function. Initiate at lowest effective dose.

Renal/Hepatic Impairment:

• Severe Hepatic Impairment:
  Use not recommended.
• Moderate Hepatic Impairment:
  Start with reduced oral dose (25 mg).

Administration Notes:

• Not intended for prophylactic therapy or for treatment of hemiplegic/basilar migraines.
• Oral tablets should be swallowed whole with water.
• Subcutaneous injections are typically given in the outer thigh or upper arm.

Sumatriptan is a selective 5-HT1B and 5-HT1D receptor agonist. It acts by binding to serotonin receptors in cranial arteries, leading to vasoconstriction, which counters the vasodilation thought to contribute to migraine pathophysiology. It also inhibits trigeminal nerve transmission, suppressing the release of pro-inflammatory neuropeptides such as CGRP (calcitonin gene-related peptide), thereby reducing neurogenic inflammation. This dual action results in alleviation of migraine headache and associated symptoms such as photophobia and nausea.

• Absorption:
  Oral bioavailability: ~15% due to extensive first-pass metabolism.
  Subcutaneous and nasal formulations offer faster onset.
• Distribution:
  Volume of distribution: ~2.4 L/kg. Low plasma protein binding (~14–21%).
• Metabolism:
  Primarily hepatic via monoamine oxidase-A (MAO-A) to inactive metabolites.
• Elimination:
  Renal excretion is major; ~60% of dose is excreted in urine.
  Half-life: 2 hours (subcutaneous), 2.5 hours (oral).
• Onset of Action:
  Subcutaneous: ~10 minutes
  Nasal spray: ~15–30 minutes
  Oral: ~30–60 minutes

• Pregnancy:
  FDA Pregnancy Category C (old system). Use only if potential benefit justifies potential risk.
  Human data are limited; some studies suggest possible vascular effects.
• Lactation:
  Sumatriptan is excreted in breast milk in small amounts.
  Breastfeeding may be resumed 12 hours after dosing or after discarding milk.
  Generally considered compatible with breastfeeding when used at standard doses.

• Primary Class: Antimigraine Agent
• Subclass: Serotonin (5-HT1B/1D) Receptor Agonist
• Generation: First-generation Triptan

• Hypersensitivity to sumatriptan or formulation components
• History of ischemic heart disease, coronary vasospasm (e.g., Prinzmetal’s angina)
• Cerebrovascular syndromes (stroke, TIA)
• Uncontrolled hypertension
• Severe hepatic impairment
• Peripheral vascular disease
• Use within 24 hours of other triptans or ergotamine-containing medications
• Hemiplegic or basilar migraine

• Cardiac Risk:
  May cause coronary artery vasospasm, myocardial infarction, or arrhythmia. Perform cardiovascular evaluation in patients with risk factors.
• Serotonin Syndrome:
  Risk increases when used with SSRIs, SNRIs, MAOIs, or other serotonergic agents.
• Seizures:
  Rare cases reported; caution in patients with epilepsy.
• Hepatic Impairment:
  Dose adjustment required or avoidance.
• Medication Overuse Headache (MOH):
  Chronic use can worsen headache frequency.
• Monitoring Required:
  Blood pressure monitoring, especially in elderly or hypertensive patients.

Common (≥1%):

• Central Nervous System:
  Dizziness, drowsiness, paresthesia, fatigue
• Cardiovascular:
  Chest discomfort or tightness, palpitations, flushing
• Gastrointestinal:
  Nausea, dry mouth
• Musculoskeletal:
  Heaviness, pressure sensation (neck, jaw, limbs)

Serious/Rare:

• Myocardial infarction, arrhythmias
• Stroke or transient ischemic attack
• Anaphylaxis or angioedema
• Hypertensive crisis
• Seizures
• Serotonin syndrome (especially with interacting drugs)

• Ergot Alkaloids (e.g., ergotamine):
  Additive vasospasm risk – avoid use within 24 hours.
• Other Triptans:
  Avoid within 24 hours due to additive vasoconstrictive effects.
• MAO Inhibitors (e.g., phenelzine):
  Increase plasma levels of sumatriptan – contraindicated within 2 weeks of MAOI use.
• SSRIs/SNRIs (e.g., fluoxetine, venlafaxine):
  Risk of serotonin syndrome – monitor closely.
• CYP450 Enzymes:
  Sumatriptan is primarily metabolized by MAO-A, not by CYP450.

• NICE (UK) Guidelines (recent update):
  Sumatriptan remains first-line for acute migraine.
  Nasal and subcutaneous routes emphasized for patients with severe nausea/vomiting.
• FDA Update:
  Reminder issued regarding serotonin syndrome risk with serotonergic drug combinations.
• Cluster Headache Use:
  Subcutaneous sumatriptan remains the gold standard for acute treatment of cluster headaches.

• Oral Tablets:
  Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C.
• Nasal Spray:
  Store between 2°C and 30°C; do not freeze.
• Injection (prefilled syringe):
  Store at 2°C to 25°C; protect from light and freezing.
• General Handling:
  Keep away from moisture and direct sunlight. Do not use if solution is discolored or contains particles.