Hematopoietic Stem Cell Mobilizer

Mozobil

Approved 15 Dec 2008SubcutaneousSolution

Indications

Mozobil is indicated in combination with filgrastim to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM). Mozobil, a hematopoietic stem cell mobilizer, is indicated in combination with filgrastim to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma or multiple myeloma.

( 1 )

Contraindications

Mozobil is contraindicated in patients with a history of hypersensitivity to plerixafor [see Warnings and Precautions (5.1) ] . Anaphylactic shock has occurred with use of Mozobil. History of hypersensitivity to Mozobil. ( 4 )

Warnings and precautions

Anaphylactic Shock and Serious Hypersensitivity Reactions have occurred. Monitor patients during and after completion of Mozobil administration. ( 5.1 ) Tumor Cell Mobilization in Leukemia Patients: Mozobil may mobilize leukemic cells and should not be used in leukemia patients. ( 5.2 ) Hematologic Effects: Increased circulating leukocytes and decreased platelet counts have been observed. Monitor blood cell counts and platelet counts during Mozobil use.

( 5.3 ) 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. ( 5.4 ) Splenic Rupture: Evaluate patients who report left upper abdominal and/or scapular or shoulder pain. ( 5.5 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise women not to become pregnant when taking Mozobil. ( 5.6 , 8.1 )

5.1Anaphylactic Shock and Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening with clinically significant hypotension and shock have occurred in patients receiving Mozobil [see Adverse Reactions (6.2) ] . 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. In clinical studies, mild or moderate allergic reactions occurred within approximately 30 minutes after Mozobil administration in less than 1% of patients [see Adverse Reactions (6.1) ] .

At a glance

Brand name: Mozobil
Active substance: plerixafor
Pharmacologic class: Hematopoietic Stem Cell Mobilizer
Route: Subcutaneous
Dosage form: Solution
Applicant: Genzyme
Status: Prescription
FDA approval: 15 Dec 2008
Application: NDA022311-001

Indications

( 1 )

Warnings and precautions

5.1Anaphylactic Shock and Hypersensitivity Reactions

Adverse reactions

The following clinically significant 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) ] 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.

6.1Clinical 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). 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 filgrastim group and 292 patients were treated in the placebo and filgrastim group.

Patients received daily morning doses of filgrastim 10 mcg/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 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.

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.

6.2Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been reported from postmarketing 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. Blood and Lymphatic System: Splenomegaly and splenic rupture Immune System Disorders: Anaphylactic reactions, including anaphylactic shock Psychiatric Disorders: Abnormal dreams and nightmares

Mozobil

Indications

Contraindications

Warnings and precautions

5.1Anaphylactic Shock and Hypersensitivity Reactions

At a glance

Two medicines in one question?

Mozobil

Indications

Contraindications

Warnings and precautions

5.1Anaphylactic Shock and Hypersensitivity Reactions

At a glance

Two medicines in one question?

5.3Hematologic Effects Leukocytosis Administration of Mozobil

5.4Potential for Tumor Cell Mobilization When

5.5Splenic Enlargement and Rupture

5.6Embryo-Fetal Toxicity Based

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information