voxelotor

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 effects:

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/Excretion: Primarily metabolized in liver via the CYP3A4 isoenzyme, with minor metabolism by the 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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	6–18 hr	unknown

Contraind./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 risk;
Pedi: Children <4 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

GI: abdominal pain, diarrhea, nausea

Neuro: fatigue, headache

Misc: fever, hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

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

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥12 yr): 1500 mg once daily. Concurrent use of strong CYP3A4 inducers: 2500 mg once daily. Concurrent use of moderate CYP3A4 inducers: 2000 mg once daily.
PO (Children 4–<12 yr and ≥40 kg): 1500 mg once daily. Concurrent use of strong CYP3A4 inducers: 2500 mg (five 500-mg tablets) once daily or 2400 mg (eight 300-mg oral tablets for suspension) once daily. Concurrent use of moderate CYP3A4 inducers: 2000 mg (four 500-mg tablets) once daily or 2100 mg (seven 300-mg oral tablets for suspension) once daily.
PO (Children 4–<12 yr and 20–<40 kg): 900 mg once daily. Concurrent use of strong CYP3A4 inducers: 1500 mg once daily. Concurrent use of moderate CYP3A4 inducers: 1200 mg once daily.
PO (Children 4–<12 yr and 10–<20 kg): 600 mg once daily. Concurrent use of strong or moderate CYP3A4 inducers: 900 mg once daily.

Hepatic Impairment

PO (Adults and Children ≥12 yr): Severe hepatic impairment: 1000 mg once daily.

Hepatic Impairment

PO (Children 4–<12 yr and ≥40 kg): Severe hepatic impairment: 1000 mg (two 500-mg tablets) once daily or 900 mg (three 300-mg oral tablets for suspension) once daily.

Hepatic Impairment

PO (Children 4–<12 yr and 20–<40 kg): Severe hepatic impairment: 600 mg once daily.

Hepatic Impairment

PO (Children 4–<12 yr and 10–<20 kg): Severe hepatic impairment: 300 mg once daily.

Availability ⬆ ⬇

Tablets: 300 mg; 500 mg
Tablets for oral suspensiongrape flavor: 300 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.
Monitor for DRESS (a combination of skin rash, fever, peripheral eosinophilia, and internal systemic organ involvement [hepatic, renal, pulmonary]). If signs occur, discontinue voxelotor and do not reinitiate.

Lab Test Considerations:

May interfere with measurement of Hgb subtypes (HgbA, HgbS, and HgbF) by high-performance liquid chromatography. 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.
- Disperse tablets for oral suspension immediately before administration in a cup and in room-temperature clear liquid (drinking water, clear soda, apple juice, clear electrolyte drinks, clear flavored drinks, clear sports drinks) before swallowing. DNC: Do not swallow whole, cut, crush, or chew the tablets for oral suspension. After tablets start to disintegrate, swirl contents of cup until tablets are dispersed, wait 1 to 5 min, swirl contents of cup again, and then orally administer contents of cup. Tablet(s) will not completely dissolve; small tablet clumps remain in the mixture. Resuspend any residue left in cup in more clear drink and administer. Repeat until no tablet residue is left in the cup. May be substituted for tablets in adults and pediatric patients >12 yr with difficulty swallowing tablets.

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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆