Pharmacology Update

Zolmitriptan Tablets for Migraine Relief

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

Asecond triptan has been introduced into the multimillion dollar migraine market. Zolmitriptan (Zomig, Zeneca) joins sumatriptan (Imitrex) for the treatment of acute migraine. Several more triptans are currently working their way through the FDA approval process. Like sumatriptan, zolmitriptan is a selective serotonin (5-hydroxytryptamine, 5-HT) 1B/1D receptor agonist.1 Unlike sumatriptan, which is available in a self-injectable kit, as a nasal spray, or in an oral preparation, zolmitriptan is only available in an oral form. Recently, the FDA has approved intranasal dihydroergotamine, an ergot derivative, for the same indication.

Indications

Zolmitriptan is indicated for the acute treatment of migraine, with or without aura, in adults.

Potential Advantages

Zolmitriptan is well absorbed and has an oral bioavailability of about 40% compared to 15% for sumatriptan.2,3 This may be associated with lower inter-individual variability in efficacy. Zolmitriptan appears to penetrate the central nervous system (CNS) across an intact blood-brain barrier and has been reported to have both central and peripheral actions on the trigeminovascular system.3 Sumatriptan does not penetrate the CNS well.4 The clinical advantages of this dual action remain to be established.

Potential Disadvantages

As with sumatriptan, zolmitriptan should not be administered to patients with ischemic heart disease or those with symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal’s variant angina, or other significant underlying cardiovascular disease. Zolmitriptan should not be used in patients with uncontrolled hypertension. The same precautions exist for zolmitriptan as with sumatriptan regarding drug interactions with ergot-type drugs, MAO inhibitors, and SSRIs (e.g., fluoxetine, paroxetine, sertraline). Cimetidine doubles the half-life of zolmitriptan.5 Common side effects compared to placebo include nausea (6-8% vs 5%), dizziness (8-13% vs 4%), somnolence (7% vs 4%), paresthesia (6-10% vs 0%), warm sensation (5-6% vs 1%), and tightness of throat (3-5% vs 0%).4

Dosing Information

Zolmitriptan is supplied as 2.5 mg and 5 mg tablets. Patients should be started with the 2.5 mg dose or lower (1/2 of a 2.5 mg tablet). There is generally little added benefit with the 5 mg dose, and side effects are generally increased with the higher dose. Dosing with 2.5 mg appears to provide an optimal balance between efficacy and safety.4 If the headache returns, the dose may be repeated after two hours, not to exceed 10 mg within a 24-hour period. It is not clear whether a second dose would be beneficial if the initial dose was ineffective.5

In patients with moderate-to-severe hepatic impairment, a lower dose of zolmitriptan should be used and blood pressure should be monitored.5

Comments

Zolmitriptan is the second "triptan" to be introduced for the management of migraine headaches. With a 2.5 mg dose, the headache response rates in patients with a moderate or severe headache compared to placebo were 33-44% vs. 26% at one hour, 62-65% vs. 34-36% at two hours, and 70-75% vs. 32-37% at four hours. Headache pain free rates were 6-8% vs. 2-2% at one hour, 22-27% vs. 7-10% at two hours, and 38-45% vs. 11-13% at four hours.4,6 The headache recurrence rate is 37%.6 Statistical significance was achieved at two and four hours in two studies and at one hour in one study. Numerically, the response appeared to be similar to those reported for sumatriptan.3,7 A placebo-controlled study showed no significant difference in complete response between zolmitriptan 5 mg and sumatriptan 100 mg.8 Zolmitriptan also reduced the symptoms associated with migraine such as nausea, photophobia, and phonophobia.6 It has been reported to be effective in migraine associated with menses and is effective whether the headache is present on awakening or develops afterward.8 The tolerability of zolmitriptan is similar to that of sumatriptan.9

Clinical Implications

Migraine headache affects 8-12% of the general adult population, with greater prevalence in women. The one-year prevalence is 3-6% in men and 13-18% in women, with the highest prevalence between the ages of 25 and 55.10 Sumatriptan, the first triptan, has been a mainstay in the pharmacotherapeutic management.

Zolmitriptan provides an alternative to sumatriptan in the management of migraine headaches. Although it may have some theoretical advantages (e.g., CNS action, greater bioavailability), it is not clear if these advantages address some of the shortcomings of sumatriptan (e.g., headache recurrence, nonresponders). Zolmitriptan will be launched the first quarter of 1998. The 2.5 mg tablets are priced similar to sumatriptan 50 mg tablets.11 The wholesale acquisition cost per tablet for Zomig is $11.30 for the 2.5 mg tablets and $12.85 for the 5 mg tablets. Imitrex 25 mg is $9.45, and 50 mg is $10.70.

References

1. Martin GR. Cephalalgia 1997;17(suppl 18):4-14.

2. Dixon R, et al. Cephalalgia 1997;17(suppl 18):15-20.

3. Imitrex Product Information. Glaxo Wellcome; February 1997.

4. Rapoport AM, et al. Neurology 1997;49:1210-1218.

5. Zomig Product Information. Zeneca Pharmaceuticals; November 1997.

6. Solomon GD, et al. Neurology 1997;49:1219-1225.

7. Plosker GL, et al. Drugs 1994;47(6):622-651.

8. Schoenen J, et al. Cephalalgia 1997;17(suppl 18):28-40.

9. Edmeads JG, et al. Cephalalgia 1997;17(suppl 18):41-52.

10. Coukell AL, et al. Pharmacoeconomics 1997;11: 473-490.

11. F-D-C Reports—The Pink Sheet; December 1, 1997.

Gemfibrozil treatment of post-CABG patients with isolated low HDL has been associated with marked reduction in subsequent clinical events despite lack of any demonstrated angiographic benefit.

Which is not true about zolmitriptan?

a. The drug passes through the blood brain barrier.

b. The maximal dose is 10 mg daily.

c. It is available as a tablet and a nasal spray.

d. The drug is similar in efficacy to sumitriptan.