Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine

Abstract

Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatriptan is a second-generation triptan with a longer terminal elimination half-life in blood than other triptans (~26 hours). Three double-blind, randomized crossover preference studies have been recently conducted, assessing efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan, respectively. Frovatriptan showed favorable tolerability and sustained effect, with a significantly lower rate of relapse over 48 hours versus the other triptans. These findings were confirmed in a series of analyses of patient subsets from the three studies, including patients with menstrually related and oral contraceptive-induced migraine, hypertension, obesity, weekend migraine, as well as patients with migraine with aura. In all patient subsets analyzed, lower headache recurrence rates were observed versus the comparator triptans, indicating a more sustained pain-relieving effect on migraine symptoms. A further randomized, double-blind study demonstrated that frovatriptan given in combination with the fast-acting cyclooxygenase inhibitor dexketoprofen provided improved migraine pain-free activity at 2 hours, and gave more sustained pain-free activity at 24 hours, versus frovatriptan alone. These benefits were observed both when the combination was administered early (<1 hour after symptom onset) or late (>1 hour after onset). Different pharmacokinetic, but synergistic, properties between frovatriptan and dexketoprofen may make the combination of these agents particularly effective in migraine treatment, with rapid onset of action and sustained effect over 48 hours. These benefits, together with potential cost-effectiveness advantages versus other triptans could drive selection of the most appropriate treatment for acute migraine attacks.

Keywords: dexketoprofen; frovatriptan; menstrual; migraine; migraine with aura; triptans.

Figure 1

Treatment algorithm for migraine. Note: Republished from Touch Medical Media from An algorithm of migraine treatment, Evers S, Lisotto C. Eur Neurol Rev. 2013;8(2); permission conveyed through Copyright Clearance Center, Inc. Abbreviations: MOH, medication-overuse headache; NSAIDs, nonsteroidal anti-inflammatory drugs.

Figure 2

Cumulative hazard of recurrence over 48 hours during treatment with frovatriptan or comparators (n=346). Notes: Data are shown separately for each comparator (A) or by pooling together data from the three comparators (B). Reproduced from Neurol Sci. Frovatriptan versus other triptans in the acute treatment of migraine: pooled analysis of three double-blind, randomized, cross-over, multicenter, Italian studies. Volume 32(Suppl 1), 2011, pages S95–S98. Cortelli P, Allais G, Tullo V, et al. With permission of Springer.

Figure 3

Cumulative hazard of recurrence over 48 hours in females with menstrual migraine during treatment with frovatriptan versus comparators. Note: Reproduced from Allais G, Tullo V, Omboni S, et al. Efficacy of frovatriptan versus other triptans in the acute treatment of menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies. Neurol Sci. 2012; 33(Suppl 1):S65–S69.

Figure 4

Proportion (%) of pain-free at 2 and 4 hours, and of pain relief at 2 and 4 hours, after administration of frovatriptan 2.5 mg, frovatriptan 2.5 mg plus dexketoprofen 25 mg, and frovatriptan 2.5 mg plus dexketoprofen 37.5 mg, by early and late drug intake. Notes: White bars: frovatriptan 2.5 mg monotherapy. Gray bars: frovatriptan 2.5 mg plus dexketoprofen 25 mg. Black bars: frovatriptan 2.5 mg plus dexketoprofen 37.5 mg. *P<0.05 and between the combination treatment and the monotherapy; **P<0.01 between the combination treatment and the monotherapy. Reproduced from Neurol Sci. Early (≤1 h) vs late (>1 h) administration of frovatriptan plus dexketoprofen combination vs frovatriptan monotherapy in the acute treatment of migraine attacks with or without aura: a post hoc analysis of a double-blind, randomized, parallel group study. Volume 36 (Suppl 1), 2015, pages 161–167. Allais G, Bussone G, Tullo V, et al. With permission of Springer.