Zolmitriptan

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.Zolmitriptan 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

There are small pharmacokinetic studies of zolmitriptan showing varying results, none which were adjudicated to be of clinical importance [11, 12]. Other studies found differences in pharmacokinetics only between young men and women (18-39 years) but not in the elderly (65-75 years) [13, 14]. Although some sex differences in zolmitriptan pharmacokinetics have been reported in young adults [11-14], no dosage adjustment based on patient’s sex is recommended. [15].

Effects

Headache relief after administration of zolmitriptan has been evaluated in open-label clinical trials. Two-hour headache response rates to an initial dose of 2.5 mg or 5 mg zolmitriptan were 85% and 79-81%, respectively. Responses were unaffected by patient’s sex [16, 17]. Also, the pharmaceutical company reports that the efficacy of zolmitriptan was similar in men and women, for both drug formulations [8].

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 [18].

Adverse effects

Tolerability of zolmitriptan was evaluated in an international, open-label study (288 men, 1769 women). The types of adverse events observed were similar in men and women, although the incidence of adverse events was slightly higher in women (78%) than men (61%) [17].

A placebo-controlled clinical trial (1540 men, 1210 women) reported that the nature and type of adverse events were similar in men and women, although the frequency of reported adverse events was higher in women (48%) than men (30%). This sex difference was also observed in patients who received placebo and may reflect a difference between men and women in adverse event reporting. The frequency of serious adverse events did not differ between men and women [19]. Contrary to this, the pharmaceutical company reports that there were no sex differences in incidence of adverse events in controlled clinical trials [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 [20, 21]. In contrast, over the counter use did not show any difference between men and women [21].