Table 2.

FDA-approved Drug for the management of SCD

FDA-approved drug (FDA-approval date)	In vivo Mechanism of action	Treatment-related Benefits	Treatment-Related Adverse Events	General features
Hydroxyurea (1998)	HbF induction	↓Painful acute VOC events	Headache	Single-agent inexpensive orally administered once-daily dosing
	↓WBC and platelets	↓Inflammation	Gastrointestinal symptoms including Abdominal discomfort and nausea
	↓LDH and bilirubin levels	↓Hemolysis	Anorexia
	↓surface expression of adhesion receptors	↓Mortality Ameliorates anemia	Skin hyperpigmentation
	↑NO synthesis	Preserves splenic function	Neutropenia
		Maintains excellent growth development and sexual maturation	Reticulocytopenia
		Prevents chronic organ dysfunction
L-glutamine (2017)	↑NAD redox potential in sickle red blood cells through increasing the availability of reduced glutathione	↓Chronic pain	Headache	Single-agent
	↓ROS and oxidative damage in sickle red blood cells	↑Time to pain crisis	Nausea	orally administered
	↑NO synthesis	↓Daily narcotic use	Constipation	twice-daily dosing
		↓Episodes of acute chest syndrome	Loss of taste
			Chest and musculoskeletal pain Fatigue
			Cough
			Rare renal and hepatic impairment
Crizanlizumab (2019)	P-selectin inhibitor,	↓VOC rate episodes	Nausea	Monthly intravenous infusion
	Blocks adhesion of neutrophils, activated platelets and sickle red blood cells to the endothelial surface of the blood vessels		Arthralgia
			Back pain
			Fever
			Pruritus (pruritus and vulvovaginal pruritus)
			Pain in the extremity
Voxelotor (2019)	↑Hemoglobin’s affinity for oxygen	↓Hemolysis	Headache	Orally administered once-daily dosing
	↓HbS polymerization	↓Anemia	Gastrointestinal symptoms
		Improves red blood cell deformability	Arthralgia
		↓Whole blood viscosity	Fatigue
			Skin rash
			Fever