Drug products: Maxalt, Maxalt Rapitab, Maxalt®, Maxalt® Rapitab®, Rizasmelt, Rizatriptan 2care4, Rizatriptan Abacus Medicine, Rizatriptan Actavis, Rizatriptan Aurobindo, Rizatriptan Ebb, Rizatriptan Glenmark, Rizatriptan Mylan, Rizatriptan Orifarm, Rizatriptan Sandoz, Rizatriptan STADA, Rizatriptan Teva
ATC code: N02CC04
Substances: rizatriptan, rizatriptan benzoate
Studies show the effect of rizatriptan in acute migraine to be similar in men and women.
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  which is slightly lower than three months prevalence reported from the US .
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 .
Women who have migraine with aura have an increased risk of ischemic stroke compared to women without migraine . A prospective controlled study showed that in patients with active migraine, female sex was significantly associated with the risk of ischemic stroke .
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 . Another indication for (parenteral) triptans is cluster headache . 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 . The men-women ratio has recently been estimated to 2.5, older studies show a more pronounced male risk . 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 . 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 .
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 .
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 .
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 .
According to trials performed by the pharmaceutical company, incidence of adverse reactions did not differ between men and women .
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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 .
Date of litterature search: 2020-01-17
- Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53(3):427-36. PubMed
- Stovner LJ, Andree C. Prevalence of headache in Europe: a review for the Eurolight project. J Headache Pain. 2010;11(4):289-99. PubMed
- Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-9. PubMed
- Dahlöf C, Linde M. One-year prevalence of migraine in Sweden: a population-based study in adults. Cephalalgia. 2001;21:664-71. PubMed
- Lipton RB, Munjal S, Alam A, Buse DC, Fanning KM, Reed ML, Schwedt TJ, Dodick DW. Migraine in America Symptoms and Treatment (MAST) Study: Baseline Study Methods, Treatment Patterns, and Gender Differences. Headache. 2018;58(9):1408-1426. länk
- Kurth T, Slomke MA, Kase CS, Cook NR, Lee IM, Gaziano JM, et al. Migraine, headache, and the risk of stroke in women: a prospective study. Neurology. 2005;64(6):1020-1026. länk
- Milhaud D, Bogousslavsky J, van Melle G, Liot P. Ischemic stroke and active migraine. Neurology. 2001;57(10):1805-11. PubMed
- Maxalt (rizatriptan). DailyMed [www]. US National Library of Medicine. [updated 2019-10-01, cited 2020-01-17]. länk
- Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol. 2018;17(1):75-83. PubMed
- Russell MB. Epidemiology and genetics of cluster headache. Lancet Neurol. 2004;3(5):279-83. PubMed
- Lee Y, Conroy JA, Stepanavage ME, Mendel CM, Somers G, McLoughlin DA et al. Pharmacokinetics and tolerability of oral rizatriptan in healthy male and female volunteers. Br J Clin Pharmacol. 1999;47:373-8. PubMed
- Goldberg MR, Lowry RC, Musson DG, Birk KL, Fisher A, De Puy ME et al. Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine. J Clin Pharmacol. 1999;39:192-9. PubMed
- Dooley M, Faulds D. Rizatriptan: a review of its efficacy in the management of migraine. Drugs. 1999;58:699-723. PubMed
- Musson DG, Birk KL, Panebianco DL, Gagliano KD, Rogers JD, Goldberg MR. Pharmacokinetics of rizatriptan in healthy elderly subjects. Int J Clin Pharmacol Ther. 2001;39:447-52. PubMed
- Visser WH, Winner P, Strohmaier K, Klipfel M, Peng Y, McCarroll K et al. Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from a double-blind, single-attack study and two open-label, multiple-attack studies. Headache. 2004;44:891-9. PubMed
- Bell CF, Foley KA, Barlas S, Solomon G, Hu XH. Time to pain freedom and onset of pain relief with rizatriptan 10 mg and prescription usual-care oral medications in the acute treatment of migraine headaches: a multicenter, prospective, open-label, two-attack, crossover study. Clin Ther. 2006;28:872-80. PubMed
- Franconi F, Finocchi C, Allais G, Omboni S, Tullo V, Campesi I et al. Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs other triptans. Neurol Sci. 2014;35 Suppl 1:99-105. PubMed
- von Euler, M, Keshani, S, Baatz, K, Wettermark, B. PP261 - Utilization of triptanes in Sweden; analyses of over the counter and prescriptions sales. Clinical Therapeutics. 2013;8, Suppl(35):e99.
- Frisk P, Sporrong SK, Ljunggren G, Wettermark B, von Euler M. Utilisation of prescription and over-the-counter triptans: a cross-sectional study in Stockholm, Sweden. Eur J Clin Pharmacol. 2016;72(6):747-54. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk
Reviewed by: Mia von Euler, Diana Rydberg
Approved by: Karin Schenck-Gustafsson