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Dysmenorrhea and menstrual migraine may share a common pathogenic pathway. Both appear to be mediated, in part, by an excess of prostaglandin production that occurs during menstruation.Data were pooled from two replicate randomized controlled trials of 621 adult menstrual migraineurs with dysmenorrhea who treated migraine with sumatriptan-naproxen or placebo. Along with headache symptoms, nonpain menstrual symptoms (bloating, fatigue, and irritability) and menstrual pain symptoms (abdominal and back pain) were recorded at the time periods of 30 minutes and 1, 2, 4, and 4-24 hours. Relief of menstrual symptoms was compared using a Cochran-Mantel-Haenszel test. Logistic regression was used to determine the odds of a headache response with increasing numbers of moderate to severe dymenorrheic symptoms.Sumatriptan-naproxen was superior to placebo for relief of tiredness, irritability, and abdominal pain at the time periods of 2, 4, and 4-24 hours (p≤0.023); back pain at the time periods of 4 and 4-24 hours (p≤0.023); and bloating at 4-24 hours endpoint (p=0.01). The odds ratios (ORs) of attaining migraine pain freedom for 2 hours and for sustained 2-24 hours decreased as moderate to severe dysmenorrhea symptoms increased with sumatriptan-naproxen versus placebo.Treatment with sumatriptan-naproxen may provide relief of menstrual symptoms and migraine in female migraineurs with dysmenorrhea. The presence of moderate to severe dysmenorrhea symptoms is associated with decreased response rates for menstrual migraine, suggesting that the co-occurrence of these disorders may negatively impact the results of migraine-abortive therapy.

Objective Probable migraine is a common, disabling migraine subtype fulfilling all but one of the diagnostic criteria for migraine. This study was conducted to evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura. Methods Patients treated a headache of probable migraine without aura when pain was moderate or severe with sumatriptan/naproxen sodium ( n = 222 intent-to-treat (ITT)) or placebo ( n = 221 ITT/complete case analysis a ) in this randomized, double-blind, parallel-group study. Results Sumatriptan/naproxen sodium was more effective than placebo with respect to the co-primary efficacy endpoints two-hour pain-free response (29% sumatriptan/naproxen sodium vs 11% placebo, p Conclusion Sumatriptan/naproxen sodium is effective in the acute treatment of probable migraine as demonstrated by higher rates of freedom from pain and restoration of function.

(Headache 2010;50:357-373) Objective.— To describe the pharmacokinetic and safety profiles of sumatriptan 85 mg formulated with RT Technology (RT) and naproxen sodium 500 mg in a fixed-dose combination tablet (sumatriptan/naproxen sodium) that targets both serotonergic dysmodulation and inflammation in migraine. Methods.— Six open-label, crossover studies were conducted in healthy volunteers (Studies 1, 2, 3, 4, 5) or patients with migraine (Study 6). Results.— Consistently across studies, naproxen administered as a component of sumatriptan/naproxen sodium demonstrated a delayed-release profile similar to that of an enteric-coated product. Naproxen from the combination tablet showed a delayed time to peak plasma concentration and lower peak plasma concentration while exposures (area under the plasma concentration–time curve) were similar. The peak plasma concentration for naproxen was approximately 36% lower and the time to peak plasma concentration approximately 4 hours later when naproxen was administered as sumatriptan/naproxen sodium compared with a single naproxen sodium 550 mg tablet. Sumatriptan peak plasma concentration and area under the plasma concentration–time curve after administration of sumatriptan/naproxen sodium (containing sumatriptan 85 mg) were comparable to those after administration of a commercially available sumatriptan 100 mg (RT) tablet. Sumatriptan time to peak plasma concentration occurred, on average, 30 minutes earlier with sumatriptan/naproxen sodium compared with sumatriptan 100 mg (RT). No clinically significant differences between sumatriptan/naproxen sodium and sumatriptan tablets 100 mg (RT) were identified with respect to electrocardiograms, blood pressure, or heart rate. In addition, food had no significant effect on the bioavailability of naproxen or sumatriptan after administration of sumatriptan/naproxen sodium but slightly delayed the time to peak plasma concentration of sumatriptan by approximately 40 minutes. The pharmacokinetics of sumatriptan and naproxen did not differ according to whether sumatriptan/naproxen sodium was administered during a migraine attack or a migraine-free period. The pharmacokinetics of 2 sumatriptan/naproxen sodium tablets administered 2 hours apart were consistent with the pharmacokinetic predictions from a single dose of the combination tablet. The adverse-event profile of the sumatriptan/naproxen sodium combination tablet did not appear to differ from that of the individual components of the same or similar dosage strengths administered alone or in combination. In addition, the incidence of adverse events with 2 sumatriptan/naproxen sodium tablets administered 2 hours apart was lower than that with the single dose. Conclusion.— The combination tablet of sumatriptan/naproxen sodium has unique pharmacokinetic properties. The rapid absorption of sumatriptan with the delayed-release properties of naproxen sodium from sumatriptan/naproxen sodium might contribute to its therapeutic advantage over monotherapy with either component. No clinically meaningful effects of food, administration during a migraine attack, or administration of a second tablet (2 hours after initial dose) on the pharmacokinetics or safety of sumatriptan/naproxen sodium were observed.

Two identical randomized, placebo-controlled, crossover studies were conducted to evaluate consistency of response to sumatriptan/naproxen sodium 85/500 mg (S/NS) over four attacks in adults with migraine. Patients were instructed to treat within 1 h of pain onset while pain was mild. Co-primary end-points were pain-free response at 2 h (2hPF) and 24-h sustained pain-free response (24hSPF) calculated as percentages of all attacks. In Study 1, 570 patients treated 1693 attacks with S/NS and 424 with placebo. In Study 2, 565 patients treated 1678 attacks with S/NS and 422 with placebo. Compared with placebo, S/NS conferred higher 2hPF rates (Study 1: S/NS 52%, placebo 25%; Study 2: S/NS 50%, placebo 20%; both P < 0.001) and higher 24hSPF rates (Study 1: S/NS 37%, placebo 17%; Study 2: S/NS 34%, placebo 12%; both P < 0.001). 2hPF was reported in at least two of the first three S/NS-treated attacks in 55.0% of patients in Study 1 and 52.1% of patients in Study 2. 24hSPF was reported in at least two of the first three S/NS-treated attacks in 35.7% of patients in Study 1 and 32.6% of patients in Study 2. The incidences of any adverse event and of specific adverse events were low and generally similar between S/NS and placebo.

Objective.— To evaluate efficacy and tolerability of a single, fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan/naproxen sodium) vs placebo in migraineurs who had discontinued treatment with a short-acting triptan because of poor response or intolerance. Background.— Triptan monotherapy is ineffective or poorly tolerated in 1 of 3 migraineurs and in 2 of 5 migraine attacks. In April, 2008, the Food and Drug Administration approved the combination therapy sumatriptan/naproxen sodium, developed specifically to target multiple migraine mechanisms. This combination product offers an alternative migraine therapy for patients who have reported poor response or intolerance to short-acting triptans. Methods.— Two replicate, randomized, multicenter, double-blind, placebo-controlled, 2-attack crossover trials evaluated migraineurs who had discontinued a short-acting triptan in the past year because of poor response or intolerance. Patients were instructed to treat within 1 hour and while pain was mild. Results.— Patients (n = 144 study 1; n = 139 study 2) had discontinued an average of 3.3 triptans before study entry. Sumatriptan/naproxen sodium was superior (P

OBJECTIVES To evaluate the long-term safety and tolerability of sumatriptan-naproxen sodium for the treatment of moderate to severe acute migraines and to assess the safety of administration of an optional second dose. PATIENTS AND METHODS A 12-month, multicenter, open-label safety study was conducted in adults treated for migraine attacks of moderate to severe intensity from April 14, 2004, to August 18, 2005. Safety evaluations included adverse events and laboratory tests. RESULTS Of 600 patients enrolled, 565 (94%) were treated for at least 1 migraine. Of treated patients, 414 (73%) and 362 (64%) completed 6 and 12 months of treatment, respectively. Of the 24,485 attacks treated, 17,144 (70%) were treated with only 1 dose. On average, patients treated 5 migraine attacks per month, with a median of 6 days between attacks. The most common treatment-related adverse events were nausea, muscle tightness, and dizziness. Fourteen patients reported 1 or more serious adverse event with only 1 judged probably related to treatment. No deaths occurred. Eight percent of patients discontinued participation in the study because of adverse events or pregnancy. The rates of adverse events reported were no higher after treatment with 2 tablets (at least 2 hours apart) compared with 1 tablet. CONCLUSIONS In this 12-month data set of more than 24,000 migraine attacks in 565 patients, sumatriptan-naproxen sodium formulated in a single tablet was well tolerated when used episodically for the treatment of acute migraine. The adverse events did not differ from those expected for the individual components alone, and no new or unexpected findings occurred.

A novel composite endpoint, sustained pain-free/no adverse events, was recently proposed as a more rigorous means of capturing in a single measure the attributes of migraine pharmacotherapy that patients consider most important: rapid and sustained pain-free response with no side-effects. Using pooled data from two replicate randomized, double-blind, parallel-group, placebo-controlled studies, this post hoc analysis compared the fixed-dose combination tablet sumatriptan/naproxen sodium (n = 726) with sumatriptan monotherapy (n = 723), naproxen sodium monotherapy (n = 720), and placebo (n = 742) with respect to sustained pain-free/no adverse events and closely related composite measures. Sustained pain-free/no adverse events was defined as having both a sustained pain-free response from 2 through 24 hours post-dose with no use of rescue medication and having no adverse events within up to 5 days after dosing with study medication. The percentage of patients with sustained pain-free/no adverse events was 16% with sumatriptan/naproxen sodium compared with 11%, 9% and 7% for sumatriptan, naproxen sodium and placebo, respectively (p

Background: Rescue medication options that are consistent with the product labeling for sumatriptan/ naproxen sodium (S/N) and that have been permitted in ≥1 clinical trial include the use of a second tablet of S/N, sumatriptan tablets (to a total daily dose of 200 mg), and naproxen sodium tablets (within the maximum limits recommended in the labeling). Sumatriptan subcutaneous (SC) injection might be especially useful as rescue medication mostly because of its rapid onset of activity. Objective: The aim of this study was to assess the pharmacokinetics and tolerability of sumatriptan SC used as rescue medication after the administration of oral S/N for the treatment of migraine. Methods: This randomized, open-label, 3-period crossover study compared the exposure to sumatriptan (Cmax and AUC to 14 hours after the administration of the second dose [AUC 0–14 ]) between 3 treatment regimens: an initial dose of S/N 85/500 mg followed 2 hours later by sumatriptan 4 or 6 mg SC (S/N + S4 and S/N + S6, respectively) (test), or sumatriptan 100 mg PO (2 tablets administered 2 hours apart) (S100 + S100) (reference). Healthy adults aged 18 to 55 years were randomly assigned to receive all 3 regimens in a randomized sequence. On day 1 of each treatment period, continuous cardiovascular monitoring (ECG telemetry), serial 12-lead ECG, and serial blood pressure (BP) measurements were conducted 1 hour before to 10 hours after the administration of the first dose. Blood samples for pharmacokinetic assessment were collected up to 14 hours after the administration of the first dose. Adverse events (AEs) were monitored from the time of consent until study completion. Participants returned to the clinic for pharmacokinetic blood sampling (for S/N + S4 and S/N + S6) and for tolerability assessment at 24, 48, and 72 hours after S/N administration. Results: A total of 30 healthy adults were randomized. Five withdrew prematurely (3, withdrawn consent; 1, AE; and 1, protocol deviation). Half of the subjects were men, the mean age was 27.8 years, and the mean weight was 79.3 kg (range, 54.6–100.8 kg). With S/N + S4, sumatriptan Cmax and AUC 0–14 did not exceed those with S100 + S100. Sumatriptan Cmax was 1.26-fold higher with S/N + S6 than with S100 + S100. Sumatriptan AUC 0–14 with S/N + S6 was not significantly greater than that with S100 + S100. Differences in serial BP measurements between the SC and S100 + S100 regimens were not statistically significant. The numbers of subjects in whom any AE was reported were 10 (37%) with S/N + S4, 14 (54%) with S/N + S6, and 13 (48%) with S100 + S100. Conclusions: Sumatriptan 4 and 6 mg SC administered 2 hours after an S/N tablet yielded sumatriptan exposure that did not exceed that of S100 + S100. Cmax with the S/N + S6 regimen was 1.26-fold higher than reference values. Both regimens were reasonably well tolerated. Randomized controlled trials are needed to test the efficacy and tolerability of these SC regimens. ClinicalTrials.gov identifier: NCT00875784.

To evaluate the efficacy and tolerability of sumatriptan-naproxen during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea.Two replicate randomized, multicenter, double-blind, placebo-controlled, trials of adults with menstrual migraine and dysmenorrhea were conducted. Participants treated their menstrual migraine attack during the mild pain phase (within 1 hour of onset) with sumatriptan 85 mg and naproxen sodium 500 mg in a single fixed-dose formulation (sumatriptan-naproxen) or placebo. The primary endpoint was 2-hour pain-free response.Sumatriptan-naproxen was statistically superior to placebo in both studies (n=311, Study 1; n=310, Study 2) for 2-hour and, 2- to 24-hour sustained pain-free response, use of headache and menstrual rescue medications, and several nonpain menstrual symptom categories. Two-hour pain-free rates were Study 1, 42% compared with 23%, and Study 2, 52% compared with 22%, P.001. Two- to 24-hour sustained pain-free rates were Study 1, 29% compared with 18%, P=.022; Study 2, 38% compared with 10%, P.001. Headache and menstrual medication rates were Study 1, 37% compared with 53%, P=.005; Study 2, 31% compared with 69%, P.001. Women treated with sumatriptan-naproxen continued to be pain free through 48 hours compared with placebo: Study 1, 26% compared with 17%, P=.040; Study 2, 28% compared with 8%, P.001. No serious adverse events were reported in either study; nausea and dizziness were the most frequently reported adverse events.Sumatriptan-naproxen provided an effective pain-free response at 2 hours, which was maintained up to 48 hours in menstrual migraineurs with dysmenorrhea. Sumatriptan-naproxen was well-tolerated and resulted in decreased rescue medication use and relief of nonpainful menstrual symptoms.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00329459 and NCT00329355I.

Objective.—To describe the pain relief, satisfaction, and health-related quality of life results of moderate or severe migraines treated with a sumatriptan/naproxen sodium combination tablet. Methods.—Sumatriptan and naproxen sodium as a single-dose formulation tablet was used to treat moderate to severe migraines over a 12-month period in a phase 3, open-label, multicenter study (n = 565) in patients with at least 6 months' history of migraine headaches. Results.—Seventy percent of all attacks were treated with 1 dose of sumatriptan/naproxen sodium. Overall subjects treated 24,485 attacks; of these, 81% attacks achieved pain relief and 60% pain-free by 2 hours. At 3 months, the percentage of patients satisfied or very satisfied increased from baseline on all 8 Patient Perception of Migraine Questionnaire (PPMQ) items and remained high throughout the study. Mean Migraine-Specific Quality of Life Questionnaire (MSQ) domain scores also increased by 13–15 points from baseline during this time and remained high. Conclusions.—Sumatriptan/naproxen sodium provides consistent relief of migraine attacks over 12 months, resulting in improved patient satisfaction and migraine specific quality of life.

ContextMultiple pathogenic mechanisms may be involved in generating the migraine symptom complex, and multimechanism-targeted therapy may confer advantages over monotherapy.ObjectiveTo evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine.Design, Setting, and ParticipantsTwo replicate, randomized, double-blind, single-attack, parallel-group studies conducted among 1461 (study 1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack.InterventionsPatients were randomized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan, 85 mg, and naproxen sodium, 500 mg; sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or placebo, to be used after onset of a migraine with moderate to severe pain.Main Outcome MeasuresPrimary outcome measures included the percentages of patients with headache relief 2 hours after dosing, absence of photophobia, absence of phonophobia, and absence of nausea for the comparison between sumatriptan–naproxen sodium and placebo, and the percentages of patients with sustained pain-free response for the comparison between sumatriptan–naproxen sodium and each monotherapy.ResultsSumatriptan–naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing (study 1, 65% vs 28%; P