ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Voxelotor: Drug information

Voxelotor: Drug information
(For additional information see "Voxelotor: Pediatric drug information" and see "Voxelotor: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Oxbryta
Pharmacologic Category
  • Hemoglobin S (HbS) Polymerization Inhibitor
Dosing: Adult
Sickle cell disease

Sickle cell disease: Oral: 1.5 g once daily; may be administered with or without hydroxyurea (Vichinsky 2019).

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

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl 15 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically significant differences in pharmacokinetics were observed in patients with mild to severe renal impairment.

End-stage renal disease requiring dialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild (Child Pugh class A) or moderate (Child Pugh class B) impairment: No dosage adjustment is necessary.

Severe (Child Pugh class C) impairment: Reduce voxelotor dose to 1 g once daily.

Dosing: Adjustment for Toxicity: Adult

Hypersensitivity reactions: Discontinue voxelotor and manage as clinically necessary; do not reinitiate voxelotor.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Voxelotor: Pediatric drug information")

Sickle cell disease, treatment

Sickle cell disease, treatment: Note: May be given with or without hydroxyurea. Available as tablets or tablets for oral suspension; use caution during product selection based on patient's ability to swallow tablets whole.

Children 4 to <12 years:

10 to <20 kg: Oral: 600 mg once daily.

20 to <40 kg: Oral: 900 mg once daily.

≥40 kg: Oral: 1,500 mg once daily.

Children ≥12 years and Adolescents: Oral: 1,500 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Mild to severe renal impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant pharmacokinetic differences were observed in pharmacokinetic studies in patients with CrCl of 15 to 89 mL/minute.

End-stage renal disease requiring hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Children 4 to <12 years:

Mild to moderate impairment: No dosage adjustment needed.

Severe impairment (Child Pugh class C):

10 to <20 kg: Oral: Reduce dose to 300 mg once daily.

20 to <40 kg: Oral: Reduce dose to 600 mg once daily.

≥40 kg: Depends upon dosage form used:

Tablets: Oral: Reduce dose to 1,000 mg once daily.

Tablets for oral suspension: Oral: Reduce dose to 900 mg once daily.

Children ≥12 years and Adolescents:

Mild to moderate impairment: No dosage adjustment needed.

Severe impairment (Child Pugh class C): Tablets: Oral: Reduce dose to 1,000 mg once daily.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adolescents and adults.

>10%:

Dermatologic: Skin rash (15%)

Gastrointestinal: Abdominal pain (23%), diarrhea (23%), nausea (19%)

Nervous system: Headache (32%; severe headache: 1%)

Miscellaneous: Fever (15%)

1% to 10%:

Cardiovascular: Pulmonary embolism (1%)

Hypersensitivity: Hypersensitivity reaction (<10%; severe hypersensitivity reaction: 1%)

Postmarketing:

Dermatologic: Pruritus

Hypersensitivity: Angioedema, drug reaction with eosinophilia and systemic symptoms

Contraindications

Serious hypersensitivity (eg, generalized rash, urticaria, mild shortness of breath, mild facial swelling, eosinophilia) to voxelotor or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Serious hypersensitivity reactions have occurred rarely, and may include generalized rash, urticaria, mild dyspnea, mild facial swelling, and eosinophilia. Drug reaction with eosinophilia and systemic symptoms (DRESS) has also occurred. Discontinue voxelotor if a hypersensitivity reaction, including DRESS, occurs and manage as clinically necessary. Do not reinitiate voxelotor in patients who developed a hypersensitivity reaction with prior voxelotor exposure.

Disease-related concerns:

• Hepatic impairment: Severe hepatic impairment increases voxelotor exposure. Reduce dose in patients with severe (Child Pugh class C) impairment.

Other warnings/precautions:

• Laboratory test interference: Voxelotor may interfere with high-performance liquid chromatography measurement of Hb subtypes (HbA, HbS, and HbF). Chromatography should be performed when voxelotor has not been administered in the immediate 10 days prior if precise Hb species quantitation is required.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Oxbryta: 300 mg, 500 mg

Tablet Soluble, Oral:

Oxbryta: 300 mg

Generic Equivalent Available: US

No

Pricing: US

Tablet,Dispersible (Oxbryta Oral)

300 mg (per each): $242.28

Tablets (Oxbryta Oral)

300 mg (per each): $242.28

500 mg (per each): $161.52

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: Administer orally with or without food.

Tablets: Swallow tablets whole; do not cut, crush, or chew the tablets.

Tablets for oral solution: May be used in patients unable to swallow tablets; do not swallow whole, cut, crush, or chew the tablets. Disperse the number of tablets needed to achieve the recommended dose in a cup with room temperature clear liquid (eg, water, clear soda, apple juice, clear electrolyte drinks, clear flavored drinks, clear sports drinks). Use at least 5 mL of liquid per each 300 mg tablet. Swirl contents of cup for 1 to 5 minutes as tablets start to disintegrate until fully dispersed. Swirl contents again prior to administration; small tablet clumps will still be visible in the mixture. Resuspend any residue left in the cup with more clear liquid and drink; repeat until all residue is administered.

Administration: Pediatric

Oral: Administer without regard to food.

Tablet: Swallow tablet whole; do not cut, crush, or chew tablet.

Tablet for oral suspension: Dose can be dispersed in room temperature clear drink; the minimum volume of liquid required to disperse tablet(s) varies with dose (see table). Place dose in cup with appropriate volume of clear drink (water, soda, apple juice, electrolyte drinks, flavored drinks, or sports drinks). Once tablets start to dissolve, swirl cup until contents fully dispersed; wait 1 to 5 minutes and then swirl contents in cup again; tablet(s) will not completely dissolve and there may be small clumps in the mixture. Administer orally. Resuspend any residue remaining in cup with more clear drink and administer, to ensure full dose received; repeat until no residue left in dosing cup. Do not swallow whole, cut, crush, or chew tablets for oral suspension.

Volume (mL) to Disperse Tablets

Daily Dose

Number of 300 mg Tablets for Oral Suspension

MINIMUM Volume of Clear Drink

300 mg

1

5 mL

600 mg

2

10 mL

900 mg

3

15 mL

1,200 mg

4

20 mL

1,500 mg

5

25 mL

2,100 mg

7

35 mL

2,400 mg

8

40 mL

Missed or incomplete dose: If dose missed or not entirely consumed, resume dosing the following day.

Use: Labeled Indications

Sickle cell disease: Treatment of sickle cell disease in adults and pediatric patients ≥4 years of age.

Medication Safety Issues
Sound-alike/look-alike issues:

Voxelotor may be confused with venetoclax, vorinostat.

Metabolism/Transport Effects

Substrate of CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (minor), UGT1A1, UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,500 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Exagamglogene Autotemcel: Voxelotor may diminish the therapeutic effect of Exagamglogene Autotemcel. Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

Lovotibeglogene Autotemcel: Voxelotor may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Sickle cell disease increases the risk of adverse maternal and fetal outcomes, including an increased risk for vaso-occlusive crises, preeclampsia, eclampsia, intrauterine growth restriction, preterm delivery, low birth weight, and maternal and perinatal mortality.

Breastfeeding Considerations

It is not known if voxelotor is present in breast milk

Due to the potential for serious adverse events in the breastfed child, including changes in the hematopoietic system, breastfeeding is not recommended by the manufacturer during treatment and for at least 2 weeks after the last voxelotor dose.

Monitoring Parameters

Monitor hepatic function. Monitor for signs/symptoms of hypersensitivity reactions and drug reaction with eosinophilia and systemic symptoms (DRESS). Monitor adherence.

Mechanism of Action

Voxelotor is an HbS polymerization inhibitor that reversibly binds to Hb and stabilizes the oxygenated Hb state. Through the increased Hb affinity for oxygen, voxelotor demonstrates dose-dependent inhibition of HbS polymerization, and may inhibit RBC sickling, improve RBC deformability, and reduce whole blood viscosity. Voxelotor may also extend RBC half-life and reduce anemia and hemolysis (Vichinsky 2019).

Pharmacokinetics (Adult Data Unless Noted)

Note: Exposures in children ≥4 years and adolescents are similar to in adults.

Absorption: A high-fat, high-calorie meal increased voxelotor whole blood AUC and Cmax by 42% and 45%, respectively (compared to a fasted state); likewise, plasma AUC and Cmax increased by 42% and 95%, respectively.

Distribution: Vd: Central compartment: 333 L; Peripheral compartment: 72.3 L; distributed predominantly into RBCs.

Protein binding: 99.8%.

Metabolism: Primarily hepatic through phase I metabolism (oxidation and reduction), phase II metabolism (glucuronidation), and combinations of phase I and II metabolism. Oxidation is mediated by CYP3A4, CYP3A5, CYP2C19, CYP2B6, CYP2C9, UGT1A1, and UGT1A9.

Half-life elimination: 38.7 hours.

Time to peak: Median: 2 hours.

Excretion: Feces: ~63% (33% as unchanged drug); Urine: ~36% (0.08% as unchanged drug).

Clearance: 6.1 L/hour.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Following a single 900 mg dose, whole blood exposures in subjects with severe renal impairment (eGFR <30 mL/minute/1.73 m2) were 25% lower compared to subjects with normal renal function.

Hepatic function impairment: Voxelotor AUC in whole blood were 14%, 15%, and 90% higher in subjects with mild (Child Pugh class A), moderate (Child Pugh class B), and severe (Child Pugh class C) impairment, respectively, as compared to subjects with normal hepatic function.

HbSC genotype: Voxelotor steady-state whole blood AUC and Cmax were 50% and 45% higher, respectively, in patients with the HbSC genotype compared to patients with the HbSS genotype; plasma AUC and Cmax were 23% and 15% higher, respectively, in patients with the HbSC genotype compared to patients with the HbSS genotype.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Oxbryta;
  • (KW) Kuwait: Oxbryta;
  • (NL) Netherlands: Oxbryta;
  • (PR) Puerto Rico: Oxbryta;
  • (SA) Saudi Arabia: Oxbryta
  1. Oxbryta (voxelotor) [prescribing information]. South San Francisco, CA: Global Blood Therapeutics Inc; August 2023.
  2. Vichinsky E, Hoppe CC, Ataga KI, et al; HOPE Trial Investigators. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl Med. 2019;381(6):509-519. doi: 10.1056/NEJMoa1903212. [PubMed 31199090]
Topic 126260 Version 78.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟