Mozobil

Mozobil is indicated in combination with filgrastim to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

• Initiate Mozobil treatment after the patient has received filgrastim once daily for 4 days. (
  2.1 Recommended Dosage and Administration

  Begin treatment with Mozobil after the patient has received filgrastim once daily for 4 days

  [see

  Dosage and Administration (2.2)]

  . Administer Mozobil approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days.

  The recommended dose of Mozobil by subcutaneous injection is based on body weight:

  • 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing less than or equal to 83 kg.
    [see Clinical Pharmacology (12.3)]
  • 0.24 mg/kg of body weight for patients weighing greater than 83 kg

  Use the patient's actual body weight to calculate the volume of Mozobil to be administered. Each vial delivers 1.2 mL of 20 mg/mL solution, and the volume to be administered to patients should be calculated from the following equation:

  • 0.012 × patient's actual body weight (in kg) = volume to be administered (in mL)

  In clinical studies, Mozobil dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Mozobil dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated.

  Based on increasing exposure with increasing body weight, the Mozobil dose should not exceed 40 mg/day

  [see Clinical Pharmacology (12.3)]

  .

  Vials should be inspected visually for particulate matter and discoloration prior to administration and should not be used if there is particulate matter or if the solution is discolored.

  Discard unused portion.
  )
• Repeat Mozobil dose up to 4 consecutive days. (
  2.1 Recommended Dosage and Administration

  Begin treatment with Mozobil after the patient has received filgrastim once daily for 4 days

  [see

  Dosage and Administration (2.2)]

  . Administer Mozobil approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days.

  The recommended dose of Mozobil by subcutaneous injection is based on body weight:

  • 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing less than or equal to 83 kg.
    [see Clinical Pharmacology (12.3)]
  • 0.24 mg/kg of body weight for patients weighing greater than 83 kg

  Use the patient's actual body weight to calculate the volume of Mozobil to be administered. Each vial delivers 1.2 mL of 20 mg/mL solution, and the volume to be administered to patients should be calculated from the following equation:

  • 0.012 × patient's actual body weight (in kg) = volume to be administered (in mL)

  In clinical studies, Mozobil dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Mozobil dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated.

  Based on increasing exposure with increasing body weight, the Mozobil dose should not exceed 40 mg/day

  [see Clinical Pharmacology (12.3)]

  .

  Vials should be inspected visually for particulate matter and discoloration prior to administration and should not be used if there is particulate matter or if the solution is discolored.

  Discard unused portion.
  )
• Dose based on patient weight
  • Less than or equal to 83 kg: 20 mg dose or select dose based on 0.24 mg/kg actual body weight. (
    2.1 Recommended Dosage and Administration

    Begin treatment with Mozobil after the patient has received filgrastim once daily for 4 days

    [see

    Dosage and Administration (2.2)]

    . Administer Mozobil approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days.

    The recommended dose of Mozobil by subcutaneous injection is based on body weight:

    • 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing less than or equal to 83 kg.
      [see Clinical Pharmacology (12.3)]
    • 0.24 mg/kg of body weight for patients weighing greater than 83 kg

    Use the patient's actual body weight to calculate the volume of Mozobil to be administered. Each vial delivers 1.2 mL of 20 mg/mL solution, and the volume to be administered to patients should be calculated from the following equation:

    • 0.012 × patient's actual body weight (in kg) = volume to be administered (in mL)

    In clinical studies, Mozobil dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Mozobil dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated.

    Based on increasing exposure with increasing body weight, the Mozobil dose should not exceed 40 mg/day

    [see Clinical Pharmacology (12.3)]

    .

    Vials should be inspected visually for particulate matter and discoloration prior to administration and should not be used if there is particulate matter or if the solution is discolored.

    Discard unused portion.
    )
  • greater than 83 kg: select dose based on 0.24 mg/kg actual body weight. (
    2.1 Recommended Dosage and Administration

    Begin treatment with Mozobil after the patient has received filgrastim once daily for 4 days

    [see

    Dosage and Administration (2.2)]

    . Administer Mozobil approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days.

    The recommended dose of Mozobil by subcutaneous injection is based on body weight:

    • 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing less than or equal to 83 kg.
      [see Clinical Pharmacology (12.3)]
    • 0.24 mg/kg of body weight for patients weighing greater than 83 kg

    Use the patient's actual body weight to calculate the volume of Mozobil to be administered. Each vial delivers 1.2 mL of 20 mg/mL solution, and the volume to be administered to patients should be calculated from the following equation:

    • 0.012 × patient's actual body weight (in kg) = volume to be administered (in mL)

    In clinical studies, Mozobil dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Mozobil dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated.

    Based on increasing exposure with increasing body weight, the Mozobil dose should not exceed 40 mg/day

    [see Clinical Pharmacology (12.3)]

    .

    Vials should be inspected visually for particulate matter and discoloration prior to administration and should not be used if there is particulate matter or if the solution is discolored.

    Discard unused portion.
    )
• Administer by subcutaneous injection approximately 11 hours prior to initiation of apheresis. (
  2.1 Recommended Dosage and Administration

  Begin treatment with Mozobil after the patient has received filgrastim once daily for 4 days

  [see

  Dosage and Administration (2.2)]

  . Administer Mozobil approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days.

  The recommended dose of Mozobil by subcutaneous injection is based on body weight:

  • 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing less than or equal to 83 kg.
    [see Clinical Pharmacology (12.3)]
  • 0.24 mg/kg of body weight for patients weighing greater than 83 kg

  Use the patient's actual body weight to calculate the volume of Mozobil to be administered. Each vial delivers 1.2 mL of 20 mg/mL solution, and the volume to be administered to patients should be calculated from the following equation:

  • 0.012 × patient's actual body weight (in kg) = volume to be administered (in mL)

  In clinical studies, Mozobil dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Mozobil dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated.

  Based on increasing exposure with increasing body weight, the Mozobil dose should not exceed 40 mg/day

  [see Clinical Pharmacology (12.3)]

  .

  Vials should be inspected visually for particulate matter and discoloration prior to administration and should not be used if there is particulate matter or if the solution is discolored.

  Discard unused portion.
  )
• Renal impairment:  If creatinine clearance is ≤50 mL/min, decrease dose by one-third to 0.16 mg/kg. (
  2.3 Dose Modifications in Renal Impairment

  In patients with moderate and severe renal impairment (estimated creatinine clearance (CL_CR) less than or equal to 50 mL/min), reduce the dose of Mozobil by one-third based on body weight category as shown in Table 1. If CL_CRis less than or equal to 50 mL/min the dose should not exceed 27 mg/day, as the mg/kg-based dosage results in increased plerixafor exposure with increasing body weight

  [see Clinical Pharmacology (12.3)]

  .  Similar systemic exposure is predicted if the dose is reduced by one-third in patients with moderate and severe renal impairment compared with subjects with normal renal function

  [see Clinical Pharmacology (12.3)]

  .

  Table 1: Recommended Dosage of Mozobil in Patients with Renal Impairment

  Estimated Creatinine Clearance (mL/min)	Dose
  	Body Weight less than or equal to 83 kg	Body Weight greater than 83 kg and less than 160 kg
  greater than 50	20 mg or 0.24 mg/kg once daily	0.24 mg/kg once daily (not to exceed 40 mg/day)
  less than or equal to 50	13 mg or 0.16 mg/kg once daily	0.16 mg/kg once daily (not to exceed 27 mg/day)

  The following (Cockcroft-Gault) formula may be used to estimate CL_CR:

  Males:
  
  Creatinine clearance (mL/min) =

  weight (kg) × (140 – age in years)

  
  
  

  72 × serum creatinine (mg/dL)

  Females:
  
  Creatinine clearance (mL/min) = 0.85 × value calculated for males

  There is insufficient information to make dosage recommendations in patients on hemodialysis.
  )

Injection: 24 mg/1.2 mL (20 mg/mL) sterile, clear, colorless to pale-yellow solution in a single-dose vial.

Lactation: Advise not to breastfeed. (

• Anaphylactic Shock and Serious Hypersensitivity Reactions have occurred. Monitor patients during and after completion of Mozobil administration. (
  5.1 Anaphylactic Shock and Hypersensitivity Reactions

  Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening with clinically significant hypotension and shock have occurred in patients receiving Mozobil

  [see Adverse Reactions (6.2)]

  . Observe patients for signs and symptoms of hypersensitivity during and after Mozobil administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Mozobil when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions.

  In clinical studies, mild or moderate allergic reactions occurred within approximately 30 minutes after Mozobil administration in less than 1% of patients

  [see Adverse Reactions (6.1)]

  .
  )
• Tumor Cell Mobilization in Leukemia Patients: Mozobil may mobilize leukemic cells and should not be used in leukemia patients. (
  5.2 Tumor Cell Mobilization in Leukemia Patients

  For the purpose of HSC mobilization, Mozobil may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, Mozobil is not intended for HSC mobilization and harvest in patients with leukemia.
  )
• Hematologic Effects: Increased circulating leukocytes and decreased platelet counts have been observed.  Monitor blood cell counts and platelet counts during Mozobil use. (
  5.3 Hematologic Effects

  Leukocytosis

  Administration of Mozobil in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during Mozobil use

  [see Adverse Reactions (6.1)]

  .

  Thrombocytopenia

  Thrombocytopenia has been observed in patients receiving Mozobil. Monitor platelet counts in all patients who receive Mozobil and then undergo apheresis.
  )
• Potential for Tumor Cell Mobilization:  Tumor cells may be released from marrow during HSC mobilization with Mozobil and filgrastim.  Effect of reinfusion of tumor cells is unknown. (
  5.4 Potential for Tumor Cell Mobilization

  When Mozobil is used in combination with filgrastim for HSC mobilization‚ tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
  )
• Splenic Rupture: Evaluate patients who report left upper abdominal and/or scapular or shoulder pain. (
  5.5 Splenic Enlargement and Rupture

  Higher absolute and relative spleen weights associated with extramedullary hematopoiesis were observed following prolonged (2 to 4 weeks) daily plerixafor SC administration in rats at doses approximately 4-fold higher than the recommended human dose based on body surface area. The effect of Mozobil on spleen size in patients was not specifically evaluated in clinical studies. Cases of splenic enlargement and/or rupture have been reported following the administration of Mozobil in conjunction with filgrastim. Evaluate individuals receiving Mozobil in combination with filgrastim who report left upper abdominal pain and/or scapular or shoulder pain for splenic integrity.
  )
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise women not to become pregnant when taking Mozobil.  (
  5.6 Embryo-Fetal Toxicity

  Based on findings from animal reproduction studies, Mozobil can cause fetal harm when administered to a pregnant woman. Plerixafor administration to pregnant rats during organogenesis resulted in embryo-fetal mortality, structural abnormalities, and alterations to growth at exposures approximately 10 times the exposure at the recommended human dose.

  Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use an effective form of contraception during treatment with Mozobil and for one week after the final dose

  [see Use in Specific Populations (8.1)]

  .
  ,
  8.1 Pregnancy

  Risk Summary

  Limited available data with Mozobil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, subcutaneous administration of plerixafor to pregnant rats during organogenesis at doses 10-times the maximum recommended human doses resulted in embryo-fetal mortality, structural abnormalities, and alterations to growth

  [see Data]

  .

  Advise pregnant women of the potential risk to the fetus.

  Advise women of reproductive potential to avoid becoming pregnant while receiving treatment with Mozobil

  [see Warnings and Precautions (5.6)].

  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. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriages for the indicated population is unknown.

  Data

  Animal data

  Plerixafor administered to pregnant rats induced embryo-fetal toxicity, including fetal death, increased resorptions and postimplantation loss, decreased fetal weights, anophthalmia, shortened digits, cardiac interventricular septal defect, ringed aorta, globular heart, hydrocephaly, dilatation of olfactory ventricles, and retarded skeletal development. Embryo-fetal toxicities occurred mainly at a dose of 90 mg/m²(approximately 10 times the recommended human dose of 0.24 mg/kg when compared on a mg/m²basis).
  )