Mozobil · 4.6 Fertility, pregnancy and lactation · 1

HOS-095364 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile Safety data for Mozobil in conjunction with G-CSF in oncology patients with lymphoma and multiple myeloma were obtained from 2 placebo-controlled Phase III studies (301 patients) and 10 uncontrolled Phase II studies (242 patients). Patients were primarily treated with daily doses of 0.24 mg/kg plerixafor by subcutaneous injection. The exposure to plerixafor in these studies ranged from 1 to 7 consecutive days (median = 2 days). In the two Phase III studies in non-Hodgkin’s lymphoma and multiple myeloma patients (AMD3100-3101 and AMD3100-3102, respectively), a total of 301 patients were treated in the Mozobil and G-CSF group and 292 patients were treated in the placebo and G-CSF group. Patients received daily morning doses of G-CSF 0.01 mg/kg for 4 days prior to the first dose of plerixafor or placebo and on each morning prior to apheresis. Adverse reactions that occurred more frequently with Mozobil and G-CSF than placebo and G-&6)DQGZHUHUHSRUWHGDVUHODWHGLQ•RIWKHSDWLHQWVZKR received Mozobil, during haematopoietic stem cell mobilisation and apheresis and prior to chemotherapy/ablative treatment in preparation for transplantation are shown in Table 1. From chemotherapy/ablative treatment in preparation of transplantation through 12 months post-transplantation, no significant differences in the incidence of adverse reactions were observed across treatment groups. Tabulated list of adverse reactions Adverse reactions are listed by System Organ Class and frequency. Frequencies are defined according WRWKHIROORZLQJFRQYHQWLRQYHU\FRPPRQ •  FRPPRQ • 1/100 to < 1/10); uncommon • 1/1,000 to <  UDUH • 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Table 1. Adverse reactions occurring more frequently with Mozobil than placebo and considered related to Mozobil during mobilisation and apheresis in phase III studies Blood and lymphatic system disorders Not known Splenomegaly, splenic rupture (see section 4.4)** Immune system disorders Uncommon Allergic reaction* Anaphylactic reactions, including anaphylactic shock (see section 4.4) ** Psychiatric disorders Common Insomnia

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HOS-095360 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-095359 · has-indication-information · PDF-Seite 2

Adult patients Mozobil is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to enhance mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in adult patients with lymphoma or multiple myeloma whose cells mobilise poorly (see section 4.2). Paediatric patients (1 to less than 18 years) Mozobil is indicated in combination with G-CSF to enhance mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in children with lymphoma or solid malignant tumours, either: - pre-emptively, when circulating stem cell count on the predicted day of collection after adequate mobilization with G-CSF (with or without chemotherapy) is expected to be insufficient with regards to desired hematopoietic stem cells yield, or - who previously failed to collect sufficient haematopoietic stem cells (see section 4.2).

HOS-095362 · has-interaction-information · PDF-Seite 5

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.

HOS-095363 · has-pregnancy-information · PDF-Seite 5

Women of childbearing potential Women of childbearing potential have to use effective contraception during treatment. Pregnancy There are no adequate data on the use of plerixafor in pregnant women. Based on the pharmacodynamic mechanism of action, plerixafor is suggested to cause congenital malformations when administered during pregnancy. Studies in animals have shown teratogenicity (see section 5.3). 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. Fertility The effects of plerixafor on male and female fertility are not known (see section 5.3).

HOS-095361 · has-warning-information · PDF-Seite 4

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 x 109/L. 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 (see section 4.8). Symptoms responded to treatments (e.g., antihistamines, corticosteroids, hydration or supplemental oxygen) or resolved spontaneously. Cases of anaphylactic reactions, including anaphylactic shock, have been 4 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 (see section 4.8). Appropriate precautions should be taken because of the potential for these reactions.

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