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

Figures & data

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.

Table 1 Overview of frovatriptan for the treatment of migraine

Pharmacologic characteristics	Efficacy	Safety	Patient preference	Cost-effectiveness
High affinity for 5-HT(1B/1D) receptors^Citation58 60%–70% of plasma maximum concentration achieved within 1 hour of dosing^Citation9 Time to maximum concentration 2–3 hours^Citation9 Longer half-life than other triptans (~26 hours)^Citation9 Elimination route and metabolism: hepatic metabolism via CYP1A2 isoenzyme of cytochrome P450; renal clearance accounts for ~40% of total clearance^Citation9 Recommended dose: 2.5 mg (tablets)^Citation35 Maximum daily dose: 5 mg^Citation35	Similar immediate efficacy to comparators (rizatriptan, zolmitriptan, and almotriptan)^Citation30 Greater sustained antimigraine effect versus comparators^Citation30 Effective in menstrually related migraine with lower risk of recurrence versus comparators^Citation19 When given with dexketoprofen, the combination is similarly effective regardless of early (<1 hour) or late (>1 hour) administration^Citation27 Effective in both migraine with and without aura (when taken in the headache phase)^Citation24	Generally well tolerated^Citation30 Most common AEs (dizziness, fatigue, paresthesia, headache, and vascular flushing) are transient, generally of mild-to-moderate intensity, and resolve spontaneously^Citation35 Favorable safety profile compared to other triptans^Citation30	Similar patient preference results versus other triptans^Citation13^–^Citation15	Model analysis suggests economical advantage versus other triptans^Citation49 Lower acquisition cost, need for fewer doses, and loss of fewer working hours versus other triptans^Citation49 Significantly more cost-effective than rizatriptan^Citation49

Abbreviation: AEs, adverse events.

Table 2 Summary of key studies and subanalyses evaluating the efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan

Study	Primary end points	Key secondary end points
Key studies
Frovatriptan versus rizatriptan^Citation13	Average preference score: 2.9±1.3 for frovatriptan; 3.2±1.1 for rizatriptan (P=NS)	Pain-free at 2 hours: No significant difference between treatments Recurrence within 48 hours according to protocol: 22% versus 32% for frovatriptan and rizatriptan, respectively; P<0.001 Recurrence within 48 hours according to IHS criteria: 21% versus 43% for frovatriptan and rizatriptan, respectively; P<0.001 Sustained pain-free at 48 hours: No significant difference between treatments Pain relief at 2 hours: No significant difference between treatments
Frovatriptan versus zolmitriptan^Citation14	Average preference score: 2.9±1.3 for frovatriptan; 3.0±1.3 for zolmitriptan (P=NS)	Pain-free at 2 hours: No significant difference between treatments Rate of recurrence within 48 hours: No significant difference between treatments Time to recurrence within 48 hours: Significantly better for frovatriptan, especially between 4 and 16 hours (P<0.05) Sustained pain-free at 48 hours: No significant difference between treatments Pain relief at 2 hours: No significant difference between treatments
Frovatriptan versus almotriptan^Citation15	Average preference score: 3.1±1.3 for frovatriptan; 3.4±1.3 for almotriptan (P=NS)	Pain-free at 2 hours: No significant difference between treatments Recurrence within 48 hours according to protocol: 28% versus 34% for frovatriptan and almotriptan, respectively; P<0.05 Recurrence within 48 hours according to IHS criteria: 30% versus 44% for frovatriptan and almotriptan, respectively; P<0.05 Sustained pain-free at 48 hours: No significant difference between treatments Pain relief at 2 hours: No significant difference between treatments
Subanalyses
Frovatriptan versus rizatriptan in menstrual migraine^Citation16	Pain relief at 2 hours: No significant difference between treatments Pain relief at 24 hours: No significant difference between treatments Pain-free at 2 hours: No significant difference between treatments Pain-free at 24 hours: No significant difference between treatments Recurrence within 24 hours: 10% versus 32% for frovatriptan and rizatriptan, respectively; P<0.01	Pain relief and pain-free after frovatriptan intake for MRM and non-MRM Pain relief at 2 hours: No significant difference between MRM and non-MRM Pain relief at 24 hours: No significant difference between MRM and non-MRM Pain-free at 2 hours: No significant difference between MRM and non-MRM Pain-free at 24 hours: No significant difference between MRM and non-MRM Migraine intensity: Significantly larger reduction with frovatriptan than with rizatriptan at 24 and 48 hours (P<0.01)
Frovatriptan versus zolmitriptan in menstrual migraine^Citation17	Pain relief at 2 hours: No significant difference between treatments Pain relief at 24 hours: No significant difference between treatments Pain-free at 2 hours: No significant difference between treatments Pain-free at 24 hours: No significant difference between treatments Recurrence within 24 hours: 15% versus 22% for frovatriptan and zolmitriptan, respectively; P<0.05	Pain relief and pain-free after frovatriptan intake for MRM and non-MRM Pain relief at 2 hours: No significant difference between MRM and non-MRM Pain relief at 24 hours: No significant difference between MRM and non-MRM Pain-free at 2 hours: No significant difference between MRM and non-MRM Pain-free at 24 hours: No significant difference between MRM and non-MRM
Frovatriptan versus almotriptan in menstrual migraine^Citation18	Pain relief at 2 hours: No significant difference between treatments Pain relief at 4 hours: No significant difference between treatments Pain relief at 24 hours: No significant difference between treatments Pain-free at 2 hours: No significant difference between treatments Pain-free at 4 hours: No significant difference between treatments Pain-free at 24 hours: No significant difference between treatments Recurrence within 24 hours: 8% versus 21% for frovatriptan and rizatriptan, respectively; P<0.05 Recurrence within 48 hours: 9% versus 24% for frovatriptan and rizatriptan, respectively; P<0.05	Migraine intensity: Significantly larger reduction with frovatriptan than with almotriptan at 24 and 48 hours (P<0.05)
Frovatriptan versus comparators in menstrual migraine: Pooled analysis^Citation19	Pain relief at 2 hours: No significant difference between frovatriptan versus comparators Pain relief at 4 hours: No significant difference between frovatriptan versus comparators Pain relief at 24 hours: No significant difference between frovatriptan versus comparators Pain-free at 2 hours: No significant difference between frovatriptan versus comparators Pain-free at 4 hours: No significant difference between frovatriptan versus comparators Pain-free at 24 hours: No significant difference between frovatriptan versus comparators Recurrence within 24 hours: 11% versus 24% for frovatriptan and comparators, respectively; P<0.05 Recurrence within 48 hours: 15% versus 26% for frovatriptan and comparators, respectively; P<0.05	N/A
Frovatriptan versus comparators in oral contraceptive-induced migraine: Pooled analysis^Citation20	Pain relief at 2 hours: No significant difference between frovatriptan versus comparators Pain relief at 24 hours: Frovatriptan versus comparators Pain-free at 2 hours: No significant difference between frovatriptan versus comparators Pain-free at 24 hours: 71% versus 60% for frovatriptan and comparators, respectively; P<0.05 Recurrence within 24 hours: 17% versus 27% for frovatriptan and comparators, respectively; P<0.05 Recurrence within 48 hours: 21% versus 31% for frovatriptan and comparators, respectively; P<0.05	N/A
Fovatriptan versus comparators in hypertensive and normotensive subjects^Citation21	Pain relief at 2 hours: Significantly lower for hypertensive versus normotensive subjects for either frovatriptan or comparators (41% versus 52% for frovatriptan; P<0.05 and 48% versus 58% for comparators; P<0.05) Pain-free at 2 hours: No significant difference between hypertensive and normontensive subjects for either frovatriptan or comparators Recurrence within 48 hours: No significant difference between hypertensive and normotensive subjects for frovatriptan; significantly larger in hypertensive versus normotensive subjects for comparators (62% versus 44%; P<0.05)	N/A
Frovatriptan versus comparators in obese and normal-weight subjects^Citation22	Pain relief at 2 hours: No significant difference between frovatriptan versus comparators in either nonobese or obese subjects Pain-free at 2 hours: No significant difference between frovatriptan versus comparators in either nonobese or obese subjects. Significantly greater in nonobese versus obese subjects for both frovatriptan (30% versus 24%, respectively; P<0.05) and comparators (34% versus 27%, respectively; P<0.05) Recurrence within 48 hours: No significant difference between nonobese versus obese subjects with frovatriptan, but significantly higher in obese subjects with comparators (P<0.05). Significantly lower with frovatriptan versus comparators in both nonobese (26% versus 36%; P<0.05) and obese subjects (27% versus 49%; P<0.05)	N/A
Frovatriptan versus comparators in weekend migraine^Citation23	Pain relief at 2 hours: No significant difference between weekend and workday attacks for either frovatriptan or comparators Pain-free at 2 hours: No significant difference between weekend and workday attacks for either frovatriptan or comparators Recurrence within 48 hours: 17% versus 30% for weekend versus workday attacks with frovatriptan; P<0.05; no significant difference between frovatriptan versus comparators	N/A
Frovatriptan versus comparators in migraine with aura: Pooled analysis^Citation24	Pain-free at 2 hours: 29.8% versus 10.7% for frovatriptan versus rizatriptan, respectively; P<0.05; no significant difference between frovatriptan versus other comparators Pain-free at 4 hours: No significant difference between frovatriptan versus comparators Recurrence within 24 hours: 26.3% versus 42.9% for frovatriptan versus rizatriptan, respectively; P<0.05; no significant difference between frovatriptan versus other comparators Recurrence within 48 hours: 66.7% for frovatriptan versus 89.3% for rizatriptan (P=0.025) and 91.7% for zolmitriptan (P=0.019); no significant difference between frovatriptan versus almotriptan	Migraine intensity at 2 hours: 1.2±1.0 for frovatriptan versus 1.6±1.0 for other triptans; P<0.05 Migraine intensity at 4 hours: 0.5±0.6 for frovatriptan versus 1.2±1.1 for other triptans; P<0.001 Migraine intensity at 24 hours: No significant difference between frovatriptan versus comparators Migraine intensity at 48 hours: No significant difference between frovatriptan versus comparators
Frovatriptan versus zolmitriptan in migraine with aura^Citation25	Pain relief at 2 hours: No significant difference between treatments Pain relief at 4 hours: No significant difference between treatments Pain-free at 2 hours: 45.8% for frovatriptan versus 16.7% for zolmitriptan (P<0.05) Pain-free at 4 hours: No significant difference between treatments Recurrence within 48 hours: 9% versus 24% for frovatriptan and rizatriptan, respectively; P<0.05 Sustained pain-free at 48 hours: 33.3% for frovatriptan versus 8.3% for zolmitriptan (P<0.05)	N/A

Abbreviations: IHS, International Headache Society; MRM, menstrually related migraine attacks; N/A, not applicable; NS, not significant.

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.³⁰

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–S69.¹⁹

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.²⁷

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