Zolmitriptan Nasal Spray An Important New Development in the Acute Treatment of Migraine

Zolmitriptan Nasal Spray An Important New Development in the Acute Treatment of Migraine

Carl G H Dahlöf
Published: US Neurological Disease 2006 Issue II
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Development of the triptans (5-HT 1B/1D) agonists has been a major breakthrough in the acute treatment of migraine and these agents are now considered first-line therapy for the treatment of moderate to severe attacks.1 Sumatriptan, the first triptan to the market, was launched in the early 1990s as a subcutaneous injection. Subsequently it has been marketed as a conventional oral tablet, nasal spray, suppository, and, most recently, an alternative oral-tablet form that disintegrates more rapidly in the stomach. The availability of sumatriptan was followed by a number of ‘second-generation’ triptans with improved pharmacokinetic properties and/or tolerability profiles. In order of their introduction, they are zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. All of the triptans are available as a conventional oral tablet or orally disintegrating variations of the tablet, but only sumatriptan and zolmitriptan provide alternative nonoral formulations.

Studies have shown that oral formulations are popular with migraine patients. In two studies, 80–88% of migraineurs selected a conventional tablet, a capsule, or an orally disintegrating tablet (ODT) as their preferred route of administration.2,3 Patients in another study were asked which formulations they would like to see more of in the future. The most frequently cited response was ODTs (73%), followed by skin patches (40%), conventional tablets (38%), nasal sprays (21%), syrups or liquids (18%), and injections (8%).4 This appeal of oral formulations is reflected in worldwide sales data, showing that oral formulations accounted for over 90% of triptan prescription sales in the 12 months to quarter 1 2004.5

Despite the popularity of oral formulations, they may not always be the most appropriate choice of treatment due to several disadvantages associated with this mode of administration. For example, oral absorption may be compromised by gastrointestinal dysmotility, a common symptom of migraine attacks.6 Another drawback of oral therapy is that patients with migraine-associated nausea or vomiting can experience difficulty taking a tablet. Also, vomiting during an attack will render their oral dose useless, and may leave patients unsure as to whether they should take another dose.

To date, alternatives to the oral route of administration have not been particularly popular with patients. Not surprisingly, many patients are reluctant to use a subcutaneous formulation because of the inconvenience and discomfort associated with self-injection. Sumatriptan nasal spray provided an alternative non-oral formulation to the subcutaneous injection, but many patients find the aftertaste intolerably unpleasant.7,8

Studies to investigate what patients want from a migraine treatment have found that high efficacy and rapid pain relief are the attributes that they value most highly.2,4 Importantly, patients want to be able to quickly control all symptoms of migraine in order to reduce the impact of the disease on their work, family and social lives.9

A new non-oral migraine formulation, the zolmitriptan nasal spray, has recently been introduced.This nasal spray formulation complements the conventional oral tablet and the ODT (Zomig Rapimelt) forms of zolmitriptan that are already available. Studies have shown that a dose of 5mg is optimal for the nasal spray formulation. The following sections review data from the pivotal pharmacokinetic, efficacy and tolerability and patient preference studies of zolmitriptan nasal spray.

Pharmacokinetics
Following administration by nasal spray, a proportion of the zolmitriptan dose is absorbed rapidly via the nasal mucosa. A study designed specifically to assess intranasal absorption of zolmitriptan demonstrated that approximately 30% of a single dose is absorbed via the nasal mucosa.10 This is reflected by studies showing that zolmitriptan is present in the plasma within two minutes of intranasal administration,11 and in the central nervous system within five minutes.12 Overall, intranasal absorption has been shown to contribute about 70% of exposure to zolmitriptan during the first hour after administration.10

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