Mozobil

2 DOSAGE AND ADMINISTRATION Initiate Mozobil treatment after the patient has received filgrastim once daily for 4 days. 1 ) Repeat Mozobil dose up to 4 consecutive days. 24 mg/kg actual body weight. 24 mg/kg actual body weight. 1 ) Administer by subcutaneous injection approximately 11 hours prior to initiation of apheresis.

16 mg/kg. 2) ] . Administer Mozobil approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days. 24 mg/kg of body weight for patients weighing less than or equal to 83 kg. 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.

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.

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 Recommended Concomitant Medications Administer daily morning doses of filgrastim 10 mcg/kg for 4 days prior to the first evening dose of Mozobil and on each day prior to apheresis [see Clinical Studies (14) ] .

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.

3) ] . 3) ] . 85 × value calculated for males There is insufficient information to make dosage recommendations in patients on hemodialysis.

5) ] Most common adverse reactions (≥10%): diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting. gov/medwatch. 1 Clinical Trials 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 filgrastim 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 filgrastim were obtained from two randomized placebo-controlled studies (301 patients) and 10 uncontrolled studies (242 patients). 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 filgrastim group and 292 patients were treated in the placebo and filgrastim group. 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 Filgrastim (n=301) Placebo and Filgrastim (n=292) All Grades Grades 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.

5 WARNINGS AND PRECAUTIONS Anaphylactic Shock and Serious Hypersensitivity Reactions have occurred. Monitor patients during and after completion of Mozobil administration. 1 ) Tumor Cell Mobilization in Leukemia Patients: Mozobil may mobilize leukemic cells and should not be used in leukemia patients.

2 ) Hematologic Effects: Increased circulating leukocytes and decreased platelet counts have been observed. Monitor blood cell counts and platelet counts during Mozobil use. 3 ) 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. 4 ) Splenic Rupture: Evaluate patients who report left upper abdominal and/or scapular or shoulder pain. 5 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise women not to become pregnant when taking Mozobil.

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.

1) ] . 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.

3 Hematologic Effects Leukocytosis Administration of Mozobil in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. 1) ] . Thrombocytopenia Thrombocytopenia has been observed in patients receiving Mozobil.

Monitor platelet counts in all patients who receive Mozobil and then undergo apheresis. 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.

1) ] . Anaphylactic shock has occurred with use of Mozobil. History of hypersensitivity to Mozobil. ( 4 )