voxelotor

General

Pronunciation:
vox-el-oh-tor

Trade Name(s)

  • Oxbryta

Ther. Class.

none assigned

Pharm. Class.

temporary class

hemoglobin S polymerization inhibitors

Indications

Treatment of sickle cell disease.

Action

Binds to hemoglobin S (HgbS) (sickle hemoglobin) and improves affinity of HgbS for oxygen. Through this increased affinity, it inhibits polymerization of HgbS, which inhibits sickling of red blood cells, improves deformability of red blood cells, and reduces viscosity of whole blood.

Therapeutic Effect(s):

Increase in Hgb of more than 1 g/dL compared to baseline.

Pharmacokinetics

Absorption: Absorption increased with high-fat, high-calorie meal.

Distribution: Primarily distributed into red blood cells.

Protein Binding: 99.8%.

Metabolism and Excretion: Primarily metabolized in liver via CYP3A4 isoenzyme (also undergoes minor metabolism by CYP2C19, CYP2B6, and CYP2C9 isoenzymes); also undergoes glucuronidation. Primarily excreted in feces (33% as unchanged drug), with 35% excreted in urine (mostly as metabolites).

Half-life: 35.5 hr.

TIME/ACTION PROFILE (whole blood concentrations)

ROUTEONSETPEAKDURATION
POunknown6–18 hrunknown

Contraindication/Precautions

Contraindicated in:

  • Serious hypersensitivity
  •  Lactation:  Lactation.

Use Cautiously in:

  • Severe hepatic impairment (↓ dose)
  • OB:   Use during pregnancy only if potential maternal benefit justifies potential fetal risks;
  • Pedi:   Children <12 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

CNS: headache

Derm: rash

GI: abdominal pain, diarrhea, nausea

Misc: fatigue, fever, hypersensitivity reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  Strong CYP3A4 inhibitors, including  ketoconazole , may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use unavoidable, ↓ voxelotor dosage.
  •  Fluconazole  may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use unavoidable, ↓ voxelotor dosage.
  •  Strong CYP3A4 inducers, including  rifampin, or  moderate CYP3A4 inducers, including  efavirenz , may ↓ levels and efficacy; avoid concurrent use. If concurrent use unavoidable, ↑ voxelotor dosage.
  • May ↑ levels and risk of toxicity of  CYP3A4 substrates  with narrow therapeutic index, including  midazolam ; avoid concurrent use. If concurrent use unavoidable, ↓ dosage of CYP3A4 substrate.

Route/Dosage

PO (Adults and Children ≥12 yr): 1500 mg once daily.  Concurrent use of strong CYP3A4 inhibitors or fluconazole– 1000 mg once daily.  Concurrent use of strong or moderate CYP3A4 inducers– 2500 mg once daily.

Hepatic Impairment 
PO (Adults and Children ≥12 yr): Severe hepatic impairment (Child-Pugh C)– 1000 mg once daily.

Availability

Tablets: 500 mg

Assessment

  • Monitor for signs and symptoms of hypersensitivity reaction (rash, urticaria, mild shortness of breath, mild facial swelling, eosinophilia) during therapy. If symptoms occur, treat symptoms and discontinue therapy; do not restart therapy.

Lab Test Considerations:

May interfere with measurement of Hgb subtypes (HgbA, HgbS, and HgbF) by high-performance liquid chromatography (HPLC). If precise quantitation of Hgb species is required, perform chromatography when the patient is not receiving voxelotor therapy.

Implementation

  • PO Administer once daily without regard to food.  DNC: Swallow tablets whole; do not cut, crush, or chew. 

Patient/Family Teaching

  • Instruct patient to take as directed. If a dose is missed, omit and continue with dosing on the next day. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of changes.
  • Advise patient to notify health care professional if signs and symptoms of hypersensitivity reactions (rash, hives, shortness of breath, swelling of face) occur.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Rep:   Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during and for at least 2 wk after last dose.

Evaluation/Desired Outcomes

Increase in Hgb of more than 1 g/dL compared to baseline.

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