Sumatriptan 85mg / Naproxen 457mg tablets

Migraine burden is over twice as high among females than males. Although sex differences are recognized in migraine, robust sex-specific guidance for management remains limited. To systematically review and synthesize current evidence on sex-related clinical differences in migraine, including treatment outcomes and reproductive management, and to provide evidence-based or expert consensus recommendations where high-quality data are lacking. A systematic literature review using the PICO framework addressed 24 sex-specific questions across three domains: (1) biological sex differences across the lifespan, (2) sex-specific variations in treatment outcomes, and (3) fertility and reproduction-related management. To address anticipated evidence gaps, a structured Delphi consensus process complemented the review. The protocol was registered in PROSPERO (CRD420251058438). Thirty-seven studies informed 10 evidence summaries. Acute and preventive anti-CGRP therapies seem to show similar efficacy between sexes. For menstrual-related migraine attacks (MM), triptans and lasmiditan are effective, with frovatriptan being recommended for short-term prevention; long-term prevention include topiramate and anti-CGRP mAbs. In pregnancy triptans, greater occipital nerve (GON) blocks, and onabotulinumtoxinA are safe, with GON blocks showing potential efficacy. During breastfeeding, triptans appear to be safe. Anti-CGRP mAbs are equally effective in pre and postmenopausal women. Expert consensus emphasizes the influence of hormonal transitions on migraine expression across sexes and supports the use of acetaminophen, antiemetics, magnesium, NSAIDs, steroids, beta-blockers, amitriptyline, and calcium channel blockers as generally safe in WOCBP and during pregnancy, although some agents have trimester-specific limitations. Efficacy was noted for acetaminophen, sumatriptan, antiemetics, magnesium, propranolol, amitriptyline, and onabotulinumtoxinA. During breastfeeding, acetaminophen, NSAIDs, domperidone, prochlorperazine, magnesium, caffeine, beta-blockers, tricyclics, onabotulinumtoxinA, and GON blocks were considered safe. Evidence is limited, but sex (likely mediated by sex hormones) influence the clinical course of migraine, and likely treatment response. Limitations include absence of sex-specific analyses in older trials, underrepresentation of men, and scarce reproductive safety data. Integrating sex-based analyses and broadening trial inclusion and more reproductive safety evidence are essential for personalized, equitable migraine care.

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BACKGROUND: Varied responses to acute migraine medications have been observed, with over one-third (34.5%) of patients reporting insufficient headache relief. Sumatriptan-naproxen sodium, a single, fixed-dose combination tablet comprising sumatriptan 85 mg and naproxen sodium 500 mg, was developed with the rationale of targeting multiple putative mechanisms involved in the pathogenesis of migraine to optimise acute migraine care. METHODS: A narrative review of clinical trials investigating sumatriptan-naproxen sodium for both adults and adolescents was performed in March 2024. RESULTS: Across a total of 14 clinical trials in nine publications, sumatriptan-naproxen sodium offered greater efficacy for 2-h pain freedom (14/14) and sustained pain-free response up to 24 h (13/14) compared with monotherapy and/or placebo for both adult and adolescent study participants with an acceptable and well-tolerated adverse effect profile. Clinical trial data also demonstrates the effectiveness of sumatriptan-naproxen sodium in participants with allodynia, probable migraine, menstrual-related migraine and those with poor responses to acute, non-specific, migraine medication. CONCLUSIONS: Multi-mechanistic therapeutic agents offer an opportunity to optimise acute medications by targeting multiple mediators involved in the pathogenesis of migraine. Sumatriptan-naproxen sodium resulted in greater initial and sustained pain freedom, compared with either sumatriptan, naproxen-sodium and/or placebo, for the treatment of single or multiple attacks of migraine across both adult and adolescent study populations.

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OBJECTIVE: To highlight key factors required to optimize multi-mechanistic approaches with oral combination treatments for the acute management of a migraine attack. BACKGROUND: Given the complex multi-factorial nature of migraine, combining treatments with different mechanisms of action should improve outcomes compared to monotherapies, but this has not been demonstrated with all treatment combinations. METHODS: For this narrative review, we searched PubMed using combinations of these terms: migraine, acute treatment, combination therapy, fixed-dose combination therapy, multi-mechanistic treatment, pharmacokinetics, and pharmacodynamics. All articles considered relevant were included. RESULTS: None of the existing migraine acute treatments as monotherapy effectively treat the key pathophysiological processes of migraine completely. Many patients do not achieve 2-h pain freedom, which is key to avoiding migraine recurrence, medication overuse leading to chronification, and migraine-related disability. The development of combination approaches has led to only two combinations with demonstrated superiority over their individual components: aspirin/acetaminophen/caffeine and sumatriptan/naproxen sodium. The latter is the most effective proven combination treatment because it targets peripheral activation of central pain pathways during the early migraine stages and central sensitization that develops later, independent of peripheral input. Other triptan/nonsteroidal anti-inflammatory drug combinations with higher efficacy as monotherapies could be more effective than sumatriptan/naproxen sodium, particularly if their pharmacokinetic profiles align with the vasoactive mediators of peripheral and central sensitization that they target. CONCLUSIONS: Combination treatments with different mechanisms of action targeting key distinct pathophysiological processes of migraine may be more effective than monotherapies, particularly if their pharmacokinetic profiles are optimized to target those processes at the right time. Further research in this area is warranted.

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Sumatriptan-naproxen fixed combination for acute treatment of migraine: a critical appraisal Chaouki K Khoury, James R CouchDepartment of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USAAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen and naproxen sodium, are effective yet nonspecific analgesic and anti-inflammatory drugs, which work for a variety of pain and inflammatory syndromes, including migraine. In migraine, their analgesic effect helps relieve the headache, while their anti-inflammatory effect decreases the neurogenic inflammation in the trigeminal ganglion. This is the hypothesized mechanism by which they prevent the development of central sensitization. Triptans, including sumatriptan, work early in the migraine process at the trigeminovascular unit as agonists of the serotonin receptors (5-HT receptors) 1B and 1D. They block vasoconstriction and block transmission of signals to the trigeminal nucleus and thus prevent peripheral sensitization. Therefore, combining these two drugs is an attractive modality for the abortive treatment of migraine. Sumatriptan–naproxen fixed combination tablet (Treximet® [sumatriptan–naproxen]) proves to be an effective and well tolerated drug that combines these two mechanisms; yet is far from being the ultimate in migraine abortive therapy, and further research remains essential.Keywords: Treximet®, sumatriptan–naproxen, migraine, treatment

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