Voxelotor
Indications
Voxelotor is used for:
Sickle Cell Disease
Adult Dose
Sickle Cell Disease
Indicated for treatment of sickle cell disease
1500 mg PO qDay
May take with or without hydroxyurea
Hepatic impairment
Mild-to-moderate (Child-Pugh A or B): No dose adjustment required
Severe (Child-Pugh C): Decrease dose to 1000 mg PO qDay
Child Dose
Sickle Cell Disease
Indicated for treatment of sickle cell disease in adults and pediatric patients aged ?12 years
<12 years: Safety and efficacy not established
>12 years: 1500 mg PO qDay
May take with or without hydroxyurea
Renal Dose
Renal impairment
Mild, moderate, or severe: No dose adjustment required
End-stage renal disease: Not studied
Administration
Contra Indications
Hypersensitivity; clinical manifestations may include generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia
Precautions
Serious hypersensitivity reactions have occurred in <1% of patients treated
Voxelotor may interfere with laboratory measurement of Hb subtypes (HbA, HbS, and HbF) by high-performance liquid chromatography (HPLC)
Pregnancy-Lactation
Pregnancy
Data are not available regarding use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal data
Administration to pregnant rats and rabbits during organogenesis at exposures up to 2.8-times (rats) and 0.3-times (rabbits) the exposure at the maximum recommended human dose resulted in no adverse developmental effects
Clinical considerations
Women with sickle cell disease have an increased risk of adverse pregnancy outcomes for the mother and the fetus
Pregnant women are at greater risk for vasoocclusive crises, pre-eclampsia, eclampsia, and maternal mortality
For the fetus, there is an increased risk for intrauterine growth restriction, preterm delivery, low birth weight, and perinatal mortality
Lactation
Data are not available on the presence of voxelotor in human milk, effects on the breastfed child, or effects on milk production
Voxelotor was detected in milk in lactating rats; plasma concentrations of voxelotor in pregnant rats were higher than the concentration in milk
Advise women not to breastfeed during treatment and for at least 2 weeks after the last dose
Interactions
Side Effects
Side effects of Voxelotor :
>10%
Headache (26%)
Diarrhea (20%)
Abdominal pain (19%)
Nausea (17%)
Fatigue (14%)
Rash (14%)
Pyrexia (12%)
1-10%
Drug hypersensitivity (<10%)
<1%
Serious hypersensitivity
Mode of Action
Voxelotor is a hemoglobin S (HbS) polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to RBCs
By increasing the affinity of Hb for oxygen, voxelotor demonstrates dose-dependent inhibition of HbS polymerization
Nonclinical studies suggest voxelotor may inhibit RBC sickling, improve RBC deformability, and reduce whole blood viscosity