Consequently, patients with known risk factors for thromboembolism – including prior thrombosis – should be closely monitored. Action should be taken to try to minimize all modifiable risk factors (e.g. smoking, hypertension, and hyperlipidaemia). Concomitant administration of erythropoietic agents or previous history of thromboembolic events 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 12 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 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.

If the patient experiences any thromboembolic events, treatment must be discontinued and standard anticoagulation therapy started. Once the patient has been stabilised on the anticoagulation treatment and any complications of the thromboembolic event have been managed, the lenalidomide treatment may be restarted at the original dose dependent upon a benefit risk assessment. The patient should continue anticoagulation therapy during the course of lenalidomide treatment.

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 section 4.8). 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 section 4.8). Patients should be advised to promptly report febrile episodes. A dose reduction may be required (see section 4.2). 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/dexamethasonetreated patients; see section 4.8). Patients and physicians are advised to be observant for signs and symptoms of bleeding, including petechiae and epistaxes, especially in case of concomitant medication susceptible to induce bleeding (see Section 4.8 Haemorrhagic disorders). A dose reduction of lenalidomide may be required (see section 4.2).

A complete blood cell count, including white blood cell count with differential count, platelet count, haemoglobin, and haematocrit shou