Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan injection or tablets. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation.The most common side effects reported by at least 2% of patients in controlled trials of sumatriptan (25-, 50-, and 100-mg tablets) for migraine are atypical sensations (paresthesias and warm/cold sensations) reported by 4% in the placebo group and 5–6% in the sumatriptan groups, pain and other pressure sensations (including chest pain) reported by 4% in the placebo group and 6–8% in the sumatriptan groups, neurological events (vertigo) reported by less than 1% in the placebo group and less than 1% to 2% in the sumatriptan groups. Malaise/fatigue occurred in less than 1% of the placebo group and 2–3% of the sumatriptan groups. Sleep disturbance occurred in less than 1% in the placebo group to 2% in the sumatriptan group. Mechanism of action
Sumatriptan is molecularly similar to serotonin (5-HT), and is a 5-HT receptor (types 5-HT1D and 5-HT1B) agonist. Sumatriptans primary therapeutic effect is related in its inhibition of the release of Calcitonin gene-related peptide (CGRP), likely through its 5-HT1D/1B receptor-agonist action. This has been substantiated by the efficacy of more recently developed CGRP targeting drugs and antibodies developed for the preventive treatment of migraine. How agonism of the 5-HT1D/1B receptors inhibits CGRP release is not fully understood.
Pharmacology
Mechanism of action
Reslizumab is an interleukin-5 antagonist monoclonal antibody. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Eosinophils play a role in the mediation of inflammation in the airways. Eosinophilic asthma is a phenotype of asthma that is characterized by the higher than normal presence of eosinophils in the lung and sputum. It has been shown that the numbers of eosinophils in the blood and bronchial fluid can correlate with asthma severity. Reslizumab binds to IL-5 with a dissociation constant of 81 pM and inhibiting IL-5 signaling, which reduces the production and survival of eosinophils. However, the mechanism of reslizumab action in asthma has not been definitively established. Pharmacodynamics
Reductions in blood eosinophil counts were observed following the first dose of reslizumab and maintained through 52 weeks of treatment. In phase III clinical trials, mean eosinophil counts were 696 cells/µL (n=245) and 624 cells/µL (n=244) at baseline. Following 52 weeks of reslizumab treatment, eosinophil cells were counted and were reported to be 55 cells/µL (92% reduction, n=212) and 496 cells/µL (21% reduction, n=212) for the reslizumab and placebo treatment groups, respectively. Furthermore, eosinophil count returned towards baseline in those reslizumab-treated patients who completed a follow-up assessment (n=35, 480 cells/µL), approximately 120 days after the last dose of reslizumab. Therefore, reductions of blood eosinophils were related to reslizumab serum levels. Pharmacokinetics
The pharmacokinetic characteristics of reslizumab are similar across the children and adults. Peak serum concentrations are observed at the end of infusion and declines in a biphasic manner.