Xolremdi

XOLREMDI is indicated in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lympocytes.

• Recommended dosage:
  
  
  • Weight more than 50 kg: 400 mg orally once daily. (
    
    
    2 DOSAGE AND ADMINISTRATION

    • Recommended dosage:
      • Weight more than 50 kg: 400 mg orally once daily.
      • Weight less than or equal to 50 kg: 300 mg orally once daily.
    • Administer XOLREMDI on an empty stomach after an overnight fast, and at least 30 minutes before food.

    2.1 Recommended Dosage

    The recommended dosage of XOLREMDI is:

    • Weight more than 50 kg: 400 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.
    • Weight less than or equal to 50 kg: 300 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.

    Swallow the capsules whole. Do not open, break, or chew capsules.

    If a dose of XOLREMDI is missed, the next dose should be taken as scheduled. Do not take more than 1 XOLREMDI dose each day.

    2.2 Dosage Modifications for Strong CYP3A4 inhibitors

    Reduce daily dosage of XOLREMDI to 200 mg when used concomitantly with strong CYP3A4 inhibitors

    [see Drug Interactions (7.1)]

    .
    )
    
    
  • Weight less than or equal to 50 kg: 300 mg orally once daily. (
    
    
    2 DOSAGE AND ADMINISTRATION

    • Recommended dosage:
      • Weight more than 50 kg: 400 mg orally once daily.
      • Weight less than or equal to 50 kg: 300 mg orally once daily.
    • Administer XOLREMDI on an empty stomach after an overnight fast, and at least 30 minutes before food.

    2.1 Recommended Dosage

    The recommended dosage of XOLREMDI is:

    • Weight more than 50 kg: 400 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.
    • Weight less than or equal to 50 kg: 300 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.

    Swallow the capsules whole. Do not open, break, or chew capsules.

    If a dose of XOLREMDI is missed, the next dose should be taken as scheduled. Do not take more than 1 XOLREMDI dose each day.

    2.2 Dosage Modifications for Strong CYP3A4 inhibitors

    Reduce daily dosage of XOLREMDI to 200 mg when used concomitantly with strong CYP3A4 inhibitors

    [see Drug Interactions (7.1)]

    .
    )
    
    
• Administer XOLREMDI on an empty stomach after an overnight fast, and at least 30 minutes before food. (
  
  
  2 DOSAGE AND ADMINISTRATION

  • Recommended dosage:
    • Weight more than 50 kg: 400 mg orally once daily.
    • Weight less than or equal to 50 kg: 300 mg orally once daily.
  • Administer XOLREMDI on an empty stomach after an overnight fast, and at least 30 minutes before food.

  2.1 Recommended Dosage

  The recommended dosage of XOLREMDI is:

  • Weight more than 50 kg: 400 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.
  • Weight less than or equal to 50 kg: 300 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.

  Swallow the capsules whole. Do not open, break, or chew capsules.

  If a dose of XOLREMDI is missed, the next dose should be taken as scheduled. Do not take more than 1 XOLREMDI dose each day.

  2.2 Dosage Modifications for Strong CYP3A4 inhibitors

  Reduce daily dosage of XOLREMDI to 200 mg when used concomitantly with strong CYP3A4 inhibitors

  [see Drug Interactions (7.1)]

  .
  )
  

Capsules: 100 mg mavorixafor. (

• Lactation: Advise females that breastfeeding is not recommended. (
  
  
  8.2 Lactation

  Risk Summary

  There are no data on the presence of mavorixafor in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise females that breastfeeding is not recommended during treatment with XOLREMDI and for 3 weeks after the final dose.
  )
  
• Renal Impairment: Not recommended for use in patients with severe renal impairment or end stage renal disease. (
  
  
  8.6 Renal Impairment

  XOLREMDI is not recommended in patients with severe renal impairment (creatinine clearance [CLcr] 15 to less than 30 mL/min) or end-stage renal disease (CLcr less than 15 mL/min). No dosage adjustment is recommended in patients with mild to moderate renal impairment (CLcr 30 to less than 90 mL/min).

  No clinically significant differences in the pharmacokinetics of mavorixafor were observed in mild to moderate renal impairment (CLcr 30 to less than 90 mL/min). The pharmacokinetics of mavorixafor have not been studied in subjects with severe renal impairment or end-stage renal disease

  [see Clinical Pharmacology (12.3)]

  .
  )
  
• Hepatic Impairment: Not recommended for use in patients with moderate to severe hepatic impairment. (
  
  
  8.7 Hepatic Impairment

  XOLREMDI is not recommended for use in patients with moderate to severe hepatic impairment. No dosage adjustment is recommended in patients with mild hepatic impairment.

  The pharmacokinetics of mavorixafor have not been studied in subjects with moderate to severe hepatic impairment [

  see Clinical Pharmacology (12.3)

  ].
  )
  

• Embryo-fetal toxicity: Expected to cause fetal harm. Advise women of reproductive potential to use effective contraception. (
  
  
  5.1 Embryo-Fetal Toxicity

  Based on its mechanism of action, XOLREMDI is expected to cause fetal harm when administered to a pregnant woman

  [see Clinical Pharmacology (12.2)]

  . Animal models link reductions in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and to abnormal placental development.

  Verify the pregnancy status of female patients of reproductive potential prior to starting XOLREMDI. Advise females of reproductive potential to use an effective method of contraception during treatment with XOLREMDI and for 3 weeks after the final dose

  [see Use in Specific Populations (8.1, 8.3)]

  .
  ,
  
  
  8.1 Pregnancy

  Risk Summary

  Based on its mechanism of action, XOLREMDI is expected to cause fetal harm when administered to a pregnant woman

  [see Clinical Pharmacology (12.1)]

  . There are no available data on XOLREMDI use in pregnant women informing the risk of embryo-fetal developmental toxicities. Animal models link reductions in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development

  (see Data)

  . No definitive animal studies have been conducted to evaluate the effect of mavorixafor on reproduction and fetal development.

  Advise pregnant women of the potential risk to the fetus and to use effective contraception

  [see Warnings and Precautions (5.1)

  and

  Use in Specific Populations (8.3)]

  .

  The estimated background risk of major birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

  Data

  Animal Data

  Animal reproduction studies have not been conducted with mavorixafor to evaluate effects on reproduction and embryo-fetal development. CXCR4/SDF-1 signaling plays an important role in mammalian embryo-fetal and placental development. In mice, CXCR4-/- knockout is embryo lethal and causes multiple developmental toxicities, most notably in the hematopoietic, cardiovascular and nervous systems. CXCR4/SDF-1 levels have a key role in stimulating trophoblast proliferation and differentiation necessary for appropriate placental growth and function in humans

  [see Warnings and Precautions (5.1)].
  ,
  
  
  8.3 Females and Males of Reproductive Potential

  XOLREMDI is expected to cause fetal harm when administered to pregnant women

  [see Warnings and Precautions (5.1)

  and

  Use in Specific Populations (8.1)]

  .

  Pregnancy Testing

  Verify the pregnancy status in females of reproductive potential prior to initiating XOLREMDI

  [see Use in Specific Populations (8.1)]

  .

  Contraception

  Advise females of reproductive potential to use an effective form of contraception during treatment with XOLREMDI and for 3 weeks after the final dose

  [see Use in Specific Populations (8.1)].
  )
  
• QTc Interval Prolongation: : Correct any modifiable risk factors, assess QTc at baseline and monitor QTc during treatment as clinically indicated. XOLREMDI dose reduction or discontinuation may be required due to drug-drug interactions. (
  
  
  5.2 QTc Interval Prolongation

  XOLREMDI causes concentration-dependent QTc interval prolongation. QTc interval prolongation may occur when XOLREMDI is taken with concomitant medications that increase XOLREMDI exposure and/or drug products with a known potential to prolong QTc. Correct any modifiable risk factors for QTc prolongation (e.g., hypokalemia), assess QTc at baseline and monitor QTc during treatment as clinically indicated in patients with risk factors for QTc prolongation such as those receiving concomitant medications that increase XOLREMDI exposure and drug products with a known potential to prolong QTc. A dose reduction in XOLREMDI or discontinuation of XOLREMDI may be required

  [see Drug Interactions (7.1, 7.3)and Clinical Pharmacology (12.2)].
  )