Eletriptan 20mg tablets

OBJECTIVE: To compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, as well as websites of regulatory agencies and pharmaceutical companies without language restrictions until 24 June 2023. METHODS: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Random effects network meta-analyses were conducted for the primary analyses. The primary outcomes were the proportion of participants who were pain-free at two hours post-dose and the proportion of participants with sustained pain freedom from two to 24 hours post-dose, both without the use of rescue drugs. Certainty of the evidence was graded using the confidence in network meta-analysis (CINeMA) online tool. Vitruvian plots were used to summarise findings. An international panel of clinicians and people with lived experience of migraine co-designed the study and interpreted the findings. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Double blind randomised trials of adults (≥18 years) with a diagnosis of migraine according to the International Classification of Headache Disorders. RESULTS: 137 randomised controlled trials comprising 89 445 participants allocated to one of 17 active interventions or placebo were included. All active interventions showed superior efficacy compared with placebo for pain freedom at two hours (odds ratios from 1.73 (95% confidence interval (CI) 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan), and most of them also for sustained pain freedom to 24 hours (odds ratios from 1.71 (1.07 to 2.74) for celecoxib to 7.58 (2.58 to 22.27) for ibuprofen). In head-to-head comparisons between active interventions, eletriptan was the most effective drug for pain freedom at two hours (odds ratios from 1.46 (1.18 to 1.81) to 3.01 (2.13 to 4.25)), followed by rizatriptan (1.59 (1.18 to 2.17) to 2.44 (1.75 to 3.45)), sumatriptan (1.35 (1.03 to 1.75) to 2.04 (1.49 to 2.86)), and zolmitriptan (1.47 (1.04 to 2.08) to 1.96 (1.39 to 2.86)). For sustained pain freedom, the most efficacious interventions were eletriptan and ibuprofen (odds ratios from 1.41 (1.02 to 1.93) to 4.82 (1.31 to 17.67)). Confidence in accordance with CINeMA ranged from high to very low. Sensitivity analyses on Food and Drug Administration licensed doses only, high versus low doses, risk of bias, and moderate to severe headache at baseline confirmed the main findings for both primary and secondary outcomes. CONCLUSIONS: Overall, eletriptan, rizatriptan, sumatriptan, and zolmitriptan had the best profiles and they were more efficacious than the recently marketed drugs lasmiditan, rimegepant, and ubrogepant. Although cost effectiveness analyses are warranted and careful consideration should be given to patients with a high risk cardiovascular profile, the most effective triptans should be considered as preferred acute treatment for migraine and included in the WHO List of Essential Medicines to promote global accessibility and uniform standards of care. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework https://osf.io/kq3ys/.

Abstract licence: CC BY

Introduction Migraine is a common and disabling neurological disorder that requires effective acute treatment. However, access to optimal therapies varies significantly across healthcare systems worldwide. This systematic review assesses acute pharmacological treatments for migraine from a Mexican healthcare perspective, focusing on drug availability and proposing a practical treatment algorithm. Methods Following PRISMA guidelines, we systematically searched multiple databases from inception to November 2024. We included randomized controlled trials evaluating acute treatments for migraine in adults. Treatment efficacy data were synthesized narratively in accordance with the International Headache Society guidelines. Drug availability in Mexico was assessed through regulatory databases and clinical practice surveys. Results Thirty-six randomized controlled trials met inclusion criteria, evaluating triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), calcitonin gene-related peptide antagonists, ditans, and combination therapies. Subcutaneous sumatriptan demonstrated high efficacy (83% pain relief at 2 hours), but it is limited in availability within the Mexican public healthcare system. Oral triptans (sumatriptan, zolmitriptan, eletriptan, and rizatriptan) are available; however, access varies between the public and private sectors. NSAIDs like ketorolac and ketoprofen show good efficacy and are widely accessible. Newer agents (rimegepant, lasmiditan) are available but expensive, limiting healthcare access. Conclusion Effective migraine treatment in Mexico necessitates a balance between evidence-based medicine and healthcare realities. While triptans remain first-line per international guidelines, NSAIDs offer practical alternatives given their accessibility. A structured approach considering drug availability, cost, and patient characteristics can optimize migraine care in Mexico and similar healthcare systems.

Abstract licence: CC BY-NC

Abstract Background Triptans are potent 5-HT 1B/1D/1F receptor agonists used in migraine therapy, thought to act through peripheral mechanisms. It remains unclear whether triptans cross the blood-brain barrier (BBB) sufficiently to stimulate central 5-HT 1B/1D/1F receptors. This study investigates the disposition of eletriptan and sumatriptan in central nervous system (CNS) and peripheral nervous system (PNS) regions and predicts regional 5-HT 1B/1D/1F receptor occupancies at clinically relevant concentrations. Methods Using the Combinatory Mapping Approach (CMA) for regions of interest (ROI), we assessed the unbound tissue-to-plasma concentration ratio (K p, uu, ROI ) in rats at steady state across CNS (hypothalamus, brain stem, cerebellum, frontal cortex, parietal cortex, striatum, hippocampus, whole brain, and spinal cord) and PNS (trigeminal ganglion and sciatic nerve) regions. We used K p, uu, ROI values to estimate unbound target-site concentrations and 5-HT 1B/1D/1F receptor occupancies in humans. Results We observed heterogenous triptan transport across CNS and PNS regions with the highest extent of unbound drug transport across the blood-nerve barrier in the trigeminal ganglion (K p, uu, TG : eletriptan: 0.519, and sumatriptan: 0.923). Both drugs displayed restricted entry across the BBB (K p, uu, whole brain : eletriptan: 0.058, and sumatriptan: 0.045) combined with high inter-regional variability. We estimated near-complete receptor occupancy in the trigeminal ganglion, while lower occupancies were observed in the whole brain, irrespective of the drug or receptor subtype. For instance, eletriptan was predicted to achieve 84% 5-HT 1B receptor occupancy in the trigeminal ganglion and 37% in the whole brain at clinically relevant concentrations. Conclusions This study suggests that despite low BBB transport, both eletriptan and sumatriptan achieve unbound concentrations sufficient to stimulate 5-HT 1B, 5-HT 1D , and 5-HT 1F receptors not only in the trigeminal ganglion, but also in the CNS. Further research is needed to determine whether central mechanisms contribute to triptan’s antimigraine effect and/or side effects. Graphical Abstract

Abstract licence: CC BY

Abstract Background Triptans are anti-migraine drugs with a potential central site of action. However, it is not known to what extent triptans cross the blood–brain barrier (BBB). The aim of this study was therefore to determine if triptans pass the brain capillary endothelium and investigate the possible underlying mechanisms with focus on the involvement of the putative proton-coupled organic cation (H + /OC) antiporter. Additionally, we evaluated whether triptans interacted with the efflux transporter, P-glycoprotein (P-gp). Methods We investigated the cellular uptake characteristics of the prototypical H + /OC antiporter substrates, pyrilamine and oxycodone, and seven different triptans in the human brain microvascular endothelial cell line, hCMEC/D3. Triptan interactions with P-gp were studied using the IPEC-J2 MDR1 cell line. Lastly, in vivo neuropharmacokinetic assessment of the unbound brain-to-plasma disposition of eletriptan was conducted in wild type and mdr1a/1b knockout mice. Results We demonstrated that most triptans were able to inhibit uptake of the H + /OC antiporter substrate, pyrilamine, with eletriptan emerging as the strongest inhibitor. Eletriptan, almotriptan, and sumatriptan exhibited a pH-dependent uptake into hCMEC/D3 cells. Eletriptan demonstrated saturable uptake kinetics with an apparent K m of 89 ± 38 µM and a J max of 2.2 ± 0.7 nmol·min −1 ·mg protein −1 ( n = 3). Bidirectional transport experiments across IPEC-J2 MDR1 monolayers showed that eletriptan is transported by P-gp, thus indicating that eletriptan is both a substrate of the H + /OC antiporter and P-gp. This was further confirmed in vivo, where the unbound brain-to-unbound plasma concentration ratio (K p,uu ) was 0.04 in wild type mice while the ratio rose to 1.32 in mdr1a/1b knockout mice. Conclusions We have demonstrated that the triptan family of compounds possesses affinity for the H + /OC antiporter proposing that the putative H + /OC antiporter plays a role in the BBB transport of triptans, particularly eletriptan. Our i n vivo studies indicate that eletriptan is subjected to simultaneous brain uptake and efflux, possibly facilitated by the putative H + /OC antiporter and P-gp, respectively. Our findings offer novel insights into the potential central site of action involved in migraine treatment with triptans and highlight the significance of potential transporter related drug-drug interactions. Graphical Abstract

Abstract licence: CC BY

Background Triptans revolutionized the acute treatment of migraine; however, varied responses to triptans, as a result of poor efficacy and tolerability, are reported. A standardized definition of triptan non-response was recently proposed by the European Headache Federation (EHF). There is currently limited data available on the prevalence of triptan non-response. Methods We used clinic letters over a two-year duration to evaluate the triptan response and triptan efficacy or tolerability failure, or both, in a London-based tertiary headache service. Results In total, 419 adult migraine patients (females: 83.8%, age: 46 ± 18 years, chronic migraine: 88.5%) were included in a service evaluation. In line with the EHF definitions, “triptan non-response” was seen in 63.8% of patients (264/414), whereas 37.7% of patients (156/414) had failed at least two triptans (EHF “triptan resistant”) and 4.6% of patients (19/414) had failed at least three triptans, including a subcutaneous formulation (EHF “triptan refractory”). Notably, 21.3% of patients (88/414) had failed at least three triptans inclusive and exclusive of subcutaneous triptan use. Advancing age ( p < 0.001) and the presence of medication overuse ( p = 0.006) increased the probability of triptan response, whereas an increased number of failed preventives ( p < 0.001) and the use of calcitonin gene-related peptide monoclonal antibodies ( p = 0.022) increased the probability of triptan non-response. The largest proportion of patients responded to eletriptan (49.5%), followed by nasal zolmitriptan (44.4%) and rizatriptan (35.7%). Conclusions Our findings highlight an alarming prevalence of triptan non-response among adult migraineurs receiving treatment in a London-based tertiary headache service. It is imperative for clinicians to explore methods to optimize acute medication efficacy, whether this comprises changing to a triptan with a superior response rate, advocating for early intervention or considering alternative acute medication classes, such as gepants or ditans.

Abstract licence: CC BY

A migraine is a condition of severe headaches, causing a disturbance in the daily life of the patient. The current studies were designed to develop immediate-release polymeric buccal films of Eletriptan Hydrobromide (EHBR) and Itopride Hydrochloride (ITHC) to improve their bioavailability and, hence, improve compliance with the patients of migraines and its associated symptoms. The prepared films were evaluated for various in vitro parameters, including surface morphology, mechanical strength, disintegration test (DT), total dissolving time (TDT), drug release and drug permeation, etc., and in vivo pharmacokinetic parameters, such as area under curve (AUC), mean residence time (MRT), half-life (t1/2), time to reach maximum concentration (Tmax), and time to reach maximum concentration (Cmax). The outcomes have indicated the successful preparation of the films, as SEM has confirmed the smooth surface and uniform distribution of drugs throughout the polymer matrix. The films were found to be mechanically stable as indicated by folding endurance studies. Furthermore, the optimized formulations showed a DT of 13 ± 1 s and TDT of 42.6 ± 0.75 s, indicating prompt disintegration as well as the dissolution of the films. Albino rabbits were used for in vivo pharmacokinetics, and the outcomes were evident of improved pharmacokinetics. The drug was found to rapidly permeate across the buccal mucosa, leading to increased bioavailability of the drug: Cmax of 130 and 119 ng/mL of ITHC and EHBR, respectively, as compared to 96 (ITHC) and 90 ng/mL (EHBR) of oral solution. The conclusion can be drawn that possible reasons for the enhanced bioavailability could be the increased surface area in the form of buccal films, its rapid disintegration, and faster dissolution, which led toward the rapid absorption of the drug into the blood stream.

Abstract licence: CC BY

A stability-indicating UHPLC-MS method was developed to investigate the stress degradation behavior of eletriptan hydrobromide under ICH-recommended acidic, alkaline, neutral, oxidative, thermal, and photolytic conditions. Significant degradation was observed only under acidic and oxidative stress. Four degradation products were isolated and structurally characterized using HRMS and NMR, including one novel dimeric species. The optimized UHPLC-MS method provided an 8-min runtime with good resolution, sensitivity, and suitability for routine analysis. These results offer the first complete structural insight into the degradation pathways of eletriptan hydrobromide. The study supports improved quality control and long-term stability assessment. The findings also bridge the knowledge gap left by earlier studies that reported unassigned degradation products. Three new degradation products were identified and isolated from oxidative degradation and a new degradation product isolated from the acid degradation, providing the first documented structural characterization of all four degradation products. Furthermore, we develop a UPLC MS method having 8-min runtime and good peak shape and resolution by using Acquity BEH C18 column (100 × 2.1 mm, 1.7 μm) column.

Abstract licence: CC BY