Rizatriptan

Additional information

Migraine is twice as common in women as in men [1-3]. In a Swedish population-based study the one-year prevalence was 9.5% in men and 16.7 % in women [4] which is slightly lower than three months prevalence reported from the US [1].

Among adults with migraine, sex and gender differences were found in a cross-sectional longitudinal internet-based study (11 049 women, 4 084 men). Compared with men, women had significantly higher amount of monthly headache days, were more likely to have been diagnosed with migraine and to report headache-related disability and cutaneous allodynia. Among prescription medication users, women took more triptans than men, while men were more likely to take opioids and, besides oral formulations, use nasal spray and injectable medication. Men also used more daily oral preventive medication than women [5].

Women who have migraine with aura have an increased risk of ischemic stroke compared to women without migraine [6]. A prospective controlled study showed that in patients with active migraine, female sex was significantly associated with the risk of ischemic stroke [7].

It should be noted that most studies include more women than men, and the low number of men included can affect the ability to make statistically significant analyses.Rizatriptan is used to treat acute migraine attacks [8]. Another indication for (parenteral) triptans is cluster headache [9]. This is a trigeminal autonomic cephalgia with very painful, unilateral and short-lasting headache attacks. Cluster headache is rare with an estimated prevalence of 0.1%. In contrast to migraine, cluster headache is more common in men than in women [9]. The men-women ratio has recently been estimated to 2.5, older studies show a more pronounced male risk [10]. Smoking is a risk factor for cluster headache and the increased risk in women has been associated with more smoking in women [9, 10].

Pharmacokinetics and dosing

The pharmacokinetics of single oral doses of rizatriptan 2.5-15 mg administrated to healthy volunteers was studied in a randomized, crossover study (12 men, 12 women). The mean AUC of oral rizatriptan was 19-35% higher in women than in men. However, the difference is not likely to be of clinical relevance. Plasma clearance of rizatriptan was about 25% higher in men than in women. No difference in the dose-effect relationship between men and women was noted [11]. In another study (6 men, 6 women), where healthy volunteers received a single dose rizatriptan 10 mg, half-life was longer in men. Other pharmacokinetic parameters showed no sex differences [12, 13]. No pharmacokinetic differences between elderly men and women have been found [14].

Effects

The efficacy of rizatriptan 5 mg in adolescents (12-17 years old) was established in two randomized, placebo-controlled trials (212 men, 263 women). Rizatriptan 5 mg was shown to be more effective than standard care (patient’s usual migraine therapy) during long-term use (over 1 year). Treatment effects for pain relief were not dependent on patient’s sex [15].

Time to pain freedom in acute migraine with rizatriptan 10 mg was compared to standard care in a prospective, open-label study (197 men, 1292 women; mean age 41.7 years). There were no significant differences in time to pain freedom between men and women [16].

Results from randomized, double-blind studies of migraineurs (66 men, 280 women) show no sex differences in response to frovatriptan 2.5 mg, rizatriptan 10 mg, zolmitriptan 2.5 mg or almotriptan 12.5 mg [17].

Adverse effects

According to trials performed by the pharmaceutical company, incidence of adverse reactions did not differ between men and women [8].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

Swedish population studies on dispensed triptans found a marked gender difference with a 3.6 times higher prevalence of triptan use in women [18, 19]. In contrast, over the counter use did not show any difference between men and women [19].