OXBRYTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OXBRYTA (OXBRYTA).
Voxelotor is a hemoglobin S polymerization inhibitor. It binds to the alpha-globin chain of hemoglobin S and increases its oxygen affinity, thereby inhibiting polymerization and subsequent sickling of red blood cells.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP2C19, CYP2C9, and CYP2D6. |
| Excretion | Renal: 33% as unchanged drug and metabolites; fecal: 57% primarily as metabolites; biliary: minor. |
| Half-life | Approximately 7.6 hours in healthy adults; clinical context: supports twice-daily dosing. |
| Protein binding | 99.5% bound to albumin. |
| Volume of Distribution | 0.11 L/kg; indicates limited extravascular distribution, primarily in plasma. |
| Bioavailability | Oral: 65% (relative to IV reference) under fed conditions; absorption decreased by high-fat meal (AUC reduced by 30%). |
| Onset of Action | Oral: 1-2 hours for plasma concentration peak; clinical effect (hemoglobin increase) observed within 2-4 weeks of initiation. |
| Duration of Action | 12-24 hours; clinical notes: sustained hemoglobin improvement with continuous dosing. |
1500 mg orally twice daily with food (for patients weighing ≥45 kg). For patients weighing 40–44 kg, 1000 mg orally twice daily with food.
| Dosage form | TABLET, FOR SUSPENSION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Data insufficient for severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis; not recommended. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended for moderate to severe hepatic impairment (Child-Pugh B or C) due to lack of data. |
| Pediatric use | Approved for pediatric patients aged ≥12 years weighing ≥40 kg: same as adult dosing. Pediatric patients <12 years or weighing <40 kg: safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included limited numbers of patients ≥65 years. Monitor for greater sensitivity due to potential age-related renal/hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OXBRYTA (OXBRYTA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio is unknown. Due to potential for adverse effects in the infant (e.g., hemolytic anemia), advise against breastfeeding while on Oxbryta. |
| Teratogenic Risk | Oxbryta (voxelotor) is an HbS polymerization inhibitor. In animal studies, no adverse developmental effects were observed at exposures up to 3.2 times the human AUC at the recommended dose. There are no adequate and well-controlled studies in pregnant women. Due to the potential for maternal anemia and decreased oxygen delivery to the fetus, the risk cannot be excluded. First trimester: limited data, theoretical risk of fetal hypoxia. Second and third trimesters: potential for fetal distress from maternal anemia. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["None known."]
| Precautions | ["Potential for hemolytic anemia or hyperhemolysis syndrome: Monitor hemoglobin and reticulocyte count. Discontinue if worsening hemolytic anemia suspected.","Laboratory test interference: May interfere with measurement of hemoglobin A1c (HbA1c) in diabetic patients. Alternative methods for glycemic monitoring should be used."] |
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| Fetal Monitoring | Monitor maternal hemoglobin, reticulocyte count, and signs of hemolytic crises. For fetus, consider growth ultrasound and Doppler studies if maternal anemia worsens. No specific fetal monitoring required beyond standard obstetric care. |
| Fertility Effects | No clinical studies on fertility. In animal studies, no adverse effects on male or female fertility were observed at exposures up to 3 times the human AUC. |