General Information

Imitrex (sumatriptan) is a serotonin (5-HT1B/1D) receptor agonist (triptan).

Imitrex is specifically indicated for the acute treatment of migraine with or without aura in adults and the acute treatment of cluster headache in adults.

Imitrex is supplied as a solution for subcutaneous injection, a tablet for oral administration and a nasal spray. The recommended dosing/administration for each formulation is as follows:

Subcutaneous Injection:

• The maximum single recommended adult dose of Imitrex injection for the acute treatment of migraine or cluster headache is 6 mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, lower doses (1 mg to 5 mg) may be used. For the treatment of cluster headache, the efficacy of lower doses has not been established. The maximum cumulative dose that may be given in 24 hours is 12 mg, two 6-mg injections separated by at least 1 hour. A second 6-mg dose should only be considered if some response to a first injection was observed.

Tablets:

• The recommended dose of Imitrex tablets is 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25-mg dose, but doses of 100 mg may not provide a greater effect than the 50-mg dose. Higher doses may have a greater risk of adverse reactions. If the migraine has not resolved by 2 hours after taking Imitrex tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24-hour period.

Nasal Spray:

• The recommended adult dose of Imitrex nasal spray for the acute treatment of migraine is 5 mg, 10 mg, or 20 mg. The 20-mg dose may provide a greater effect than the 5-mg and 10-mg doses, but may have a greater risk of adverse reactions. The 5-mg and 20-mg doses are given as a single spray in 1 nostril. The 10-mg dose may be achieved by the administration of a single 5-mg dose in each nostril. If the migraine has not resolved by 2 hours after taking Imitrex nasal spray, or returns after a transient improvement, 1 additional dose may be administered at least 2 hours after the first dose. The maximum daily dose is 40 mg in a 24-hour period. The safety of treating an average of more than 4 headaches in a 30-day period has not been established.

Mechanism of Action

Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Side Effects

Adverse effects associated with the use of Imitrex subcutaneous injection may include, but are not limited to, the following:

• injection site reactions
• tingling
• dizziness/vertigo
• warm/hot sensation
• burning sensation
• feeling of heaviness
• pressure sensation
• flushing
• feeling of tightness
• numbness

Adverse effects associated with the use of Imitrex tablets may include, but are not limited to, the following:

• paresthesia
• warm/cold sensation
• chest pain/tightness/pressure and/or heaviness
• neck/throat/jaw pain/tightness/pressure
• other sensations of pain/pressure/tightness/heaviness
• vertigo
• malaise/fatigue

Adverse effects associated with the use of Imitrex nasal spray may include, but are not limited to, the following:

• burning sensation
• disorder/discomfort of nasal cavity/sinuses
• throat discomfort
• nausea and/or vomiting
• bad/unusual taste
• dizziness/vertigo

Clinical Trial Results

Imitrex subcutaneous injection: 

• Migraine Headaches: In controlled clinical trials enrolling more than 1,000 patients during migraine attacks who were experiencing moderate or severe pain and 1 or more of migraine symptoms, onset of relief began as early as 10 minutes following a 6-mg Imitrex injection. In 2 randomized, placebo-controlled clinical trials of Imitrex injection 6 mg in 1,104 patients with moderate or severe migraine pain (Studies 2 and 3), the onset of relief was less than 10 minutes. Headache relief, as defined by a reduction in pain from severe or moderately severe to mild or no headache, was achieved in 70% of the patients within 1 hour of a single 6-mg subcutaneous dose of Imitrex injection. Approximately 82% and 65% of patients treated with Imitrex 6 mg had headache relief and were pain free within 2 hours, respectively. Imitrex injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attack.
• Cluster Headaches: The efficacy of Imitrex injection in the acute treatment of cluster headache was demonstrated in 2 randomized, double-blind, placebo-controlled, 2-period crossover trials (Studies 4 and 5). Patients aged 21 to 65 years were enrolled and were instructed to treat a moderate to very severe headache within 10 minutes of onset. Headache relief was defined as a reduction in headache severity to mild or no pain. In both trials, the proportion of individuals gaining relief at 10 or 15 minutes was significantly greater among patients receiving 6 mg of Imitrex injection compared with those who received placebo.

The efficacy of Imitrex tablets in the acute treatment of migraine headaches was demonstrated in 3 randomized, double-blind, placebo-controlled trials. Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 4 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours post-dose. A second dose of Imitrex tablets or other medication was allowed 4 to 24 hours after the initial treatment for recurrent headache. In all trials, doses of 25, 50, and 100 mg were compared with placebo in the treatment of migraine attacks. In 1 trial, doses of 25, 50, and 100 mg were also compared with each other. In all 3 trials, the percentage of patients achieving headache response 2 and 4 hours after treatment was significantly greater among patients receiving Imitrex tablets at all doses compared with those who received placebo. In 1 of the 3 trials, there was a statistically significant greater percentage of patients with headache response at 2 and 4 hours in the 50-mg or 100-mg group when compared with the 25-mg dose groups. There were no statistically significant differences between the 50-mg and 100-mg dose groups in any trial. For patients with migraine-associated nausea, photophobia, and/or phonophobia at baseline, there was a lower incidence of these symptoms at 2 hours (Trial 1) and at 4 hours (Trials 1, 2, and 3) following administration of Imitrex tablets compared with placebo.

Imitrex Nasal Spray has been studied in clinical trials with more than 3,700 patients to treat more than 10,000 attacks. In these studies, 55% to 64% of patients achieved headache relief at two hours with a 20 mg dose. In four out of five studies, there was a significantly greater percentage of patients with headache response at two hours in the 20 mg group when compared with the lower dose groups (5 mg and 10 mg).