Mozobil

/ Sanofi

The recommended dose of plerixafor is 0.24 mg/kg body weight/day. It should be administered by subcutaneous injection 6 to 11 hours prior to initiation of each apheresis following 4 day pre-treatment with granulocyte-colony stimulating factor (G-CSF). In clinical trials, Mozobil has been commonly used for 2 to 4 (and up to 7) consecutive days.
The weight used to calculate the dose of plerixafor should be obtained within 1 week before the first dose of plerixafor. In clinical studies, the dose of plerixafor has been calculated based on body weight in patients up to 175% of ideal body weight. Plerixafor dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated. Ideal body weight can be determined using the following equations:
male (kg): 50 + 2.3 x ((Height (cm) x 0.394) – 60);
female (kg): 45.5 + 2.3 x ((Height (cm) x 0.394) – 60).
Based on increasing exposure with increasing body weight, the plerixafor dose should not exceed 40 mg/day.
Recommended concomitant medicinal products: In pivotal clinical studies supporting the use of Mozobil, all patients received daily morning doses of 10 µg/kg G-CSF for 4 consecutive days prior to the first dose of plerixafor and on each morning prior to apheresis.
Renal impairment: Patients with creatinine clearance 20-50 ml/min should have their dose of plerixafor reduced by onethird to 0.16 mg/kg/day. Clinical data with this dose adjustment are limited. There is insufficient clinical experience to make alternative posology recommendations for patients with a creatinine clearance <20 ml/min, as well as to make posology recommendations for patients on haemodialysis.
Based on increasing exposure with increasing body weight the dose should not exceed 27 mg/day if the creatinine clearance is lower than 50 ml/min.
Paediatric population: The experience in paediatric patients is limited. The safety and efficacy of Mozobil in paediatric patients have not been established in controlled clinical studies.
Elderly patients (> 65 years old): No dose modifications are necessary in elderly patients with normal renal function. Dose adjustment in elderly patients with creatinine clearance ≤ 50 ml/min is recommended (see Renal impairment above). In general, care should be taken in dose selection for elderly patients due to the greater frequency of decreased renal function with advanced age. Method of administration: For subcutaneous injection. Each vial of Mozobil is intended for single use only. Vials should be inspected visually prior to administration and not used if there is particulate matter or discolouration. Since Mozobil is supplied as a sterile, preservative-free formulation, aseptic technique should be followed when transferring the contents of the vial to a suitable syringe for subcutaneous administration.

In combination with G-CSF, to enhance mobilisation of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with lymphoma and multiple myeloma.

Hypersensitivity to the active substance or to any of the excipients.

Tumour cell mobilisation in patients with lymphoma and multiple myeloma:
When Mozobil is used in conjunction with G-CSF for haematopoietic stem cell mobilisation in patients with lymphoma or multiple myeloma‚ tumour cells may be released from the marrow and subsequently collected in the leukapheresis product. Results showed that, in case tumour cells are mobilised, the number of tumour cells mobilised is not increased upon Mozobil plus G-CSF compared to G-CSF alone.
Tumour cell mobilisation in leukaemia patients: In a compassionate use programme, Mozobil and G-CSF have been administered to patients with acute myelogenous leukaemia and plasma cell leukaemia. In some instances, these patients experienced an increase in the number of circulating leukaemia cells. For the purpose of haematopoietic stem cell mobilisation, plerixafor may cause mobilisation of leukaemic cells and subsequent contamination of the apheresis product. Therefore, plerixafor is not recommended for haematopoietic stem cell mobilisation and harvest in patients with leukaemia.
Haematological effects:
Hyperleukocytosis: Administration of Mozobil in conjunction with G-CSF increases circulating leukocytes as well as haematopoietic stem cell populations. White blood cell counts should be monitored during Mozobil
therapy. Clinical judgment should be exercised when administering Mozobil to patients with peripheral blood neutrophil counts above 50 x10^9L.
Thrombocytopenia: Thrombocytopenia is a known complication of apheresis and has been observed in patients receiving Mozobil. Platelet counts should be monitored in all patients receiving Mozobil and undergoing apheresis.
Allergic reactions: Mozobil has been uncommonly associated with potential systemic reactions related to subcutaneous injection such as: urticaria, periorbital swelling, dyspnoea, or hypoxia. Symptoms responded to treatments (e.g., antihistamines, corticosteroids, hydration or supplemental oxygen) or resolved spontaneously. Cases of anaphylactic reactions, including anaphylactic shock, have been reported from world-wide post-marketing experience. Appropriate precautions should be taken because of the potential for these reactions.
Vasovagal reactions: Vasovagal reactions, orthostatic hypotension, and/or syncope can occur following subcutaneous injections. Appropriate precautions should be taken because of the potential for these reactions.
Effects on the spleen: In preclinical studies, higher absolute and relative spleen weights associated with extramedullary haematopoiesis were observed following prolonged (2 to 4 weeks) daily plerixafor subcutaneous administration in rats at doses approximately 4 fold higher than the recommended human dose.
The effect of plerixafor on spleen size in patients has not been specifically evaluated in clinical studies. Cases of splenic enlargement and/or rupture following the G-CSF administration of Mozobil in conjunction with growth factor G-CSF. Individuals receiving Mozobil in conjunction with G-CSF who report left upper abdominal pain and/or scapular or shoulder pain should be evaluated for splenic integrity.
Sodium: Mozobil contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.

Very common: Diarrhea, nausea, injection and infusion site reactions.
Common: Insomnia, dizziness, headache, vomiting, abdominal pain, stomach discomfort, dyspepsia, abdominal distention, constipation, flatulence, oral hypoesthesia, dry mouth, hyperhidrosis, erythema, arthralgia, musculoskeletal pain, fatigue, malaise.
See prescribing information for full details.

No interaction studies have been performed. In vitro tests showed that plerixafor was not metabolised by P450 CYP enzymes, did not inhibit or induce P450 CYP enzymes. Plerixafor did not act as a substrate or inhibitor of P-glycoprotein in an in vitro study.
In clinical studies of patients with Non-Hodgkin’s lymphoma, the addition of rituximab to a mobilisation regimen of plerixafor and G-CSF did not impact patient safety or CD34+ cell yield.

Pregnancy: Mozobil should not be used during pregnancy unless the clinical condition of the woman requires treatment with plerixafor.
Breast-feeding: It is unknown whether plerixafor is excreted in human milk. A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with Mozobil.
See prescribing information for full details.

No case of overdose has been reported. Based on limited data at doses above the recommended dose and up to 0.48 mg/kg the frequency of gastrointestinal disorders, vasovagal reactions, orthostatic hypotension, and/or syncope may be higher.