Data from FDA (Food and Drug Administration, USA) - Curated by Marshall Pearce - Last updated 25 October 2017

Indication(s)

1 INDICATIONS AND USAGE Mozobil® (plerixafor) injection is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Mozobil, a hematopoietic stem cell mobilizer, is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. (1)

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Advisory information

contraindications
4 CONTRAINDICATIONS History of hypersensitivity to Mozobil [see Warnings and Precautions (5.1)]. Anaphylactic shock has occurred with use of Mozobil. History of hypersensitivity to Mozobil. (4)
Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Anaphylactic shock and hypersensitivity reactions [see Warnings and Precautions (5.1)] Potential for tumor cell mobilization in leukemia patients [see Warnings and Precautions (5.2)] Increased circulating leukocytes and decreased platelet counts [see Warnings and Precautions (5.3)] Potential for tumor cell mobilization [see Warnings and Precautions (5.4)] Potential for splenic enlargement [see Warnings and Precautions (5.5)] Most common adverse reactions (≥ 10%): diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting. (6) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-877-4MOZOBIL or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (≥ 10%) reported in patients who received Mozobil in conjunction with G-CSF regardless of causality and more frequent with Mozobil than placebo during HSC mobilization and apheresis were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting. Safety data for Mozobil in combination with G-CSF were obtained from two randomized placebo-controlled studies (301 patients) and 10 uncontrolled studies (242 patients). Patients were primarily treated with Mozobil at daily doses of 0.24 mg/kg SC. Median exposure to Mozobil in these studies was 2 days (range 1 to 7 days). In the two randomized studies in patients with NHL and MM, a total of 301 patients were treated in the Mozobil and G-CSF group and 292 patients were treated in the placebo and G-CSF group. Patients received daily morning doses of G-CSF 10 micrograms/kg for 4 days prior to the first dose of Mozobil 0.24 mg/kg SC or placebo and on each morning prior to apheresis. The adverse reactions that occurred in ≥ 5% of the patients who received Mozobil regardless of causality and were more frequent with Mozobil than placebo during HSC mobilization and apheresis are shown in Table 2. Table 2: Adverse Reactions in ≥ 5% of Non-Hodgkin's Lymphoma and Multiple Myeloma Patients Receiving Mozobil® and More Frequent than Placebo During HSC Mobilization and Apheresis Percent of Patients (%) Mozobil® and G-CSF (n = 301) Placebo and G-CSF (n = 292) All GradesGrades based on criteria from the World Health Organization (WHO) Grade 3 Grade 4 All Grades Grade 3 Grade 4 Gastrointestinal disorders Diarrhea 37 < 1 0 17 0 0 Nausea 34 1 0 22 0 0 Vomiting 10 < 1 0 6 0 0 Flatulence 7 0 0 3 0 0 General disorders and administration site conditions Injection site reactions 34 0 0 10 0 0 Fatigue 27 0 0 25 0 0 Musculoskeletal and connective tissue disorders Arthralgia 13 0 0 12 0 0 Nervous system disorders Headache 22 < 1 0 21 1 0 Dizziness 11 0 0 6 0 0 Psychiatric disorders Insomnia 7 0 0 5 0 0 In the randomized studies, 34% of patients with NHL or MM had mild to moderate injection site reactions at the site of subcutaneous administration of Mozobil. These included erythema, hematoma, hemorrhage, induration, inflammation, irritation, pain, paresthesia, pruritus, rash, swelling, and urticaria. Mild to moderate allergic reactions were observed in less than 1% of patients within approximately 30 min after Mozobil administration, including one or more of the following: urticaria (n = 2), periorbital swelling (n = 2), dyspnea (n = 1) or hypoxia (n = 1). Symptoms generally responded to treatments (e.g., antihistamines, corticosteroids, hydration or supplemental oxygen) or resolved spontaneously. Vasovagal reactions, orthostatic hypotension, and/or syncope can occur following subcutaneous injections. In Mozobil oncology and healthy volunteer clinical studies, less than 1% of subjects experienced vasovagal reactions following subcutaneous administration of Mozobil doses ≤ 0.24 mg/kg. The majority of these events occurred within 1 hour of Mozobil administration. Because of the potential for these reactions, appropriate precautions should be taken. Other adverse reactions in the randomized studies that occurred in < 5% of patients but were reported as related to Mozobil during HSC mobilization and apheresis included abdominal pain, hyperhidrosis, abdominal distention, dry mouth, erythema, stomach discomfort, malaise, hypoesthesia oral, constipation, dyspepsia, and musculoskeletal pain. Hyperleukocytosis: In clinical trials, white blood cell counts of 100,000/mcL or greater were observed, on the day prior to or any day of apheresis, in 7% of patients receiving Mozobil and in 1% of patients receiving placebo. No complications or clinical symptoms of leukostasis were observed. 6.2 Post-marketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been reported from post-marketing experience with Mozobil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Anaphylactic reactions, including anaphylactic shock Psychiatric disorders: Abnormal dreams and nightmares

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Initiate Mozobil treatment after the patient has received G-CSF once daily for 4 days. (2.1) Repeat Mozobil dose up to 4 consecutive days. (2.1) Dose based on patient weight ≤ 83 kg: 20 mg dose or select dose based on 0.24 mg/kg actual body weight. (2.1) > 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 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. Begin treatment with Mozobil after the patient has received G-CSF once daily for four 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 ≤83 kg. [see Clinical Pharmacology (12.3)] 0.24 mg/kg of body weight for patients weighing >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) ] 2.2 Recommended Concomitant Medications Administer daily morning doses of G-CSF 10 micrograms/kg for 4 days prior to the first evening dose of Mozobil and on each day prior to apheresis. [see Clinical Studies (14) ] 2.3 Dosing in Renal Impairment In patients with moderate and severe renal impairment (estimated creatinine clearance (CLCR) ≤ 50 mL/min), reduce the dose of Mozobil by one-third based on body weight category as shown in Table 1. If CLCR is ≤ 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 ≤ 83 kg Body Weight > 83 kg and < 160 kg > 50 20 mg or 0.24 mg/kg once daily 0.24 mg/kg once daily (not to exceed 40 mg/day) ≤ 50 13 mg or 0.16 mg/kg once daily 0.16 mg/kg once daily (not to exceed 27 mg/day) The following (Cockroft-Gault) formula may be used to estimate CLCR: 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.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category D Risk Summary Mozobil may cause fetal harm when administered to a pregnant woman. Plerixafor is teratogenic in animals. Animal Data Plerixafor administered to pregnant rats induced embryo-fetal toxicities including fetal death, increased resorptions and post-implantation 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/m2 basis or 10 times the AUC in subjects with normal renal function who received a single dose of 0.24 mg/kg). 8.3 Nursing Mothers It is not known whether plerixafor is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Mozobil, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and efficacy of Mozobil in pediatric patients have not been established in controlled clinical studies. 8.5 Geriatric Use Of the total number of subjects in controlled clinical studies of Mozobil, 24% were 65 and over, while 0.8% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Since plerixafor is mainly excreted by the kidney, no dose modifications are necessary in elderly individuals with normal renal function. In general, care should be taken in dose selection for elderly patients due to the greater frequency of decreased renal function with advanced age. Dosage adjustment in elderly patients with CLCR ≤ 50 mL/min is recommended. [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ] 8.6 Renal Impairment In patients with moderate and severe renal impairment (CLCR ≤ 50 mL/min), reduce the dose of Mozobil by one-third to 0.16 mg/kg. [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ]
Pregnancy and lactation
8.3 Nursing Mothers It is not known whether plerixafor is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Mozobil, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Interactions

7 DRUG INTERACTIONS Based on in vitro data, plerixafor is not a substrate, inhibitor or inducer of human cytochrome P450 isozymes. Plerixafor is not likely to be implicated in in vivo drug-drug interactions involving cytochrome P450s. At concentrations similar to what are seen clinically, plerixafor did not act as a substrate or inhibitor of P-glycoprotein in an in vitro study. [see Clinical Pharmacology (12.3)]

More information

Category Value
Authorisation number NDA022311
Agency product number S915P5499N
Orphan designation No
Product NDC 0024-5862
Date Last Revised 19-01-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 828703
Storage and handling Store at 25oC (77oF); excursions permitted to 15o–30oC (59o–86oF). [see USP Controlled Room temperature] Each vial of Mozobil is intended for single use only. Any unused drug remaining after injection must be discarded.
Marketing authorisation holder sanofi-aventis U.S. LLC