The patch form was created in part to overcome food restrictions; clinical trials showed that it was successful. Additionally, in post-marketing surveillance from April 2006 to October 2010, only 13 self-reports of possible hypertensive events or hypertension were made out of 29,141 exposures to the drug, and none were accompanied by objective clinical data. The lowest dose of the patch method of delivery, 6 mg/24 hours, does not require any dietary restrictions. Higher doses of the patch and oral formulations, whether in combination with the older non-selective MAOIs or in combination with the reversible MAO-A inhibitor moclobemide, require a low-tyramine diet. Pharmacology
Pharmacodynamics
Selegiline is a selective inhibitor of MAO-B, irreversibly inhibiting it by binding to it covalently. It is generally believed to exert its effects by blocking the breakdown of dopamine, thus increasing its activity; however, recent evidence suggests that MAO-A is solely or almost entirely responsible for the metabolism of dopamine. Its possible neuroprotective properties may be due to protecting nearby neurons from the free oxygen radicals that are released by MAO-B activity. At higher doses, selegiline loses its selectivity for MAO-B and inhibits MAO-A as well.Selegiline also inhibits CYP2A6 and can increase the effects of nicotine as a result. Selegiline also appears to activate σ1 receptors, having a relatively high affinity for these receptors of approximately 400 nM. Pharmacokinetics
Selegiline has an oral bioavailability of about 10%, which increases when ingested together with a fatty meal, as the molecule is fat soluble. Selegiline and its metabolites bind extensively to plasma proteins (at a rate of 94%).
Crizanlizumab, sold under the brand name Adakveo & Ryverna both by Novartis, is a monoclonal antibody medication that binds to P-selectin. It is a drug used to reduce the frequency of vaso-occlusive crisis in people aged 16 years and older who have sickle cell anemia. Vaso-occlusive crisis is a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells (red cells are usually round and flexible, but sometimes many red cells in a person with sickle cell anemia will become rigid and crescent-shaped due to polymerization of hemoglobin).The result of the Phase II SUSTAIN clinical trial was published in December 2016, and in November 2019, crizanlizumab-tmca was approved in the United States. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Pathophysiology
P-selectin molecules are present on the surface of activated platelets and vascular endothelial cells and have been linked to sickle cell vaso-occlusive crises. History
The U.S. Food and Drug Administration (FDA) approved crizanlizumab based on evidence from one clinical trial (Trial 1/NCT01895361) of 132 patients with sickle cell diseases who had a history of vaso-occlusive crisis. The trial was conducted at 60 sites in the United States, Brazil and Jamaica.The FDA granted the application for crizanlizumab-tmca priority review, breakthrough therapy designation, and orphan drug designation. The FDA granted approval of Adakveo to Novartis. References
External links
"Crizanlizumab". Drug Information Portal. U.S. National Library of Medicine.