Oxbryta is indicated for the treatment of sickle cell disease (SCD) in adults and pediatric patients 12 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.
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 by (HbA, HbS, and HbF) HPLC. If precise quantitation of Hb species is required, chromatography should be performed when the patient is not receiving Oxbryta therapy.
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.
Adverse Reactions (≥10%) in patients receiving Oxbryta with a difference of >3% compared to placebo: Headache (26% vs. 22%), Diarrhea (20% vs. 10%), Abdominal Pain (19% vs. 13%), Nausea (17% vs. 10%), Fatigue (14% vs. 10%), Rash (14% vs. 10%), and Pyrexia (12% vs. 7%).
Sensitive CYP3A4 Substrates
Voxelotor increased the systemic exposure of midazolam (a sensitive CYP3A4 substrate). Avoid co-administration with sensitive CYP3A4 substrates with a narrow therapeutic index. If unavoidable, consider dose reduction of the CYP3A4 substrate(s).
Strong CYP3A4 Inhibitors or Fluconazole
Co-administration of strong CYP3A4 inhibitors or fluconazole may increase voxelotor plasma concentrations and may lead to increased toxicity. Avoid co-administration of strong CYP3A4 inhibitors or fluconazole. Decrease Oxbryta dosage if unavoidable.
Strong or Moderate CYP3A4 Inducers
Co-administration of strong or moderate CYP3A4 inducers may decrease voxelotor plasma concentrations and may lead to reduced efficacy. Avoid co-administration of strong or moderate CYP3A4 inducers. Increase the Oxbryta dosage if unavoidable.
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. Reduce dose to 1,000 mg orally once daily for severe hepatic (Child Pugh C) impairment.