Mozobil 20mg / 1ml Injection

Mozobil u00ae is indicated to enhance mobilisation of hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with lymphoma and multiple myeloma (MM) (see DOSAGE AND DIRECTIONS FOR USE).

The recommended dose of Mozobil u00ae is 0,24 mg/kg body weight by subcutaneous injection. Mozobil u00ae should be administered 6 to 11 hours prior to initiation of apheresis following 4 days of treatment with G-CSF. Mozobil u00ae should be administered by a nurse, physician, or other healthcare professional. Mozobil u00ae has been commonly used for 2 to 4 consecutive days. It has been used for up to 7 consecutive days in a clinical setting. The patientu2019s actual body weight will be used to calculate the volume of Mozobil u00ae to be administered. Each vial delivers 1,2 ml of 20 mg/ml solution, and the volume to be administered to patients will be calculated from the following equation: 0,012 x patientu2019s actual body weight (in kg) = dose to be administered (in ml). In clinical studies, Mozobil u00ae dose has been calculated based on actual body weight in patients up to 175 % of ideal body weight. Mozobil u00ae dose and treatment of patients weighing more than 175 % of ideal body weight have not been investigated. The weight used to calculate the volume of Mozobil u00ae should be obtained within 1 week of the first dose of Mozobil u00ae. Recommended concomitant medications: In pivotal clinical studies supporting the use of Mozobil u00ae, all patients received daily morning doses of granulocyte-colony stimulating factor (G-CSF) 10 u03bcg/kg for 4 days prior to the first dose of Mozobil u00ae and on each morning prior to apheresis. Patient with renal impairment: Patients with moderate and severe renal insufficiency (creatinine clearance (CrCl) u2264 50 ml/min) should have their dose of Mozobil u00ae reduced by one-third to 0,16 mg/kg. Similar systemic exposure is expected if the dose is reduced by one-third in patients with moderate and severe renal impairment compared with subjects with normal renal function. Clinical data with this dose adjustment in patients with renal impairment are limited.

Hypersensitivity to any of the ingredients of this formulation. Pregnancy and lactation (see PREGNANCY AND LACTATION).

Tumour cell mobilisation in leukemia patients: In a compassionate use program, Mozobil u00ae and G-CSF have been administered to patients with acute myelogenous leukemia and plasma cell leukemia. In some instances, these patients experienced an increase in the number of circulating leukemia cells. For the purpose of HSC mobilisation, Mozobil u00ae may cause mobilisation of leukemic cells and subsequent contamination of the apheresis product. Therefore, Mozobil u00ae is not intended for HSC mobilisation and harvest in patients with leukemia.

Hematologic effects: Leukocytosis: Administration of Mozobil u00ae in conjunction with G-CSF increases circulating leukocytes as well as HSC populations. White blood cell counts should be monitored during Mozobil u00ae use. Clinical judgment should be exercised when administering Mozobil u00ae to patients with peripheral blood neutrophil counts above 50 000 cells/u03bcl. Thrombocytopenia: Thrombocytopenia is a known complication of apheresis and has been observed in patients receiving Mozobil u00ae. Platelet counts should be monitored in all patients who receive Mozobil u00ae and then undergo apheresis.

Potential for tumour cell mobilisation in lymphoma and multiple myeloma patients: When Mozobil u00ae is used in conjunction with G-CSF for HSC mobilisation in patients with lymphoma or MM, tumour cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumour cells has not been well-studied. In clinical studies of patients with non-Hodgkinu2019s lymphoma (NHL) and MM, mobilisation of tumour cells has not been observed with Mozobil u00ae.

Systemic reactions: In Mozobil u00ae oncology clinical studies, less than 1 % of patients experienced mild or moderate systemic reactions within approximately 30 minutes after Mozobil u00ae administration. Events included one or more of the following: urticaria (n = 2), periorbital swelling (n = 2), dyspnoea (n = 1) or hypoxia (n = 1). Symptoms generally responded to treatments (e.g. antihistamines, corticosteroids, hydration or supplemental oxygen) or resolved spontaneously. Appropriate precautions should be taken because of the potential for these reactions.

Vasovagal reactions: Vasovagal reactions, orthostatic hypotension, and/or syncope can occur following SC injections. In Mozobil u00ae oncology and healthy volunteer clinical studies, less than 1 % of subjects experienced vasovagal reactions (orthostatic hypotension and/or syncope) following SC administration of Mozobil u00ae doses u2264 0,24 mg/kg. The majority of these events occurred within 1 hour of Mozobil u00ae administration. Appropriate precautions should be taken because of the potential for these reactions.

Potential effect on spleen size: Higher absolute and relative spleen weights associated with extramedullary haematopoiesis 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. The effect of Mozobil u00ae on spleen size in patients has not been specifically evaluated in clinical studies. The possibility that Mozobil u00ae in conjunction with the growth factor G-CSF can cause splenic enlargement cannot be excluded. Due to the rare occurrence of splenic rupture following G-CSF administration, individuals receiving Mozobil u00ae in conjunction with G-CSF who report left upper abdominal pain and/or scapular or shoulder pain should be evaluated for splenic integrity.

Based on in vitro studies, plerixafor is not a substrate, inhibitor, or inducer of human cytochrome P450 enzymes. Formal drug interaction studies have not been conducted (see Pharmacokinetics). In clinical studies of patients with NHL, the addition of rituximab to a mobilisation regimen of Mozobil u00ae and G-CSF did not impact patient safety or CD34+ cell yield.

Safety and efficacy in pregnancy and lactation has not been established. Pregnancy: Mozobil u00ae may cause foetal harm when administered to a pregnant woman. Studies in animals have shown teratogenicity. There are no adequate and well-controlled studies in pregnant women using Mozobil u00ae. If Mozobil u00ae is used during pregnancy, or if the patient becomes pregnant while taking Mozobil u00ae, the patient should be informed of the potential hazard to the foetus. Advise women of childbearing potential to use effective contraception during treatment. Lactation: It is not known whether Mozobil u00ae is excreted in human milk. You should not breastfeed your baby whilst on treatment with Mozobil u00ae.

No studies on the ability to drive and use machines have been conducted with Mozobil u00ae.

In the two Phase 3 studies in patients with NHL and MM (AMD3100-3101 and AMD3100-3102, respectively), a total of 301 patients were treated in the Mozobil u00ae 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 u03bcg/kg for 4 days prior to the first dose of Mozobil u00ae or placebo and on each morning prior to apheresis. Adverse events that occurred more frequently with Mozobil u00ae than placebo and were reported as related in u2265 1 % of the patients who received Mozobil u00ae during HSC mobilisation and apheresis and prior to chemotherapy/ablative treatment in preparation for transplantation are shown in Table 2. From chemotherapy/ablative treatment in preparation of transplantation through 12 months post-transplantation, no notable differences in the incidence of adverse events were observed across treatment groups.

Table 2: Adverse events occurring more frequently with Mozobil u00ae than placebo and considered related to Mozobil u00ae during HSC mobilisation and apheresis (Very common = u2265 1/10; Common = u2265 1/100 to < 1/10)

MedDRA System Organ Class MedDRA preferred term Frequency Cardiac disorders Extrasystoles Uncommon Ear and labyrinth disorders Vertigo Uncommon Eye disorders Eye swelling Uncommon Gastrointestinal disorders Diarrhoea, nausea Very common Flatulence, abdominal pain, vomiting, abdominal distension, dry mouth, stomach discomfort, constipation, dyspepsia, hypoaesthesia oral Common Abdominal discomfort, eructation, retching, stomatitis Uncommon General disorders and administrative site conditions Injection site reactions Very common Fatigue, malaise Common Asthenia, influenza like illness, irritability Uncommon Injury, poisoning and procedural complications Procedural hypertension, procedural nausea Uncommon Investigations Aspartate aminotransferase increased Uncommon Metabolism and nutrition disorders Decreased appetite, hypocalcaemia, hyponatraemia, hypophosphataemia Uncommon Musculoskeletal, connective tissue and bone disorders Arthralgia, musculoskeletal pain Common Muscular weakness, musculoskeletal stiffness, neck pain Uncommon Nervous system disorders Headache, dizziness Common Dysgeusia Uncommon Psychiatric disorders Insomnia Common Anticipatory anxiety, anxiety, nightmare Uncommon Renal and urinary disorders Pollakiuria Uncommon Respiratory, thoracic and mediastinal disorders Sinus congestion Uncommon Skin and subcutaneous tissue disorders Hyperhidrosis, erythema Common Cold sweat, ecchymosis, hypoaesthesia facial, night sweats, urticaria, urticaria localised Uncommon Vascular disorders Flushing, hot flush, hypotension Uncommon

The adverse reactions reported in oncology patients who received Mozobil u00ae in the controlled Phase 3 studies and uncontrolled studies, including a Phase 2 study of Mozobil u00ae as monotherapy for HSC mobilization, are similar. No notable differences in the incidence of adverse reactions were observed for oncology patients by disease, age, or sex.

Myocardial infarction: In clinical studies, seven of 679 oncology patients experienced myocardial infarctions after HSC mobilisation with Mozobil u00ae and G-CSF. All events occurred at least 14 days after last Mozobil u00ae administration. Additionally, two female oncology patients in the compassionate use program experienced myocardial infarctions following HSC mobilisation with Mozobil u00ae and G-CSF. One of these events occurred 4 days after last Mozobil u00ae administration. Lack of temporal relationship in 8 of 9 patients coupled with risk profile of patients with myocardial infarction does not suggest Mozobil u00ae confers an independent risk for myocardial infarction in patients who also receive G-CSF.

Gastrointestinal disorders: In Mozobil u00ae clinical studies of oncology patients, there have been rare reports of severe gastrointestinal events, including diarrhoea, nausea, vomiting, and abdominal pain. Paraesthesias: Paraesthesias are commonly observed in oncology patients undergoing autologous transplantation following multiple disease interventions. In the placebo-controlled Phase 3 studies, the incidence of paraesthesias was 20,6 % and 21,2 % in the Mozobil u00ae and placebo groups, respectively.

Symptoms: Based on limited data at doses above the recommended dose of 0,24 mg/kg SC and up to 0,48 mg/kg SC, the frequency of gastrointestinal disorders, vasovagal reactions, orthostatic hypotension, and/or syncope may be higher. Treatment: Treatment is symptomatic and supportive.