Voxelotor

OXBRYTA is indicated for the treatment of sickle cell disease (SCD) in adults and pediatric patients 4 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). OXBRYTA is a hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease in adults and pediatric patients 4 years of age and older.

Voxelotor is a hemoglobin S (HbS) polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to red blood cells (RBCs). By increasing the affinity of Hb for oxygen, voxelotor demonstrates dose-dependent inhibition of HbS polymerization. Nonclinical studies suggest that voxelotor may inhibit RBC sickling, improve RBC deformability, and reduce whole blood viscosity.

OXBRYTA can be taken with or without food. Recommended dosage: • Adults and pediatric patients 12 years and older: 1,500 mg orally once daily. • Pediatric patients 4 to less than 12 years: Dosing with OXBRYTA is based on body weight. See Table 1 for complete dosing recommendations. Recommended dosage for severe hepatic impairment (Child Pugh C): • Adults and pediatric patients 12 years and older: 1,000 mg orally once daily. • Pediatric patients 4 to less than 12 years: Reduce the dose of OXBRYTA based on body weight. See Table 2 for complete dosing recommendations.

OXBRYTA is contraindicated in patients with a history of serious drug hypersensitivity reaction to voxelotor or excipients. Clinical manifestations may include generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia. Prior drug hypersensitivity to voxelotor or excipients.

• Hypersensitivity Reactions: Observe for signs and symptoms and manage promptly. • Laboratory Test Interference: Perform quantification of hemoglobin species when patient is not receiving OXBRYTA.

The following clinically significant adverse reaction is discussed in other sections of the labeling: • Hypersensitivity Reactions. Most common adverse reactions (incidence ≥10% with a difference of >3% compared to placebo) are headache, diarrhea, abdominal pain, nausea, rash, and pyrexia. Most common adverse reactions (incidence >10%) reported in pediatric patients 4 to <12 years are pyrexia, vomiting, rash, abdominal pain, diarrhea, and headache.

• Sensitive CYP3A4 Substrates: Avoid coadministration of sensitive CYP3A4 substrates with a narrow therapeutic index. • Strong or moderate CYP3A4 Inducers: Avoid coadministration with strong or moderate CYP3A4 inducers. If unavoidable, increase the dose of OXBRYTA.

Store OXBRYTA at 20°C to 30°C (68°F to 86°F).