Rizatriptan an Option for Migraine in Sumatriptan Nonresponders

Allison Gandey

July 07, 2010

July 7, 2010 (Los Angeles, California) — Patients with migraine who have not experienced relief with sumatriptan may benefit from another 5-hydroxytryptamine receptor agonist, report researchers presenting here at the American Headache Society (AHS) 52nd Annual Scientific Meeting.

"Rizatriptan has greater oral bioavailability compared to sumatriptan," lead investigator Jeffrey Seeburger, PhD, from Merck in Upper Gwynedd, Pennsylvania, presented. "It is about 47% vs 14% and has a faster Tmax," he noted.

Rizatriptan (Maxalt) is a Merck product available in strengths of 5- and 10-mg tablets. Other products, such as almotriptan, naratriptan, and eletriptan, have also been shown to be effective in patients with migraine who do not respond to sumatriptan.

"Approximately 30% to 40% of patients report dissatisfaction with sumatriptan due to a lack of efficacy," Dr. Seeburger noted in a late-breaking poster presentation.

Response rate (percentage of attacks).

This Merck-funded study shows rizatriptan is effective compared with placebo in patients who tried 100-mg sumatriptan. The company did not provide a head-to-head comparison between its drug and other triptans.

This US-based multicenter, randomized, double-blind, crossover trial included 109 adults with migraine. Patients had taken sumatriptan but experienced no pain relief at 2 hours.

The trial had a 3-attack crossover design and patients received rizatriptan, 10-mg orally disintegrating tablets, for at least 2 migraine attacks and 1 placebo. Treatment continued for up to 4 months.

The primary endpoint was 2-hour pain relief. Relief was considered no pain or pain that reduced to mild. The secondary endpoint was 2-hour pain freedom.

Not surprisingly, investigators found that rizatriptan was superior to placebo in providing pain relief and pain freedom. They also report that rizatriptan was generally well tolerated.

Table 1. Adverse Event Summary

Event Rizatriptan, % (n = 102) Placebo, % (n = 100)
Upper abdominal pain 2.0 1.0
Nausea 3.9 0
Dizziness 3.9 1.0
Paraesthesia 2.0 1.0
Somnolence 2.0 0


Prescribing information for rizatriptan emphasizes the drug should not be given to patients with ischemic heart disease or other underlying cardiovascular problems. Because rizatriptan may increase blood pressure, it should not be administered to patients with uncontrolled hypertension.

Rizatriptan should not be used within 24 hours of treatment with another 5-hydroxytryptamine receptor agonist or an ergotamine-containing or ergot-type medication, such as dihydroergotamine or methysergide.

Rizatriptan should also not be administered to patients with hemiplegic or basilar migraine. The product is a second-generation triptan and has been on the US market since 1998.

In a recent review article, Hartmut Göbel, MD, from the Kiel Headache Center in Germany, pointed out the 7 currently available triptans show many similar characteristics, but there are also "some clinically relevant pharmacological differences."

One and done is what we're after.

Rizatriptan, 10 mg, he notes, has demonstrated higher response rates and a more rapid onset of action than sumatriptan, 100 mg, with a favorable tolerability profile (Expert Rev Neurother. 2010;10:499-506).

"Owing to the limited efficacy of sumatriptan," Dr. Göbel added, "a more effective triptan treatment is needed in the majority of patients with acute migraine attacks."

Asked by Medscape Medical News to comment, Fred Sheftell, MD, from the New England Center for Headache in Stamford, Connecticut, said "Though there are different pharmacokinetic profiles and interactions, there are 5 rapid-onset higher recurrence triptans." He lists sumatriptan and rizatriptan among them. "I don't see one as being distinctly superior to any other in clinical practice and among patients. It's a matter of finding the best profile for patient satisfaction."

Some will need parenteral administration, he notes, which may include nasal sprays or injection. Some may require simultaneous administration with a nonsteroidal anti-inflammatory drug for improved efficacy and reduced recurrence. Dr. Sheftell is the past president of the AHS.

"One and done is what we're after," he said, "to prevent and or reduce disability."

This study was funded by Merck. Lead study author Dr. Jeffrey Seeburger is an employee of the company. Dr. Göbel and Dr. Sheftell have worked on previous Merck-funded projects.

American Headache Society (AHS) 52nd Annual Scientific Meeting: Late-breaking poster 121. Presented June 26, 2010.


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