Rizatriptan benzoate

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Maxalt (MSD)
10 mg wafers
Approved indication: migraine
Australian Medicines Handbook section 16.3.2

It is almost twenty years since the launch of sumatriptan, the first serotonin (5HT1) receptor agonist. While sumatriptan benefited many patients with migraine, it was not ideal because of its low oral bioavailability and short half-life. This led to the development of other 'triptans'.

Rizatriptan is a serotonergic agonist which mainly acts on 5HT1B and 5HT1D receptors. This constricts the extracerebral and intracranial arteries which become dilated during an attack of migraine.

The wafers have a bioavailability of 45%. Food may affect absorption, but appears to have no effect on efficacy. Rizatriptan is metabolised by monoamine oxidase so it should not be prescribed for patients who have taken monoamine oxidase inhibitors in the previous two weeks. Plasma concentrations are also increased by propranolol, so a lower dose of rizatriptan is recommended in patients taking this beta blocker. Most of the metabolites of rizatriptan are excreted in the urine. The half-life is similar to that of sumatriptan (2-3 hours).

An early dose-ranging study compared rizatriptan with sumatriptan and placebo. The study assessed 449 patients and found that headache was reduced within two hours in 18% of the placebo group, 46% of the sumatriptan group and 52% of the patients who took 10 mg rizatriptan. This dose relieved pain completely in 26% of patients compared with 22% of the sumatriptan group and 3% of the placebo group. The headache returned in 41% of the patients taking rizatriptan 10 mg and 41% of the sumatriptan group.¹ If the headache returns, patients can take another dose of rizatriptan, but doses must be at least two hours apart and not exceed 30 mg in 24 hours.

As rizatriptan has been marketed overseas for several years, there are many studies of its use in migraine, however only some of these studied the wafer formulation. Two hours after a dose, 66% of patients with moderate to severe headache will respond to a wafer and 47% will respond to a placebo.

A meta-analysis found more patients responded to a 10 mg dose of rizatriptan than to a 100 mg dose of sumatriptan. Significantly more were pain free after two hours, but the headache was more likely to return within 24 hours in patients taking rizatriptan.²

The meta-analysis was used to calculate the number of patients who need to be treated for 100 to have sustained relief for 24 hours. These figures were 490 for sumatriptan 100 mg, and 458 for rizatriptan 10 mg. To treat 100 patients successfully required a total of 534 doses of sumatriptan 100 mg, or 516 doses of rizatriptan 10 mg.³

Rizatriptan has also been compared with other analgesics for migraine. In one placebo-controlled study 200 patients were randomised to take rizatriptan tablets, paracetamol, or both. After two hours 90% of the patients taking both drugs had responded compared with 77% of the rizatriptan group, 70% of the paracetamol group and 46% of the placebo group. Over 24 hours 62% of the patients taking both drugs had sustained relief, but this was not statistically superior to the 53% of the rizatriptan group and the 42% of the paracetamol group.⁴

Adverse events occur at a similar frequency to reactions to sumatriptan 100 mg.² Common adverse effects of rizatriptan include tiredness and dizziness. Like other drugs in the class, rizatriptan can cause pain in the chest and neck. It is contraindicated in ischaemic heart disease or uncontrolled hypertension. There is a risk of serotonin syndrome, particularly in patients taking serotonin reuptake inhibitors. Ergot alkaloids should not be used within six hours of rizatriptan.

manufacturer provided additional useful information

The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Note on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).