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 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.
Serious hypersensitivity reactions after administration of OXBRYTA have occurred in <1% of patients treated. Clinical manifestations may include generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia.
If hypersensitivity reactions occur, discontinue OXBRYTA and administer appropriate medical therapy. Do not reinitiate OXBRYTA in patients who experience these symptoms with previous use.
OXBRYTA administration may interfere with measurement of Hb subtypes (HbA, HbS, and HbF) by high-performance liquid chromatography (HPLC). If precise quantitation of Hb species is required, chromatography should be performed when the patient has not received OXBRYTA therapy in the immediately preceding 10 days.
Adults and Pediatric Patients 12 Years of Age and Older
Serious adverse reactions occurred in 3% (3/88) of patients receiving OXBRYTA 1,500 mg, which included headache, drug hypersensitivity, and pulmonary embolism occurring in 1 patient each. Permanent discontinuation due to an adverse reaction (Grades 1-4) occurred in 5% (4/88) of patients who received OXBRYTA 1,500 mg.
The most common adverse reactions (≥10%) in patients receiving OXBRYTA 1,500 mg with a difference of >3% compared to placebo: Headache (32% vs. 25%), Diarrhea (23% vs. 11%), Abdominal Pain (23% vs. 16%), Nausea (19% vs. 10%), Rash (15% vs. 11%), and Pyrexia (15% vs. 8%).
Pediatric Patients 4 to <12 Years
The safety of OXBRYTA in pediatric patients 4 to <12 years with SCD was evaluated in an open-label, Phase 2 study. In this study, 45 patients 4 to <12 years of age received doses of OXBRYTA tablets for oral suspension based on weight at baseline. Thirty-five patients received OXBRYTA for 24 weeks and 26 patients for 48 weeks. The most common adverse reactions (>10%) reported in pediatric patients 4 to <12 years were pyrexia (36%), vomiting (33%), rash (20%), abdominal pain (18%), diarrhea (18%), and headache (18%).
The overall safety profile of OXBRYTA in pediatric patients 4 to <12 years was similar to that seen in adults and pediatric patients 12 years and older.
Strong or Moderate CYP3A4 Inducers
Coadministration of strong or moderate CYP3A4 inducers may decrease voxelotor plasma and whole blood concentrations and may lead to reduced efficacy. Avoid coadministration of OXBRYTA with strong or moderate CYP3A4 inducers. Increase the OXBRYTA dosage when coadministration with a strong or moderate CYP3A4 inducer is unavoidable.
Sensitive CYP3A4 Substrates
Voxelotor increased the systemic exposure of midazolam (a sensitive CYP3A4 substrate). Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. If unavoidable, consider dose reduction of the CYP3A4 substrate(s).
Because of the potential for serious adverse reactions in the breastfed child, including changes in the hematopoietic system, advise patients not to breastfeed while taking OXBRYTA and for at least 2 weeks after the last dose.
Severe hepatic impairment increases voxelotor exposures. For severe hepatic impairment (Child Pugh C) reduce dose to 1,000 mg orally once daily for adults and pediatric patients ≥ 12 years. Dose reduction for pediatric patients 4 to <12 years is dependent on body weight (please refer to Table 2 in the Full Prescribing Information).