Rizatriptan in the treatment of migraine

Figures & data

Figure 1 Patients reporting pain relief at time points up to 2 hours following dosing with rizatriptan or sumatriptan in a randomized, double-blind, placebo-controlled, cross-over study (Goldstein et al 1998). Adults with at least a 6-month history of migraine with or without aura were randomized to treat 2 sequential migraine attacks of moderate to severe intensity separated by at least 5 days. Treatment sequences included (a) rizatriptan 5 mg followed by sumatriptan 25 mg or vice versa, (b) rizatriptan 10 mg followed by sumatriptan 50 mg or vice versa, or placebo followed by placebo (data not shown). Hazard ratios for time to pain relief indicate that patients receiving rizatriptan were significantly more likely to achieve pain relief during the 2-hour period than patients receiving sumatriptan. *p < 0.05. Reproduced from Goldstein J, Ryan R, Jiang K, et al. 1998. Crossover comparison of rizatriptan 5 mg and 10 mg vs sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group. Headache, 38:737–47. Copyright © 1998, with permission from Blackwell Publishing Ltd.

Table 1 Comparative efficacy of rizatriptan in the acute treatment of migraine in randomized, double-blind, comparative studies

					Patients achieving efficacy measures at 2 hours (%)			Time to efficacy within 2 hours (hazard ratio)
Reference	Study design	n	Agents by dose (mg)		Headache response–pain relief	Pain-free	Normal function	Headache response–pain relief	Pain free	Overall efficacya
(Visser et al 1996)	PG, PC	449	R 10		52%bc	26%c	27%c	NR	NR	R 10 ≡S 100
			R 20		56%bc	35%c	32%c			R 20 ≡S 100
			R 40		67%bc	49%c	29%c			R 40 > S 200
			S 100		46%bc	22%c	25%c
			P		18%b	3%	5%
(Goldstein et al 1998)	CO, PC	1329	R 5	]	68%bde	33%de	44%dfg	1.16be	NR	R 5 > S 25
			S 25		62%d	28%d	39%dg	–
			R 10	]	72%bdf	41%df	48%dfg	1.14be		R 10 > S 50
			S 50		68%d	37%d	43%dg	–
			R (combined)	]	70%e	37%e	NR	1.15be
			S (combined)		65%	32%	NR	–
			P		38%	9%	21%	–
(Tfelt-Hansen et al 1998)	PG, PC	1099	R 5		60%bc	25%c	32%dg	NR	NR
			R 10		67%bc	40%ceh	42%cegh	1.20be		R 10 > S 100
			S 100		62%c	33%c	33%dg
			P		40%	9%	20%
(Kolodny et al 2004)	CO, PC	1447	R 5		66%di	33%e	44%i	1.22be	NR	R 5 > S 25
			S 25	]	58%d	27%	38%	–
			R 10		68%df	38%f	47%f	1.10bf		R 10 > S 50
			S 50	]	66%d	34%	43%	–
			P		NR	NR	NR	–
(Pascual et al 2000)	PC	766	R 10		71%cf	43%ce	45%ce	1.22f	1.26bf	R 10 > Z 2.5
			Z 2.5		67%c	36%c	37%c	–	–
			P		30%	10%	17%	–	–
(Bomhof et al 1999)	PC	522	R 10		69%ci	45%ci	39%ci	1.62bi	2.68i	R 10 > N 2.5
			N 2.5		48%c	21%d	23%	–	–
			P		22%	8%	14%	–	–
(Christie et al 2003)	CO	439	R 10		76%i	49%bi	57%i	2.05i	2.45i	R 10 > E/C 2/200
			E/C 2/200		47%	24%b	28%	–	–

a Conclusions reached by study authors based on consideration of all primary and secondary efficacy outcomes, including those not summarized here.

b Primary efficacy measure.

c p ≤ 0.005 vs placebo.

d p ≤ 0.05 vs placebo.

e p ≤ 0.05 vs comparator.

f Nonsignificant difference vs comparator (p>0.05).

g Comparison of all functional disability categories combined.

h p < 0.05 vs rizatriptan 5 mg.

i p ≤ 0.005 vs comparator.

Brackets indicate treatment groups compared in statistical analyses.

Abbreviations: CO, cross over; E/C, ergotamine–caffeine; n, patients who took study medication; N, naratriptan; PG, parallel group; PC, placebo-controlled; R, rizatriptan; S, sumatriptan; Z, zolmitriptan.

Table 2 Efficacy of rizatriptan in the acute treatment of migraine in retrospective analyses of comparative studies

	Proportion of patients achieving efficacy measures, % (odds ratio)
Agents by dose (mg) and compator	Pain-free at 2 hours (Adelman et al 2001)	Symptom-free at 2 hours (Adelman et al 2001)	24-hour sustained pain-free response (Adelman et al 2001)	Normal function at 2 hours (Bussone et al 2002)	Nausea-free at 2 hours (Lipton et al 2001)
R 10 S 25	38% (1.7)a27%	33% (1.6)a24%	27% (1.5)a20%	48% (1.7)a36%	68% (1.4)b59%
R 10 S 50	40% (1.2)b35%	33% (1.2)a28%	30% (1.2)b26%	47% (1.2)b42%	68% (1.5)b57%
R 10 S 100	40% (1.4)b33%	31% (1.7)a22%	27% (1.3)c23%	39% (1.4)b32%	66% (1.4)b58%
R 10 N 2.5	45% (3.3)a21%	30% (3.6)a11%	29% (2.0)a17%	39% (2.5)a22%	59% (1.8)b45%
R 10 Z 2.5	43% (1.4)b36%	31% (1.4)b24%	32% (1.6)b24%	45% (1.6)b36%	65% (1.3)c61%

a p ≤ 0.005 vs comparator.

b p ≤ 0.05 vs comparator.

c Nonsignificant difference vs comparator (p > 0.05).

Abbreviations: N, naratriptan; R, rizatriptan; S, sumatriptan; Z, zolmitriptan.

Figure 2 Median percent of migraine attacks in which patients achieved pain relief or pain-free status 2 hours after dosing. (a) Results in patients enrolled in an open-label, randomized, 6-month extension study who treated at least 1 moderate or severe migraine attack with rizatriptan 5-mg wafers (median of 16 attacks treated), rizatriptan 10-mg wafers (median 13 attacks treated), or standard care (primarily sumatriptan) (median 14 attacks treated). (b) Results in patients enrolled in a 12-month, randomized extension study who treated at least 1 migraine with rizatriptan 5-mg tablets (median of 14 attacks treated), rizatriptan 10-mg tablets (median 21 attacks treated), or standard care (primarily nonsteroidal anti-inflammatory drugs) (median 19 attacks treated). *p < 0.05 vs rizatriptan 5 mg and vs standard care. Figure 2a reproduced from Cady R, Crawford G, Ahrens S, et al. 2001. Long-term efficacy and tolerability of rizatriptan wafers in migraine. Medscape General Medicine, 3(4): http://www.medscape.com/viewarticle/408137 © 2001 Medscape; Figure 2b reproduced from Block GA, Goldstein J, Polis A, et al. 1998. Efficacy and safety of rizatriptan vs standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups. Headache, 38:764–71. Copyright © 1998, with permission from Blackwell Publishing Ltd.

Table 3 Clinical summary of rizatriptan in the treatment of migraine

Key pharmacologic features	Patient preference	Tolerability	Efficacy	Potential economic benefits
Rapidly and completely (~90%) absorbed from gastrointestinal tract Shorter time to maximum plasma concentration (1–1.5 hours) than other triptans Pharmacokinetics unaffected by occurrence of migraine attack Plasma concentration increased in patients receiving propranolol	Higher degree of patient satisfaction than other migraine- specific agentss Important reasons for patient preference include rapid pain relief, ease of use (wafer), and tolerability	Generally well tolerated Overall incidence of adverse events similar to other triptans Commonest adverse events (dizziness, somnolence, asthenia–fatigue, dry mouth, nausea, chest pain) are predominantly transient and mild to moderate in intensity Migraine-specific quality of life benefits comparable to other triptans	Efficacious in placebo-controlled trials Comparable or superior efficacy to sumatriptan 50 or 100 mg zolmitriptan 2.5 or 5.0 mg naratriptan 2.5 mg almotriptan 12.5 mg ergotamine/ caffeine 2 mg/200 mg Provides more rapid pain relief than other migraine-specific agents Consistent efficacy over 6–12 months More consistent intra-patient efficacy than other triptans One of three triptans closest to a hypothetical “ideal” Effective in menstrually associated migraine Effective for mild pain of early migraine attack Some evidence of efficacy in adolescents	Reduction in use of medical services vs prior therapies Reduced productivity costs compared with usual therapy Advantageous cost-effective ratio vs other triptans, including sumatriptan

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