Naratriptan Tablets: A New Triptan for Migraine
By William T. Elliott, MD, and James Chan, PharmD, PhD
A third triptan has joined the lucrative >migraine market. Glaxo Wellcome has received approval from the FDA to market naratriptan (Amerge) for the treatment of acute migraine. Naratriptan is a selective agonist at serotonin or 5-hydroxytryptamine (5HT) 1D/1B receptors. It has a pharmacologic profile similar to that of sumatriptan but is about two- to three-fold more potent.1 Naratriptan does not appear to possess any activity at other 5HT receptor subtypes, adrenergic, dopaminergic, muscarinic, or benzodiazepine receptors.2
Glaxo's new drug competes with its own sumatriptan (Imitrex) and with Zeneca's zolmitriptan (Zomig). These drugs are similar, although each has unique properties. Several other triptans are in the FDA pipeline and should be released in the next few years (e.g., eletriptan, almotriptan, and frovatriptan).
Indications
Naratriptan is indicated for the acute treatment of migraine attacks, with or without aura, in adults. The safety and effectiveness of naratriptan have not been established for cluster headache.
Potential Advantages
Naratriptan is well absorbed orally, with a bioavailability of about 70%. This is compared to sumatriptan's oral bioavailability of 14%.3 The elimination half life of naratriptan is about six hours, compared to two hours for sumatriptan. Naratriptan appears to be well tolerated, as the most common adverse event that occurred at a rate at least two times the placebo rate was malaise/fatigue (3%).2
Potential Disadvantages
Naratriptan may have a slower onset of action than sumatriptan. It appears that only four-hour response rates have been reported with naratriptan compared to two-hour and four-hour data reported for sumatriptan and zolmitriptan.4,5 Naratriptan may also have a lower response rate compared to sumatriptan and zolmitriptan. The percentage of patients with headache responses (from moderate or severe pain to mild or no pain) at four hours was 60-68% for 2.5 mg compared to 68-77% for sumatriptan 50 mg and 70-75% for zolmitriptan 2.5 mg.2,3,5,7 The response rates of naratriptan are similar to those reported for nasal sumatriptan at two hours, (55-64%).8 The above studies have generally similar placebo responses.
Dosing Information
The recommended initial dose of naratriptan is either 1 mg or 2.5 mg. A greater proportion of patients responds to the 2.5-mg dose than the 1-mg dose. The dose may be repeated after four hours if the headache returns or response is inadequate. No more than 5 mg should be administered in a 24-hour period.1 In patients with mild-to-moderate liver or renal impairment, the starting dose should be 1 mg and should not exceed 2.5 mg in a 24-hour period. Food does not affect the pharmacokinetics of naratriptan.2
Comments
Naratriptan is the third 5HT agonist to be approved by the FDA. It appears to be well tolerated but may have a slower onset of action and a lower success rate compared to its predecessors, sumatriptan and zolmitriptan. The published data for naratriptan are reported as four-hour response, and response is defined as reduction in headache severity from moderate or severe pain to mild or no pain. Since studies with sumatriptan, zolmitriptan, and rizatriptan have reported two-hour and four-hour response rates, this certainly creates the impression of a slower onset of action with naratriptan. Percentage of patients with no headache pain or complete headache relief, a more rigorous end point, has not been reported. However, of the patients that responded to naratriptan, the majority had relief of the headache at 24 hours, with no second dose of the medication or use of rescue medication.6
Clinical Implications
Naratriptan and rizatriptan (which will be reviewed in a future issue) are the recent additions to the "triptans." Naratriptan does not appear to offer any significant advantage in onset of action or efficacy over sumatriptan or zolmitriptan. The drug, however, is well tolerated and appears to have a favorable side effect profile. But, whether naratriptan's apparent benign side effect profile, good bioavailability, and long elimination half life will be clinically relevant remains to be determined. The average wholesale cost of naratriptan (1 mg or 2.5mg) is $14.92 per tablet, which is similar to sumatriptan 50 mg ($14.26) and more expensive than zolmitriptan 2.5 mg ($12.60).
References
1. Connor HE, et al. Cephalalgia 1997;17(3):145-152.
2. Amerge Product Information. Glaxo Wellcome, Inc. January 1998.
3. Perry CM, et al. Drugs 1998;55(6):889-922.
4. Ferrari MD. Lancet 1998;351:1043-1051.
5. Rapoport AM, et al. Neurology 1997;49:1210-1218.
6. Mathew NT, et al. Neurology 1997;49(6):1485-1490.
7. Solomon GD, et al. Neurology 1997;49:1219-1225.
8. Imitrex Nasal Spray Product Information. Glaxo Wellcome Inc, August 1997.
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