Skip to Content

Voxelotor

Class: Blood Formation, Coagulation, and Thrombosis Agents; Miscellaneous
Chemical Name: 2-hydroxy-6-[[2-(2-propan-2-ylpyrazol-3-yl)pyridin-3-yl]methoxy]benzaldehyde
Molecular Formula: C19H19N3O3
CAS Number: 1446321-46-5
Brands: Oxbryta

Medically reviewed by Drugs.com on Jan 13, 2020. Written by ASHP.

Introduction

Voxelotor is a hemoglobin S polymerization inhibitor.

Uses for Voxelotor

Voxelotor has the following uses:

Voxelotor is a hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease 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).

Voxelotor Dosage and Administration

General

Voxelotor is available in the following dosage form(s) and strength(s):

Tablets 500 mg.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Patients should swallow voxelotor tablets whole. Do not cut, crush, or chew the tablets.

If a dose is missed, continue dosing on the day following the missed dose.

Voxelotor may be given with or without hydroxyurea.

Pediatric Patients

Dosage in Pediatric Patients 12 Years of Age and Older
  • Recommended dosage: 1,500 mg orally once daily with or without food.

  • Recommended dosage for severe hepatic impairment (Child Pugh C): 1,000 mg orally once daily.

  • Avoid concomitant use of strong or moderate CYP3A4 inducers, strong CYP3A4 inhibitors, or fluconazole with voxelotor; if concomitant use is unavoidable, adjust the voxelotor dosage as recommended in Table 1.

Table 1: Recommended Dosage of Voxelotor for Use with Certain Concomitant Medications

Concomitant Medication

Recommended Voxelotor Dosage

Strong CYP3A4 inhibitors or fluconazole

1,000 mg once daily

Strong or moderate CYP3A4 inducers

2,500 mg once daily

Adults

Dosage in Adults
  • Recommended dosage: 1,500 mg orally once daily with or without food.

  • Recommended dosage for severe hepatic impairment (Child Pugh C): 1,000 mg orally once daily.

  • Avoid concomitant use of strong or moderate CYP3A4 inducers, strong CYP3A4 inhibitors, or fluconazole with voxelotor; if concomitant use is unavoidable, adjust the voxelotor dosage as recommended in Table 1.

Cautions for Voxelotor

Contraindications

Prior drug hypersensitivity to voxelotor or excipients.

Warnings/Precautions

Hypersensitivity Reactions

Serious hypersensitivity reactions after administration of voxelotor 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 voxelotor and administer appropriate medical therapy. Do not reinitiate voxelotor in patients who experience these symptoms with previous use.

Laboratory Test Interference

Voxelotor 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 is not receiving voxelotor therapy.

Specific Populations

Pregnancy

Risk Summary: There are no available data on voxelotor use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of voxelotor to pregnant rats and rabbits during organogenesis at exposures up to 2.8-times (rats) and 0.3-times (rabbits) the exposure at the maximum recommended human dose resulted in no adverse developmental effects.

The estimated background risk of major birth defects and miscarriage for the indicated population is approximately 14% and up to 43%, respectively. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

There are adverse effects on maternal and fetal outcomes associated with sickle cell disease in pregnancy. Voxelotor should only be used during pregnancy if the benefit of the drug outweighs the potential risk.

Clinical Considerations: Women with sickle cell disease have an increased risk of adverse pregnancy outcomes for the mother and the fetus. Pregnant women are at greater risk for vasoocclusive crises, pre-eclampsia, eclampsia, and maternal mortality. For the fetus, there is an increased risk for intrauterine growth restriction, preterm delivery, low birth weight, and perinatal mortality.

Animal Data: In embryo-fetal development studies, voxelotor was administered orally to pregnant rats at 15, 50, and 250 mg/kg/day (gestation days 7 through 17) and rabbits at 25, 75, and 150 mg/kg/day (gestation days 7 through 19) through organogenesis. Maternal toxicity was observed at the highest dose levels in these studies equivalent to 2.8-times (rats) and 0.3-times (rabbits) the exposures in patients receiving voxelotor at the recommended daily dose. There was no evidence of adverse developmental outcomes in rats or rabbits.

In a pre- and postnatal development study, voxelotor was administered orally to pregnant rats at 15, 50 and 250 mg/kg/day (gestation day 6 through lactation day 20). Maternal gestational body weights were decreased at 250 mg/kg/day, which continued to the end of lactation. The findings in offspring included reduced survival and reduced body weights throughout lactation, weaning and maturation. The effects in offspring were observed at the maternal dose of 250 mg/kg/day with an exposure approximately 2.8-times the exposure in patients at the recommended dose.

Lactation

Risk Summary: There are no data on the presence of voxelotor in human milk, the effects on the breastfed child, or the effects on milk production. Voxelotor was detected in milk in lactating rats. Plasma concentrations of voxelotor in pregnant rats were higher than the concentration in milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The concentration of voxelotor in animal milk does not necessarily predict the concentration of drug in human milk. Because of the potential for serious adverse reactions in the breastfed child, including changes in the hematopoietic system, advise patients that breastfeeding is not recommended during treatment with voxelotor, and for at least 2 weeks after the last dose.

Pediatric Use

The safety and effectiveness of voxelotor for sickle cell disease have been established in pediatric patients aged 12 years and older. Use of voxelotor for sickle cell disease is supported by evidence from an adequate and well-controlled study in adults and pediatric patients (HOPE trial). The HOPE trial enrolled a total of 26 pediatric patients aged 12 to <17 years, in which 12 pediatric patients received voxelotor 1,500 mg once daily and 14 pediatric patients received voxelotor 900 mg once daily. The safety and efficacy of voxelotor in pediatric patients below the age of 12 years have not been established.

Pharmacokinetics, safety and efficacy in pediatric patients 12 years to <17 years were similar to that observed in adults.

The adverse reactions observed in pediatric patients 12 to <17 years treated with voxelotor were similar in type and frequency to those observed in adults.

Geriatric Use

Clinical studies of voxelotor did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Hepatic Impairment

Severe hepatic impairment increases voxelotor exposures. Reduce voxelotor dose.

Common Adverse Effects

Most common adverse reactions (incidence >10%) are headache, diarrhea, abdominal pain, nausea, fatigue, rash, and pyrexia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • Sensitive CYP3A4 Substrates: Avoid co-administration of sensitive CYP3A4 substrates with a narrow therapeutic index.

  • Strong CYP3A4 Inhibitors or Fluconazole: Avoid co-administration with strong CYP3A4 inhibitors or fluconazole. If unavoidable, reduce the dose of voxelotor.

  • Strong or Moderate CYP3A4 Inducers: Avoid co-administration with strong or moderate CYP3A4 inducers. If unavoidable, increase the dose of voxelotor.

Actions

Mechanism of Action

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.

Advice to Patients

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (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 voxelotor therapy.

Continue taking voxelotor every day for as long as their physician tells them. This is a long-term treatment.

Swallow voxelotor tablets whole. Do not cut, crush, or chew the tablets.

Take with or without food.

If a dose is missed, continue dosing on the day following the missed dose.

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Voxelotor

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablet, Film Coated

500 mg

Oxbryta

Global Blood Therapeutics Inc.

AHFS Drug Information. © Copyright 2021, Selected Revisions January 13, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Show article references