Sumatriptan Tablets Research Articles

Patient Case Report: Memantine for the Treatment of Occipital Neuralgia

Occipital neuralgia (ON) is described as a shooting, stabbing pain in the posterior part of the scalp that involves the occipital nerve. The epidemiology and pathophysiology are uncertain, but ON is considered distinct from other headache types. At the time of this writing, memantine for the treatment of ON has not been described in the literature. The following details a case report of successful treatment of ON with memantine. A 64-year-old, 91-kg, White man presented with severe headache associated with ON. Previous trials of oral medications, acupuncture, or physical therapy did not provide relief. The patient reported 15 ON headache days per month, use of 18 sumatriptan tablets per month, and daily use of as-needed ibuprofen. Because of inadequate relief of ON from other treatments, memantine was started. After titration to memantine 10 mg by mouth twice daily, the patient reported he was "100% headache free" from his ON pain. The patient tolerated memantine well without adverse effects. This case report displays safe, effective, and novel treatment of ON with memantine 10 mg by mouth daily, twice daily. The known safety, tolerability, and pharmacodynamics of memantine may warrant its off-label use in future studies exploring efficacy in ON.

Two-Hour CGRP Infusion Causes Gastrointestinal Hyperactivity: Possible Relevance for CGRP Antibody Treatment.

The monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor are new antimigraine drugs from which many patients already benefit. Very few side effects have been reported from the antibody trials, including very few gastrointestinal (GI) side effects. The current data derive from a double-blind cross-over study of CGRP infusion for 2hours. We present the GI side effects of the infusion and raise the question if underreporting of GI symptoms in CGRP antibody trials has occurred. We also discuss why constipation may be more likely with CGRP receptor blockade than with CGRP neutralizing antibodies. Thirty healthy volunteers were recruited to receive a 2-hour infusion of CGRP 1.5µg/minutes on 2 different days. The participants were pretreated with sumatriptan tablets (2×50mg) 1day and with placebo the other day. During the infusion, the participants were asked about side effects including a detailed description about their GI symptoms. Clinical observations like flatulence, rumbling, and use of bedpan were also noted. After the infusion, the participants filled out a questionnaire about side effects at home until 12-hour after the infusion start. The study was conducted at the Danish Headache Center at Rigshospitalet Glostrup in the period February 2018 to July 2018. On both study days 93% (27/29 participants) experienced symptoms from the GI system during the infusion. Rumbling, stomach pain, nausea, diarrhea, and an urge to defecate were the most commonly experienced GI side effects. There was no difference in symptoms between placebo and sumatriptan pretreatment. We conclude that a 2-hour infusion of CGRP causes frequent and sometimes severe symptoms from the GI system. The symptoms are not antagonized by sumatriptan. More attention should be paid to constipation as a possible side effect of CGRP receptor antagonists.

Subcutaneous sumatriptan reduces cilostazol induced headache in migraine patients.

The authors have previously tried to develop a model for the testing of novel drug candidates for migraine, using the headache and migraine provoking agent cilostazol. Previous studies have used sumatriptan tablets as the validating drug, but they were not sufficiently effective. In this study we test the effect of subcutaneous sumatriptan on cilostazol induced headache in patients with migraine without aura. Thirty patients with migraine without aura received 200 mg cilostazol on two different study days. The induced headache was treated with subcutaneous sumatriptan in a randomized, double-blind cross-over design. The patients filled out a self-reported headache questionnaire until 12 h after cilostazol. All 30 patients experienced headache (range 3-10) on both study days and the headache fulfilled the criteria for a migraine-like attack in 73% on the sumatriptan day and in 77% on the placebo day. Sumatriptan injection reduced the headache score 2 h after treatment (p = 0.003). The difference between headache intensity on the sumatriptan day and the placebo day was significant at both 2 h (p = 0.01) and 4 h (p = 0.0007) after treatment. Subcutaneous sumatriptan reduces cilostazol induced headache in migraine patients. The cilostazol model may be useful as a tool to test the potential of new anti-migraine drugs.Trial registration: The study is registered on clinicaltrials.gov (NCT03422796).

Comparison between the Effects of Sumatriptan Versus Naratriptan in the Treatment of Postdural Puncture Headache in Obstetric Patients: A Randomized Controlled Trial.

Background:Postdural puncture headache (PDPH) in the obstetric anesthesia practice is one of the most annoying, common, and important problems.Aim:This comparative study was designed to assess the efficacy of naratriptan in relieving PDPH in parturients who gave birth by cesarean section under intrathecal anesthesia and to compare its efficacy with sumatriptan.Settings and Design:One hundred and eighty-nine adult parturients who complained of PDPH in the first 3 days postpartum period were enrolled in this study. They were divided into three equal parallel groups of 63 each.Materials and Methods:Group-1 controlled (C-group) received multivitamin tablets, Group-2 sumatriptan (S-group) received sumatriptan tablets and Group-3 naratriptan (N-group) received naratriptan tablets. The efficacy of naratriptan in relieving PDPH was studied and compared with that of sumatriptan. Incidences of complications of both drugs were also noted.Statistical Analysis:The collected data were organized, tabulated, and statistically analyzed using SPSS software statistical computer package version 18 (SPSS Inc., USA).Results:After the first 6 h, there were statistically significant differences between Groups S and N from one side and control group from the other side (P < 0.0001 and 0.001), respectively, and the difference between Group S and Group N was statistically significant (P = 0.004). After 12 h, there were statistically significant differences between Groups S and N from one side and the control group from the other side (P < 0.0001) and the difference between Group S and Group N was statistically significant (P = 0.002). After 72 h, there were statistically significant differences between Groups S and N from one side and control group from the other side (P < 0.001 and 0.009), respectively. The difference was nonsignificant between S and N group (P = 0.717).Conclusion:The study revealed that anti-migraine drug naratriptan in combination with supportive treatment was effective in relieving PDPH in parturients.

AVP‐825 (Sumatriptan Nasal Powder) Reduces Nausea Compared to Sumatriptan Tablets: Results of the COMPASS Randomized Clinical Trial

Migraine-related nausea is associated with significant disability, increased burden of disease, and personal distress. Nausea can lead to delays or avoidance of initiating oral migraine treatment, sometimes resulting in treatment failures and poor outcomes. Nausea is often a symptom of migraine, but nausea may also be a consequence of treatment (ie, treatment emergent nausea [TEN]). Relieving nausea and minimizing TEN are important goals in acute migraine therapy. We analyzed data from the COMPASS study, a randomized, double blind, double-dummy, comparative efficacy study that contrasted two active treatments, AVP-825 (breath-powered intranasal delivery of powdered sumatriptan 22 mg) and oral sumatriptan tablets (100 mg). Three-level logistic multilevel models were used to examine longitudinal changes in nausea from three distinct perspectives across multiple attacks. Model 1 (Overall Nausea) examined longitudinal change in nausea from pre-dose through 120 minutes post-dose for the entire sample, independent of baseline nausea. Model 2 examined TEN from 10 minutes through 120 minutes post-dose in attacks free of nausea at baseline to investigate whether or not nausea developed following treatment. Model 3 examined Nausea Relief from 10 minutes through 120 minutes post-dose in eligible attacks with nausea at baseline to examine whether or not nausea was relieved over the first 2 hours post-dose. Models tested for differences in rate of change in nausea over time and odds of nausea at specific time-points. Longitudinal nausea trajectories differed for AVP-825 and oral sumatriptan in the Overall Nausea model (Model 1) and TEN model (Model 2), but were more comparable across treatments for the Nausea Relief (Model 3). More specifically, in the Overall Nausea model (Model 1), an individual treating an attack with AVP-825 had a significantly faster decrease in nausea through the first 60 minutes post-dose and reduced odds of nausea at each time-point from 30 minutes through 120 minutes post-dose compared to oral sumatriptan. In Model 2, an individual's risk for TEN increased at a significantly faster rate through the first 45 minutes post-dose when treating an attack with oral sumatriptan, with significantly greater odds of experiencing TEN at 45, 60, and 90 minutes post-dose compared to AVP-825. The Nausea Relief model (Model 3) showed similar rates of change in nausea over time for the two treatments, but there was a constant difference in nausea level leading to reduced odds of nausea when treating with AVP-825 compared to oral sumatriptan. All three longitudinal models showed that AVP-825 had more favorable nausea outcomes compared to oral sumatriptan. AVP-825 treatment led to more rapid early reductions in Overall Nausea rates during the first hour, reduced odds of nausea from 30 minutes to 2 hours following treatment and reduced risk of TEN compared to oral sumatriptan. These results highlight the importance of separately assessing TEN and Nausea Relief in acute treatment trials of migraine.

Comparing Average Level and Within-person Consistency in Clinical Disability Using AVP-825 vs. Sumatriptan Tablets: Applying Location Scale Mixed-effects Models (P2.166)

Comparing Average Level and Within-person Consistency in Clinical Disability Using AVP-825 vs. Sumatriptan Tablets: Applying Location Scale Mixed-effects Models (P2.166)

AVP-825 Reduces Nausea Faster Than Sumatriptan Tablets: A Comparative Effectiveness Study (P2.217)

AVP-825 Reduces Nausea Faster Than Sumatriptan Tablets: A Comparative Effectiveness Study (P2.217)

Reduced Treatment-Emergent Nausea Using AVP-825 vs. Sumatriptan Tablets: A Comparative Effectiveness Study (P2.215)

Reduced Treatment-Emergent Nausea Using AVP-825 vs. Sumatriptan Tablets: A Comparative Effectiveness Study (P2.215)

(478) Faster migraine pain and disability relief using AVP-825 compared to Sumatriptan tablet: applying a novel method for evaluating migraine relief across multiple outcomes

(478) Faster migraine pain and disability relief using AVP-825 compared to Sumatriptan tablet: applying a novel method for evaluating migraine relief across multiple outcomes

Sumatriptan formulated with RT technology™ as early intervention for migraine in adolescents

To assess the feasibility, efficacy, and tolerability of early intervention with sumatriptan tablets formulated with RT Technology™ (sumatriptan RT) for adolescent migraine. Conventional triptan tablets, a treatment of choice for migraine in adults, have not been demonstrated reliably effective in adolescents in prospective, placebo-controlled studies. Neither the early-intervention approach nor sumatriptan RT, a fast-disintegrating/rapid-release oral tablet, has previously been studied in adolescent migraineurs. Males or females 12 to 17-year-old diagnosed with migraine with or without aura were asked to treat four migraine attacks over a 6 mo period with sumatriptan RT 100 mg as early intervention (i.e., administered within 30 min of attack onset while pain was still mild). Of the 35 patients who enrolled, 32 treated at least one migraine attack, and 23 treated all four-migraine attacks. Pain-free response 2 hr postdose (primary endpoint) was reported in 71% of the 112 attacks treated. Migraine-free response (i.e., no pain; no nausea, vomiting, photophobia, or phonophobia; and no use of rescue medication) 2 hr postdose was reported in 69% of attacks. Response rates were consistent from attack to attack. Rescue medication was used in 19% of migraine attacks. In 112 attacks, a total of 25 adverse events (none serious) were reported in nine patients. The most common adverse events were worsening of symptoms ( n = 5), neck pain ( n = 4), and chest tightening ( n = 4). Early intervention with sumatriptan RT constitutes a promising approach to treating migraine in adolescents and warrants further assessment in controlled clinical trials.

Oral sumatriptan for the acute treatment of migraine in children and adolescents: Yet another failed study

Sumatriptan, a serotonin-1 receptor agonist specially developed for migraine, became available as a licensed product for adults more than 20 years ago. Since then, numerous controlled studies with sumatriptan have been carried out and it is widely used in adults. However, the story has not been as successful in children and adolescents as in adults. Of the few studies performed, most have shown a high placebo response rate (1–4). High placebo response has been found also in other triptan studies in children (1–4). It may be due to several factors, such as study design and shorter duration of migraine attacks in young patients (1–4). Shorter duration means a strong tendency to spontaneous recovery, which is found in placebo-treated acute attacks. Two controlled clinical studies have been reported to show efficacy against placebo with sumatriptan nasal spray (5,6), which is licensed for the treatment of migraine in children aged 12 years or older in the European Union (EU), Australia and New Zealand, but not in the United States and Canada. Only a few clinical studies have evaluated sumatriptan tablets in children and adolescents. In one of the studies, both the response to sumatriptan and to placebo was low and not statistically different (7). In one study with sumatriptan and naproxen sodium combination tablets, the pain-free response rate to the active combination was statistically significantly higher than to placebo (8). In other sumatriptan studies, the response rates both to sumatriptan and to placebo have been similarly high as in other studies with triptan tablets. Sumatriptan tablets have not yet been licensed for the treatment of migraine in children and adolescents. A group of Japanese investigators bring their contribution to a small series of pediatric sumatriptan studies (9). They report results of a double blind, placebo-controlled, 17-center, parallel-group study in adolescents, who treated one acute migraine attack either with a 25mg sumatriptan tablet or with a 50 mg sumatriptan tablet or with placebo. They enrolled 178 patients, of whom 144 patients completed the study and were included in the analysis. As the primary endpoint (i.e. pain relief) was considered at two hours postdose, the percentage was higher for placebo than for the active drug (38.6% vs 31.1%). The same endpoint at four hours post-dose was reported more often after sumatriptan (63.5%) than after placebo (51.4%), but the difference failed to achieve statistical significance (p1⁄4 0.142). The authors conclude that sumatriptan did not show statistically significant pain relief at two hours post-dose as compared to placebo. Both doses of sumatriptan tablets were well tolerated. The pain relief measures that Japanese investigators chose as primary endpoint were clinically useful, even if the best two-hour primary endpoint according to the International Headache Society (IHS) recommendations is pain freedom (10). In almost all earlier triptan trials, the lowest response rates have been approximately 49% of the active drug. Japanese response rates to both placebo and sumatriptan are lower. It is hard to say why. But one could speculate that it may be because of the patients selected for the study—either their migraine characteristics or perhaps even their ethnic pharmacogenetic specificity. Future studies could include also crossover designs (to reduce the number of patients needed and placebo effect (3,10)) with clinically meaningful endpoints (such as complete pain relief, time to onset of relief and time to meaningful relief of symptoms (11)). Clinical efficacy of sumatriptan and other triptans in children and adolescents with migraine still needs to be reported in controlled trials.

Consistency of Return to Normal Function, Productivity, and Satisfaction Following Migraine Attacks Treated With Sumatriptan/Naproxen Sodium Combination

To assess the consistency of improved functioning, productivity, and medication satisfaction in migraines treated with a single tablet of sumatriptan 85 mg/naproxen sodium 500 mg (S/NS) using an early intervention approach. Two randomized, double-blind, placebo-controlled, 4-period crossover, multi-attack, multi-center, outpatient studies of moderate to severe adult migraineurs were conducted to compare S/NS with placebo. Participants recorded outcome assessments in a diary during the 24 hours following study medication. Analyses were conducted on the intent-to-treat population who treated at least 1 attack. Statistical significance between treatment groups used analysis of variance repeated measures models and the intent-to-treat population. There were no corrections for multiplicity. Almost half (48.5%) of migraineurs treated with S/NS returned to normal functioning at 2 hours and 73.3% at 4 hours postdose, compared with 28.7% (2 hours) and 43.3% (4 hours) of placebo-treated attacks. Total productivity loss over the 24 hours postdose was significantly reduced following S/NS treatment (2.5 hours on average) compared with placebo (4.0 hours). Sumatriptan/naproxen treatment resulted in significantly higher medication satisfaction scores on the efficacy, functionality, and total efficacy subscales compared with placebo in all attacks in both studies. Sumatriptan/naproxen treatment also provided significantly greater ease of use in 7 of the 8 attacks. Although tolerability was high in both treatment groups (over 90%), the placebo group was significantly less bothered by side effects in 6 of 8 attacks. Results from these 2 randomized, double-blind, placebo-controlled, multi-attack, crossover studies demonstrated the rapid and consistent restoration of patients' functioning, the consistent reduction in productivity loss, and high satisfaction ratings from patients treating multiple migraine attacks with S/NS using an early intervention approach.

Influence of sumatriptan on gastric accommodation and on antral contraction in healthy subjects assessed by ultrasonography

Oral sumatriptan administration has been reported to delay gastric emptying after liquid meals. The aim of this study was to determine whether delayed gastric emptying is caused by enhanced gastric accommodation, impaired antral contractions, or both using ultrasonography. Ten healthy volunteers were enrolled in this randomized two-way crossover study. After overnight fasting, the subjects received the liquid meal 60 min after ingesting a 50 mg sumatriptan tablet with 50 mL of water or 50 mL of water alone (control). The cross-sectional area of the proximal stomach was measured in a supine position after every 100 mL. The frequency and amplitude of the antral contractions were measured in a slightly backward sitting position. The intragastric distribution of the liquid meal was assessed by calculating the proximal stomach/distal stomach ratio (prox/distal ratio). The cross-sectional area after drinking 100, 200, and 300 mL of the liquid meal (oral sumatriptan vs control) was 34.49 vs 15.11 cm(2) (P = 0.0051), 48.00 vs 30.61 cm(2) (P = 0.0166), and 58.67 vs 47.19 cm(2) (P = 0.0125), respectively. There was no significant difference in the amplitude of contractions, contraction cycle, motility index, and prox/distal ratio (97.15 vs 97.93%, P = 0.0745; 19.42 vs 19.5 s, P= 0.8590; and 887.58 vs 889.22, P = 0.5751; 9.75 vs 8.41, P = 0.8785; respectively). Oral sumatriptan administration enhanced gastric accommodation after the ingestion of liquid nutrients, but had no significant effect on antral contractions or intragastric distribution in healthy subjects.

Efficacy endpoints in migraine clinical trials: the importance of assessing freedom from pain

Many efficacy endpoints have been used in clinical trials of acute migraine pharmacotherapy. Headache response or headache relief (i.e., moderate/severe pain reduced to mild/no pain) at a single, specified time-point, traditionally the primary endpoint, and headache recurrence (i.e., return of pain after initial postdose relief) are inadequate. Headache relief does not provide information about pain-free response and counts a partial response as a treatment success. Headache recurrence can reflect sustained efficacy but is confounded by initial response to treatment, because ineffective drugs have low recurrence rates. The International Headache Society (IHS) guidelines state that 2 hour pain-free response and sustained pain-free response (i.e., freedom from pain with no recurrence or use of rescue or study medication 2-24 hours postdose) provide the most clinically relevant information about the efficacy of migraine pharmacotherapy. The pain-free criterion counts partial responses as failures and thus is a more rigorous test of therapeutic benefit than headache relief, and the two endpoints together incorporate the main treatment attributes that determine patient satisfaction. As an example, consider needle-free subcutaneous sumatriptan and oral triptan tablets. An open-label study of needle-free subcutaneous sumatriptan by Cady and colleagues found that 2 hour pain-free response and sustained pain-free response were 64% and 42% respectively. For oral triptan tablets, the 2001 metaanalysis by Ferrari and colleagues reported 2 hour pain-free response rates ranging from 23% to 38% and sustained pain-free response rates ranging from 11% to 26%. The measures of pain-free response 2 hours postdose and sustained pain-free response can differentiate among treatments and be used to guide therapeutic choices.

Randomized Trial of Sumatriptan and Naproxen Sodium Combination in Adolescent Migraine

Treatment of adolescent migraine remains a significant unmet medical need. We compared the efficacy and safety of 3 doses of sumatriptan and naproxen sodium (suma/nap) combination tablets to placebo in the acute treatment of adolescent migraine. This randomized, parallel group study in 12 to 17 year olds required 2 to 8 migraines per month (typically lasting >3 hours untreated) for ≥ 6 months. Subjects entered a 12-week run-in phase, treating 1 moderate-to-severe migraine (attack 1) with single-blind placebo. Subjects reporting headache pain 2 hours after dosing were randomly assigned into a 12-week double-blind phase, treating 1 moderate-to-severe migraine (attack 2) with placebo (n = 145), suma/nap 10/60 mg (n = 96), 30/180 mg (n = 97), or 85/500 mg (n = 152). The primary end point was the percentage of subjects pain-free at 2 hours. The attack 2 adjusted (age; baseline pain severity) 2-hour pain-free rates were higher with suma/nap 10/60 mg (29%; adjusted P = .003), 30/180 mg (27%; adjusted P = .003), and 85/500 mg (24%; adjusted P = .003) versus placebo (10%). Posthoc primary end-point analyses did not demonstrate differences among the 3 doses or an age-by-treatment interaction. Statistically significant differences were found for 85/500 mg versus placebo for sustained pain-free 2 to 24 hours (23% vs 9%; adjusted P = .008), 2-hour photophobia-free (59% vs 41%; adjusted P = .008), and 2-hour phonophobia-free (60% vs 42%; adjusted P = .008). Analyses of other pain, associated symptoms, rescue medication use, and health outcome end points supported higher efficacy for active doses versus placebo. All active doses were well tolerated. All doses of suma/nap were well tolerated, providing similarly effective acute treatment of adolescent migraine pain and associated symptoms, as compared with placebo.

Sumatriptan–Naproxen Migraine Efficacy in Allodynic Patients: Early Intervention

This study evaluated the effectiveness of a single fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan-naproxen) using a very early treatment paradigm in migraine patients whose attacks were historically accompanied by cutaneous allodynia. Evidence suggests that allodynic migraineurs may demonstrate a better response when treated prior to developing central sensitization, and that these patients are treated more effectively with a compound of sumatriptan and naproxen sodium than either drug alone. This study targeted patients who have accompanying allodynia using a very early treatment paradigm where treatment was initiated while symptoms were still mild. This was an open-label prospective, outpatient study of adult migraineurs who had screened positive for cutaneous allodynia and typically experienced moderate to severe pain preceded by an identifiable mild pain phase. Patients were treated with sumatriptan-naproxen using a very early intervention paradigm in 4 test migraines over 12 weeks where dosage occurred within 30 minutes of symptom onset. Data from diaries and questionnaires were used to evaluate the primary endpoints of sustained pain-free response at 24 hours post dose (using no second dose of study drug and no other rescue drugs), and overall satisfaction with sumatriptan-naproxen. Forty allodynic migraineurs enrolled in this study and reported a total of 160 migraines. Of these migraines, 78 (49%) achieved sustained pain-free at 24 hours and 94 (59%) were reported as pain-free at 2 hours. The number of patients who rated their Overall Satisfaction following treatment with sumatriptan-naproxen as "Satisfied" (satisfied or very satisfied) was 32 (80%) after the first migraine and 25 (63%) after 3 or more migraines. In this open-label study, allodynic patients reported that their migraine attacks responded well and they achieved a high degree of satisfaction following treatment with a fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg administered in a very early treatment paradigm.

Multi‐Center Comparison of Response to a Single Tablet of Sumatriptan 85 mg and Naproxen 500 mg vs Usual Therapy Treating Multiple Migraine Attacks as Measured by the Completeness of Response Survey

To investigate a broad definition of migraine resolution that extends beyond specific migraine-associated diagnostic symptoms as measured by the Completeness of Response Survey. Conducted at 8 sites, 135 subjects treated migraines with SumaRT/Nap over 2 months. To measure subjects' experiences with SumaRT/Nap compared to their usual migraine medication, the Headache Impact Test, Revised Patient Perception of Migraine Questionnaire, and Completeness of Response Survey were administered at baseline and at 2 months. The effects of the study medicine compared to the subjects' usual migraine medicine reached statistical significance in decreasing headache severity, lessening of associated symptoms, and attaining complete relief with a single dose (60.04% of attacks resolved at 2 hours post-treatment). Compared to a subject's usual treatment, SumaRT/Nap used early and consistently for treatment of acute migraine offers important clinical improvements, including lessening of associated symptoms beyond International Headache Society criteria. NCT00893737.

Sumatriptan–Naproxen Sodium for Menstrual Migraine and Dysmenorrhea: Satisfaction, Productivity, and Functional Disability Outcomes

To evaluate the impact of a sumatriptan/naproxen sodium combination tablet on patient satisfaction, productivity, and functional disability in menstrual migraine treated during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea. Menstrual migraineurs with dysmenorrhea represent a unique patient population not previously studied. When health outcomes end points are analyzed alongside traditional efficacy end points in migraine studies, a more comprehensive and robust understanding of the many factors that may influence patients' choice of and adherence to pharmacological treatments for migraine is observed. In 2 replicate, multicenter, randomized, double-blind, placebo-controlled trials, participants with menstrual migraine and dysmenorrhea treated a single menstrual migraine attack with a single fixed-dose tablet of sumatriptan 85 mg formulated with RT Technology™ and naproxen sodium 500 mg (sumatriptan-naproxen sodium) or placebo. Participants randomized to sumatriptan-naproxen sodium were significantly more satisfied than those randomized to placebo at 24 hours post dose, as demonstrated by higher satisfaction subscale scores for efficacy (P < .001 for both studies), functionality (P = .003 for study 1; P < .001 for study 2), and ease of use (P = .027 for study 1; P = .011 for study 2). There was little bothersomeness of side effects associated with either treatment. Use of sumatriptan-naproxen sodium was also associated with lower reported "lost-time equivalents" in work and leisure time (pooled analysis, P = .003) and lower rates of functional disability (P = .05, study 1; P < .001, study 2) compared with placebo. A fixed-dose combination tablet containing sumatriptan and naproxen sodium significantly improved patient satisfaction, productivity, and restoration of normal functioning in menstrual migraineurs with dysmenorrhea.

Pharmacokinetics and tolerability of sumatriptan after single-dose administration of a fixed-dose combination tablet of sumatriptan/naproxen sodium 85/500 mg followed two hours later by subcutaneous sumatriptan 4- or 6-mg injection: A randomized, open-label, three-period crossover study in healthy volunteers

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.

Distinct Pharmacokinetic Profile and Safety of a Fixed‐Dose Tablet of Sumatriptan and Naproxen Sodium for the Acute Treatment of Migraine

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. Six open-label, crossover studies were conducted in healthy volunteers (Studies 1, 2, 3, 4, 5) or patients with migraine (Study 6). 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. 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.