Plerixafor Injection (Mozobil)
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Plerixafor Injection (Mozobil)

MOZOBIL
(plerixafor) Injection, Solution for Subcutaneous Use

DRUG DESCRIPTION

Mozobil (plerixafor injection) is a sterile, preservative-free, clear, colorless to pale yellow, isotonic solution for subcutaneous injection. Each mL of the sterile solution contains 20 mg of plerixafor. Each single-use vial is filled to deliver 1.2 mL of the sterile solution that contains 24 mg of plerixafor and 5.9 mg of sodium chloride in Water for Injection adjusted to a pH of 6.0 to 7.5 with hydrochloric acid and with sodium hydroxide, if required.

Plerixafor is a hematopoietic stem cell mobilizer with a chemical name 1, l'-[l,4-phenylenebis (methylene)]-bis-l,4,8,11- tetraazacyclotetradecane. It has the molecular formula C28H54N8. The molecular weight of plerixafor is 502.79 g/mol. The structural formula is provided in Figure 1.

Figure 1: Structural Formula

Mozobil (plerixafor) Structural Formula Illustration

Plerixafor is a white to off-white crystalline solid. It is hygroscopic. Plerixafor has a typical melting point of 131.5 °C. The partition coefficient of plerixafor between 1 -octanol and pH 7 aqueous buffer is < 0.1.

What are the possible side effects of plerixafor (Mozobil)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have a serious side effect such as:

  • easy bruising or bleeding, unusual weakness;
  • feeling like you might pass out; or
  • pain in your upper stomach, spreading to your shoulder or back.

Less serious side effects may include:

  • nausea, vomiting;
  • diarrhea, constipation;
  • dry mouth, numbness in or around your mouth;
  • upset...

Read All Potential Side Effects and See Pictures of Mozobil »

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

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

DOSAGE AND ADMINISTRATION

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 (plerixafor injection) after the patient has received G-CSF once daily for four days. Administer Mozobil (plerixafor injection) approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days.

The recommended dose of Mozobil (plerixafor injection) is 0.24 mg/kg body weight by subcutaneous (SC) injection. Use the patient's actual body weight to calculate the volume of Mozobil (plerixafor injection) 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 x patient's actual body weight (in kg) = volume to be administered (in mL)

In clinical studies, Mozobil (plerixafor injection) dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Mozobil (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 dose should not exceed 40 mg/day. [see CLINICAL PHARMACOLOGY]

Recommended Concomitant Medications

Administer daily morning doses of G-CSF 10 micrograms/kg for 4 days prior to the first evening dose of Mozobil (plerixafor injection) and on each day prior to apheresis. [see Clinical Studies]

Dosing in Renal Impairment

In patients with moderate and severe renal impairment (estimated creatinine clearance (CLCr) ≤ 50 mL/min), reduce the dose of Mozobil (plerixafor injection) by one-third to 0.16 mg/kg 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] 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]

Table 1: Recommended Dosage of Plerixafor in Patients with Renal Impairment

Estimated Creatinine Clearance (mL/min) Dose
> 50 0.24 mg/kg once daily (not to exceed 40 mg/day)
≤ 50 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) X (140 - age in years)/72 X serum creatinine (mg/dL)

Females:

Creatinine clearance (mL/min) = 0.85 X value calculated for males

There is insufficient information to make dosage recommendations in patients on hemodialysis.

HOW SUPPLIED

Dosage Forms And Strengths

Single-use vial containing 1.2 mL of a 20 mg/mL solution.

Storage And Handling

Each single-use vial is filled to deliver 1.2 mL of 20 mg/mL solution containing 24 mg of plerixafor.

NDC Number: 58468-0140-1

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). [see USP Controlled Room temperature]

Each vial of Mozobil (plerixafor injection) is intended for single use only. Any unused drug remaining after injection must be discarded.

Manufactured by: Patheon UK Ltd., Swindon, UK. Manufactured for: Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 USA.

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trial Experience

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Potential for tumor cell mobilization in leukemia patients [see WARNINGS AND PRECAUTIONS]
  • Increased circulating leukocytes and decreased platelet counts [see WARNINGS AND PRECAUTIONS]
  • Potential for splenic enlargement [see WARNINGS AND PRECAUTIONS]

The most common adverse reactions ( > 10%) reported in patients who received Mozobil (plerixafor injection) in conjunction with G-CSF regardless of causality and more frequent with Mozobil (plerixafor injection) than placebo during HSC mobilization and apheresis were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting.

Safety data for Mozobil (plerixafor injection) 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 (plerixafor injection) at daily doses of 0.24 mg/kg SC. Median exposure to Mozobil (plerixafor injection) 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 (plerixafor injection) 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 (plerixafor injection) 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 (plerixafor injection) regardless of causality and were more frequent with Mozobil (plerixafor injection) than placebo during HSC mobilization and apheresis are shown in Table 2.

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.

Table 2: Adverse Reactions in ≥ 5% of Non-Hodgkin's Lymphoma and Multiple Myeloma Patients Receiving Mozobil (plerixafor injection) 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 Gradesa 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
a Grades based on criteria from the World Health Organization (WHO)

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 (plerixafor injection) . These included erythema, hematoma, hemorrhage, induration, inflammation, irritation, pain, paresthesia, pruritus, rash, swelling, and urticaria.

Mild to moderate systemic reactions were observed in less than 1% of patients approximately 30 min after Mozobil (plerixafor injection) administration. Events included 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 (plerixafor injection) oncology and healthy volunteer clinical studies, less than 1% of subjects experienced vasovagal reactions following subcutaneous administration of Mozobil (plerixafor injection) doses ≤ 0.24 mg/kg. The majority of these events occurred within 1 hour of Mozobil (plerixafor injection) 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 (plerixafor injection) during HSC mobilization and apheresis included abdominal pain, hyperhidrosis, abdominal distention, dry mouth, erythema, stomach discomfort, malaise, hypoesthesia oral, constipation, dyspepsia, and musculoskeletal pain.

Read the Mozobil (plerixafor injection) Side Effects Center for a complete guide to possible side effects »

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]

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Tumor Cell Mobilization in Leukemia Patients

For the purpose of HSC mobilization, Mozobil (plerixafor injection) may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, Mozobil (plerixafor injection) is not intended for HSC mobilization and harvest in patients with leukemia.

Hematologic Effects

Leukocytosis

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

Thrombocytopenia

Thrombocytopenia has been observed in patients receiving Mozobil (plerixafor injection) . Monitor platelet counts in all patients who receive Mozobil (plerixafor injection) and then undergo apheresis.

Potential for Tumor Cell Mobilization

When Mozobil (plerixafor injection) 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 (plerixafor injection) on spleen size in patients was not specifically evaluated in clinical studies. Evaluate individuals receiving Mozobil (plerixafor injection) 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 (plerixafor injection) 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 (plerixafor injection) . Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Mozobil (plerixafor injection) . 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]

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies with plerixafor have not been conducted.

Plerixafor was not genotoxic in an in vitro bacterial mutation assay (Ames test in Salmonella), an in vitro chromosomal aberration test using V79 Chinese hamster cells, or an in vivo bone marrow micronucleus test in rats after subcutaneous doses up to 25 mg/kg (150mg/m²).

The effect of plerixafor on human fertility is unknown. The effect of plerixafor on male or female fertility was not studied in designated reproductive toxicology studies. The staging of spermatogenesis measured in a 28-day repeated dose toxicity study in rats revealed no abnormalities considered to be related to plerixafor. No histopathological evidence of toxicity to male or female reproductive organs was observed in 28-day repeated dose toxicity studies.

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 (plerixafor injection) , 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 (plerixafor injection) 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 (plerixafor injection) , 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]

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

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

CONTRAINDICATIONS

None

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Plerixafor is an inhibitor of the CXCR4 chemokine receptor and blocks binding of its cognate ligand, stromal cell-derived factor-l a (SDF-la ). SDF-l a 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-la 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.

Pharmacodynamics

Data on the fold increase in peripheral blood CD34+ cell count (cells/mcL) by apheresis day were evaluated in two placebo-controlled clinical studies in patients with NHL and MM (Study 1 and Study 2, respectively). The fold increase in CD34+ cell count (cells/mcL) over the 24-hour period starting from the day prior to the first apheresis and ending the next morning just before the first apheresis is summarized in Table 3. During this 24-hour period, a single dose of Mozobil (plerixafor injection) or placebo was administered 10 to 11 hours prior to apheresis.

Table 3: Fold Increase in Peripheral Blood CD34+ Cell Count Following Pretreatment with G-CSF and Administration of Plerixafor

Study Mozobil and G-CSF Placebo and G-CSF
Median Mean (SD) Median Mean (SD)
Study 1 5.0 6.1 (5.4) 1.4 1.9(1.5)
Study 2 4.8 6.4 (6.8) 1.7 2.4 (7.3)

In pharmacodynamic studies of Mozobil (plerixafor injection) in healthy volunteers, peak mobilization of CD34+ cells was observed between 6 and 9 hours after administration. In pharmacodynamic studies of Mozobil (plerixafor injection) in conjunction with G-CSF in healthy volunteers, a sustained elevation in the peripheral blood CD34+ count was observed from 4 to 18 hours after plerixafor administration with a peak CD34+ count between 10 and 14 hours.

Pharmacokinetics

The single-dose pharmacokinetics of plerixafor 0.24 mg/kg were evaluated in patients with NHL and MM following pre-treatment with G-CSF (10 micrograms/kg once daily for 4 consecutive days). Plerixafor exhibits linear kinetics between the 0.04 mg/kg to 0.24 mg/kg dose range. The pharmacokinetics of plerixafor were similar across clinical studies in healthy subjects who received plerixafor alone and NHL and MM patients who received plerixafor in combination with G-CSF.

A population pharmacokinetic analysis incorporated plerixafor data from 63 subjects (NHL patients, MM patients, subjects with varying degrees of renal impairment, and healthy subjects) who received a single SC dose (0.04 mg/kg to 0.24 mg/kg) of plerixafor. A two-compartment disposition model with first order absorption and elimination was found to adequately describe the plerixafor concentration-time profile. Significant relationships between clearance and creatinine clearance (CLcr), as well as between central volume of distribution and body weight were observed. The distribution half-life (t½a) was estimated to be 0.3 hours and the terminal population half-life (t½b) was 5.3 hours in patients with normal renal function.

The population pharmacokinetic analysis showed that the mg/kg-based dosage results in an increased plerixafor exposure (AUC0-24h) with increasing body weight. There is limited experience with the 0.24 mg/kg dose of plerixafor in patients weighing above 160 kg. Therefore the dose should not exceed that of a 160 kg patient (i.e., 40 mg/day if CLCr is > 50 mL/min and 27 mg/day if CLCR is ≤ 50 mL/min). [see DOSAGE AND ADMINISTRATION]

Absorption

Peak plasma concentrations occurred at approximately 30-60 minutes after a SC dose.

Distribution

Plerixafor is bound to human plasma proteins up to 58%. The apparent volume of distribution of plerixafor in humans is 0.3 L/kg demonstrating that plerixafor is largely confined to, but not limited to, the extravascular fluid space.

Metabolism

The metabolism of plerixafor was evaluated with in vitro assays. Plerixafor is not metabolized as shown in assays using human liver microsomes or human primary hepatocytes and does not exhibit inhibitory activity in vitro towards the major drug metabolizing cytochrome P450 enzymes (1A2, 2C9, 2C19, 2D6, and 3A4/5). In in vitro studies with human hepatocytes, plerixafor does not induce CYP1A2, CYP2B6, or CYP3A4 enzymes. These findings suggest that plerixafor has a low potential for involvement in cytochrome P450-dependent drug-drug interactions.

Elimination

The major route of elimination of plerixafor is urinary. Following a 0.24 mg/kg dose in healthy volunteers with normal renal function, approximately 70% of the dose was excreted in the urine as the parent drug during the first 24 hours following administration. In studies with healthy subjects and patients, the terminal half-life in plasma ranges between 3 and 5 hours. 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 with MDCKII and MDCKII-MDR1 cell models.

Renal Impairment

Following a single 0.24 mg/kg SC dose, plerixafor clearance was reduced in subjects with varying degrees of renal impairment and was positively correlated with CLCr. The mean AUC0-24h of plerixafor in subjects with mild (CLCr 51-80 mL/min), moderate (CLCr 31-50 mL/min), and severe (CLcr < 31 mL/min) renal impairment was 7%, 32%, and 39% higher than healthy subjects with normal renal function, respectively. Renal impairment had no effect on Cmax. A population pharmacokinetic analysis indicated an increased exposure (AUC0-24h) in patients with moderate and severe renal impairment compared to patients with CLCr > 50 mL/min. These results support a dose reduction of one-third in patients with moderate to severe renal impairment (CLCr ≤ 50 mL/min) in order to match the exposure in patients with normal renal function. The population pharmacokinetic analysis showed that the mg/kg-based dosage results in an increased plerixafor exposure (AUC0-24h) with increasing body weight; therefore if CLCr is ≤ 50 mL/min the dose should not exceed 27 mg/day. [see DOSAGE AND ADMINISTRATION]

Since plerixafor is primarily eliminated by the kidneys, coadministration of plerixafor with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of plerixafor or the coadministered drug. The effects of coadministration of plerixafor with other drugs that are renally eliminated or are known to affect renal function have not been evaluated.

Race

Clinical data show similar plerixafor pharmacokinetics for Caucasians and African-Americans, and the effect of other racial/ethnic groups has not been studied.

Gender

Clinical data show no effect of gender on plerixafor pharmacokinetics.

Age

Clinical data show no effect of age on plerixafor pharmacokinetics.

QT/QTc Prolongation

There is no indication of a QT/QTc prolonging effect of Mozobil (plerixafor injection) in single doses up to 0.40 mg/kg. In a randomized, double-blind, crossover study, 48 healthy subjects were administered a single subcutaneous dose of Mozobil (plerixafor injection) (0.24 mg/kg and 0.40 mg/kg) and placebo. Peak concentrations for 0.40 mg/kg Mozobil (plerixafor injection) were approximately 1.8-fold higher than the peak concentrations following the 0.24 mg/kg single subcutaneous dose.

Clinical Studies

The efficacy and safety of Mozobil (plerixafor injection) in conjunction with G-CSF in non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) were evaluated in two placebo-controlled studies (Studies 1 and 2). Patients were randomized to receive either Mozobil (plerixafor injection) 0.24 mg/kg or placebo on each evening prior to apheresis. Patients received daily morning doses of G-CSF 10 micrograms/kg for 4 days prior to the first dose of Mozobil (plerixafor injection) or placebo and on each morning prior to apheresis. Two hundred and ninety-eight (298) NHL patients were included in the primary efficacy analyses for Study 1. The mean age was 55.1 years (range 29-75) and 57.5 years (range 22-75) in the Mozobil (plerixafor injection) and placebo groups, respectively, and 93% of subjects were Caucasian. Three hundred and two (302) MM patients were included in the primary efficacy analyses for Study 2. The mean age was 58.2 years (range 28-75) and 58.5 years (range 28-75) in the Mozobil (plerixafor injection) and placebo groups, respectively, and 81% of subjects were Caucasian.

In Study 1, 59% of NHL patients who were mobilized with Mozobil (plerixafor injection) and G-CSF collected > 5 X 106 CD34+ cells/kg from the peripheral blood in four or fewer apheresis sessions, compared with 20% of patients who were mobilized with placebo and G-CSF (p < 0.001). Other CD34+ cell mobilization outcomes showed similar findings (Table 4).

Table 4: Study 1 Efficacy Results – CD34+ Cell Mobilization in NHL Patients

Efficacy Endpoint Mozobil (plerixafor injection) and
G-CSF
(n = 150)
Placebo
and G-CSF
(n = 148)
p-valuea
Patients achieving ≥ 5 X 106 cells/kg in ≤ 4 apheresis days 89 (59%) 29 (20%) < 0.001
Patients achieving ≥ 2 X 106 cells/kg in ≤ 4 apheresis days 130 (87%) 70 (47%) < 0.001
a p-value calculated using Pearson's Chi-Squared test

The median number of days to reach ≥ 5 x 106 CD34+ cells/kg was 3 days for the Mozobil (plerixafor injection) group and not evaluable for the placebo group. Table 5 presents the proportion of patients who achieved ≥ 5 x 106 CD34+ cells/kg by apheresis day.

Table 5: Study 1 Efficacy Results - Proportion of Patients Who Achieved ≥ 5 x 106 CD34+ cells/kg by Apheresis Day in NHL Patients

Days Proportiona in Mozobil (plerixafor injection) and
G-CSF(n=147b)
Proportiona in Placebo and G-CSF
(n=142b)
1 27.9% 4.2%
2 49.1% 14.2%
3 57.7% 21.6%
4 65.6% 24.2%
a Percents determined by Kaplan Meier method
b n includes all patients who received at least one day of apheresis

In Study 2, 72% of MM patients who were mobilized with Mozobil (plerixafor injection) and G-CSF collected ≥ 6 X 106 CD34+ cells/kg from the peripheral blood in two or fewer apheresis sessions, compared with 34% of patients who were mobilized with placebo and G-CSF (p < 0.001). Other CD34+ cell mobilization outcomes showed similar findings (Table 6).

Table 6: Study 2 Efficacy Results - CD34+ Cell Mobilization in Multiple Myeloma Patients

Efficacy Endpoint Mozobil (plerixafor injection) and G-CSF
(n = 148)
Placebo and G-CSF
(n =154)
p-valuea
Patients achieving ≥ 6 X 106 cells/kg in ≤ 2 apheresis days 106(72%) 53 (34%) < 0.001
Patients achieving ≥ 6 X 106 cells/kg in ≤ 4 apheresis days 112(76%) 79(51%) < 0.001
Patients achieving ≥ 2 X 106 cells/kg in ≤ 4 apheresis days 141 (95%) 136 (88%) 0.028
a p-value calculated using Pearson's Chi-Squared test

The median number of days to reach ≥ 6 x 106 CD34+ cells/kg was 1 day for the Mozobil (plerixafor injection) group and 4 days for the placebo group. Table 7 presents the proportion of patients who achieved ≥ 6 x 106 CD34+ cells/kg by apheresis day.

Table 7: Study 2 - Proportion of Patients Who Achieved > 6 x 106 CD34+ cells/kg by Apheresis Day in MM Patients

Days Proportiona in Mozobil (plerixafor injection) and G-CSF
(n=144b)
Proportiona in Placebo and G-CSF
(n=150b)
1 54.2% 17.3%
2 77.9% 35.3%
3 86.8% 48.9%
4 86.8% 55.9%
aPercents determined by Kaplan Meier method
b n includes all patients who received at least one day of apheresis

 

Multiple factors can influence time to engraftment and graft durability following stem cell transplantation. For transplanted patients in the Phase 3 studies, time to neutrophil and platelet engraftment and graft durability were similar across the treatment groups.

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Advise patients of the signs and symptoms of potential systemic reactions such as urticaria, periorbital swelling, dyspnea, or hypoxia during and following Mozobil injection, [see ADVERSE REACTIONS]

Patients should inform a health care professional immediately if symptoms of vasovagal reactions such as orthostatic hypotension or syncope occur during or shortly after their Mozobil injection. [see ADVERSE REACTIONS]

If patients experience itching, rash, or reaction at the site of injection, they should notify a health care professional as these symptoms have been treated with over-the-counter medications during clinical trials. [see ADVERSE REACTIONS]

Inform patients that Mozobil (plerixafor injection) may cause gastrointestinal disorders, including diarrhea, nausea, vomiting, flatulence, and abdominal pain. Patients should be told how to manage specific gastrointestinal disorders and to inform their health care professional if severe events occur following Mozobil injection. [see ADVERSE REACTIONS ]

Advise female patients with reproductive potential to use effective contraceptive methods during Mozobil use. [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Advise patients of the signs and symptoms of potential systemic reactions such as urticaria, periorbital swelling, dyspnea, or hypoxia during and following Mozobil injection, [see ADVERSE REACTIONS]

Patients should inform a health care professional immediately if symptoms of vasovagal reactions such as orthostatic hypotension or syncope occur during or shortly after their Mozobil injection. [see ADVERSE REACTIONS]

If patients experience itching, rash, or reaction at the site of injection, they should notify a health care professional as these symptoms have been treated with over-the-counter medications during clinical trials. [see ADVERSE REACTIONS]

Inform patients that Mozobil (plerixafor injection) may cause gastrointestinal disorders, including diarrhea, nausea, vomiting, flatulence, and abdominal pain. Patients should be told how to manage specific gastrointestinal disorders and to inform their health care professional if severe events occur following Mozobil injection. [see ADVERSE REACTIONS ]

Advise female patients with reproductive potential to use effective contraceptive methods during Mozobil use. [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

MOZOBIL
(plerixafor) Injection, Solution for Subcutaneous Use

DRUG DESCRIPTION

Mozobil (plerixafor injection) is a sterile, preservative-free, clear, colorless to pale yellow, isotonic solution for subcutaneous injection. Each mL of the sterile solution contains 20 mg of plerixafor. Each single-use vial is filled to deliver 1.2 mL of the sterile solution that contains 24 mg of plerixafor and 5.9 mg of sodium chloride in Water for Injection adjusted to a pH of 6.0 to 7.5 with hydrochloric acid and with sodium hydroxide, if required.

Plerixafor is a hematopoietic stem cell mobilizer with a chemical name 1, l'-[l,4-phenylenebis (methylene)]-bis-l,4,8,11- tetraazacyclotetradecane. It has the molecular formula C28H54N8. The molecular weight of plerixafor is 502.79 g/mol. The structural formula is provided in Figure 1.

Figure 1: Structural Formula

Mozobil (plerixafor) Structural Formula Illustration

Plerixafor is a white to off-white crystalline solid. It is hygroscopic. Plerixafor has a typical melting point of 131.5 °C. The partition coefficient of plerixafor between 1 -octanol and pH 7 aqueous buffer is < 0.1.

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

MOZOBIL
(plerixafor) Injection, Solution for Subcutaneous Use

DRUG DESCRIPTION

Mozobil (plerixafor injection) is a sterile, preservative-free, clear, colorless to pale yellow, isotonic solution for subcutaneous injection. Each mL of the sterile solution contains 20 mg of plerixafor. Each single-use vial is filled to deliver 1.2 mL of the sterile solution that contains 24 mg of plerixafor and 5.9 mg of sodium chloride in Water for Injection adjusted to a pH of 6.0 to 7.5 with hydrochloric acid and with sodium hydroxide, if required.

Plerixafor is a hematopoietic stem cell mobilizer with a chemical name 1, l'-[l,4-phenylenebis (methylene)]-bis-l,4,8,11- tetraazacyclotetradecane. It has the molecular formula C28H54N8. The molecular weight of plerixafor is 502.79 g/mol. The structural formula is provided in Figure 1.

Figure 1: Structural Formula

Mozobil (plerixafor) Structural Formula Illustration

Plerixafor is a white to off-white crystalline solid. It is hygroscopic. Plerixafor has a typical melting point of 131.5 °C. The partition coefficient of plerixafor between 1 -octanol and pH 7 aqueous buffer is < 0.1.

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

MOZOBIL
(plerixafor) Injection, Solution for Subcutaneous Use

DRUG DESCRIPTION

Mozobil (plerixafor injection) is a sterile, preservative-free, clear, colorless to pale yellow, isotonic solution for subcutaneous injection. Each mL of the sterile solution contains 20 mg of plerixafor. Each single-use vial is filled to deliver 1.2 mL of the sterile solution that contains 24 mg of plerixafor and 5.9 mg of sodium chloride in Water for Injection adjusted to a pH of 6.0 to 7.5 with hydrochloric acid and with sodium hydroxide, if required.

Plerixafor is a hematopoietic stem cell mobilizer with a chemical name 1, l'-[l,4-phenylenebis (methylene)]-bis-l,4,8,11- tetraazacyclotetradecane. It has the molecular formula C28H54N8. The molecular weight of plerixafor is 502.79 g/mol. The structural formula is provided in Figure 1.

Figure 1: Structural Formula

Mozobil (plerixafor) Structural Formula Illustration

Plerixafor is a white to off-white crystalline solid. It is hygroscopic. Plerixafor has a typical melting point of 131.5 °C. The partition coefficient of plerixafor between 1 -octanol and pH 7 aqueous buffer is < 0.1.

Last reviewed on RxList: 7/13/2010
This monograph has been modified to include the generic and brand name in many instances.

Mozobil Patient Information Including Side Effects

Brand Names: Mozobil

Generic Name: plerixafor (Pronunciation: pler IX a fore)

What is plerixafor (Mozobil)?

Plerixafor works by helping your bone marrow release stem cells into your bloodstream so they can be collected and transplanted back into the body.

Plerixafor is used in people with non-Hodgkin's lymphoma or multiple myeloma.

Plerixafor may also be used for purposes not listed in this medication guide.

What are the possible side effects of plerixafor (Mozobil)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have a serious side effect such as:

  • easy bruising or bleeding, unusual weakness;
  • feeling like you might pass out; or
  • pain in your upper stomach, spreading to your shoulder or back.

Less serious side effects may include:

  • nausea, vomiting;
  • diarrhea, constipation;
  • dry mouth, numbness in or around your mouth;
  • upset stomach, bloating, gas;
  • tired feeling, trouble sleeping;
  • headache, dizziness;
  • joint or muscle pain;
  • increased sweating; or
  • itching, rash, or other irritation where the medication was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Mozobil (plerixafor injection) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about plerixafor (Mozobil)?

You should not receive this medication if you are allergic to plerixafor, or if you have leukemia.

Before receiving plerixafor, tell your doctor if you have kidney disease.

Plerixafor is given as an injection in a hospital or clinic setting. Before receiving plerixafor, you will be given another medication that will help your bone marrow produce stem cells and certain white blood cells that help support your immune system.

To be sure this medication is not causing harmful effects, your blood will need to be tested often.

Side Effects Centers

Mozobil Patient Information including How Should I Take

What should I discuss with my health care provider before receiving plerixafor (Mozobil)?

You should not receive this medication if you are allergic to plerixafor, or if you have leukemia.

To make sure you can safely use plerixafor, tell your doctor if you have kidney disease.

FDA pregnancy category D. Do not receive plerixafor if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether plerixafor passes into breast milk or if it could harm a nursing baby. You should not breast-feed while receiving this medication.

How is plerixafor given (Mozobil)?

Plerixafor is injected under the skin. You will receive this injection in a hospital or clinic setting.

Before receiving plerixafor, you will be given a medication called a granulocyte (GRAN-yoo-loe-site) colony stimulating factor, also called G-CSF. Some examples of a G-CSF are filgrastim (Neupogen), pegfilgrastim (Neulasta), and sargramostim (Leukine).

A G-CSF will cause your bone marrow to produce stem cells and certain white blood cells called granulocytes, which help support your immune system.

Plerixafor works together with the G-CSF by causing stem cells and granulocytes produced in the bone marrow to circulate into your blood stream where they can be collected in blood drawn from your vein.

After your blood is drawn, it will be processed so that the needed stem cells and granulocytes can be separated from other unneeded parts of the blood. These stem cells and granulocytes will then be "transplanted" back into your vein through an IV injection.

To be sure plerixafor is not causing harmful effects, your blood will need to be tested often during your treatment.

Side Effects Centers

Mozobil Patient Information including If I Miss a Dose

What happens if I miss a dose (Mozobil)?

Because you will receive plerixafor in a clinical setting, you are not likely to miss a dose.

What happens if I overdose (Mozobil)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include stomach discomfort, severe dizziness, or fainting.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while receiving plerixafor (Mozobil)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

What other drugs will affect plerixafor (Mozobil)?

There may be other drugs that can interact with plerixafor. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about plerixafor.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 2.02. Revision date: 12/15/2010.

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