Biomedical subjects

Jayasena Hettiarachchi

Publications and source records attributed to Jayasena Hettiarachchi.

7 recordsLinked to original sources

PubMed2005

Effects of sumatriptan and eletriptan on diseased epicardial coronary arteries.

BACKGROUND: Triptans are contraindicated in patients with known or suspected coronary artery disease (CAD); however, few studies have evaluated triptans in patients with obstructive CAD to quantify the vasoconstrictive effect on diseased coronary vessels. METHODS: Patients undergoing percutaneous transluminal coronary angioplasty for symptomatic single-vessel CAD were randomised to one of three parallel cohorts to receive (1) 6 mg intravenously (IV) infused eletriptan plus subcutaneous (SC) placebo, (2) IV infused placebo plus 6 mg SC sumatriptan or (3) IV infused placebo plus SC placebo, as simultaneous administrations in a double-blind manner. Serial arteriograms, hemodynamic indices, electrocardiography and triptan plasma concentrations were obtained. RESULTS: . Fifteen minutes after triptan challenge, median (95% confidence interval) changes in coronary artery diameter (CADM) at the focal point of the stenosed segment were: dilation of 2.6% (-5.0, 11.4), eletriptan 6 mg IV (n = 18); constriction of 6.8% (-12.6, 0.4), sumatriptan 6 mg SC (n = 17), and constriction of 4.5% (-7.0, 7.9), placebo (n = 10). One patient had angiographic evidence of a new thrombus at the stenosis site, necessitating termination of study infusion and successful stenting of the lesion. There was no correlation between effects on CADM and triptan concentration, or between hemodynamic or electrocardiograph changes and the presence (n = 13) or absence (n = 33) of chest pain. CONCLUSIONS: Triptans had very little effect on diseased epicardial coronary arteries in a small group of angina sufferers with established CAD. Results should be interpreted cautiously since there may be instances where even modest triptan-associated epicardial constriction is sufficient to precipitate myocardial ischemia in patients with severe obstructive CAD.

Adult↗

PubMed2004

The 40-mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg.

Meta-analysis provides valuable information regarding relative efficacies of triptans, but head-to-head comparator studies remain the gold standard. Three similar head-to-head trials comparing eletriptan 40 mg (E40) with sumatriptan 100 mg (S100) provide a rare opportunity and sufficient power, for robust comparisons of efficacy. Data were combined from three double-blind, placebo-controlled, first-dose, first-attack acute migraine treatment studies comparing E40 (n=1132), S100 (n=1129), and placebo (n=645). The primary outcome was headache response at 2 h. Secondary outcomes included headache response at 1 h, pain-free and functional responses, and sustained headache and pain-free responses. Odds ratios were calculated for summary estimates of probability of response. There were higher headache response rates with eletriptan versus sumatriptan at 2 h (67% vs. 57%; P<0.0001) and 1 h (34% vs. 26%; P<0.0001). Eletriptan also had higher 2 h pain-free (35% vs. 25%; P<0.0001) and functional responses (67% vs. 58%; P<0.0001). Sustained headache (42%) and pain-free (22%) response rates were higher for eletriptan versus sumatriptan (34%, P<0.0001; 15%, P<0.0001). The probability of response for eletriptan versus sumatriptan ranged from 36% higher (relief of nausea) to 64% higher (sustained pain-free rate). Combined analysis demonstrates that E40 has superior efficacy versus S100 across all clinically relevant outcomes.

Adolescent↗

PubMed2004

Effectiveness of eletriptan in acute migraine: primary care for Excedrin nonresponders.

OBJECTIVE: To evaluate the effectiveness of eletriptan as a treatment for acute migraine in patients who were poor responders to Excedrin and had not yet been exposed to a triptan. BACKGROUND: Self-medication with over-the-counter drugs, such as Excedrin, is the most common treatment for migraine. Guidelines, however, recommend that triptans be used as first-line treatment of moderate to severe migraine--the severity affecting approximately 80% of migraineurs. Since over-the-counter medications, such as Excedrin, continue to be used in many patients, it is important that clinicians have information on the efficacy of triptans as first-line treatment and on treatment of migraineurs who have shown poor response to over-the-counter medications. METHODS: One hundred ten patients meeting criteria for migraine who were poor responders to Excedrin received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. RESULTS: At 1 hour, the headache response rate was 44%; at 2 hours, 81%. The pain-free response rate at 1 hour was 14% and at 2 hours, 48%. At 2 hours, relief of baseline-associated symptoms ranged from 74% to 80%. Functional response was achieved by 82% of patients by 2 hours, and 68% of patients achieved relief of migraine that was sustained across 24 hours with no need for a second dose of eletriptan or for rescue medication. Eletriptan was well tolerated with adverse events being transient and mild to moderate in intensity. CONCLUSION: Previous studies have established the efficacy of eletriptan as a first-line treatment for migraine. The results of this open-label trial demonstrate that the 40-mg dose of eletriptan had a high degree of efficacy and tolerability among patients who were poor responders to Excedrin.

Acute Disease↗

PubMed2003

Tolerability and safety of eletriptan in the treatment of migraine: a comprehensive review.

OBJECTIVE: To provide a comprehensive review of the tolerability and safety of eletriptan. Background.-Eletriptan is a potent and selective 5-HT1B/1D agonist that has demonstrated significant efficacy in the acute treatment of migraine in doses of 20 mg, 40 mg, and 80 mg. DESIGN: This review reports the tolerability and safety of eletriptan across a broad spectrum of preclinical studies and clinical trials that collectively included treatment of more than 11 000 subjects and more than 74 000 migraine attacks. RESULTS: In clinical trials, eletriptan was well tolerated and safe across its dosing range of 20 mg to 80 mg. The adverse event profile of eletriptan 20 mg was similar to placebo, while the most commonly used dose, eletriptan 40 mg, has an adverse event profile that is only marginally higher than placebo. Eletriptan was safe and well tolerated regardless of age or gender, and for both short- and long-term treatment. Eletriptan is metabolized primarily by the CYP3A4 enzyme. Coadministration of potent CYP3A4 inhibitors was not associated with clinically meaningful change in eletriptan tolerability or safety in the population included in these clinical trials. The margin of cardiovascular safety for eletriptan was also confirmed by a well-controlled clinical study in which intravenous eletriptan in excess of an 80-mg dose was rapidly infused in patients undergoing coronary angiography; nonetheless, it is recommended that eletriptan not be coadministered with a limited list of 7 potent CYP3A4 inhibitors; in addition, the triptan class in general (including eletriptan) is contraindicated in patients with symptoms or findings consistent with ischemic heart disease or other significant underlying cardiovascular disease. CONCLUSIONS: This comprehensive review found that eletriptan is safe and well tolerated, and that relatively large changes in dose and plasma concentration result in minimal changes in tolerability.

Acute Disease↗

PubMed2003

Efficacy of eletriptan in migraineurs with persistent poor response to nonsteroidal anti-inflammatory drugs.

BACKGROUND/OBJECTIVE: Nonsteroidal anti-inflammatory drugs continue to be one of the most widely used therapies for migraine, but their efficacy in treating moderate to severe migraine headache has not been well documented. In contrast, the efficacy of triptans in this group of patients is well documented, although no systematic research is available that evaluates the effectiveness of switching to a triptan in patients who respond poorly to nonsteroidal anti-inflammatory drugs. METHODS: One hundred thirteen patients who met International Headache Society criteria for migraine and who did not experience satisfactory response to nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Global ratings of treatment effectiveness and preference were obtained at 24 hours. RESULTS: The pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%; the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours postdose, relief of baseline associated symptoms was achieved by 41% of patients with nausea compared to 82% of patients at 4 hours; for patients with phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional response was achieved by 70% of patients by 2 hours postdose. The high level of acute response was maintained over 24 hours, with only 24% of patients experiencing a headache recurrence and only 10% using rescue medication. At 24 hours postdose, 74% of patients rated eletriptan as preferable to any previous treatment for migraine. The most frequent reasons cited for this treatment preference were faster headache improvement (83%) and functional response (78%). Overall, eletriptan was well tolerated; most adverse events were transient and mild to moderate in severity. No serious adverse events were reported. CONCLUSION: Results of this open-label trial found the 40-mg dose of eletriptan to have a high degree of efficacy and tolerability among patients who responded poorly to nonsteroidal anti-inflammatory drugs.

Acute Disease↗

PubMedDate not supplied

A cost-effectiveness analysis of eletriptan 40 and 80 mg versus sumatriptan 50 and 100 mg in the acute treatment of migraine.

OBJECTIVES: This article explores the application of cost-effectiveness analysis in a comparison of eletriptan and sumatriptan in the acute treatment of migraine. METHODS: The study employs data from a randomized, double-blind, placebo-controlled clinical trial comparison of oral eletriptan (40 and 80 mg) and oral sumatriptan (50 and 100 mg). Analyses were undertaken using two composite measures of treatment outcome constructed to reflect the requirements of patients more comprehensively than the conventional efficacy indicator of headache response at 2 hours. On the cost side of the equation, reflecting the health-care system perspective of the analysis, drug costs for initial dosing, second dosing for nonresponse, and recurrence and rescue medication were taken into account. RESULTS: The analysis found that eletriptan treatment resulted in lower costs per successfully treated attack than those of sumatriptan under both outcome criteria. CONCLUSION: Further refinement of outcomes measurement in migraine would be valuable and eletriptan has a potentially important role to play in the cost-effective management of the disorder.

Acute Disease↗

PubMedDate not supplied

Eletriptan issues.

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Cytochrome P-450 CYP3A↗