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Andrew J. Dowson - One of the best experts on this subject based on the ideXlab platform.
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Part III: the convenience of, and patient preference for, Zolmitriptan orally disintegrating tablet.
Current medical research and opinion, 2020Co-Authors: Andrew J. Dowson, Per AlmqvistAbstract:As part of an optimal strategy for the management of migraine, the individual needs and preferences of patients need to be considered when of patients need to be considered when prescribing treatments. Zolmitriptan has been available as a conventional oral tablet for more than seven years, and is established as a highly effective, well-tolerated compound for the acute treatment of migraine. A bioequivalent, orally disintegrating tablet (ODT) of Zolmitriptan, which dissolves on the tongue without the need for additional fluid intake, has been developed. In a study designed to compare patient preference for Zolmitriptan ODT and conventional oral sumatriptan tablets, > 60% of the 186 patients questioned had an overall preference for Zolmitriptan ODT, with > 80% of patients reporting that this was the more convenient and less disruptive therapy to take. Approximately 90% of patients agreed that, unlike a conventional tablet, Zolmitriptan ODT can be taken wherever and whenever a migraine occurs. When patient preference for Zolmitriptan ODT and the ODT formulation of rizatriptan was compared in 171 migraineurs, 70% had an overall preference for Zolmitriptan ODT to be superior to rizatriptan ODT with respect to taste and aftertaste, as well as packaging. In summary, not only is Zolmitriptan ODT a convenient tablets, such as the sumatriptan oral tablet, but patients generally consider it to be a more attractive option for the acute treatment of migraine than the orally disintegrating version of rizatriptan.
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patient preference for triptan formulations a prospective study with Zolmitriptan
Headache, 2007Co-Authors: Andrew J. Dowson, Michael Bundy, Rebecca Salt, Shaun G KilminsterAbstract:Objectives.—To investigate patterns of patient preference for 3 formulations of Zolmitriptan, in a primary care study utilizing a naturalistic longitudinal design. Background.—Although differences in efficacy between individual triptans tend to be small, migraine patients show clear preferences for individual triptans and formulations. The groups of patients suitable for the different triptan formulations, and the reasons underlying individual preferences, are not clearly understood. Methods.—Migraine patients entered a prospective, randomized, open, crossover, longitudinal design study, with patients receiving Zolmitriptan formulations according to UK prescribing recommendations. Patients naive to Zolmitriptan received Zolmitriptan 2.5-mg film-coated tablets or 2.5-mg Orally Disintegrating Tablets (ODT) for 1 month, before being crossed over to receive the alternative formulation for Month 2. All patients then received Zolmitriptan nasal spray 5 mg for Month 3. Patients could then choose the formulation(s) of their choice for a further 7 months. Patients recorded their preferences for individual formulations, the reasons for their preferences, and also the headache-related disability (measured by the Migraine Disability Assessment [MIDAS] score) at clinic visits. Primary endpoints were the individual preferences and changes in MIDAS scores. Adverse events were also recorded. Results.—Forty-eight patients took part in the study. At baseline, most patients expressed a preference for conventional tablets. After 4 months, 46.9% of patients preferred Zolmitriptan ODT, 43.8% Zolmitriptan nasal spray, and 6.3% the conventional tablet. The most common reasons given for preferring conventional tablets were personal reasons: for Zolmitriptan ODT, convenience and, to a lesser extent, speed of onset: for Zolmitriptan nasal spray, speed of onset, and overall efficacy. MIDAS scores decreased significantly following treatment with Zolmitriptan. Zolmitriptan was well tolerated. Conclusions.—Patient experience of newer Zolmitriptan formulations influenced a change in preference away from conventional tablets. Speed and efficacy were the key drivers of preference for Zolmitriptan nasal spray, while convenience mostly drove preference for the ODT formulation. Open, longitudinal, naturalistic studies may, allowing for biases, sometimes be an appropriate way of conducting migraine studies in primary care.
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part iii the convenience of and patient preference for Zolmitriptan orally disintegrating tablet
Current Medical Research and Opinion, 2005Co-Authors: Andrew J. Dowson, Per AlmqvistAbstract:ABSTRACTAs part of an optimal strategy for the management of migraine, the individual needs and preferences of patients need to be considered when prescribing treatments. Zolmitriptan has been available as a conventional oral tablet for more than seven years, and is established as a highly effective, well-tolerated compound for the acute treatment of migraine. A bioequivalent, orally disintegrating tablet (ODT) of Zolmitriptan, which dissolves on the tongue without the need for additional fluid intake, has been developed. In a study designed to compare patient preference for Zolmitriptan ODT and conventional oral sumatriptan tablets, > 60% of the 186 patients questioned had an overall preference for Zolmitriptan ODT, with > 80% of patients reporting that this was the more convenient and less disruptive therapy to take. Approximately 90% of patients agreed that, unlike a conventional tablet, Zolmitriptan ODT can be taken wherever and whenever a migraine occurs. When patient preference for Zolmitriptan ODT ...
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Part II: clinical efficacy and tolerability of Zolmitriptan orally disintegrating tablet in the acute treatment of migraine.
Current Medical Research and Opinion, 2005Co-Authors: Elizabeth Loder, Andrew J. Dowson, Egilius L.h. SpieringsAbstract:ABSTRACTControlled clinical trials and extensive clinical use of conventional oral tablets of Zolmitriptan, a selective agonist of serotonin1B/1D receptors, have proven the compound to be fast-acting, highly effective, and well-tolerated in the acute treatment of migraine. An orally disintegrating tablet (ODT) of Zolmitriptan that dissolves on the tongue without the need for fluid intake has been developed in order to provide an acceptable, convenient alternative for patients who prefer not to, or cannot, take conventional tablets. A fast onset of effective, sustained pain relief was predicted for Zolmitriptan ODT on the basis of its bioequivalence with the conventional tablet, which has been confirmed in three randomised, double-blind, placebo-controlled trials of Zolmitriptan ODT in the acute treatment of migraine. Compared with placebo, significantly higher proportions of patients treated with Zolmitriptan ODT responded to treatment (reduction of moderate or severe headache to mild or no pain) as early...
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Tolerability and Consistency of Effect of Zolmitriptan Nasal Spray in a Long-Term Migraine Treatment Trial
CNS Drugs, 2003Co-Authors: Andrew J. Dowson, Bruce R. Charlesworth, Allan Purdy, Werner J. Becker, Steen Boes-hansen, Markus FärkkiläAbstract:Objectives: To primarily assess the tolerability of Zolmitriptan (Zomig®) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). Methods: This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1093 patients aged 18–65 years with an established diagnosis of migraine with or without aura received intranasal Zolmitriptan 5,2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of Zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres. Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. Results: Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with Zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with Zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with Zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1093 patients who treated 13 806 attacks during the pre-crossover phase, headache response rates at 2 hours over all attacks were 73.2%, 70.5%, 49.9% and 41.5% for Zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg, respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%, 24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in either the pre- or post-crossover phases, the 2-hour headache response rates were 72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day 360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term usage of Zolmitriptan nasal spray 5mg was also associated with a consistently effective response, with 57.8% of patients experiencing a 2-hour headache response in over 75% of attacks. The majority of patients (70.3%) rated their overall satisfaction with Zolmitriptan nasal spray 5mg as good or excellent. Conclusion: Zolmitriptan nasal spray 5mg provides good tolerability and efficacy in long-term use in a clinical setting, with consistently high 2-hour headache and pain-free rates. This combination of benefits translates to high patient satisfaction with this formulation of Zolmitriptan.
Bruce R. Charlesworth - One of the best experts on this subject based on the ideXlab platform.
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Zolmitriptan 5 mg nasal spray efficacy and onset of action in the acute treatment of migraine results from phase 1 of the realize study
Headache, 2005Co-Authors: Marek Gawel, Jurgen Aschoff, Bruce R. CharlesworthAbstract:Objectives.—The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of Zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. Background.—Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. Methods.—In the double-blind first phase of the study, patients with migraine were randomized to receive Zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. Results.—The intention-to-treat population comprised 461 Zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the Zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with Zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P= .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P= .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. Conclusions.—These findings confirm the efficacy demonstrated by Zolmitriptan nasal spray in previous clinical trials.
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Tolerability and Consistency of Effect of Zolmitriptan Nasal Spray in a Long-Term Migraine Treatment Trial
CNS Drugs, 2003Co-Authors: Andrew J. Dowson, Bruce R. Charlesworth, Allan Purdy, Werner J. Becker, Steen Boes-hansen, Markus FärkkiläAbstract:Objectives: To primarily assess the tolerability of Zolmitriptan (Zomig®) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). Methods: This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1093 patients aged 18–65 years with an established diagnosis of migraine with or without aura received intranasal Zolmitriptan 5,2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of Zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres. Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. Results: Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with Zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with Zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with Zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1093 patients who treated 13 806 attacks during the pre-crossover phase, headache response rates at 2 hours over all attacks were 73.2%, 70.5%, 49.9% and 41.5% for Zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg, respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%, 24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in either the pre- or post-crossover phases, the 2-hour headache response rates were 72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day 360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term usage of Zolmitriptan nasal spray 5mg was also associated with a consistently effective response, with 57.8% of patients experiencing a 2-hour headache response in over 75% of attacks. The majority of patients (70.3%) rated their overall satisfaction with Zolmitriptan nasal spray 5mg as good or excellent. Conclusion: Zolmitriptan nasal spray 5mg provides good tolerability and efficacy in long-term use in a clinical setting, with consistently high 2-hour headache and pain-free rates. This combination of benefits translates to high patient satisfaction with this formulation of Zolmitriptan.
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speed of onset and efficacy of Zolmitriptan nasal spray in the acute treatment of migraine a randomised double blind placebo controlled dose ranging study versus Zolmitriptan tablet
CNS Drugs, 2003Co-Authors: Bruce R. Charlesworth, Andrew J. Dowson, Allan Purdy, Werner J. Becker, Steen Boeshansen, Markus FärkkiläAbstract:Objective: Zolmitriptan oral tablet is highly effective and well tolerated in the acute treatment of migraine with and without aura in adults. A nasal spray formulation has now been developed. The objective of this study was to compare the efficacy and tolerability of fixed doses of Zolmitriptan administered via a nasal spray with placebo and Zolmitriptan oral tablet in the acute treatment of migraine.
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review of Zolmitriptan and its clinical applications in migraine
Expert Opinion on Pharmacotherapy, 2002Co-Authors: Andrew J. Dowson, Bruce R. CharlesworthAbstract:Preclinical studies have shown that Zolmitriptan is a selective serotonin 5-HT1B/1D receptor agonist (triptan). Randomised, placebo-controlled, double-blind trials in patients with migraine have shown that Zolmitriptan has good efficacy measured using 2 h response and pain-free rates. Migraine-associated symptoms, including nausea, photophobia and phonophobia, are also improved with Zolmitriptan. Oral Zolmitriptan (2.5 and 5 mg) has an onset of action within 45 min and efficacy is sustained in most patients who respond at 2 h. The orally-disintegrating Zolmitriptan tablet has the advantage that it may be taken immediately, without the need for additional fluids, any time a migraine headache occurs. Patients may benefit in terms of improved efficacy from the convenience of the disintegrating tablet, since there is evidence that taking triptan therapy as early as possible in an attack is advantageous. For similar reasons, as well as improved efficacy, a nasal spray formulation is in development. Zolmitripta...
Werner J. Becker - One of the best experts on this subject based on the ideXlab platform.
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Tolerability and Consistency of Effect of Zolmitriptan Nasal Spray in a Long-Term Migraine Treatment Trial
CNS Drugs, 2003Co-Authors: Andrew J. Dowson, Bruce R. Charlesworth, Allan Purdy, Werner J. Becker, Steen Boes-hansen, Markus FärkkiläAbstract:Objectives: To primarily assess the tolerability of Zolmitriptan (Zomig®) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). Methods: This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1093 patients aged 18–65 years with an established diagnosis of migraine with or without aura received intranasal Zolmitriptan 5,2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of Zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres. Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. Results: Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with Zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with Zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with Zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1093 patients who treated 13 806 attacks during the pre-crossover phase, headache response rates at 2 hours over all attacks were 73.2%, 70.5%, 49.9% and 41.5% for Zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg, respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%, 24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in either the pre- or post-crossover phases, the 2-hour headache response rates were 72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day 360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term usage of Zolmitriptan nasal spray 5mg was also associated with a consistently effective response, with 57.8% of patients experiencing a 2-hour headache response in over 75% of attacks. The majority of patients (70.3%) rated their overall satisfaction with Zolmitriptan nasal spray 5mg as good or excellent. Conclusion: Zolmitriptan nasal spray 5mg provides good tolerability and efficacy in long-term use in a clinical setting, with consistently high 2-hour headache and pain-free rates. This combination of benefits translates to high patient satisfaction with this formulation of Zolmitriptan.
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speed of onset and efficacy of Zolmitriptan nasal spray in the acute treatment of migraine a randomised double blind placebo controlled dose ranging study versus Zolmitriptan tablet
CNS Drugs, 2003Co-Authors: Bruce R. Charlesworth, Andrew J. Dowson, Allan Purdy, Werner J. Becker, Steen Boeshansen, Markus FärkkiläAbstract:Objective: Zolmitriptan oral tablet is highly effective and well tolerated in the acute treatment of migraine with and without aura in adults. A nasal spray formulation has now been developed. The objective of this study was to compare the efficacy and tolerability of fixed doses of Zolmitriptan administered via a nasal spray with placebo and Zolmitriptan oral tablet in the acute treatment of migraine.
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Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine
Cephalalgia, 2002Co-Authors: Andrew J. Dowson, Werner J. Becker, E A Macgregor, R A Purdy, J Green, S L LevyAbstract:A new formulation of Zolmitriptan has been developed that dissolves on the tongue without the need for additional fluid intake. In this double-blind, parallel study, 471 patients were randomized to receive the Zolmitriptan orally disintegrating tablet 2.5 mg (n=231) or matching placebo (n=240) to treat a single moderate or severe migraine. Headache relief following Zolmitriptan 2.5 mg (63%) was significantly greater than with placebo (22%) at 2 h post-dose (primary endpoint; P < 0.0001). The Zolmitriptan orally disintegrating tablet was also significantly more effective than placebo for 1-, 2- and 4-h pain-free response (8% vs. 3%, P=0.0207, 27% vs. 7%, P < 0.0001, and 37% vs. 11%, P < 0.0001, respectively). Of those patients stating a preference, 70% of patients preferred the orally disintegrating tablet to a conventional tablet. Zolmitriptan orally disintegrating tablets are an effective and convenient alternative to a conventional tablet, allowing migraine attacks to be treated anytime a migraine strikes, which can facilitate earlier treatment.
Markus Färkkilä - One of the best experts on this subject based on the ideXlab platform.
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Tolerability and Consistency of Effect of Zolmitriptan Nasal Spray in a Long-Term Migraine Treatment Trial
CNS Drugs, 2003Co-Authors: Andrew J. Dowson, Bruce R. Charlesworth, Allan Purdy, Werner J. Becker, Steen Boes-hansen, Markus FärkkiläAbstract:Objectives: To primarily assess the tolerability of Zolmitriptan (Zomig®) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). Methods: This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1093 patients aged 18–65 years with an established diagnosis of migraine with or without aura received intranasal Zolmitriptan 5,2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of Zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres. Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. Results: Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with Zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with Zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with Zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1093 patients who treated 13 806 attacks during the pre-crossover phase, headache response rates at 2 hours over all attacks were 73.2%, 70.5%, 49.9% and 41.5% for Zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg, respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%, 24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in either the pre- or post-crossover phases, the 2-hour headache response rates were 72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day 360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term usage of Zolmitriptan nasal spray 5mg was also associated with a consistently effective response, with 57.8% of patients experiencing a 2-hour headache response in over 75% of attacks. The majority of patients (70.3%) rated their overall satisfaction with Zolmitriptan nasal spray 5mg as good or excellent. Conclusion: Zolmitriptan nasal spray 5mg provides good tolerability and efficacy in long-term use in a clinical setting, with consistently high 2-hour headache and pain-free rates. This combination of benefits translates to high patient satisfaction with this formulation of Zolmitriptan.
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speed of onset and efficacy of Zolmitriptan nasal spray in the acute treatment of migraine a randomised double blind placebo controlled dose ranging study versus Zolmitriptan tablet
CNS Drugs, 2003Co-Authors: Bruce R. Charlesworth, Andrew J. Dowson, Allan Purdy, Werner J. Becker, Steen Boeshansen, Markus FärkkiläAbstract:Objective: Zolmitriptan oral tablet is highly effective and well tolerated in the acute treatment of migraine with and without aura in adults. A nasal spray formulation has now been developed. The objective of this study was to compare the efficacy and tolerability of fixed doses of Zolmitriptan administered via a nasal spray with placebo and Zolmitriptan oral tablet in the acute treatment of migraine.
Roger Yates - One of the best experts on this subject based on the ideXlab platform.
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distribution of intranasal 11c Zolmitriptan assessed by positron emission tomography
Cephalalgia, 2005Co-Authors: Roger Yates, Kevin Nairn, Mats Bergström, Gunnar Antoni, Bengt Långström, John Kemp, Jens Norkaer Sorensen, Aaron DaneAbstract:Nine healthy volunteers aged 18-28 years were recruited into this open, single-centre, two-phase trial. In phase 1, two volunteers received a single dose of "C-Zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron emission tomography (PET) scanning to determine the most appropriate times for scanning in phase 2. In phase 2, six volunteers received two doses and an additional volunteer one dose of 1 1 C-Zolmitriptan 2.5 mg intranasally. Volunteers underwent PET scanning over sectors covering one of the nasopharynx, lungs or abdomen, for up to 1.5 h postdose. The brain was also scanned and plasma Zolmitriptan levels were measured. Almost 100% of the administered dose was detected in the nasopharynx immediately after dosing. This declined thereafter to about 50% at 20 min and to 35% at 80 min after dosing. Radioactivity appeared slowly in the upper abdomen, with 25% of given radioactivity detected at 20 min and persisting until 80 min after dosing. Minimal radioactivity was detected in the lungs. Radioactivity was detectable within brain tissue suggesting central penetration of Zolmitriptan. Zolmitriptan in plasma had approached its maximum concentration by 15 min postdose. The data indicate initial absorption across the nasal mucosa contributing to an early systemic availability. 1 1 C-Zolmitriptan administered intranasally was well tolerated.
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Distribution of Zolmitriptan into the CNS in Healthy Volunteers
Drugs in R & D, 2005Co-Authors: Anders Wall, Matts Kågedal, Mats Bergström, Eva Jacobsson, Dag Nilsson, Gunnar Antoni, Pernilla Frändberg, Sven-Åke Gustavsson, Bengt Långström, Roger YatesAbstract:Objective: Triptans are highly effective in the treatment of migraine. Both central and peripheral mechanisms of action have been suggested. Until now, firm data about the passage of triptans into the CNS in humans have been lacking. The aim of the current study was to evaluate, using positron emission tomography (PET), the uptake and distribution of Zolmitriptan into the CNS after intranasal administration. Subjects and methods: Eight healthy volunteers, five males and three females (mean ages 23 and 26 years, respectively), were included. Radioactive [ carbonyl -^11C]Zolmitriptan was infused intravenously for 5 minutes on two occasions: once alone, and once 30–40 minutes after intranasal administration of unlabelled Zolmitriptan 5mg. PET was used to measure the concentration of labelled Zolmitriptan in the brain, from the start of the tracer infusion for 90 minutes. Regional cerebral blood volume was determined with [^15O]carbon monoxide. In addition, an MRI scan was performed to obtain anatomical information. The PET images were analysed quantitatively for different areas of the brain, generating [^11C]Zolmitriptan time-activity data corrected for circulating tracer activity. The rate of uptake of intranasal Zolmitriptan into the CNS was estimated by kinetic modelling using the PET data. Results: PET data from this study demonstrate a rapid dose-proportional uptake of [^11C]Zolmitriptan into the brain. Significant concentrations of [^11C]Zolmitriptan were found in all brain regions studied. Calculated CNS concentrations after intranasal Zolmitriptan administration showed a gradual increase, reaching about 2nM (0.5 μg/L) 30 minutes after administration and 3.5nM (1.0 μg/L), or one-fifth of the plasma concentration, 1 hour after administration. Five minutes after Zolmitriptan administration, the mean CNS concentration had already reached 0.5nM, which is higher than in vitro values for initiation of the agonistic action on 5-HT_1B/1D receptors. Conclusion: This study demonstrates by direct measurements that Zolmitriptan enters the brain parenchyma in humans, achieving an uptake rate and concentration compatible with a central mode of action.
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Zolmitriptan nasal spray: advances in migraine treatment.
Neurology, 2003Co-Authors: Nick Syrett, Susan Abu-shakra, Roger YatesAbstract:Zolmitriptan nasal spray was developed specifically to achieve fast, high effectiveness and to overcome many of the limitations associated with oral and sc migraine therapies. Pharmacokinetic studies have demonstrated a very rapid appearance of Zolmitriptan in plasma as early as 5 minutes after intranasal dosing, with about 40% of peak plasma concentration (C(max)) being achieved within 10 to 15 minutes of dosing. Comparison of plasma concentration-time profiles of Zolmitriptan and its active metabolite after oral and intranasal administration, together with PET scanning, clearly indicate direct absorption of Zolmitriptan across the nasal mucosa after intranasal administration. The remainder of the dose is then swallowed and is absorbed through the gastrointestinal tract. In one blinded, randomized, placebo-controlled, multiple-attack study of Zolmitriptan nasal spray, headache response was superior to placebo as early as 15 minutes after dosing (p < 0.05). In the Zolmitriptan 5 mg treatment group, the primary end point of 2-hour headache response was achieved in 70% (300/427) of attacks versus 31% of attacks (119/389 attacks) in the placebo group (p < 0.001). Patients achieved a 2-hour headache response, had no recurrence, and used no additional or escape medications for up to 24 hours in 49% of attacks versus 14% of attacks in the placebo group (p < 0.001). Zolmitriptan 5 mg nasal spray was well tolerated. These data and those from other similar studies demonstrate that Zolmitriptan nasal spray combines early, sustained efficacy and good tolerability, making it an optimal acute treatment for migraine.
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Zolmitriptan nasal spray: advances in migraine treatment.
Neurology, 2003Co-Authors: Nick Syrett, Susan Abu-shakra, Roger YatesAbstract:Zolmitriptan nasal spray was developed specifically to achieve fast, high effectiveness and to overcome many of the limitations associated with oral and sc migraine therapies. Pharmacokinetic studies have demonstrated a very rapid appearance of Zolmitriptan in plasma as early as 5 minutes after intranasal dosing, with about 40% of peak plasma concentration (Cmax) being achieved within 10 to 15 minutes of dosing. Comparison of plasma concentration-time profiles of Zolmitriptan and its active metabolite after oral and intranasal administration, together with PET scanning, clearly indicate direct absorption of Zolmitriptan across the nasal mucosa after intranasal administration. The remainder of the dose is then swallowed and is absorbed through the gastrointestinal tract. In one blinded, randomized, placebo-controlled, multiple-attack study of Zolmitriptan nasal spray, headache response was superior to placebo as early as 15 minutes after dosing (p
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Preliminary studies of the pharmacokinetics and tolerability of Zolmitriptan nasal spray in healthy volunteers.
The Journal of Clinical Pharmacology, 2002Co-Authors: Roger Yates, Kevin Nairn, Ruth Dixon, Emma SeaberAbstract:: Two preliminary studies of the pharmacokinetics and tolerability of Zolmitriptan nasal spray were conducted, each involving 12 healthy volunteers. In study 1, an initial double-blind, dose escalation phase (placebo or 2.5, 5.0, or 10 mg Zolmitriptan intranasally) was followed by an open crossover phase in which all subjects received 10 mg Zolmitriptan as a nasal spray, tablet, and oral solution. In study 2, subjects received, on three separate occasions, Zolmitriptan 2.5 mg as an intranasal solution at pH 7.4, at pH 5.0, and as an oral tablet. In study 1, plasma concentrations of Zolmitriptan and its active metabolite, 183C91, were broadly dose proportional. Plasma concentrations of Zolmitriptan were detected earlier following nasal spray administration than after either tablet or oral solution. Similarly, in study 2, Zolmitriptan was absorbed more rapidly following nasal spray administration with detectable plasma concentrations 5 minutes after dosing. Plasma levels were maintained at a plateau between 1 and 6 hours postdose, then decreased with a half-life of approximately 3 hours. There was no statistically significant difference for AUG or C(max) values between the two nasal spray solutions or between nasal spray and oral formulations. Other pharmacokinetic parameters for Zolmitriptan were similar between the formulations. Plasma concentrations of 183C91 were higher for the first 2 hours after oral than after nasal spray administration. All formulations of Zolmitriptan were well tolerated.
