care professionals to reinforce the warnings about the potential teratogenicity of lenalidomide, to provide advice on contraception before therapy is started, and to provide guidance on the need for pregnancy testing.
Full patient information about the potential teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy Prevention Programme should be given by the physician to women of childbearing potential and, as appropriate, to male patients.
Other special warnings and precautions for use Venous thromboembolism The combination of lenalidomide with dexamethasone is associated with an increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with multiple myeloma (See Interactions and Adverse Reactions).
Concomitant administration of erythropoietic agents or previous history of DVT may also increase thrombotic risk in these patients.
Therefore, erythropoietic agents, or other agents that may increase the risk of thrombosis, such as hormone replacement therapy, should be used with caution in multiple myeloma patients receiving lenalidomide with dexamethasone.
A haemoglobin concentration above 13 g/dl should lead to discontinuation of erythropoietic agents. Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, arm or leg swelling.
Prophylactic antithrombotic medicines, such as low molecular weight heparins or warfarin, should be recommended, especially in patients with additional thrombotic risk factors.
The decision to take antithrombotic prophylactic measures should be made after careful assessment of an individual patient’s underlying risk factors. Neutropenia and thrombocytopenia The combination of lenalidomide with dexamethasone in multiple myeloma patients is associated with a higher incidence of grade 4 neutropenia (5.1% in lenalidomide/dexamethasone-treated patients compared with 0.6% in placebo/dexamethasone-treated patients; see Adverse Reactions). Grade 4 febrile neutropenia episodes were observed infrequently (0.6% in lenalidomide/dexamethasone-treated patients compared to 0.0% in placebo/dexamethasone treated patients; see adverse Reactions). Patients should be advised to promptly report febrile episodes.
A dose reduction may be required (See Adult Dosage). In case of neutropenia, the physician should consider the use of growth factors in patient management.
The combination of lenalidomide with dexamethasone in multiple myeloma patients is associated with a higher incidence of grade 3 and grade 4 thrombocytopenia (9.9% and 1.4%, respectively, in lenalidomide/dexamethasone-treated patients compared to 2.3% and 0.0% in placebo/dexamethasone-treated patients; see section 4.8). Patients and physicians are advised to be observant for signs and symptoms of bleeding, including petechiae and epistaxes. A dose reduction may be required (See Adult Dosage).
A complete blood cell count, including white blood cell count with differential count, platelet count, haemoglobin, and haematocrit should be performed at baseline, every week for the first 8 weeks of lenalidomide treatment and monthly thereafter to monitor for cytopenias.
The major dose limiting toxicities of lenalidomide include neutropenia and thrombocytopenia.
Therefore, co-administr |
