1.2 ML plerixafor 20 MG/ML Injection [Mozobil]

INDICATIONS AND USAGE Plerixafor injection 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). Plerixafor injection, a hematopoietic stem cell mobilizer, 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 or multiple myeloma. ( 1 )

DOSAGE AND ADMINISTRATION Initiate Plerixafor Injection treatment after the patient has received filgrastim once daily for 4 days. ( 2.1 ) Repeat Plerixafor Injection dose up to 4 consecutive days. ( 2.1 ) 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 ) Greater than 83 kg: select dose based on 0.24 mg/kg actual body weight. ( 2.1 ) Administer by subcutaneous injection approximately 11 hours prior to initiation of apheresis. ( 2.1 ) Renal impairment: If creatinine clearance is ≤50 mL/min, decrease dose by one-third to 0.16 mg/kg. ( 2.3 ) 2.1 Recommended Dosage and Administration Begin treatment with Plerixafor Injection after the patient has received filgrastim once daily for 4 days [see Dosage and Administration ( 2.2 )]. Administer Plerixafor Injection approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days. The recommended dose of Plerixafor Injection 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 Plerixafor Injection to be administered. Each vial delivers 1.2 mL of 20 mg per 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, Plerixafor Injection dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Plerixafor Injection 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 Plerixafor Injection 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. 2.2 Recommended Concomitant Medications Administer daily morning doses of filgrastim 10 mcg/kg for 4 days prior to the first evening dose of Plerixafor Injection and on each day prior to apheresis [see Clinical Studies ( 14 )]. 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 Plerixafor Injection by one-third based on body weight category as shown in Table 1 . If CL CR is 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 Plerixafor Injection 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. 2.1 Recommended Dosage and Administration Begin treatment with Plerixafor Injection after the patient has received filgrastim once daily for 4 days [see Dosage and Administration ( 2.2 )]. Administer Plerixafor Injection approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days. The recommended dose of Plerixafor Injection 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 Plerixafor Injection to be administered. Each vial delivers 1.2 mL of 20 mg per 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, Plerixafor Injection dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Plerixafor Injection 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 Plerixafor Injection 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.

WARNINGS AND PRECAUTIONS Anaphylactic Shock and Serious Hypersensitivity Reactions have occurred. Monitor patients during and after completion of Plerixafor Injection administration. ( 5.1 ) Tumor Cell Mobilization in Leukemia Patients: Plerixafor Injection may mobilize leukemic cells and should not be used in leukemia patients. ( 5.2 ) Hematologic Effects: Increased circulating leukocytes and decreased platelet counts have been observed. Monitor blood cell counts and platelet counts during Plerixafor Injection use. ( 5.3 ) Potential for Tumor Cell Mobilization: Tumor cells may be released from marrow during HSC mobilization with Plerixafor Injection and filgrastim. Effect of reinfusion of tumor cells is unknown. ( 5.4 ) Splenic Rupture: Evaluate patients who report left upper abdominal and/or scapular or shoulder pain. ( 5.5 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise women not to become pregnant when taking Plerixafor Injection. ( 5.6 , 8.1 ) 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 Plerixafor Injection [see Adverse Reactions ( 6.2 )] . Observe patients for signs and symptoms of hypersensitivity during and after Plerixafor Injection administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Plerixafor Injection 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 Plerixafor Injection administration in less than 1% of patients [see Adverse Reactions ( 6.1 )] . 5.2 Tumor Cell Mobilization in Leukemia Patients For the purpose of HSC mobilization, Plerixafor Injection may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, Plerixafor Injection is not intended for HSC mobilization and harvest in patients with leukemia. 5.3 Hematologic Effects Leukocytosis Administration of Plerixafor Injection in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during Plerixafor Injection use [see Adverse Reactions ( 6.1 )]. Thrombocytopenia Thrombocytopenia has been observed in patients receiving Plerixafor Injection. Monitor platelet counts in all patients who receive Plerixafor Injection and then undergo apheresis. 5.4 Potential for Tumor Cell Mobilization When Plerixafor Injection 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. 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 Plerixafor Injection 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 Plerixafor Injection in conjunction with filgrastim. Evaluate individuals receiving Plerixafor Injection in combination with filgrastim who report left upper abdominal pain and/or scapular or shoulder pain for splenic integrity. 5.6 Embryo-Fetal Toxicity Based on findings from animal reproduction studies, Plerixafor Injection 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 Plerixafor Injection and for one week after the final dose [see Use in Specific Populations ( 8.1 )] .

CONTRAINDICATIONS Plerixafor Injection is contraindicated in patients with a history of hypersensitivity to plerixafor [see Warnings and Precautions ( 5.1 )] . Anaphylactic shock has occurred with use of Plerixafor Injection. History of hypersensitivity to Plerixafor Injection. ( 4 )

Mechanism of Action Plerixafor is an inhibitor of the CXCR4 chemokine receptor and blocks binding of its cognate ligand, stromal cell-derived factor-1α (SDF-1α). SDF-1α and CXCR4 are recognized to play a role in the trafficking and homing of human hematopoietic stem cells (HSCs) to the marrow compartment. Once in the marrow, stem cell CXCR4 can act to help anchor these cells to the marrow matrix, either directly via SDF-1α or through the induction of other adhesion molecules. Treatment with plerixafor resulted in leukocytosis and elevations in circulating hematopoietic progenitor cells in mice, dogs and humans. CD34+ cells mobilized by plerixafor were capable of engraftment with long-term repopulating capacity up to one year in canine transplantation models.