Mg Of Naproxen Sodium Research Articles

37-Year-Old Woman With Bilateral Lower Extremity Edema, Proteinuria, and Microscopic Hematuria

37-Year-Old Woman With Bilateral Lower Extremity Edema, Proteinuria, and Microscopic Hematuria

Efficacy of Intrauterine Lidocaine and Naproxen for Pain Control With Intrauterine Device Insertion [1A

INTRODUCTION: One of the barriers to IUD insertion is discomfort during the placement of the device. This study was designed to compare the efficacy of intrauterine lidocaine and oral naproxen sodium on discomfort and pain of patients undergoing intrauterine device insertion. METHODS: This is a randomized, double-blind, placebo-controlled study where women were randomly assigned to receive either 5mL of intrauterine 2% lidocaine or saline and either 375mg of naproxen sodium or placebo tablet. Patients were randomized into one of four randomly assigned groups: A placebo/normal saline infusion; B placebo/lidocaine infusion; C: naproxen/normal saline; D: naproxen/lidocaine. We enrolled 80 women into the Mirena IUD arm of the study. RESULTS: There was no significant difference between the 4 groups in age, parity, chronic pelvic pain, menopausal status, or difficulty in placing the IUD. The mean pain scores of the women in the naproxen only (2.89+/-2.05), lidocaine only (2.37+/-1.98), and combined naproxen/lidocaine (3.55+/-2.46) groups were not significantly different as compared to placebo (3.2+/-2.25). Pain rated by the physician was not significantly lower in the treatment groups as compared to placebo. CONCLUSION: Oral naproxen and intrauterine lidocaine instillation does not appear to significantly decrease pain associated with Mirena IUD insertion.

Adding NSAIDs to triptans: Could less be more?

Used as monotherapy, triptans and nonsteroidal antiinflammatory drugs (NSAIDs) work well to treat individual attacks of migraine. Both are first-line treatment choices for patients who have episodic headaches and no contraindications to their use. They are not effective for all patients, however, and for others they provide only unreliable or incomplete relief. A substantial body of evidence supports the strongly held clinical belief that triptans work best when an optimal dose is given parenterally while pain is mild or moderate. One expert has observed that ‘‘most patients respond to triptans if the right drug and the right formulation are used’’ (1). Still, even 10mg of naratriptan given parenterally—a dose and formulation that are not clinically available—results in elimination of headache pain two hours after treatment for only 88% of patients (1). This shortfall in treatment success meant that as soon as the triptans entered clinical use, patients and doctors began to try them in combination with other drugs in an effort to obtain synergistic results. The combination of triptans and NSAIDs makes particular sense because the two drug classes have different adverse event profiles and mechanisms of action. In 2008 the United States Food and Drug Administration approved a fixed-dose combination tablet containing 85mg of sumatriptan and 500mg of naproxen sodium. The approval was based on clinical trial results showing that the combination worked better than placebo or either drug alone (2). In this issue of Cephalalgia, Tullo and colleagues report results of a study that evaluated a combination of a different triptan/NSAID pair: frovatriptan with dexketoprofen (3). Frovatriptan has an elimination half-life of roughly 25 hours, in comparison with about two hours for sumatriptan, while dexketoprofen is an NSAID with a relatively short half-life and rapid onset of action (4,5). The investigators hypothesized that dexketoprofen would provide good early relief of migraine pain while the longer half-life of frovatriptan would reduce headache recurrence, defined as ‘‘a headache of any severity returning within 48 hours, in a subject who was pain free at two hours and who had not taken rescue treatment.’’ The study tested 2.5mg of frovatriptan in combination with 25mg or 37.5mg of dexketoprofen, against the combination of 2.5mg of frovatriptan with placebo. This made it possible to assess not only whether the combination of frovatriptan and dexketoprofen was superior to frovatriptan alone, but also whether a higher dose of an NSAID was better than a lower dose. When results from the 279/314 participants with evaluable data were analyzed, the researchers found that both frovatriptan/dexketoprofen combinations were statistically significantly more effective than frovatriptan alone for outcomes of pain-free status at two hours and sustained pain-free status at 24 and 48 hours. Time to pain relief was statistically significantly improved with the combination compared with frovatriptan alone, although headache recurrence with the combination was not different. An unexpected finding, though, was that the combination with the higher 37.5mg dose of dexketoprofen showed no clear advantage over that with the lower dose of 25mg (3). The lack of a dose-response relationship was seen across a variety of study end points, which increases confidence that it is not a chance finding. This is surprising because, at least when used as standalone treatments, previous research suggests that there is a dose-response relationship for the efficacy of many NSAIDs, including dexketoprofen (6–9). This raises an interesting and clinically relevant question: Could it be that when it comes to using NSAIDs in combination with triptans, more is not always better?

SumaRT/Nap vs Naproxen Sodium in Treatment and Disease Modification of Migraine: A Pilot Study

This pilot study explored the potential for 2 recognized acute migraine medications, 85 mg of sumatriptan plus 500 mg of naproxen sodium in a combination tablet (SumaRT/Nap) and 500 mg of naproxen sodium, to treat and modify the disease progression of migraine. In other words, can these medications both abort an acute attack of migraine and reduce the number of future migraine attacks? Patients suffering with moderate to severe attacks of migraine desire acute treatment. As migraine frequency increases, so does the need for more frequent relief of acute attacks. This may lead to medication overuse and potentially medication overuse headache (MOH). Ideally, acute medication would have the ability to abort an attack of migraine and reduce the likelihood of future attacks. The primary endpoint of this study was a reduction in migraine headache days from baseline through month 3 of the study. Subjects were randomized 1:1 to treat 14 or fewer migraines per month with SumaRT/Nap (Group A) or naproxen sodium (Group B) for 3 months. Subjects in group A utilized SumaRT/Nap were encouraged, but not required, to treat migraine headache within 1 hour of onset of headache when the pain was mild. They could re-treat if needed after 2 hours. Subjects in group B utilized the same treatment strategy with 500 mg of naproxen sodium. Tablets of study medication were identical for both groups. Subjects recorded headache days, migraine attacks, duration of attacks, treatment, and treatment results daily on paper diaries. Subjects took the Migraine Disability Assessment Test (MIDAS) at randomization and 3 months later at the end of study. Naproxen sodium was associated with a statistically significant reduction in migraine headache days at month 3 compared to baseline (P = .0002). SumaRT/Nap was also associated with a reduction of migraine headache days, but this decrease did not reach statistical significance (P = .2). In addition, subjects in the naproxen sodium group had a statistically significant reduction of migraine attacks in all 3 months of the study compared to baseline. A greater than 50% reduction in the number of migraine headache days at month 3 occurred in 43% (6/14) of subjects in group B compared to 17% (3/18) of subjects in group A. Consistent with large regulatory studies comparing the efficacy of SumaRT/Nap with naproxen sodium, SumaRT/Nap in this study was statistically superior to naproxen sodium at 2 hours in reducing headache severity during months 2 and 3. There was a reduction of acute medication used from baseline to month 3 and improvement in MIDAS scores for both groups. Naproxen sodium, when used as a sole acute treatment early in attacks, appears to reduce the frequency of headache days and migraine attacks for a select number of subjects over a 3-month period. SumaRT/Nap is more effective at 2-hour headache reduction than naproxen sodium alone, but has less impact on reducing attack frequency or the number of headache days. Both treatments were well tolerated, and there was no convincing evidence that either medication led to MOH.

Pharmacological Synergy: The Next Frontier on Therapeutic Advancement for Migraine

The burden of migraine significantly impacts the individual sufferer, their families, the workplace, and society. The World Health Organization has identified migraine as an urgent public health priority and has initiated a global initiative to reduce the burden of migraine. Underlying the World Health Organization initiative is the need to discover means of optimizing migraine treatments and make them accessible to the broader portion of the world population. Development of acute migraine medications over the past several decades has largely centered on engineering highly specific receptor molecules that alter migraine pathophysiological mechanisms to abort or reverse the acute attack of migraine. The first product of this line of discovery was sumatriptan and heralded as a landmark therapeutic breakthrough. Sumatriptan is a 5-HT-1B/D receptor agonist considered to activate receptors involved in the pathophysiology specific to migraine. Large-scale regulatory/clinical studies demonstrated statistical superiority for sumatriptan over placebo in reduction or elimination of headache, nausea, photophobia, and phonophobia. Since the introduction of sumatriptan, 6 other triptan products have been released in the United States as acute treatments for migraine, all having the same mechanism of action and similar efficacy. Despite their utility as migraine abortive medications, the triptans do not successfully treat all attacks of migraine or necessarily treat all migraine associated symptoms. In fact, in less than 25% of attacks do subjects obtain and maintain a migraine-free response to treatment for at least beyond 24 hours. A wide range of non-triptan medications also have demonstrated efficacy in acute migraine. These include non-steroidal anti-inflammatory drugs (NSAIDs), opioids, phenothiazines, and valproic acid to name a few. Given the distinctly different mechanisms of actions of these various medications, it is likely that several unique pathophysiological mechanisms are involved in terminating acute episodes of migraine. Clinicians now capitalize on this observation and use migraine medication in combination with another to improve patient outcomes, for example, using an antiemetic with an opioid or a triptan and NSAIDs. More recently, the Food and Drug Adminstration has approved a combination product containing 85mg of sumatriptan plus 500mg of naproxen sodium for acute treatment of migraine. Clinical trials conducted prior to approval demonstrated that the combination of sumatriptan and naproxen was more effective as a migraine abortive than either of its components but that each component and the combination were more effective than placebo. Exactly how sumatriptan and naproxen interact to create therapeutic synergism is unknown though its mere occurrence suggests that models assisting medical understanding and prediction of pharmacological synergism may improve clinical outcome over products acting through a single receptor mechanism. Migraine is a syndrome, meaning it is defined by observed symptoms rather than known pathophysiology. Multiple pathogenic mechanisms are likely involved in generating this diverse array of symptoms understood as the migraine symptom complex. Sumatriptan and naproxen have independent mechanisms of action and target distinct aspects of the vascular and inflammatory processes hypothesized to underlie migraine. Sumatriptan acts on the 5-HT(1B) and 5-HT(1D) receptors, whereas naproxen inhibits the COX-1 and COX-2 enzymes. Sumatriptan has vasoconstricting effects as well as effects on neurogenic inflammation by decreasing the release of substance P and calcitonin gene-related peptide. In contrast, naproxen affects prostaglandins and other inflammatory mediators. Because sumatriptan and naproxen both relieve migraine yet interact with different cellular targets within the migraine pathway, it is reasonable to assume there is a unique synergy between these medications that improves treatment outcomes. Clinical trials supported this contention by demonstrating the combination of sumatriptan/naproxen alleviated migraine pain quickly (primarily based on the sumatriptan mechanism of action), and sustained the response longer (primarily based on the naproxen mechanism of action) than is possible when either drug is given alone. The working hypothesis is that when sumatriptan and naproxen are given at the same time, they affect different mechanisms of the migraine pathway and produce an enhanced therapeutic effect. The purpose of this article is to apply statistical analyses to data from phase II and phase III studies of the combination of sumatriptan and naproxen to determine if this enhanced therapeutic effect is synergistic. This methodology of accessing synergy can be used in the development of future combination migraine treatments to improve treatment outcomes.

The influence of anxiety and locus of control on adolescents' response to naproxen sodium for mild to moderate pain

This study assessed the influence of internal health locus of control (IHLC) and anxiety on the adolescent's response to the treatment of mild and moderate pain. Fifty-four adolescents (ages 16–22 years) front two adolescent clinics presenting with mild to moderate pain caused by dysmenorrhea, muscle sprain or strain, headache, or backache were studied. Following a physical examination and a pretest assessment of pain, IHLC, and the Spielberger State-Trait Anxiety Inventory, subjects were randomly assigned in a double-blind fashion to groups receiving placebo ( n = 16), 100 mg of naproxen sodium ( n = 19), or 200 mg naproxen sodium ( n = 19) and assessed at 1, 2, 3, and 4 hours Based on a repeated-measure analysis of covariance test, there were no differences between groups in the pretest measurements. All treatment groups had a decrease in pain over the 4 hours ( p < 0.0001). Patients from one institution had more pain reduction than at the other ( p < 0.0001), and females had more pain reduction than males ( p < 0.034). Subjects receiving 200 mg of naproxen sodium had more pain relief ( p < 0.034) than subjects taking placebo at hour 2. Baseline anxiety was positively associated with pain after receiving placebo, but inversely associated with pain after taking naproxen sodium. The IHLC appeared to have a positive effect on the response to naproxen sodium, but no effect on the response to placebo.

Differential response by adolescents to naproxen sodium therapy for spasmodic and congestive dysmenorrhea

The purpose of this study was to determine whether adolescents with "spasmodic" dysmenorrhea (SD) versus "congestive" dysmenorrhea (CD) respond differently to naproxen sodium therapy. Forty-five females ages 12-18 years were pretested and randomly assigned in a double-blind fashion to one of five treatment regimens of various dosages of naproxen sodium and placebo. Subjects were posttested at one, two, and three months. Subjects with initial Menstrual Symptom Questionnaire (MSQ) scores of greater than or equal to 76 were classified as SD (n = 28) and those with scores of less than or equal to 75 were classified as CD (n = 17). Subjects with SD had a significant (p less than or equal to 0.05) reduction in MSQ scores after the first month of naproxen sodium therapy. By the second month, the degree of reduction was associated with a loading dose of 550 mg of naproxen sodium. Subjects with CD had a dose-related (p less than or equal to 0.05) response to naproxen sodium therapy that appeared to be influenced by other factors. At the first month follow-up, greater post menarchal age and parents' education were associated with increased symptom relief following naproxen sodium therapy (p less than or equal to 0.05). At the second month, CD subjects with increased life crisis events and lower self-concepts had more severe symptoms following naproxen sodium therapy (p less than 0.05). Our subjects with SD symptoms had a greater response to naproxen sodium therapy than those with CD symptoms.