WARNINGS AND PRECAUTIONS
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
Leukocytosis
Administration of Mozobil in conjunction with 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/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 leukapheresis 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 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. 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
Pregnancy Category D
Mozobil may cause fetal harm when administered to a pregnant
woman. Plerixafor 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.
[see
Use In
Specific Populations
]
USE IN SPECIFIC POPULATIONS
Pregnancy
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 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.
Pediatric Use
The safety and efficacy of Mozobil in pediatric patients have not
been established in controlled clinical studies.
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
and
Clinical
Pharmacology
]
Renal Impairment
In patients with moderate and severe renal impairment
(CLCR ≤ 50 mL/min), reduce the dose of plerixafor by one-third
to 0.16 mg/kg.
[see
Dosage and
Administration
and
Clinical
Pharmacology
]
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