From: Advances in the diagnosis and treatment of sickle cell disease
Drug and FDA approval | FDA approval date and indications | Mechanism of action | Dosing | Common adverse effects |
---|---|---|---|---|
Hydroxyurea | 1998: Adults to reduce frequency of painful crises 2017: Children ≥ 2 years to reduce frequency of painful crises and need for blood transfusions | ↑ Fetal Hb via temporary arrest of hematopoiesis and stress erythropoiesis ↓ Inflammation through ↓ in WBC and platelets ↓ Adhesion molecule expression ↑ Nitric oxide production | Usual starting dose 20 mg/kg/day Dose escalate to maximum tolerated dose (~ 30–35 mg/kg/day) Alternatively, dose escalate to absolute neutrophil count of 1500–2000/µL | Neutropenia (13%) Thrombocytopenia (7%) Nausea (3%) |
l-glutamine | 2017: Children and adults ≥ 5 years old to reduce severe complications (sickle cell crises and acute chest syndrome) | ↑ NAD redox potential in sickle red blood cells Protects red blood cells from oxidative stress | Dose by weight  < 30 kg—1 packet (5 g) BID 30–65 kg—2 packets (10 g) BID  > 65 kg—3 packets (15 g) BID May take with or without hydroxyurea | Constipation (21%) Nausea (19%) Abdominal pain (17%) Headache (18%) Cough (16%) |
Crizanlizumab | 2019: Adolescents and adults ≥ 16 years old to reduce frequency of vaso-occlusive crises | Binds to P-selectin Blocks interactions with ligands, including P-selectin glycoprotein ligand 1 | 5 mg/kg/dose IV on weeks 0, 2 and every 4 weeks thereafter May take with or without hydroxyurea | Infusion-related adverse events (< 10%) Nausea (18%) Arthralgia (18%) Back pain (15%) Fever (11%) |
Voxelotor | 2019: Children and adults ≥ 12 years old to increase hemoglobin concentration | Allosteric modifier of hemoglobin to stabilize oxygenated state ↓ Sickle Hb polymerization ↓ Hemolysis | 1500 mg po daily May take with or without hydroxyurea | Headache (26%) Diarrhea (20%) Nausea (17%) Abdominal pain (19%) Skin rash (14%) Fever (12%) Fatigue (14%) |