Mozobil Important Safety Information

Contraindications

No contraindications have been reported for Mozobil use.

Warnings and Precautions

Tumor Cell Mobilization in Leukemia Patients

For the purposes of hematopoietic stem cell (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

Leukocytosis
Administration with Mozobil in conjunction with granulocyte-colony stimulating factor (G-CSF) increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during Mozobil use. Exercise clinical judgment when administering Mozobil to patients with peripheral blood neutrophil counts above 50,000 cells/mcL.

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

When Mozobil is used in combination with G-CSF for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukopheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.

Splenic Enlargement and Potential for Rupture

Higher absolute and relative spleen weights associated with extramedullary hematopoiesis were observed following prolonged (2 to 4 weeks) daily Mozobil 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. Evaluate individuals receiving Mozobil in combination with G-CSF who report left upper abdominal pain and/or scapular or shoulder pain for splenic integrity.

Pregnancy Category D

Mozobil may cause fetal harm when administered to a pregnant woman. Mozobil was teratogenic in animals. There are no adequate and well-controlled studies in pregnant women using Mozobil. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Mozobil. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Clinical Adverse Reactions

Clinical safety data for Mozobil in combination with G-CSF were obtained from two placebo-controlled phase 3 studies (study 1 and study 2) and 10 uncontrolled studies in 543 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 1-7).

The most common adverse reactions (AR), (≥ 10%) more frequently reported with Mozobil + G-CSF than placebo + G-CSF during HSC mobilization and apheresis in the Mozobil clinical program regardless of cause were: diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting. The most common (≥ 5%) AR’s that occurred more often with Mozobil + G-CSF than with placebo + G-CSF in the phase 3 studies of NHL and MM patients are presented in this table.

In Mozobil oncology clinical studies, less than 1% of patients experienced mild or moderate systemic reactions within approximately 30 minutes after Mozobil administration. Events included 1 or more of the following: urticaria (n = 2), periorbital swelling (n = 2), dyspnea (n = 1), or hypoxia (n = 1). Symptoms generally responded to treatments (eg, 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.

AR that occurred in less than 5% of patients but were reported to be related to Mozobil during HSC mobilization and apheresis include: abdominal pain, hyperhidrosis, abdominal distention, dry mouth, erythema, stomach discomfort, malaise, oral hypoaesthesia, constipation, dyspepsia, and musculoskeletal pain.

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.

Use in Specific Populations

Pregnancy Category D
Plerixafor was teratogenic in animals. 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).

Nursing Mothers
It is unknown whether Mozobil is excreted in breast milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, 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.

Pediatric Patients
The safety and efficacy of Mozobil in pediatric patients have not been established in controlled clinical studies.

Geriatric Use
In the phase 3 trials of Mozobil, 24% of patients were aged 65 years or older and 0.8% were 75 years or older. There were no observed differences in AR by age in these studies, but greater sensitivity to adverse events in some older individuals cannot be ruled out and decreased renal function is more common with advanced age. As with all patients, dosage adjustment in elderly patients with creatinine clearance ≤ 50 mL/min is recommended. Refer to dosing information.

Renal Impairment
Dose reduction by one-third (to 0.16 mg/kg) is necessary in patients with moderate or severe renal impairment. Refer to dosing information.

Overdosage

Based on limited data at doses above the recommended dose of 0.24 mg/kg SC, the frequency of the gastrointestinal disorders, vasovagal reactions, orthostatic hypotension, and/or syncope may be higher.

To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-877-4MOZOBIL (1-877-466-9624) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.