Efficacy Of Rizatriptan Research Articles

Development of mucoadhesive in-situ nasal gel formulation for enhanced bioavailability and efficacy of rizatriptan in migraine treatment

This research article focuses on the development of an in-situ nasal gel formulation for the antimigraine agent, Rizatriptan (RZT), to enhance its bioavailability and efficacy in treating migraine. The aim of the study was to overcome the challenges of rapid mucociliary clearance. Carbopol 934P (1–2 %w/v) was added to the primary solution, followed by HPMC K4M (0.4–1.2 %w/v). Different copolymers were tested, and HPMC K4M was chosen due to its compatibility with the other ingredients. The pH of all formulations was in the nasal pH range, and the drug content was above 97% in all batches. Gelling time varied from 1.3 to 8.6 sec, with low gelling time observed when viscosity and mucoadhesive strength were high. The results were analyzed using a statistical model with interactive and polynomial terms. The statistical analysis showed a good correlation between dependent and independent variables, with R2 values of 0.97758 and 0.948931 for viscosity and mucoadhesive strength, respectively. The Cmax of RZT in the brain was significantly higher (p < 0.05) via intra-nasal (340.27 ng) route as compared to the oral route and the same was the case for AUC. Finally, it was concluded that the RZT nasal in-situ gel system improves bioavailability compared with oral route and could provide fast action in migraine therapy.

Long‐Term Open‐Label Safety Study of Rizatriptan Acute Treatment in Pediatric Migraineurs

To evaluate the safety/tolerability of rizatriptan in the long-term acute treatment of migraine in pediatric patients. Acute migraine treatment options for children are limited. A recent single-attack trial demonstrated that rizatriptan is effective in eliminating migraine headache pain in this population. We evaluated the long-term safety and efficacy of rizatriptan when used for intermittent acute treatment. Open-label study in pediatric migraineurs ages 12-17 years. Patients weighing <40 kg received rizatriptan (orally disintegrating tablet) 5 mg, and those weighing ≥40 kg received 10 mg. Patients could treat up to 8 mild/moderate/severe migraine attacks per month for up to 12 months. One dose of study medication was allowed in a 24-hour period. A total of 674 patients were enrolled, and 606 patients were treated with study medication (N = 583 for 10 mg, N = 23 for 5 mg). The mean duration in the study was 292 days, and the mean number of doses of study medication taken was 20. Over the course of the study within 14 days post-any-dose, 66.0% (400) of the 606 treated patients had any adverse event, 2.3% (14) discontinued due to an adverse event, 2.6% (16) had a serious adverse event, and 23.4% (142) had a triptan-related adverse event. Of the 16 patients with serious adverse events within 14 days post-any-dose, the adverse events in 3 were considered drug-related; all 3 patient's adverse events were classified as serious only because they were associated with an overdose (use of >1 dose of study medication in a 24-hour period). The mean percentage of patient's attacks with pain freedom at 2-hours post-dose was 46.3%; this was relatively consistent over time (Months 1-3 = 43.7%, Months 4-6 = 51.9%, Months 7-9 = 49.9%, Months 10-12 = 49.5%). Rizatriptan was generally safe and well tolerated in the long-term acute treatment of migraine in pediatric patients aged 12-17 years and demonstrated a consistent treatment effect over time.

Long-Term Safety and Tolerability of Rizatriptan for Intermittent Acute Treatment of Migraine in Pediatric Migraineurs (P03.232)

Objective: To evaluate the safety/tolerability of rizatriptan in the long-term acute treatment of migraine in pediatric patients. Background Acute migraine treatment options for children are limited. A recent single-attack trial demonstrated that rizatriptan was statistically significantly more effective than placebo in eliminating pain in this population. We evaluated the long-term safety and efficacy of rizatriptan for intermittent acute migraine treatment. Design/Methods: Open-label study in pediatric migraineurs ages 12-17yrs. Patients weighing 1 dose of study medication in a 24-hour period was considered an overdose, and any AE associated with an overdose was automatically classified as serious. Results: 606 patients treated with study-medication (N=583, for 10-mg, N=23 for 5-mg). The mean duration in the study was 292 days and the mean number of study-medication doses taken was 20. Over the course of the study within 14 days post-any-dose, 400/606 (66.0%) patients had any AE, 14/606 (2.3%) discontinued due to an AE, 16/606 (2.6%) had a serious AE, and 142/606 (23.4%) had a triptan-related AE. Of the 16 patients with serious AEs, the AEs in 3 were considered drug-related; all 3 patient9s AEs were classified as serious because they were associated with an overdose. The mean percentage of patient9s attacks with pain freedom at 2-hours postdose was 46.3%; this was relatively consistent over time (Months 1-3=43.7%, Months 4-6=51.9%, Months 7-9=49.9%, Months 10-12=49.5%). Conclusions: Rizatriptan was generally safe and well-tolerated in the long-term acute treatment of migraine in pediatric patients age 12-17 years, and demonstrated a consistent treatment effect over time. Supported by: Merck & Co., Inc. Disclosure: Dr. Hewitt has received personal compensation for activities with Merck & Co., Inc. as an employee. Dr. Pearlman has received personal compensation for activities with GSK, Merck, Allergan, and Nautilus Pharmaceuticals as a consultant.Dr. Pearlman has received research support from GSK, Merck, and AstraZenenca. Dr. Lewis has received personal compensation for activities with Merck, Astra Zeneca, and GlaxoSmithKline.Dr. Lewis has received research support from Abbott, Astra Zeneca, Almirall, GlaxoSmithKline, Merck, and Ortho-McNeil. Dr. Hamalainen has received personal compensation for activities with Merck. Ms. Connor has received personal compensation for activities with Merck & Co., Inc. Ms. Connor holds stock and/or stock options in Merck & Co., Inc. Dr. Michelson has nothing to disclose. Dr. Ceesay has received personal compensation for activities with Merck & Co., Inc. Dr. Ceesay holds stock and/or stock options in Merck & Co., Inc. Mr. Bachman has received personal compensation for activities with Merck & Co., Inc. as an employee. Mr. Bachman holds stock and/or stock options in Merck & Co., Inc. Dr. Harper-Mozley has received personal compensation for activities with Merck as an employee.Dr. Harper-Mozley holds stock and/or stock options in Merck. Dr. Dupre has received personal compensation for activities with Merck as an employee.Dr. Dupre holds stock and/or stock options in Merck. Ms. Strickler has received personal compensation for activities with Merck & Co., Inc., as an employee. Ms. Strickler holds stock and/or stock options in Merck & Co., Inc. Dr. Mahoney has received personal compensation for activities with Merck & Co, Inc. as an employee. Dr. Mahoney holds stock and/or stock options in Merck & Co, Inc. Dr. Lines has received personal compensation for activities with Merck as an employee.Dr. Lines holds stock and/or stock options in Merck. Dr. Ho has received personal compensation for activities with Merck & Co., Inc. as an employee.Dr. Ho holds stock and/or stock options in Merck & Co., Inc.

Efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 100 mg: an evidence-based analysis

Acute migraine attacks have a strong impact on quality of life and require immediate therapeutic intervention to achieve rapid pain relief. The introduction of triptans into the market in 1993 has increased the therapeutic options in migraine patients considerably. The seven currently available triptans show many similar characteristics but there are also some clinically relevant pharmacological differences. Rizatriptan 10 mg has demonstrated, in a head-to-head study, higher response rates and a more rapid onset of action than sumatriptan 100 mg, together with a favorable tolerability profile. Meta-analyses of double-blind placebo-controlled studies confirmed the superior efficacy of rizatriptan. Owing to the limited efficacy of sumatriptan, a more effective triptan treatment is needed in the majority of patients with acute migraine attacks.

Rizatriptan: an update of its use in the management of migraine.

Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials demonstrated that rizatriptan 5 or 10mg is more effective than placebo at providing pain relief and a pain-free state, relieving associated symptoms of migraine, normalising functional ability and improving patient quality of life, and showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at producing a pain-free state 2 hours postdose. Furthermore, compared with naratriptan, significantly more patients who received rizatriptan were pain free or had pain relief from 1 hour onwards. The number of patients with normal functional ability at 2 hours was significantly higher after rizatriptan than after naratriptan or zolmitriptan. Rizatriptan was also generally more effective than zolmitriptan or naratriptan at relieving migraine-associated symptoms. Rizatriptan is generally well tolerated and adverse events are usually mild and transient. The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There was a trend towards a lower incidence of adverse events with rizatriptan compared with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a significantly higher incidence of adverse events than naratriptan (39 vs 29%). The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2 to 4%). Rizatriptan is an effective drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5 and 10mg have shown greater efficacy than placebo in providing pain relief, an absence of pain, relief from associated symptoms, normal functional ability and an improvement in patient quality of life. Earlier results showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recent studies have shown that rizatriptan 10mg provides faster pain relief and a higher percentage of patients with an absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the long term and the drug is generally well tolerated. Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest rizatriptan should be considered as a first-line treatment option in the management of migraine.

Spotlight on rizatriptan in migraine.

Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials demonstrated that rizatriptan 5 or 10mg is more effective than placebo at providing pain relief and a pain-free state, relieving associated symptoms of migraine, normalising functional ability and improving patient quality of life, and showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at producing a pain-free state 2 hours postdose. Furthermore, compared with naratriptan, significantly more patients who received rizatriptan were pain free or had pain relief from 1 hour onwards. The number of patients with normal functional ability at 2 hours was significantly higher after rizatriptan than after naratriptan or zolmitriptan. Rizatriptan was also generally more effective than zolmitriptan or naratriptan at relieving migraine-associated symptoms. Rizatriptan is generally well tolerated, and adverse events are usually mild and transient. The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There was a trend towards a lower incidence of adverse events with rizatriptan compared with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a significantly higher incidence of adverse events than naratriptan (39 vs 29%). The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2-4%). In conclusion, rizatriptan is an effective drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5 and 10mg have shown greater efficacy than placebo in providing pain relief, an absence of pain, relief from associated symptoms, normal functional ability and an improvement in patient quality of life. Earlier results showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recent studies have shown that rizatriptan 10mg provides faster pain relief and a higher percentage of patients with an absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the long term, and the drug is generally well tolerated. Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest that rizatriptan should be considered as a first-line treatment option in the management of migraine.

Rizatriptan 5 mg for the Acute Treatment of Migraine in Adolescents: A Randomized, Double‐Blind, Placebo‐Controlled Study

To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs. Randomized, double-blind, placebo-controlled study. Patients aged 12 to 17 years received rizatriptan 5 mg (n = 149) or placebo (n = 147) for a moderate or severe headache and for up to two recurrences. Headache severity, presence or absence of associated symptoms, and functional disability were assessed over a 4-hour postdose period, and any adverse events were recorded. The primary efficacy measure was pain-free status at 2 hours postdose. Rizatriptan 5 mg was well tolerated. The most commonly reported adverse events (all with incidence of 5% or less) among patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue, nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32% for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients with pain relief (reduction of predose pain intensity to mild or none) at 2 hours was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates were higher than those typically observed in previous studies of rizatriptan in adults. Compared with placebo, rizatriptan significantly improved functional disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis showed a significant benefit of rizatriptan versus placebo in the percentage of patients who had pain relief when their migraine attacks were treated on weekends (65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the weekend placebo response rate was similar to that seen in adults. Rizatriptan 5 mg was well tolerated and effective on some measures when used in adolescents for the treatment of a migraine attack.

Migraine treatment outcomes with rizatriptan in triptan-naive patients: a naturalistic study

Background: The 5-hydroxytryptamine 1B/1D agonists, or triptans, are the newest class of drugs to become available for the acute treatment of migraine. The class currently includes sumatriptan, zolmitriptan, naratriptan, and rizatriptan. The efficacy of rizatriptan in the acute treatment of migraine has been established against placebo and other oral triptans in controlled comparative trials. Objective: The US Migraine Assessment Protocol (USMAP) collected data on the use of rizatriptan in a naturalistic setting reflecting clinical practice. This paper presents results for patients enrolled in the USMAP study who had never taken a triptan before the study. Methods: At enrollment, 216 patients completed a questionnaire describing their responses to their current nontriptan medications. They were then given specially packaged samples of 4 standard 10-mg rizatriptan tablets and 4 orally disintegrating 10-mg rizatriptan tablets (wafers) and were asked to take a different formulation for each of their next 2 attacks, the sequence to be at their discretion. Within ∼24 hours after taking rizatriptan, patients were to call a toll-free number to report their responses to rizatriptan using an interactive voice-response system. Results: Within 2 hours after initial dosing of rizatriptan, significantly more patients taking either the rizatriptan tablet or the rizatriptan wafer reported onset of pain relief, had become largely symptom free, and were able to resume usual activities compared with their baseline responses to nontriptans ( P < 0.05). In addition, compared with their baseline responses to nontriptans, significantly more patients taking either rizatriptan formulation had mild or no pain 2 hours after dosing ( P < 0.05). More than twice as many patients taking the rizatriptan tablets or wafers were either somewhat or very satisfied with the medication compared with their satisfaction with nontriptans ( P < 0.05). Conclusions: In the naturalistic setting of this study, migraineurs who had not previously taken a triptan medication reported more rapid relief of pain, more effective pain relief, and more rapid resumption of normal activities when taking rizatriptan tablets or wafers than when taking a nontriptan medication. Patients dissatisfied with their current non-triptan migraine therapy may benefit from treatment with rizatriptan.

Pharmacologic Profile and Clinical Efficacy of Rizatriptan

Pharmacologic Profile and Clinical Efficacy of Rizatriptan