Adult Dosing

• 1,500 mg PO once daily with or without food. Do not cut, crush or chew.

Pediatric Dosing

Children: 12 years and above

• 1,500 mg PO once daily.

Children: 4 years to less than 12 years and

• Weight 40 Kg or more: 1,500 mg PO once daily
• Weight 20 Kg to less than 40 kg: 900 mg PO once daily
• Weight 10 Kg to less than 20 kg: 600 mg PO once daily

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of Sickle cell disease in adults and pediatric patients 4 years of age and older.

• Prior drug hypersensitivity to drug or excipients.
• Generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia.

Renal Dose Adjustment

• Mild to severe renal impairment (eGFR 15–89 mL/min/1.73 m²): No adjustment required.

Hepatic Dose Adjustment

Hepatic impairment (Adults):

Note: Avoid concomitant use of strong or moderate CYP3A4 inducers.

• Adults with Child-Pugh Class C: 1,000 mg PO once daily
• Mild or Moderate impairment: No dosage adjustment is required.
• Concomitant use of strong CYP3A4 inhibitors: 2,500 mg PO once daily
• Concomitant use of moderate CYP3A4 inhibitors: 2,000 mg PO once daily

Hepatic impairment (Children):

Note: Avoid concomitant use of strong or moderate CYP3A4 inducers.

• 12 years and above with Child-Pugh Class C: 1,000 mg PO once daily.
• 12 years and above with Mild or Moderate impairment: No dosage adjustment is required.
• 12 years and above with Concomitant use of strong CYP3A4 inhibitors: 2,500 mg PO once daily
• 12 years and above with Concomitant use of moderate CYP3A4 inhibitors: 2,000 mg PO once daily
• 4 years to less than 12 years with Child-Pugh Class C and
• Weight 40 Kg or more: 1,000 mg PO once daily or 900 mg for oral suspension once daily
• Weight 20 Kg to less than 40 kg: 600 mg PO once daily
• Weight 10 Kg to less than 20 kg: 300 mg PO once daily

• 4 years to less than 12 years with Concomitant use of strong CYP3A4 inhibitors and
• Weight 40 Kg or more: 2,500 mg PO once daily or 2,400 mg for oral suspension once daily
• Weight 20 Kg to less than 40 kg: 1,500 mg PO once daily
• Weight 10 Kg to less than 20 kg: 900 mg PO once daily

• 4 years to less than 12 years with Concomitant use of moderate CYP3A4 inhibitors and
• Weight 40 Kg or more: 2,000 mg PO once daily or 2,100 mg for oral suspension once daily
• Weight 20 Kg to less than 40 kg: 1,200 mg PO once daily
• Weight 10 Kg to less than 20 kg: 900 mg PO once daily

See Supplemental Patient Information

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

Interactions

• 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.

Supplemental Patient Information

• Advise patients that serious hypersensitivity reactions may occur, and to notify their healthcare providers if they develop generalized rash, urticaria, shortness of breath, facial swelling and eosinophilia
• Advise women not to breastfeed while they are on the treatment.
• For oral dose, instruct patientto swallow each tablet whole. Do not cut, crush, or chew the tablets.
• For oral suspension, instruct patient not to swallow whole, cut, crush, or chew tablets.

Pregnancy Category:NR

Breastfeeding: Not recommended during treatment and for at least 2 weeks after the last dose.

• CNS: headache
• DERM: rash
• GI: diarrhea, abdominal pain, nausea, vomiting
• MISC: pyrexia

• Mechanism of Action: 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.
• Absorption: A high-fat, high-calorie meal increased the absorption.
• Distribution: Volume of distribution of the central compartment and peripheral compartment are 333 L and 72.3 L in plasma, respectively.
• Protein Binding: 99.8% bound to plasma protein
• Metabolism/Excretion: extensively metabolized through Phase I (oxidation and reduction), Phase II (glucuronidation) and combinations of Phase I and II metabolism. Metabolism of voxelotor is mediated by CYP3A4, CYP3A5, CYP2B6, CYP2C19, CYP2C9, UGT1A1, and UGT1A9. Approximately 62.6% of the dose and its metabolites are excreted into feces (33.3% unchanged) and 35.5% in urine (0.08% unchanged).
• Half-life: 38.7 hrs.

US Trade Name(s)

• Oxbryta

US Availability

Oxbryta

• TABS: 500 mg
• TABS for oral suspension: 300 mg

[Outline]

Hematology/Oncology

hemoglobin S (HbS) Polymerization Inhibitor