Revlimid

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



 2 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 2.5 mg hard capsules 

Revlimid 5 mg hard capsules 

Revlimid 7.5 mg hard capsules 

Revlimid 10 mg hard capsules 

Revlimid 15 mg hard capsules 

Revlimid 20 mg hard capsules 

Revlimid 25 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Revlimid 2.5 mg hard capsules 

Each capsule contains 2.5 mg of lenalidomide. 

Excipient(s) with known effect 

Each capsule contains 73.5 mg of lactose (as anhydrous lactose). 

 

Revlimid 5 mg hard capsules 

Each capsule contains 5 mg of lenalidomide. 

Excipient(s) with known effect 

Each capsule contains 147 mg of lactose (as anhydrous lactose). 

 

Revlimid 7.5 mg hard capsules 

Each capsule contains 7.5 mg of lenalidomide. 

Excipient(s) with known effect 

Each capsule contains 144.5 mg of lactose (as anhydrous lactose). 

 

Revlimid 10 mg hard capsules 

Each capsule contains 10 mg of lenalidomide. 

Excipient(s) with known effect 

Each capsule contains 294 mg of lactose (as anhydrous lactose). 

 

Revlimid 15 mg hard capsules 

Each capsule contains 15 mg of lenalidomide. 

Excipient(s) with known effect 

Each capsule contains 289 mg of lactose (as anhydrous lactose). 

 

Revlimid 20 mg hard capsules 

Each capsule contains 20 mg of lenalidomide. 

Excipient(s) with known effect 

Each capsule contains 244.5 mg of lactose (as anhydrous lactose). 

 

Revlimid 25 mg hard capsules 

Each capsule contains 25 mg of lenalidomide. 

Excipient(s) with known effect 

Each capsule contains 200 mg of lactose (as anhydrous lactose). 

 

For the full list of excipients, see section 6.1. 

 

 



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3. PHARMACEUTICAL FORM 

 

Hard capsule. 

 

Revlimid 2.5 mg hard capsules 

Blue-green/white capsules, size 4, 14.3 mm, marked “REV 2.5 mg”. 

 

Revlimid 5 mg hard capsules 

White capsules, size 2, 18.0 mm, marked “REV 5 mg”. 

 

Revlimid 7.5 mg hard capsules 

Pale yellow/white capsules, size 2, 18.0 mm, marked “REV 7.5 mg”. 

 

Revlimid 10 mg hard capsules 

Blue-green/pale yellow capsules, size 0, 21.7 mm, marked “REV 10 mg”. 

 

Revlimid 15 mg hard capsules 

Pale blue/white capsules, size 0, 21.7 mm, marked “REV 15 mg”. 

 

Revlimid 20 mg hard capsules 

Blue-green/pale blue capsules, size 0, 21.7 mm, marked “REV 20 mg”. 

 

Revlimid 25 mg hard capsules 

White capsules, size 0, 21.7 mm, marked “REV 25 mg”. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Multiple myeloma 

Revlimid as monotherapy is indicated for the maintenance treatment of adult patients with newly diagnosed 

multiple myeloma who have undergone autologous stem cell transplantation. 

 

Revlimid as combination therapy with dexamethasone, or bortezomib and dexamethasone, or melphalan and 

prednisone (see section 4.2) is indicated for the treatment of adult patients with previously untreated multiple 

myeloma who are not eligible for transplant. 

 

Revlimid in combination with dexamethasone is indicated for the treatment of multiple myeloma in adult 

patients who have received at least one prior therapy. 

 

Myelodysplastic syndromes 

Revlimid as monotherapy is indicated for the treatment of adult patients with transfusion-dependent anaemia 

due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q 

cytogenetic abnormality when other therapeutic options are insufficient or inadequate. 

 

Mantle cell lymphoma 

Revlimid as monotherapy is indicated for the treatment of adult patients with relapsed or refractory mantle 

cell lymphoma (see sections 4.4 and 5.1). 

 

Follicular lymphoma 

Revlimid in combination with rituximab (anti-CD20 antibody) is indicated for the treatment of adult patients 

with previously treated follicular lymphoma (Grade 1 – 3a). 

 

4.2 Posology and method of administration 

 

Revlimid treatment should be supervised by a physician experienced in the use of anti-cancer therapies. 

 



 4 

For all indications described below: 

• Dose is modified based upon clinical and laboratory findings (see section 4.4). 

• Dose adjustments, during treatment and restart of treatment, are recommended to manage Grade 3 or 
4 thrombocytopenia, neutropenia, or other Grade 3 or 4 toxicity judged to be related to lenalidomide. 

• In case of neutropenia, the use of growth factors in patient management should be considered. 

• If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 
12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, 

but take the next dose at the normal time on the following day.  
 

Posology 

Newly diagnosed multiple myeloma (NDMM) 

• Lenalidomide in combination with dexamethasone until disease progression in patients who are not 
eligible for transplant 

Lenalidomide treatment must not be started if the Absolute Neutrophil Count (ANC) is < 1.0 x 109/L, and/or 

platelet counts are < 50 x 109/L. 

 

Recommended dose 

The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 

28-day cycles. 

The recommended dose of dexamethasone is 40 mg orally once daily on days 1, 8, 15 and 22 of repeated 

28-day cycles. Patients may continue lenalidomide and dexamethasone therapy until disease progression or 

intolerance.  

 

• Dose reduction steps 

 Lenalidomidea Dexamethasonea 

Starting dose 25 mg 40 mg 

Dose level -1 20 mg 20 mg 

Dose level -2 15 mg 12 mg 

Dose level -3 10 mg 8 mg 

Dose level- 4 5 mg 4 mg 

Dose level -5 2.5 mg Not applicable 
ª Dose reduction for both products can be managed independently 

 

• Thrombocytopenia 

When platelets Recommended course 

Falls to < 25 x 109/L Stop lenalidomide dosing for remainder of cycleª 

Returns to ≥ 50 x 109/L Decrease by one dose level when dosing resumed 

at next cycle 

ª If Dose limiting toxicity (DLT) occurs on > day15 of a cycle, lenalidomide dosing will be interrupted for at least the remainder of the current 28-
day cycle. 
 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC Recommended courseª 

First falls to < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 1 x 109/L when neutropenia is the only 

observed toxicity 

Resume lenalidomide at starting dose once daily 

Returns to ≥ 0.5 x 109/L when dose-dependent 

haematological toxicities other than neutropenia are 

observed 

Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level 

once daily.  
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain 

the dose level of lenalidomide. 

 

For hematologic toxicity the dose of lenalidomide may be re-introduced to the next higher dose level (up to 

the starting dose) upon improvement in bone marrow function (no hematologic toxicity for at least 2 

consecutive cycles: ANC ≥1,5 x 109/L with a platelet count ≥ 100 x 109/L at the beginning of a new cycle). 



 5 

 

• Lenalidomide in combination with bortezomib and dexamethasone followed by lenalidomide and 
dexamethasone until disease progression in patients who are not eligible for transplant 

Initial treatment: Lenalidomide in combination with bortezomib and dexamethasone 

Lenalidomide in combination with bortezomib and dexamethasone must not be started if the ANC is 

< 1.0 x 109/L, and/or platelet counts are < 50 x 109/L.  

 

The recommended starting dose is lenalidomide 25 mg orally once daily days 1-14 of each 21-day cycle in 

combination with bortezomib and dexamethasone. Bortezomib should be administered via subcutaneous 

injection (1.3 mg/m2 body surface area) twice weekly on days 1, 4, 8 and 11 of each 21-day. For additional 

information on the dose, schedule and dose adjustments of medicinal products administered with 

lenalidomide, see Section 5.1 and the corresponding Summary of Product Characteristics.  

 

Up to eight 21-day treatment cycles (24 weeks of initial treatment) are recommended.  

 

Continued treatment: Lenalidomide in combination with dexamethasone until progression 

Continue lenalidomide 25 mg orally once daily on days 1-21 of repeated 28-day cycles in combination with 

dexamethasone. Treatment should be continued until disease progression or unacceptable toxicity.  

 

• Dose reduction steps 

 Lenalidomidea 

Starting dose 25 mg 

Dose level -1 20 mg 

Dose level -2 15 mg 

Dose level -3 10 mg 

Dose level- 4 5 mg 

Dose level -5 2.5 mg 
ª Dose reduction for all products can be managed independently 

 

• Thrombocytopenia 

When platelets Recommended course 

Falls to < 30 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 50 x 109/L Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below 30 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 50 x 109/L Resume lenalidomide at next lower dose level 

once daily 

 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC Recommended coursea 

First falls to < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 1 x 109/L when neutropenia is the only 

observed toxicity 

Resume lenalidomide at starting dose once daily 

Returns to ≥ 0.5 x 109/L when dose-dependent 

haematological toxicities other than neutropenia are 

observed 

Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level 

once daily.  
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain 

the dose level of lenalidomide. 

 

• Lenalidomide in combination with melphalan and prednisone followed by lenalidomide 
maintenance in patients who are not eligible for transplant 

Lenalidomide treatment must not be started if the ANC is < 1.5 x 109/L, and/or platelet counts are 

< 75 x 109/L. 

 



 6 

Recommended dose 

The recommended starting dose is lenalidomide 10 mg orally once daily on days 1 to 21 of repeated 

28-day cycles for up to 9 cycles, melphalan 0.18 mg/kg orally on days 1 to 4 of repeated 28-day cycles, 

prednisone 2 mg/kg orally on days 1 to 4 of repeated 28-day cycles. Patients who complete 9 cycles or 

who are unable to complete the combination therapy due to intolerance are treated with lenalidomide 

monotherapy as follows: 10 mg orally once daily on days 1 to 21 of repeated 28-day cycles given until 

disease progression.  

 

• Dose reduction steps 

 Lenalidomide Melphalan Prednisone 

Starting dose 10 mgª 0.18 mg/kg 2 mg/kg 

Dose level -1 7.5 mg 0.14 mg/kg 1 mg/kg 

Dose level -2 5 mg 0.10 mg/kg 0.5 mg/kg 

Dose level -3 2.5 mg Not applicable 0.25 mg/kg 
ª If neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain the dose level of lenalidomide 

 

• Thrombocytopenia 

When platelets Recommended course 

First falls to < 25 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 25 x 109/L Resume lenalidomide and melphalan at dose 

level -1  

For each subsequent drop below 30 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 30 x 109/L Resume lenalidomide at next lower dose level 

(dose level -2 or -3) once daily.  

 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC Recommended courseª 

First falls to < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L when neutropenia is the only 

observed toxicity 

Resume lenalidomide at starting dose once daily 

Returns to ≥ 0.5 x 109/L when dose-dependent 

haematological toxicities other than neutropenia are 

observed 

Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level 

once daily.  
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain 

the dose level of lenalidomide. 

 

• Lenalidomide maintenance in patients who have undergone autologous stem cell transplantation 
(ASCT) 

Lenalidomide maintenance should be initiated after adequate haematologic recovery following ASCT in 

patients without evidence of progression. Lenalidomide must not be started if the ANC is < 1.0 x 109/L, 

and/or platelet counts are < 75 x 109/L. 

 

Recommended dose 

The recommended starting dose is lenalidomide 10 mg orally once daily continuously (on days 1 to 28 of 

repeated 28-day cycles) given until disease progression or intolerance. After 3 cycles of lenalidomide 

maintenance, the dose can be increased to 15 mg orally once daily if tolerated.  

 

• Dose reduction steps 

 Starting dose (10 mg) If dose increased (15 mg)a 

Dose level -1 5 mg 10 mg 

Dose level -2 5 mg (days 1-21 every 28 days) 5 mg 

Dose level -3 Not applicable 5 mg (days 1-21 every 28 days) 

 Do not dose below 5 mg (days 1-21 every 28 days) 
a After 3 cycles of lenalidomide maintenance, the dose can be increased to 15 mg orally once daily if tolerated. 

 



 7 

• Thrombocytopenia 

When platelets Recommended course 

Falls to < 30 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 30 x 109/L Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below 30 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 30 x 109/L Resume lenalidomide at next lower dose level 

once daily 

 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC Recommended coursea 

Falls to < 0.5 x 109/L Interrupt lenalidomide treatment  

Returns to ≥ 0.5 x 109/L Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level 

once daily 
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain 

the dose level of lenalidomide. 
 

Multiple myeloma with at least one prior therapy 

Lenalidomide treatment must not be started if the ANC < 1.0 x 109/L, and/or platelet counts < 75 x 109/L or, 

dependent on bone marrow infiltration by plasma cells, platelet counts < 30 x 109/L. 

 

Recommended dose 

The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 

28-day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1 to 4, 9 to 12, 

and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg once daily on days 1 to 4 

every 28 days. 

Prescribing physicians should carefully evaluate which dose of dexamethasone to use, taking into account 

the condition and disease status of the patient. 

 

• Dose reduction steps 

Starting dose 25 mg 

Dose level -1 15 mg 

Dose level -2 10 mg 

Dose level -3 5 mg 

 

• Thrombocytopenia 

When platelets Recommended course 

First falls to < 30 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 30 x 109/L Resume lenalidomide at dose level -1  

For each subsequent drop below 30 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 30 x 109/L Resume lenalidomide at next lower dose level 

(dose level -2 or -3) once daily. Do not dose 

below 5 mg once daily. 

 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC Recommended coursea 

First falls to < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L when neutropenia is the only 

observed toxicity 

Resume lenalidomide at starting dose once daily 

Returns to ≥ 0.5 x 109/L when dose-dependent 

haematological toxicities other than neutropenia are 

observed 

Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level 

(dose level -1, -2 or -3) once daily. Do not dose 

below 5 mg once daily. 



 8 

a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain 

the dose level of lenalidomide. 

 

Myelodysplastic syndromes (MDS) 

Lenalidomide treatment must not be started if the ANC < 0.5 x 109/L and/or platelet counts < 25 x 109/L. 

 

Recommended dose 

The recommended starting dose of lenalidomide is 10 mg orally once daily on days 1 to 21 of repeated 

28-day cycles.  

 

• Dose reduction steps 

Starting dose 10 mg once daily on days 1 to 21 every 28 days 

Dose level -1 5 mg once daily on days 1 to 28 every 28 days 

Dose level -2 2.5 mg once daily on days 1 to 28 every 28 days 

Dose level -3 2.5 mg every other day 1 to 28 every 28 days 

 

• Thrombocytopenia 

When platelets Recommended course 

Falls to < 25 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 25 x 109/L - < 50 x 109/L on at least 2 

occasions for ≥ 7 days or when the platelet count 

recovers to ≥ 50 x 109/L at any time 

Resume lenalidomide at next lower dose level 

(dose level -1, -2 or -3) 

 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC Recommended course 

Falls to < 0.5 x 109/L Interrupt lenalidomide treatment 

Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level 

(dose level -1, -2 or -3) 

 

Discontinuation of lenalidomide 
Patients without at least a minor erythroid response within 4 months of therapy initiation, demonstrated by at 

least a 50% reduction in transfusion requirements or, if not transfused, a 1g/dl rise in haemoglobin, should 

discontinue lenalidomide treatment. 

 

Mantle cell lymphoma (MCL) 

Recommended dose 

The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 

28-day cycles.  

 

• Dose reduction steps 

Starting dose 25 mg once daily on days 1 to 21, every 28 days 

Dose Level -1 20 mg once daily on days 1 to 21, every 28 days 

Dose Level -2 15 mg once daily on days 1 to 21, every 28 days 

Dose Level -3 10 mg once daily on days 1 to 21, every 28 days 

Dose Level -4 5 mg once daily on days 1 to 21, every 28 days 

Dose Level -5 2.5 mg once daily on days 1 to 21, every 28 days1 

5 mg every other day on days 1 to 21, every 28 days 
1 - In countries where the 2.5 mg capsule is available. 

 

• Thrombocytopenia 

When platelets Recommended course 

Falls to < 50 x 109/L Interrupt lenalidomide treatment and conduct 

Complete Blood Count (CBC) at least every 

7 days 

Returns to ≥ 60 x 109/L Resume lenalidomide at next lower level (dose 

level -1) 



 9 

For each subsequent drop below 50 x 109/L 

 

Returns to ≥60 x 109/L 

Interrupt lenalidomide treatment and conduct the 

CBC at least every 7 days 

Resume lenalidomide at next lower level (dose 

level -2, -3, -4 or -5). Do not dose below dose 

level -5  

 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC Recommended course 

Falls to < 1 x 109/L for at least 7 days or  

Falls to < 1 x 109/L with associated fever (body 

temperature ≥ 38.5°C) or  

Falls to < 0.5 x 109/L  

Interrupt lenalidomide treatment and conduct the 

CBC at least every 7 days 

 

Returns to ≥ 1 x 109/L Resume lenalidomide at next lower dose level 

(dose level -1) 

For each subsequent drop below 1 x 109/L for at least 

7 days or drop to < 1 x 109/L with associated fever 

(body temperature ≥ 38.5°C) or drop to < 0.5 x 109/L  

Interrupt lenalidomide treatment 

Returns to ≥1 x 109/L Resume Lenalidomide at next lower dose level 

(dose level -2, -3, -4, -5). Do not dose below dose 

level -5 

 

Follicular lymphoma (FL) 

Lenalidomide treatment must not be started if the ANC is < 1 x 109/L, and/or platelet count < 50 x 109/L, 

unless secondary to lymphoma infiltration of bone marrow.  

 

Recommended dose 

The recommended starting dose of lenalidomide is 20 mg, orally once daily on days 1 to 21 of repeated 28-

day cycles for up to 12 cycles of treatment. The recommended starting dose of rituximab is 375 mg/m2 

intravenously (IV) every week in Cycle 1 (days 1, 8, 15, and 22) and day 1 of every 28-day cycle for cycles 2 

through 5. 

 

• Dose reduction steps 

Starting dose  20 mg once daily on days 1-21, every 28 days 

Dose Level -1 15 mg once daily on days 1-21, every 28 days 

Dose Level -2  10 mg once daily on days 1-21, every 28 days 

Dose Level -3 5 mg once daily on days 1-21, every 28 days 

 

For dose adjustments due to toxicity with rituximab, refer to the corresponding summary of product 

characteristics. 

 

• Thrombocytopenia 

When platelets Recommended course 

Falls to < 50 x 109/L Interrupt lenalidomide treatment and conduct 

CBC at least every 7 days 

Returns to ≥ 50 x 109/L Resume at next lower dose level (dose level -1) 

For each subsequent drop below 50 x 109/L 

 

 

Returns to ≥ 50 x 109/L 

Interrupt lenalidomide treatment and conduct 

CBC at least every 7 days 

 

Resume lenalidomide at next lower dose level 

(dose level -2, -3). Do not dose below dose level -

3.  

 



 10 

• Absolute neutrophil count (ANC) - neutropenia 

When ANC  Recommended course ª 

Falls < 1.0 x 109/L for at least 7 days or 

Falls to < 1.0 x 109/L with associated fever (body 

temperature ≥ 38.5°C) or  

Falls to < 0.5 x 109/L 

Interrupt lenalidomide treatment and conduct 

CBC at least every 7 days  

Returns to ≥ 1.0 x 109/L Resume lenalidomide at next lower dose level 

(dose level -1) 

For each subsequent drop below 1.0 x 109/L for at least 

7 days or drop to < 1.0 x 109/L with associated fever 

(body temperature ≥ 38.5°C) or drop to < 0.5 x 109/L 

 

Returns to ≥1.0 x 109/L 

Interrupt lenalidomide treatment and conduct 

CBC at least every 7 days  

 

 

Resume lenalidomide at next lower dose level 

(dose level -2, -3). Do not dose below dose level-

3 
ª At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add G-CSF 

 

Mantle cell lymphoma (MCL) or follicular lymphoma (FL)  

Tumour lysis syndrome (TLS)  

All patients should receive TLS prophylaxis (allopurinol, rasburicase or equivalent as per institutional 

guidelines) and be well hydrated (orally) during the first week of the first cycle or for a longer period if 

clinically indicated.  To monitor for TLS, patients should have a chemistry panel drawn weekly during the 

first cycle and as clinically indicated. 

Lenalidomide may be continued (maintain dose) in patients with laboratory TLS or Grade 1 clinical TLS, or 

at the physician’s discretion, reduce dose by one level and continue lenalidomide. Vigorous intravenous 

hydration should be provided and appropriate medical management according to the local standard of care, 

until correction of electrolyte abnormalities. Rasburicase therapy may be needed to reduce hyperuricaemia. 

Hospitalisation of the patient will be at physician’s discretion. 

In patients with Grade 2 to 4 clinical TLS, interrupt lenalidomide and obtain a chemistry panel weekly or as 

clinically indicated. Vigorous intravenous hydration should be provided and appropriate medical 

management according to the local standard of care, until correction of electrolyte abnormalities. 

Rasburicase therapy and hospitalisation will be at physician’s discretion. When the TLS resolves to Grade 0, 

restart lenalidomide at next lower dose per physician’s discretion (see section 4.4). 

 

Tumour flare reaction 

At the physician’s discretion, lenalidomide may be continued in patients with Grade 1 or 2 tumour flare 

reaction (TFR) without interruption or modification. At the physician’s discretion, therapy with non-steroidal 

anti-inflammatory drugs (NSAIDs), limited duration corticosteroids, and/or narcotic analgesics may be 

administered. In patients with Grade 3 or 4 TFR, withhold treatment with lenalidomide and initiate therapy 

with NSAIDs, corticosteroids and/or narcotic analgesics. When TFR resolves to ≤ Grade 1, restart 

lenalidomide treatment at the same dose level for the rest of the cycle. Patients may be treated for 

management of symptoms per the guidance for treatment of Grade 1 and 2 TFR (see section 4.4).  

 

All indications 

For other Grade 3 or 4 toxicities judged to be related to lenalidomide, treatment should be stopped and only 

restarted at next lower dose level when toxicity has resolved to ≤ Grade 2 depending on the physician’s 

discretion. 

 

Lenalidomide interruption or discontinuation should be considered for Grade 2 or 3 skin rash. Lenalidomide 

must be discontinued for angioedema, anaphylactic reaction, Grade 4 rash, exfoliative or bullous rash, or if 

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Drug Reaction with Eosinophilia and 

Systemic Symptoms (DRESS) is suspected, and should not be resumed following discontinuation from these 

reactions. 

 

Special populations 

• Paediatric population 
Revlimid should not be used in children and adolescents from birth to less than 18 years because of safety 

concerns (see section 5.1).  



 11 

 

• Elderly 
Currently available pharmacokinetic data are described in section 5.2. Lenalidomide has been used in clinical 

trials in multiple myeloma patients up to 91 years of age, in myelodysplastic syndromes patients up to 

95 years of age and in mantle cell lymphoma patients up to 88 years of age (see section 5.1).  

 

Because elderly patients are more likely to have decreased renal function, care should be taken in dose 

selection and it would be prudent to monitor renal function. 

 

Newly diagnosed multiple myeloma: patients who are not eligible for transplant 

Patients with newly diagnosed multiple myeloma aged 75 years and older should be carefully assessed 

before treatment is considered (see section 4.4). 

 

For patients older than 75 years of age treated with lenalidomide in combination with dexamethasone, the 

starting dose of dexamethasone is 20 mg once daily on days 1, 8, 15 and 22 of each 28-day treatment cycle. 

 

No dose adjustment is proposed for patients older than 75 years who are treated with lenalidomide in 

combination with melphalan and prednisone. 

 

In patients with newly diagnosed multiple myeloma aged 75 years and older who received lenalidomide, 

there was a higher incidence of serious adverse reactions and adverse reactions that led to treatment 

discontinuation. 

 

Lenalidomide combined therapy was less tolerated in newly diagnosed multiple myeloma patients older than 

75 years of age compared to the younger population. These patients discontinued at a higher rate due to 

intolerance (Grade 3 or 4 adverse events and serious adverse events), when compared to patients < 75 years. 

 

Multiple myeloma: patients with at least one prior therapy  

The percentage of multiple myeloma patients aged 65 or over was not significantly different between the 

lenalidomide/dexamethasone and placebo/dexamethasone groups. No overall difference in safety or efficacy 

was observed between these patients and younger patients, but greater pre-disposition of older individuals 

cannot be ruled out.  

 

Myelodysplastic syndromes 

For myelodysplastic syndromes patients treated with lenalidomide, no overall difference in safety and 

efficacy was observed between patients aged over 65 and younger patients. 

 

Mantle cell lymphoma 

For mantle cell lymphoma patients treated with lenalidomide, no overall difference in safety and efficacy 

was observed between patients aged 65 years or over compared with patients aged under 65 years of age.  

 

Follicular lymphoma 

For follicular lymphoma patients treated with lenalidomide in combination with rituximab, the overall rate of 

adverse events is similar for patients aged 65 years or over compared with patients under 65 years of age. No 

overall difference in efficacy was observed between the two age groups. 

 

• Patients with renal impairment 
Lenalidomide is primarily excreted by the kidney; patients with greater degrees of renal impairment can have 

impaired treatment tolerance (see section 4.4). Care should be taken in dose selection and monitoring of 

renal function is advised. 

 

No dose adjustments are required for patients with mild renal impairment and multiple myeloma, 

myelodysplastic syndromes, mantle cell lymphoma, or follicular lymphoma. 

The following dose adjustments are recommended at the start of therapy and throughout treatment for 

patients with moderate or severe impaired renal function or end stage renal disease. 

There are no phase 3 trial experiences with End Stage Renal Disease (ESRD) (CLcr < 30 mL/min, requiring 

dialysis). 

 



 12 

Multiple myeloma 

Renal function (CLcr) Dose adjustment 

Moderate renal impairment 

(30  CLcr < 50 mL/min) 

10 mg once daily1 

Severe renal impairment 

(CLcr < 30 mL/min, not requiring dialysis) 

7.5 mg once daily2 

15 mg every other day 

End Stage Renal Disease (ESRD) 

(CLcr < 30 mL/min, requiring dialysis) 

5 mg once daily. On dialysis days, 

the dose should be administered 

following dialysis.  
1 The dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment. 
2 In countries where the 7.5 mg capsule is available. 

 

Myelodysplastic syndromes 

Renal function (CLcr) Dose adjustment 

Moderate renal impairment 

(30  CLcr < 50 mL/min) 

Starting dose 5 mg once daily 

(days 1 to 21 of repeated 28-day cycles) 

Dose level -1* 2.5 mg once daily 

(days 1 to 28 of repeated 28-day cycles) 

Dose level -2* 2.5 mg once every other day 

(days 1 to 28 of repeated 28-day cycles) 

Severe renal impairment 

(CLcr < 30 mL/min, not requiring dialysis) 

Starting dose 2.5 mg once daily 

(days 1 to 21 of repeated 28-day cycles) 

Dose level -1* 2.5 mg every other day 

(days 1 to 28 of repeated 28-day cycles) 

Dose level -2* 2.5 mg twice a week 

(days 1 to 28 of repeated 28-day cycles) 

End Stage Renal Disease (ESRD) 

(CLcr < 30 mL/min, requiring dialysis) 

 

On dialysis days, the dose should be 

administered following dialysis. 

Starting dose 2.5 mg once daily 

(days 1 to 21 of repeated 28-day cycles) 

Dose level -1* 2.5 mg every other day 

(days 1 to 28 of repeated 28-day cycles) 

Dose level -2* 2.5 mg twice a week 

(days 1 to 28 of repeated 28-day cycles) 
* Recommended dose reduction steps during treatment and restart of treatment to manage Grade 3 or 4 neutropenia or thrombocytopenia, or other 

Grade 3 or 4 toxicity judged to be related to lenalidomide, as described above. 

 

Mantle cell lymphoma 

Renal function (CLcr) Dose adjustment 

(days 1 to 21 of repeated 

28-day cycles) 

Moderate renal impairment 

(30  CLcr < 50 mL/min) 

10 mg once daily1 

Severe renal impairment 

(CLcr < 30 mL/min, not requiring dialysis) 

7.5 mg once daily2 

15 mg every other day 

End Stage Renal Disease (ESRD) 

(CLcr < 30 mL/min, requiring dialysis) 

5 mg once daily. On dialysis days, 

the dose should be administered 

following dialysis.  
1 The dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment. 
2 In countries where the 7.5 mg capsule is available. 

 



 13 

Follicular lymphoma 

Renal function (CLcr) Dose adjustment 

(days 1 to 21 of repeated 

28-day cycles) 

Moderate renal impairment 

(30  CLcr < 60 mL/min) 

10 mg once daily1, 2 

Severe renal impairment 

(CLcr < 30 mL/min, not requiring dialysis) 

No data available3 

 

End Stage Renal Disease (ESRD) 

(CLcr < 30 mL/min, requiring dialysis) 

No data available3 

 
¹ The dose may be escalated to 15 mg once daily after 2 cycles if the patient has tolerated therapy. 
2 For patients on a starting dose of 10 mg, in case of dose reduction to manage Grade 3 or 4 neutropenia or thrombocytopenia, or other Grade 3 or 4. 

Toxicity judged to be related to lenalidomide do not dose below 5 mg every other day or 2.5 mg once daily. 
 3 Patients with severe renal impairment or ESRD were excluded from study. 

 

After initiation of lenalidomide therapy, subsequent lenalidomide dose modification in renally impaired 

patients should be based on individual patient treatment tolerance, as described above. 

 

• Patients with hepatic impairment 
Lenalidomide has not formally been studied in patients with impaired hepatic function and there are no 

specific dose recommendations. 

 

Method of administration  

Oral use.  

Revlimid capsules should be taken orally at about the same time on the scheduled days. The capsules should 

not be opened, broken or chewed. The capsules should be swallowed whole, preferably with water, either 

with or without food. 

 

It is recommended to press only on one end of the capsule to remove it from the blister thereby reducing the 

risk of capsule deformation or breakage. 

 

4.3 Contraindications 

 

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

• Women who are pregnant.  

• Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme 
are met (see sections 4.4 and 4.6). 

 

4.4 Special warnings and precautions for use 

 

When lenalidomide is given in combination with other medicinal products, the corresponding 

Summary of Product Characteristics must be consulted prior to initiation of treatment.  

 

Pregnancy warning 

Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active 

substance that causes severe life-threatening birth defects. Lenalidomide induced in monkeys’ malformations 

similar to those described with thalidomide (see sections 4.6 and 5.3). If lenalidomide is taken during 

pregnancy, a teratogenic effect of lenalidomide in humans is expected. 

 

The conditions of the Pregnancy Prevention Programme must be fulfilled for all patients unless there is 

reliable evidence that the patient does not have childbearing potential. 

 

Criteria for women of non-childbearing potential 

A female patient or a female partner of a male patient is considered to have childbearing potential unless she 

meets at least one of the following criteria: 

• Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year (Amenorrhoea following cancer therapy or 
during breast-feeding does not rule out childbearing potential). 

• Premature ovarian failure confirmed by a specialist gynaecologist 



 14 

• Previous bilateral salpingo-oophorectomy, or hysterectomy 

• XY genotype, Turner syndrome, uterine agenesis. 
 

Counselling 

For women of childbearing potential, lenalidomide is contraindicated unless all of the following are met: 

• She understands the expected teratogenic risk to the unborn child 

• She understands the need for effective contraception, without interruption, at least 4 weeks before 
starting treatment, throughout the entire duration of treatment, and at least 4 weeks after the end of 

treatment 

• Even if a woman of childbearing potential has amenorrhea she must follow all the advice on effective 
contraception 

• She should be capable of complying with effective contraceptive measures 

• She is informed and understands the potential consequences of pregnancy and the need to rapidly 
consult if there is a risk of pregnancy 

• She understands the need to commence the treatment as soon as lenalidomide is dispensed following a 
negative pregnancy test 

• She understands the need and accepts to undergo pregnancy testing at least every 4 weeks except in 
case of confirmed tubal sterilisation 

• She acknowledges that she understands the hazards and necessary precautions associated with the use 
of lenalidomide. 

 

For male patients taking lenalidomide, pharmacokinetic data has demonstrated that lenalidomide is present in 

human semen at extremely low levels during treatment and is undetectable in human semen 3 days after 

stopping the substance in the healthy subject (see section 5.2). As a precaution and taking into account 

special populations with prolonged elimination time such as renal impairment, all male patients taking 

lenalidomide must meet the following conditions: 

• Understand the expected teratogenic risk if engaged in sexual activity with a pregnant woman or a 
woman of childbearing potential 

• Understand the need for the use of a condom if engaged in sexual activity with a pregnant woman or a 
woman of childbearing potential not using effective contraception (even if the man has had a 

vasectomy), during treatment and for at least 7 days after dose interruptions and/or cessation of 

treatment. 

• Understand that if his female partner becomes pregnant whilst he is taking Revlimid or shortly after he 
has stopped taking Revlimid, he should inform his treating physician immediately and that it is 

recommended to refer the female partner to a physician specialised or experienced in teratology for 

evaluation and advice. 

 

The prescriber must ensure that for women of childbearing potential: 

• The patient complies with the conditions of the Pregnancy Prevention Programme, including 
confirmation that she has an adequate level of understanding 

• The patient has acknowledged the aforementioned conditions. 
 

Contraception 

Women of childbearing potential must use at least one effective method of contraception for at least 4 weeks 

before therapy, during therapy, and until at least 4 weeks after lenalidomide therapy and even in case of dose 

interruption unless the patient commits to absolute and continuous abstinence confirmed on a monthly basis. 

If not established on effective contraception, the patient must be referred to an appropriately trained health 

care professional for contraceptive advice in order that contraception can be initiated.  

 

The following can be considered to be examples of suitable methods of contraception: 

• Implant 

• Levonorgestrel-releasing intrauterine system (IUS) 

• Medroxyprogesterone acetate depot 

• Tubal sterilisation 

• Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two 
negative semen analyses 

• Ovulation inhibitory progesterone-only pills (i.e. desogestrel) 



 15 

 

Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking 

lenalidomide in combination therapy, and to a lesser extent in patients with multiple myeloma, 

myelodysplastic syndromes and mantle cell lymphoma taking lenalidomide monotherapy, combined oral 

contraceptive pills are not recommended (see also section 4.5). If a patient is currently using combined oral 

contraception the patient should switch to one of the effective methods listed above. The risk of venous 

thromboembolism continues for 4−6 weeks after discontinuing combined oral contraception. The efficacy of 

contraceptive steroids may be reduced during co-treatment with dexamethasone (see section 4.5). 

 

Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection 

at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered 

particularly in patients with neutropenia. 

 

Copper-releasing intrauterine devices are generally not recommended due to the potential risks of infection 

at the time of insertion and menstrual blood loss which may compromise patients with neutropenia or 

thrombocytopenia. 

 

Pregnancy testing 

According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL 

must be performed for women of childbearing potential as outlined below. This requirement includes women 

of childbearing potential who practice absolute and continuous abstinence. Ideally, pregnancy testing, issuing 

a prescription and dispensing should occur on the same day. Dispensing of lenalidomide to women of 

childbearing potential should occur within 7 days of the prescription. 

 

Prior to starting treatment 

A medically supervised pregnancy test should be performed during the consultation, when lenalidomide is 

prescribed, or in the 3 days prior to the visit to the prescriber once the patient had been using effective 

contraception for at least 4 weeks. The test should ensure the patient is not pregnant when she starts 

treatment with lenalidomide. 

 

Follow-up and end of treatment 

A medically supervised pregnancy test should be repeated at least every 4 weeks, including at least 4 weeks 

after the end of treatment, except in the case of confirmed tubal sterilisation. These pregnancy tests should be 

performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber. 

 

Additional precautions 

Patients should be instructed never to give this medicinal product to another person and to return any unused 

capsules to their pharmacist at the end of treatment for safe disposal. 

 

Patients should not donate blood during therapy or for at least 7 days following discontinuation of 

lenalidomide. 

 

Healthcare professionals and caregivers should wear disposable gloves when handling the blister or capsule. 

Women who are pregnant or suspect they may be pregnant should not handle the blister or capsule (see 

section 6.6). 

 

Educational materials, prescribing and dispensing restrictions 

In order to assist patients in avoiding foetal exposure to lenalidomide, the marketing authorisation holder will 

provide educational material to health care professionals to reinforce the warnings about the expected 

teratogenicity of lenalidomide, to provide advice on contraception before therapy is started, and to provide 

guidance on the need for pregnancy testing. The prescriber must inform male and female patients about the 

expected teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy 

Prevention Programme and provide patients with appropriate patient educational brochure, patient card 

and/or equivalent tool in accordance to the national implemented patient card system. A national controlled 

distribution system has been implemented in collaboration with each National Competent Authority. The 

controlled distribution system includes the use of a patient card and/or equivalent tool for prescribing and/or 

dispensing controls, and the collecting of detailed data relating to the indication in order to monitor closely 

the off-label use within the national territory. Ideally, pregnancy testing, issuing a prescription and 



 16 

dispensing should occur on the same day. Dispensing of lenalidomide to women of childbearing potential 

should occur within 7 days of the prescription and following a medically supervised negative pregnancy test 

result. Prescriptions for women of childbearing potential can be for a maximum duration of treatment of 

4 weeks according to the approved indications dosing regimens (see section 4.2), and prescriptions for all 

other patients can be for a maximum duration of treatment of 12 weeks. 

 

Other special warnings and precautions for use 

Myocardial infarction 

Myocardial infarction has been reported in patients receiving lenalidomide, particularly in those with known 

risk factors and within the first 12 months when used in combination with dexamethasone. Patients with 

known risk factors – including prior thrombosis – should be closely monitored, and action should be taken to 

try to minimize all modifiable risk factors (eg. smoking, hypertension, and hyperlipidaemia). 

 

Venous and arterial thromboembolic events 

In patients with multiple myeloma, the combination of lenalidomide with dexamethasone is associated with 

an increased risk of venous thromboembolism (predominantly deep vein thrombosis and pulmonary 

embolism). The risk of venous thromboembolism was seen to a lesser extent with lenalidomide in 

combination with melphalan and prednisone.  

 

In patients with multiple myeloma, myelodysplastic syndromes and mantle cell lymphoma, treatment with 

lenalidomide monotherapy was associated with a lower risk of venous thromboembolism (predominantly 

deep vein thrombosis and pulmonary embolism) than in patients with multiple myeloma treated with 

lenalidomide in combination therapy (see sections 4.5 and 4.8). 

 

In patients with multiple myeloma, the combination of lenalidomide with dexamethasone is associated with 

an increased risk of arterial thromboembolism (predominantly myocardial infarction and cerebrovascular 

event) and was seen to a lesser extent with lenalidomide in combination with melphalan and prednisone. The 

risk of arterial thromboembolism is lower in patients with multiple myeloma treated with lenalidomide 

monotherapy than in patients with multiple myeloma treated with lenalidomide in combination therapy. 

 

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. 

 

Pulmonary hypertension 

Cases of pulmonary hypertension, some fatal, have been reported in patients treated with lenalidomide. 

Patients should be evaluated for signs and symptoms of underlying cardiopulmonary disease prior to 

initiating and during lenalidomide therapy. 

 

Neutropenia and thrombocytopenia 

The major dose limiting toxicities of lenalidomide include neutropenia and thrombocytopenia. A complete 

blood cell count, including white blood cell count with differential count, platelet count, haemoglobin, and 



 17 

haematocrit should be performed at baseline, every week for the first 8 weeks of lenalidomide treatment and 

monthly thereafter to monitor for cytopenias. In mantle cell lymphoma patients, the monitoring scheme 

should be every 2 weeks in cycles 3 and 4, and then at the start of each cycle. In follicular lymphoma, the 

monitoring scheme should be weekly for the first 3 weeks of cycle 1 (28 days), every 2 weeks during cycles 

2 through 4, and then at the start of each cycle thereafter. A dose interruption and/or 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. 

Patients should be advised to promptly report febrile episodes.  

Patients and physicians are advised to be observant for signs and symptoms of bleeding, including petechiae 

and epistaxis, especially in patients receiving concomitant medicinal products susceptible to induce bleeding 

(see section 4.8, Haemorrhagic disorders). 

Co-administration of lenalidomide with other myelosuppressive agents should be undertaken with caution. 

 

• Newly diagnosed multiple myeloma: patients who have undergone ASCT treated with lenalidomide 
maintenance 

The adverse reactions from CALGB 100104 included events reported post-high dose melphalan and ASCT 

(HDM/ASCT) as well as events from the maintenance treatment period. A second analysis identified events 

that occurred after the start of maintenance treatment. In IFM 2005-02, the adverse reactions were from the 

maintenance treatment period only. 

 

Overall, Grade 4 neutropenia was observed at a higher frequency in the lenalidomide maintenance arms 

compared to the placebo maintenance arms in the 2 studies evaluating lenalidomide maintenance in NDMM 

patients who have undergone ASCT (32.1% vs 26.7% [16.1% vs 1.8% after the start of maintenance 

treatment] in CALGB 100104 and 16.4% vs 0.7% in IFM 2005-02, respectively). Treatment-emergent AEs 

of neutropenia leading to lenalidomide discontinuation were reported in 2.2% of patients in CALGB 100104 

and 2.4% of patients in IFM 2005-02, respectively. Grade 4 febrile neutropenia was reported at similar 

frequencies in the lenalidomide maintenance arms compared to placebo maintenance arms in both studies 

(0.4% vs 0.5% [0.4% vs 0.5% after the start of maintenance treatment] in CALGB 100104 and 0.3% vs 0% 

in IFM 2005-02, respectively). Patients should be advised to promptly report febrile episodes, a treatment 

interruption and/or dose reduction may be required (see section 4.2). 

 

Grade 3 or 4 thrombocytopenia was observed at a higher frequency in the lenalidomide maintenance arms 

compared to the placebo maintenance arms in studies evaluating lenalidomide maintenance in NDMM 

patients who have undergone ASCT (37.5% vs 30.3% [17.9% vs 4.1% after the start of maintenance 

treatment] in CALGB 100104 and 13.0% vs 2.9% in IFM 2005-02, respectively). Patients and physicians are 

advised to be observant for signs and symptoms of bleeding, including petechiae and epistaxes, especially in 

patients receiving concomitant medicinal products susceptible to induce bleeding (see section 4.8, 

Haemorrhagic disorders). 

 

• Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with 
lenalidomide in combination with bortezomib and dexamethasone 

Grade 4 neutropenia was observed at a lower frequency in the lenalidomide in combination with bortezomib 

and dexamethasone (RVd) arm compared to the Rd comparator arm (2.7% vs 5.9%) in the SWOG S0777 

study. Grade 4 febrile neutropenia was reported at similar frequencies in the RVd arm and Rd arm (0.0% vs 

0.4%). Patients should be advised to promptly report febrile episodes; a treatment interruption and/or dose 

reduction may be required (see section 4.2). 

 

Grade 3 or 4 thrombocytopenia was observed at a higher frequency in the RVd arm compared to the Rd 

comparator arm (17.2 % vs 9.4%). 

 

• Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with 
lenalidomide in combination with low dose dexamethasone 

Grade 4 neutropenia was observed in the lenalidomide arms in combination with dexamethasone to a lesser 

extent than in the comparator arm (8.5% in the Rd [continuous treatment] and Rd18 [treatment for 18 four-

week cycles] compared with 15% in the melphalan/prednisone/thalidomide arm, see section 4.8). Grade 4 

febrile neutropenia episodes were consistent with the comparator arm (0.6 % in the Rd and Rd18 

lenalidomide/dexamethasone-treated patients compared with 0.7% in the melphalan/prednisone/thalidomide 

arm, see section 4.8). 



 18 

 

Grade 3 or 4 thrombocytopenia was observed to a lesser extent in the Rd and Rd18 arms than in the 

comparator arm (8.1% vs 11.1%, respectively).  

 

• Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with 
lenalidomide in combination with melphalan and prednisone 

The combination of lenalidomide with melphalan and prednisone in clinical trials of newly diagnosed 

multiple myeloma patients is associated with a higher incidence of Grade 4 neutropenia (34.1% in 

melphalan, prednisone and lenalidomide arm followed by lenalidomide [MPR+R] and melphalan, prednisone 

and lenalidomide followed by placebo [MPR+p] treated patients compared with 7.8% in MPp+p-treated 

patients; see section 4.8). Grade 4 febrile neutropenia episodes were observed infrequently (1.7% in 

MPR+R/MPR+p treated patients compared to 0.0% in MPp+p treated patients; see section 4.8). 

 

The combination of lenalidomide with melphalan and prednisone in multiple myeloma patients is associated 

with a higher incidence of Grade 3 and Grade 4 thrombocytopenia (40.4% in MPR+R/MPR+p treated 

patients, compared with 13.7% in MPp+p-treated patients; see section 4.8). 

 

• Multiple myeloma: patients with at least one prior therapy 
The combination of lenalidomide with dexamethasone in multiple myeloma patients with at least one prior 

therapy 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). 

 

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). 

 

• Myelodysplastic syndromes 
Lenalidomide treatment in myelodysplastic syndromes patients is associated with a higher incidence of 

Grade 3 and 4 neutropenia and thrombocytopenia compared to patients on placebo (see section 4.8).  

 

• Mantle cell lymphoma 
Lenalidomide treatment in mantle cell lymphoma patients is associated with a higher incidence of Grade 3 

and 4 neutropenia compared with patients on the control arm (see section 4.8). 

 

• Follicular lymphoma 
The combination of lenalidomide with rituximab in follicular lymphoma patients is associated with a higher 

incidence of Grade 3 or 4 neutropenia compared with patients on the placebo/rituximab arm. Febrile 

neutropenia and Grade 3 or 4 thrombocytopenia were more commonly observed in the lenalidomide/ 

rituximab arm (see section 4.8).  

 

Thyroid disorders 

Cases of hypothyroidism and cases of hyperthyroidism have been reported. Optimal control of co-morbid 

conditions influencing thyroid function is recommended before start of treatment. Baseline and ongoing 

monitoring of thyroid function is recommended. 

 

Peripheral neuropathy 

Lenalidomide is structurally related to thalidomide, which is known to induce severe peripheral neuropathy.  

There was no increase in peripheral neuropathy observed with lenalidomide in combination with 

dexamethasone or melphalan and prednisone or lenalidomide monotherapy or with long term use of 

lenalidomide for the treatment of newly diagnosed multiple myeloma. 

 

The combination of lenalidomide with intravenous bortezomib and dexamethasone in multiple myeloma 

patients is associated with a higher frequency of peripheral neuropathy. The frequency was lower when 

bortezomib was administered subcutaneously. For additional information, see Section 4.8 and the SmPC for 

bortezomib. 



 19 

 

Tumour flare reaction and tumour lysis syndrome 

Because lenalidomide has anti-neoplastic activity the complications of tumour lysis syndrome (TLS) may 

occur. TLS and tumour flare reaction (TFR) have commonly been observed in patients with chronic 

lymphocytic leukemia (CLL), and uncommonly in patients with lymphomas, who were treated with 

lenalidomide. Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at 

risk of TLS and TFR are those with high tumour burden prior to treatment. Caution should be practiced when 

introducing these patients to lenalidomide. These patients should be monitored closely, especially during the 

first cycle or dose-escalation, and appropriate precautions taken. There have been rare reports of TLS in 

patients with MM treated with lenalidomide, and no reports in patients with MDS treated with lenalidomide. 

 

• Mantle cell lymphoma 
Careful monitoring and evaluation for TFR is recommended. Patients with high mantle cell lymphoma 

International Prognostic Index (MIPI) at diagnosis or bulky disease (at least one lesion that is ≥ 7 cm in the 

longest diameter) at baseline may be at risk of TFR. Tumour flare reaction may mimic progression of disease 

(PD). Patients in studies MCL-002 and MCL-001 that experienced Grade 1 and 2 TFR were treated with 

corticosteroids, NSAIDs and/or narcotic analgesics for management of TFR symptoms. The decision to take 

therapeutic measures for TFR should be made after careful clinical assessment of the individual patient (see 

sections 4.2 and 4.8). 

 

• Follicular lymphoma  
Careful monitoring and evaluation for TFR is recommended. Tumour flare may mimic PD. Patients who 

experienced Grade 1 and 2 TFR were treated with corticosteroids, NSAIDs and/or narcotic analgesics for 

management of TFR symptoms. The decision to take therapeutic measures for TFR should be made after 

careful clinical assessment of the individual patient (see sections 4.2 and 4.8). 

 

Careful monitoring and evaluation for TLS is recommended.  Patients should be well hydrated and receive 

TLS prophylaxis, in addition to weekly chemistry panels during the first cycle or longer, as clinically 

indicated (see sections 4.2 and 4.8). 

 

Tumour burden  

• Mantle cell lymphoma 
Lenalidomide is not recommended for the treatment of patients with high tumour burden if alternative 

treatment options are available.  

 

Early death 

In study MCL-002 there was overall an apparent increase in early (within 20 weeks) deaths. Patients with 

high tumour burden at baseline are at increased risk of early death, there were 16/81 (20%) early deaths in 

the lenalidomide arm and 2/28 (7%) early deaths in the control arm. Within 52 weeks corresponding figures 

were 32/81 (40%) and 6/28 (21%) (See section 5.1).  

 

Adverse events 

In study MCL-002, during treatment cycle 1, 11/81 (14%) patients with high tumour burden were withdrawn 

from therapy in the lenalidomide arm vs. 1/28 (4%) in the control group. The main reason for treatment 

withdrawal for patients with high tumour burden during treatment cycle 1 in the lenalidomide arm was 

adverse events, 7/11 (64%).  

Patients with high tumour burden should therefore be closely monitored for adverse reactions (see Section 

4.8) including signs of tumour flare reaction (TFR). Please refer to section 4.2 for dose adjustments for TFR. 

High tumour burden was defined as at least one lesion ≥5 cm in diameter or 3 lesions ≥3 cm.  

 

Allergic reactions and severe skin reactions 

Cases of allergic reactions including angioedema, anaphylactic reaction and severe cutaneous reactions 

including SJS, TEN and DRESS have been reported in patients treated with lenalidomide (see section 4.8). 

Patients should be advised of the signs and symptoms of these reactions by their prescribers and should be 

told to seek medical attention immediately if they develop these symptoms. Lenalidomide must be 

discontinued for angioedema, anaphylactic reaction, exfoliative or bullous rash, or if SJS, TEN or DRESS is 

suspected, and should not be resumed following discontinuation for these reactions. Interruption or 

discontinuation of lenalidomide should be considered for other forms of skin reaction depending on severity. 



 20 

Patients who had previous allergic reactions while treated with thalidomide should be monitored closely, as a 

possible cross-reaction between lenalidomide and thalidomide has been reported in the literature. Patients 

with a history of severe rash associated with thalidomide treatment should not receive lenalidomide. 

 

Lactose intolerance 

Revlimid capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp 

lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

Second primary malignancies 

An increase of second primary malignancies (SPM) has been observed in clinical trials in previously treated 

myeloma patients receiving lenalidomide/dexamethasone (3.98 per 100 person-years) compared to controls 

(1.38 per 100 person-years). Non-invasive SPM comprise basal cell or squamous cell skin cancers. Most of 

the invasive SPMs were solid tumour malignancies. 

 

In clinical trials of newly diagnosed multiple myeloma patients not eligible for transplant, a 4.9-fold increase 

in incidence rate of hematologic SPM (cases of AML, MDS) has been observed in patients receiving 

lenalidomide in combination with melphalan and prednisone until progression (1.75 per 100 person-years) 

compared with melphalan in combination with prednisone (0.36 per 100 person-years).  

 

A 2.12-fold increase in incidence rate of solid tumour SPM has been observed in patients receiving 

lenalidomide (9 cycles) in combination with melphalan and prednisone (1.57 per 100 person-years) 

compared with melphalan in combination with prednisone (0.74 per 100 person-years).  

 

In patients receiving lenalidomide in combination with dexamethasone until progression or for 18 months, 

the hematologic SPM incidence rate (0.16 per 100 person-years) was not increased as compared to 

thalidomide in combination with melphalan and prednisone (0.79 per 100 person-years).  

 

A 1.3-fold increase in incidence rate of solid tumour SPM has been observed in patients receiving 

lenalidomide in combination with dexamethasone until progression or for 18 months (1.58 per 100 person-

years) compared to thalidomide in combination with melphalan and prednisone (1.19 per 100 person-years). 

 

In newly diagnosed multiple myeloma patients receiving lenalidomide in combination with bortezomib and 

dexamethasone, the hematologic SPM incidence rate was 0.00 – 0.16 per 100 person-years and the incidence 

rate of solid tumour SPM was 0.21 – 1.04 per 100 person-years. 

 

The increased risk of secondary primary malignancies associated with lenalidomide is relevant also in the 

context of NDMM after stem cell transplantation. Though this risk is not yet fully characterized, it should be 

kept in mind when considering and using Revlimid in this setting. 

 

The incidence rate of hematologic malignancies, most notably AML, MDS and B-cell malignancies 

(including Hodgkin’s lymphoma), was 1.31 per 100 person-years for the lenalidomide arms and 0.58 per 100 

person-years for the placebo arms (1.02 per 100 person-years for patients exposed to lenalidomide after 

ASCT and 0.60 per 100 person-years for patients not-exposed to lenalidomide after ASCT). The incidence 

rate of solid tumour SPMs was 1.36 per 100 person-years for the lenalidomide arms and 1.05 per 100 person-

years for the placebo arms (1.26 per 100 person-years for patients exposed to lenalidomide after ASCT and 

0.60 per 100 person-years for patients not-exposed to lenalidomide after ASCT).   

 

The risk of occurrence of hematologic SPM must be taken into account before initiating treatment with 

lenalidomide either in combination with melphalan or immediately following high-dose melphalan and 

ASCT. Physicians should carefully evaluate patients before and during treatment using standard cancer 

screening for occurrence of SPM and institute treatment as indicated. 

 

Progression to acute myeloid leukaemia in low- and intermediate-1-risk MDS 

• Karyotype 
Baseline variables including complex cytogenetics are associated with progression to AML in subjects who 

are transfusion dependent and have a Del (5q) abnormality. In a combined analysis of two clinical trials of 

lenalidomide in low- or intermediate-1-risk myelodysplastic syndromes, subjects who had a complex 

cytogenetics had the highest estimated 2-year cumulative risk of progression to AML (38.6%). The estimated 



 21 

2-year rate of progression to AML in patients with an isolated Del (5q) abnormality was 13.8%, compared to 

17.3% for patients with Del (5q) and one additional cytogenetic abnormality. 

 

As a consequence, the benefit/risk ratio of lenalidomide when MDS is associated with Del (5q) and complex 

cytogenetics is unknown.  

 

• TP53 status 
A TP53 mutation is present in 20 to 25% of lower-risk MDS Del 5q patients and is associated with a higher 

risk of progression to acute myeloid leukaemia (AML). In a post-hoc analysis of a clinical trial of 

lenalidomide in low- or intermediate-1-risk myelodysplastic syndromes (MDS-004), the estimated 2-year 

rate of progression to AML was 27.5 % in patients with IHC-p53 positivity (1% cut-off level of strong 

nuclear staining, using immunohistochemical assessment of p53 protein as a surrogate for TP53 mutation 

status) and 3.6% in patients with IHC-p53 negativity (p=0.0038) (see section 4.8) 

 

Progression to other malignancies in mantle cell lymphoma 

In mantle cell lymphoma, AML, B-cell malignancies and non-melanoma skin cancer (NMSC) are identified 

risks. 

 

Second primary malignancies in follicular lymphoma 

In a relapsed/refractory iNHL study which included follicular lymphoma patients, no increased risk of SPMs 

in the lenalidomide/rituximab arm, compared to the placebo/rituximab arm, was observed. Hematologic SPM 

of AML occurred in 0.29 per 100 person-years in the lenalidomide/rituximab arm compared with 0.29 per 

100 person-years in patients receiving placebo/rituximab. The incidence rate of hematologic plus solid 

tumour SPMs (excluding non-melanoma skin cancers) was 0.87 per 100 person-years in the 

lenalidomide/rituximab arm, compared to 1.17 per 100 person-years in patients receiving placebo/rituximab 

with a median follow-up of 30.59 months (range 0.6 to 50.9 months).  

 

Non-melanoma skin cancers are identified risks and comprise squamous cell carcinomas of skin or basal cell 

carcinomas. 

 

Physicians should monitor patients for the development of SPMs. Both the potential benefit of lenalidomide 

and the risk of SPMs should be considered when considering treatment with lenalidomide. 

 

Hepatic disorders 

Hepatic failure, including fatal cases, has been reported in patients treated with lenalidomide in combination 

therapy: acute hepatic failure, toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis, and mixed 

cytolytic/cholestatic hepatitis have been reported. The mechanisms of severe drug-induced hepatotoxicity 

remain unknown although, in some cases, pre-existing viral liver disease, elevated baseline liver enzymes, 

and possibly treatment with antibiotics might be risk factors. 

 

Abnormal liver function tests were commonly reported and were generally asymptomatic and reversible 

upon dosing interruption. Once parameters have returned to baseline, treatment at a lower dose may be 

considered.  

 

Lenalidomide is excreted by the kidneys. It is important to dose adjust patients with renal impairment in 

order to avoid plasma levels which may increase the risk for higher haematological adverse reactions or 

hepatotoxicity. Monitoring of liver function is recommended, particularly when there is a history of or 

concurrent viral liver infection or when lenalidomide is combined with medicinal products known to be 

associated with liver dysfunction. 

 

Infection with or without neutropenia 

Patients with multiple myeloma are prone to develop infections including pneumonia. A higher rate of 

infections was observed with lenalidomide in combination with dexamethasone than with MPT in patients 

with NDMM who are not eligible for transplant, and with lenalidomide maintenance compared to placebo in 

patients with NDMM who had undergone ASCT. Grade ≥ 3 infections occurred within the context of 

neutropenia in less than one-third of the patients. Patients with known risk factors for infections should be 

closely monitored. All patients should be advised to seek medical attention promptly at the first sign of 

infection (eg, cough, fever, etc) thereby allowing for early management to reduce severity. 



 22 

 

Viral reactivation 

Cases of viral reactivation have been reported in patients receiving lenalidomide, including serious cases of 

herpes zoster or hepatitis B virus (HBV) reactivation. 

 

Some of the cases of viral reactivation had a fatal outcome. 

 

Some of the cases of herpes zoster reactivation resulted in disseminated herpes zoster, meningitis herpes 

zoster or ophthalmic herpes zoster requiring a temporary hold or permanent discontinuation of the treatment 

with lenalidomide and adequate antiviral treatment. 

 

Reactivation of hepatitis B has been reported rarely in patients receiving lenalidomide who have previously 

been infected with the hepatitis B virus. Some of these cases have progressed to acute hepatic failure 

resulting in discontinuation of lenalidomide and adequate antiviral treatment. Hepatitis B virus status should 

be established before initiating treatment with lenalidomide. For patients who test positive for HBV 

infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended. 

Caution should be exercised when lenalidomide is used in patients previously infected with HBV, including 

patients who are anti-HBc positive but HBsAg negative. These patients should be closely monitored for 

signs and symptoms of active HBV infection throughout therapy. 

 

Progressive multifocal leukoencephalopathy 

Cases of progressive multifocal leukoencephalopathy (PML), including fatal cases, have been reported with 

lenalidomide. PML was reported several months to several years after starting the treatment with 

lenalidomide. Cases have generally been reported in patients taking concomitant dexamethasone or prior 

treatment with other immunosuppressive chemotherapy. Physicians should monitor patients at regular 

intervals and should consider PML in the differential diagnosis in patients with new or worsening 

neurological symptoms, cognitive or behavioural signs or symptoms. Patients should also be advised to 

inform their partner or caregivers about their treatment, since they may notice symptoms that the patient is 

not aware of. 

 

The evaluation for PML should be based on neurological examination, magnetic resonance imaging of the 

brain, and cerebrospinal fluid analysis for JC virus (JCV) DNA by polymerase chain reaction (PCR) or a 

brain biopsy with testing for JCV. A negative JCV PCR does not exclude PML. Additional follow-up and 

evaluation may be warranted if no alternative diagnosis can be established.  

 

If PML is suspected, further dosing must be suspended until PML has been excluded. If PML is confirmed, 

lenalidomide must be permanently discontinued. 

 

Newly diagnosed multiple myeloma patients 

There was a higher rate of intolerance (Grade 3 or 4 adverse events, serious adverse events, discontinuation) 

in patients with age > 75 years, ISS stage III, ECOG PS≥2 or CLcr<60 mL/min when lenalidomide is given 

in combination. Patients should be carefully assessed for their ability to tolerate lenalidomide in 

combination, with consideration to age, ISS stage III, ECOG PS≥2 or CLcr<60 mL/min (see sections 4.2 and 

4.8). 

 

Cataract 

Cataract has been reported with a higher frequency in patients receiving lenalidomide in combination with 

dexamethasone particularly when used for a prolonged time. Regular monitoring of visual ability is 

recommended. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

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 (see sections 4.4 and 4.8). 

 



 23 

Oral contraceptives 

No interaction study has been performed with oral contraceptives. Lenalidomide is not an enzyme inducer. In 

an in vitro study with human hepatocytes, lenalidomide, at various concentrations tested did not induce 

CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP3A4/5. Therefore, induction leading to reduced efficacy of 

medicinal products, including hormonal contraceptives, is not expected if lenalidomide is administered 

alone. However, dexamethasone is known to be a weak to moderate inducer of CYP3A4 and is likely to also 

affect other enzymes as well as transporters. It may not be excluded that the efficacy of oral contraceptives 

may be reduced during treatment. Effective measures to avoid pregnancy must be taken (see sections 4.4 and 

4.6). 

 

Warfarin 

Co-administration of multiple 10 mg doses of lenalidomide had no effect on the single dose 

pharmacokinetics of R- and S- warfarin. Co-administration of a single 25 mg dose of warfarin had no effect 

on the pharmacokinetics of lenalidomide. However, it is not known whether there is an interaction during 

clinical use (concomitant treatment with dexamethasone). Dexamethasone is a weak to moderate enzyme 

inducer and its effect on warfarin is unknown. Close monitoring of warfarin concentration is advised during 

the treatment. 

 

Digoxin 

Concomitant administration with lenalidomide 10 mg once daily increased the plasma exposure of digoxin 

(0.5 mg, single dose) by 14% with a 90% CI (confidence interval) [0.52%-28.2%]. It is not known whether 

the effect will be different in the clinical use (higher lenalidomide doses and concomitant treatment with 

dexamethasone). Therefore, monitoring of the digoxin concentration is advised during lenalidomide 

treatment. 

 

Statins 

There is an increased risk of rhabdomyolysis when statins are administered with lenalidomide, which may be 

simply additive. Enhanced clinical and laboratory monitoring is warranted notably during the first weeks of 

treatment. 

 

Dexamethasone 

Co-administration of single or multiple doses of dexamethasone (40 mg once daily) has no clinically relevant 

effect on the multiple dose pharmacokinetics of lenalidomide (25 mg once daily). 

 

Interactions with P-glycoprotein (P-gp) inhibitors 

In vitro, lenalidomide is a substrate of P-gp, but is not a P-gp inhibitor. Co-administration of multiple doses 

of the strong P-gp inhibitor quinidine (600 mg, twice daily) or the moderate P-gp inhibitor/substrate 

temsirolimus (25 mg) has no clinically relevant effect on the pharmacokinetics of lenalidomide (25 mg). 

Co-administration of lenalidomide does not alter the pharmacokinetics of temsirolimus. 

 

4.6 Fertility, pregnancy and lactation 

 

Due to the teratogenic potential, lenalidomide must be prescribed under a Pregnancy Prevention Programme 

(see section 4.4) unless there is reliable evidence that the patient does not have childbearing potential. 

 

Women of childbearing potential / Contraception in males and females 

Women of childbearing potential should use effective method of contraception. If pregnancy occurs in a 

woman treated with lenalidomide, treatment must be stopped and the patient should be referred to a 

physician specialised or experienced in teratology for evaluation and advice. If pregnancy occurs in a partner 

of a male patient taking lenalidomide, it is recommended to refer the female partner to a physician 

specialised or experienced in teratology for evaluation and advice. 

 

Lenalidomide is present in human semen at extremely low levels during treatment and is undetectable in 

human semen 3 days after stopping the substance in the healthy subject (see section 5.2). As a precaution, 

and taking into account special populations with prolonged elimination time such as renal impairment, all 

male patients taking lenalidomide should use condoms throughout treatment duration, during dose 

interruption and for 1 week after cessation of treatment if their partner is pregnant or of childbearing 

potential and has no contraception. 



 24 

 

Pregnancy 

Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active 

substance that causes severe life-threatening birth defects. 

 

Lenalidomide induced malformation in monkeys similar to those described with thalidomide (see 

section 5.3). Therefore, a teratogenic effect of lenalidomide is expected and lenalidomide is contraindicated 

during pregnancy (see section 4.3). 

 

Breast-feeding 

It is not known whether lenalidomide is excreted in breast milk. Therefore, breast-feeding should be 

discontinued during therapy with lenalidomide. 

 

Fertility 

A fertility study in rats with lenalidomide doses up to 500 mg/kg (approximately 200 to 500 times the human 

doses of 25 mg and 10 mg, respectively, based on body surface area) produced no adverse effects on fertility 

and no parental toxicity. 

 

4.7 Effects on ability to drive and use machines 

 

Lenalidomide has minor or moderate influence on the ability to drive and use machines. Fatigue, dizziness, 

somnolence, vertigo and blurred vision have been reported with the use of lenalidomide. Therefore, caution 

is recommended when driving or operating machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile  

Newly diagnosed multiple myeloma: patients who have undergone ASCT treated with lenalidomide 

maintenance 

A conservative approach was applied to determine the adverse reactions from CALGB 100104. The adverse 

reactions described in Table 1 included events reported post-HDM/ASCT as well as events from the 

maintenance treatment period. A second analysis that identified events that occurred after the start of 

maintenance treatment suggests that the frequencies described in Table 1 may be higher than actually 

observed during the maintenance treatment period. In IFM 2005-02, the adverse reactions were from the 

maintenance treatment period only. 

 

The serious adverse reactions observed more frequently (≥5%) with lenalidomide maintenance than placebo 

were: 

• Pneumonia (10.6%; combined term) from IFM 2005-02 

• Lung infection (9.4% [9.4% after the start of maintenance treatment]) from CALGB 100104 
 

In the IFM 2005-02 study, the adverse reactions observed more frequently with lenalidomide maintenance 

than placebo were neutropenia (60.8%), bronchitis (47.4%), diarrhoea (38.9%), nasopharyngitis (34.8%), 

muscle spasms (33.4%), leucopenia (31.7%), asthenia (29.7%), cough (27.3%), thrombocytopenia (23.5%), 

gastroenteritis (22.5%) and pyrexia (20.5%). 

 

In the CALGB 100104 study, the adverse reactions observed more frequently with lenalidomide 

maintenance than placebo were neutropenia (79.0% [71.9% after the start of maintenance treatment]), 

thrombocytopenia (72.3% [61.6%]), diarrhoea (54.5% [46.4%]), rash (31.7% [25.0%]), upper respiratory 

tract infection (26.8% [26.8%]), fatigue (22.8% [17.9%]), leucopenia (22.8% [18.8%]) and anaemia (21.0% 

[13.8%]). 

 

Newly diagnosed multiple myeloma patients who are not eligible for transplant receiving lenalidomide in 

combination with bortezomib and dexamethasone 

In the SWOG S0777 study, the serious adverse reactions observed more frequently (≥ 5%) with lenalidomide 

in combination with intravenous bortezomib and dexamethasone than with lenalidomide in combination with 

dexamethasone were:  

• Hypotension (6.5%), lung infection (5.7%), dehydration (5.0%) 



 25 

 

The adverse reactions observed more frequently with lenalidomide in combination with bortezomib and 

dexamethasone than with lenalidomide in combination with dexamethasone were: Fatigue (73.7%), 

peripheral neuropathy (71.8%), thrombocytopenia (57.6%), constipation (56.1%), hypocalcaemia (50.0%).  

 

Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with lenalidomide in 

combination with low dose dexamethasone 

The serious adverse reactions observed more frequently (≥5%) with lenalidomide in combination with low 

dose dexamethasone (Rd and Rd18) than with melphalan, prednisone and thalidomide (MPT) were: 

• Pneumonia (9.8%) 

• Renal failure (including acute) (6.3%) 
 

The adverse reactions observed more frequently with Rd or Rd18 than MPT were: diarrhoea (45.5%), fatigue 

(32.8%), back pain (32.0%), asthenia (28.2%), insomnia (27.6%), rash (24.3%), decreased appetite (23.1%), 

cough (22.7%), pyrexia (21.4%), and muscle spasms (20.5%). 

 

Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with lenalidomide in 

combination with melphalan and prednisone 

The serious adverse reactions observed more frequently (≥5%) with melphalan, prednisone and lenalidomide 

followed by lenalidomide maintenance (MPR+R) or melphalan, prednisone and lenalidomide followed by 

placebo (MPR+p) than melphalan, prednisone and placebo followed by placebo (MPp+p) were: 

• Febrile neutropenia (6.0%) 

• Anaemia (5.3%) 
 

The adverse reactions observed more frequently with MPR+R or MPR+p than MPp+p were: neutropenia 

(83.3%), anaemia (70.7%), thrombocytopenia (70.0%), leucopenia (38.8%), constipation (34.0%), diarrhoea 

(33.3%), rash (28.9%), pyrexia (27.0%), peripheral oedema (25.0%), cough (24.0%), decreased appetite 

(23.7%), and asthenia (22.0%). 

 

Multiple myeloma: patients with at least one prior therapy 

In two phase 3 placebo-controlled studies, 353 patients with multiple myeloma were exposed to the 

lenalidomide/dexamethasone combination and 351 to the placebo/dexamethasone combination.  

 

The most serious adverse reactions observed more frequently in lenalidomide/dexamethasone than 

placebo/dexamethasone combination were: 

• Venous thromboembolism (deep vein thrombosis, pulmonary embolism) (see section 4.4) 

• Grade 4 neutropenia (see section 4.4). 
 

The observed adverse reactions which occurred more frequently with lenalidomide and dexamethasone than 

placebo and dexamethasone in pooled multiple myeloma clinical trials (MM-009 and MM-010) were fatigue 

(43.9%), neutropenia (42.2%), constipation (40.5%), diarrhoea (38.5%), muscle cramp (33.4%), anaemia 

(31.4%), thrombocytopenia (21.5%), and rash (21.2%). 

 

Myelodysplastic syndromes 

The overall safety profile of lenalidomide in patients with myelodysplastic syndromes is based on data from 

a total of 286 patients from one phase 2 study and one phase 3 study (see section 5.1). In the phase 2, all 148 

patients were on lenalidomide treatment. In the phase 3 study, 69 patients were on lenalidomide 5 mg, 69 

patients on lenalidomide 10 mg and 67 patients were on placebo during the double-blind phase of the study.  

 

Most adverse reactions tended to occur during the first 16 weeks of therapy with lenalidomide. 

 

Serious adverse reactions include: 

• Venous thromboembolism (deep vein thrombosis, pulmonary embolism) (see section 4.4) 

• Grade 3 or 4 neutropenia, febrile neutropenia and Grade 3 or 4 thrombocytopenia (see section 4.4). 
 

The most commonly observed adverse reactions which occurred more frequently in the lenalidomide groups 

compared to the control arm in the phase 3 study were neutropenia (76.8%), thrombocytopenia (46.4%), 



 26 

diarrhoea (34.8%), constipation (19.6%), nausea (19.6%), pruritus (25.4%), rash (18.1%), fatigue (18.1%) 

and muscle spasms (16.7%). 

 

Mantle cell lymphoma 

The overall safety profile of lenalidomide in patients with mantle cell lymphoma is based on data from 254 

patients from a phase 2 randomised, controlled study MCL-002 (see section 5.1).  

Additionally, adverse drug reactions from supportive study MCL-001 have been included in table 3. 

 

The serious adverse reactions observed more frequently in study MCL-002 (with a difference of at least 2 

percentage points) in the lenalidomide arm compared with the control arm were: 

• Neutropenia (3.6%) 

• Pulmonary embolism (3.6%) 

• Diarrhoea (3.6%) 
 

The most frequently observed adverse reactions which occurred more frequently in the lenalidomide arm 

compared with the control arm in study MCL-002 were neutropenia (50.9%), anaemia (28.7%), diarrhoea 

(22.8%), fatigue (21.0%), constipation (17.4%), pyrexia (16.8%), and rash (including dermatitis allergic) 

(16.2%).  

 

In study MCL-002 there was overall an apparent increase in early (within 20 weeks) deaths. Patients with 

high tumour burden at baseline are at increased risk of early death, 16/81 (20%) early deaths in the 

lenalidomide arm and 2/28 (7%) early deaths in the control arm. Within 52 weeks corresponding figures 

were 32/81 (39.5%) and 6/28 (21%) (see section 5.1).  

During treatment cycle 1, 11/81 (14%) patients with high tumour burden were withdrawn from therapy in the 

lenalidomide arm vs. 1/28 (4%) in the control group. The main reason for treatment withdrawal for patients 

with high tumour burden during treatment cycle 1 in the lenalidomide arm was adverse events, 7/11 (64%).  

High tumour burden was defined as at least one lesion ≥5 cm in diameter or 3 lesions ≥3 cm. 

 

Follicular lymphoma  

The overall safety profile of lenalidomide in combination with rituximab in patients with previously treated 

follicular lymphoma is based on data from 294 patients from a Phase 3 randomised, controlled study NHL-

007. Additionally, adverse drug reactions from supportive study NHL-008 have been included in Table 5. 

 

The serious adverse reactions observed most frequently (with a difference of at least 1 percentage point) in 

study NHL-007 in the lenalidomide/rituximab arm compared with the placebo/rituximab arm were: 

• Febrile neutropenia (2.7%) 

• Pulmonary embolism (2.7%) 

• Pneumonia (2.7%) 
 

In the NHL-007 study the adverse reactions observed more frequently in the lenalidomide/rituximab arm 

compared with the placebo/rituximab arm (with at least 2% higher frequency between arms) were 

neutropenia (58.2%), diarrhoea (30.8%), leucopenia (28.8%), constipation (21.9%), cough (21.9%)  and 

fatigue (21.9%). 

 

Tabulated list of adverse reactions 

The adverse reactions observed in patients treated with lenalidomide are listed below by system organ class 

and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing 

seriousness. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 

(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be 

estimated from the available data). 

 

Adverse reactions have been included under the appropriate category in the table below according to the 

highest frequency observed in any of the main clinical trials. 

 

Tabulated summary for monotherapy in MM 

The following table is derived from data gathered during NDMM studies in patients who have undergone 

ASCT treated with lenalidomide maintenance. The data were not adjusted according to the longer duration of 



 27 

treatment in the lenalidomide-containing arms continued until disease progression versus the placebo arms in 

the pivotal multiple myeloma studies (see section 5.1). 

 

Table 1. ADRs reported in clinical trials in patients with multiple myeloma treated with lenalidomide 

maintenance therapy 

System Organ Class/Preferred 

Term 

All ADRs/Frequency Grade 3-4 ADRs/Frequency 

Infections and Infestations 

Very Common 

Pneumonia◊,a, Upper respiratory 

tract infection, Neutropenic 

infection, Bronchitis◊, Influenza◊, 

Gastroenteritis◊, Sinusitis, 

Nasopharyngitis, Rhinitis 

 

Common 

Infection◊, Urinary tract 

infection◊,*, Lower respiratory 

tract infection, Lung infection◊ 

Very Common 

Pneumonia◊,a, Neutropenic 

infection 

 

Common 

Sepsis◊,b, Bacteraemia, Lung 

infection◊, Lower respiratory tract 

infection bacterial, Bronchitis◊, 

Influenza◊, Gastroenteritis◊, 

Herpes zoster◊, Infection◊ 

Neoplasms Benign, Malignant 

and Unspecified (incl cysts and 

polyps) 

Common 

Myelodysplastic syndrome◊,* 

 

Blood and Lymphatic System 

Disorders 

Very Common 

Neutropenia^,◊, Febrile 

neutropenia^,◊, 

Thrombocytopenia^,◊, Anaemia, 

Leucopenia◊, Lymphopenia 

Very Common 

Neutropenia^,◊, Febrile 

neutropenia^,◊, 

Thrombocytopenia^,◊, Anaemia, 

Leucopenia◊, Lymphopenia 

 

Common 

Pancytopenia◊ 

Metabolism and Nutrition 

Disorders 

Very Common 

Hypokalaemia 

Common 

Hypokalaemia, Dehydration 

Nervous System Disorders 

Very Common 

Paraesthesia 

 

Common 

Peripheral neuropathyc 

Common 

Headache 

Vascular Disorders 
Common 

Pulmonary embolism◊,* 

Common 

Deep vein thrombosis^,◊,d 

Respiratory, Thoracic and 

Mediastinal Disorders 

Very Common 

Cough 

 

Common 

Dyspnoea◊, Rhinorrhoea 

Common 

Dyspnoea◊ 

Gastrointestinal Disorders 

Very Common 

Diarrhoea, Constipation, 

Abdominal pain, Nausea 

 

Common 

Vomiting, Abdominal pain upper 

Common 

Diarrhoea, Vomiting, Nausea 

Hepatobiliary Disorders 
Very Common 

Abnormal liver function tests 

Common 

Abnormal liver function tests 

Skin and Subcutaneous Tissue 

Disorders 

Very Common 

Rash, Dry skin 

Common 

Rash, Pruritus 

Musculoskeletal and Connective 

Tissue Disorders 

Very Common 

Muscle spasms 

 

Common 

 



 28 

System Organ Class/Preferred 

Term 

All ADRs/Frequency Grade 3-4 ADRs/Frequency 

Myalgia, Musculoskeletal pain 

General Disorders and 

Administration Site Conditions 

Very Common 

Fatigue, Asthenia, Pyrexia 

Common 

Fatigue, Asthenia 
◊ Adverse reactions reported as serious in clinical trials in patients with NDMM who had undergone ASCT 
* Applies to serious adverse drug reactions only 

^ See section 4.8 description of selected adverse reactions 
a “Pneumonia” combined AE term includes the following PTs: Bronchopneumonia, Lobar pneumonia, Pneumocystis jiroveci pneumonia, Pneumonia, 

Pneumonia klebsiella, Pneumonia legionella, Pneumonia mycoplasmal, Pneumonia pneumococcal, Pneumonia streptococcal, Pneumonia viral, Lung 

disorder, Pneumonitis 
b “Sepsis” combined AE term includes the following PTs: Bacterial sepsis, Pneumococcal sepsis, Septic shock, Staphylococcal sepsis 
c “Peripheral neuropathy” combined AE term includes the following preferred terms (PTs): Neuropathy peripheral, Peripheral sensory neuropathy, 

Polyneuropathy 
d “Deep vein thrombosis” combined AE term includes the following PTs: Deep vein thrombosis, Thrombosis, Venous thrombosis 
 

Tabulated summary for combination therapy in MM 

The following table is derived from data gathered during the multiple myeloma studies with combination 

therapy. The data were not adjusted according to the longer duration of treatment in the 

lenalidomide-containing arms continued until disease progression versus the comparator arms in the pivotal 

multiple myeloma studies (see section 5.1). 

 

Table 2. ADRs reported in clinical studies in patients with multiple myeloma treated with lenalidomide 

in combination with bortezomib and dexamethasone, dexamethasone, or melphalan and prednisone 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

Infections and 

Infestations 

Very Common 

Pneumonia◊,◊◊, Upper respiratory tract 

infection◊, Bacterial, viral and fungal infections 

(including opportunistic infections)◊, 

Nasopharyngitis, Pharyngitis, Bronchitis◊, 

Rhinitis 

Common 

Sepsis◊,◊◊, Lung infection◊◊, Urinary tract 

infection◊◊, Sinusitis◊ 

Common 

Pneumonia◊,◊◊, Bacterial, viral and 

fungal infections (including 

opportunistic infections)◊, 

Cellulitis◊, Sepsis◊,◊◊, Lung 

infection◊◊, Bronchitis◊, 

Respiratory tract infection◊◊, 

Urinary tract infection◊◊, 

Enterocolitis infectious 

Neoplasms Benign, 

Malignant and 

Unspecified (incl 

cysts and polyps) 

Uncommon 

Basal cell carcinoma^,◊, Squamous skin 

cancer^,◊,* 

Common 

Acute myeloid leukaemia◊, 

Myelodysplastic syndrome◊, 

Squamous cell carcinoma of 

skin^,◊,** 

 

Uncommon 

T-cell type acute leukaemia◊, Basal 

cell carcinoma^,◊, Tumour lysis 

syndrome 

Blood and 

Lymphatic System 

Disorders 

Very Common 

Neutropenia^,◊,◊◊, Thrombocytopenia^,◊,◊◊, 

Anaemia◊, Haemorrhagic disorder^, 

Leucopenia, Lymphopenia 

 

Common 

Febrile neutropenia^,◊, Pancytopenia◊ 

 

Uncommon 

Haemolysis, Autoimmune haemolytic anaemia, 

Haemolytic anaemia 

Very Common 

Neutropenia^,◊,◊◊, 

Thrombocytopenia^,◊,◊◊, Anaemia◊, 

Leucopenia, Lymphopenia 

 

Common 

Febrile neutropenia^,◊, 

Pancytopenia◊, Haemolytic 

anaemia 

 

Uncommon 

Hypercoagulation, Coagulopathy 

Immune System 

Disorders 

Uncommon 

Hypersensitivity^ 

 



 29 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

Endocrine 

Disorders 

Common 

Hypothyroidism 

 

Metabolism and 

Nutrition 

Disorders 

Very Common 

Hypokalaemia◊,◊◊, Hyperglycaemia, 

Hypoglycaemia, Hypocalcaemia◊, 

Hyponatraemia◊, Dehydration◊◊, Decreased 

appetite◊◊, Weight decreased 

 

Common 

Hypomagnesaemia, Hyperuricaemia, 

Hypercalcaemia+ 

Common 

Hypokalaemia◊,◊◊, Hyperglycaemia, 

Hypocalcaemia◊, Diabetes 

mellitus◊, Hypophosphataemia, 

Hyponatraemia◊, Hyperuricaemia, 

Gout, Dehydration◊◊, Decreased 

appetite◊◊, Weight decreased 

Psychiatric 

Disorders 

Very Common 

Depression, Insomnia 

 

Uncommon 

Loss of libido 

Common 

Depression, Insomnia 

Nervous System 

Disorders 

Very Common 

Peripheral neuropathies◊◊, Paraesthesia, 

Dizziness◊◊, Tremor, Dysgeusia, Headache 

 

Common 

Ataxia, Balance impaired, Syncope◊◊, 

Neuralgia, Dysaesthesia 

Very Common 

Peripheral neuropathies◊◊ 

 

Common 

Cerebrovascular accident◊, 

Dizziness◊◊, Syncope◊◊, Neuralgia 

 

Uncommon 

Intracranial haemorrhage^, 

Transient ischaemic attack, 

Cerebral ischemia 

Eye Disorders Very Common 

Cataracts, Blurred vision 

 

Common 

Reduced visual acuity 

Common 

Cataract 

 

Uncommon 

Blindness 

Ear and Labyrinth 

Disorders 

Common 

Deafness (Including Hypoacusis), Tinnitus 

 

Cardiac Disorders Common 

Atrial fibrillation◊,◊◊, Bradycardia 

 

Uncommon 

Arrhythmia, QT prolongation, Atrial flutter, 

Ventricular extrasystoles 

Common 

Myocardial infarction (including 

acute)^,◊, Atrial fibrillation◊,◊◊, 

Congestive cardiac failure◊, 

Tachycardia, Cardiac failure◊,◊◊, 

Myocardial ischemia◊  

Vascular Disorders Very Common 

Venous thromboembolic events^, 

predominantly deep vein thrombosis and 

pulmonary embolism^,◊,◊◊, Hypotension◊◊ 

 

Common 

Hypertension, Ecchymosis^ 

Very Common 

Venous thromboembolic events^, 

predominantly deep vein 

thrombosis and pulmonary 

embolism^,◊,◊◊ 

 

Common 

Vasculitis, Hypotension◊◊, 

Hypertension 

 

Uncommon 

Ischemia, Peripheral ischemia, 

Intracranial venous sinus 

thrombosis 



 30 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

Respiratory, 

Thoracic and 

Mediastinal 

Disorders 

Very Common 

Dyspnoea◊,◊◊, Epistaxis^, Cough 

 

Common 

Dysphonia 

Common 

Respiratory distress◊, Dyspnoea◊,◊◊, 

Pleuritic pain◊◊, Hypoxia◊◊ 

Gastrointestinal 

Disorders 

Very Common 

Diarrhoea◊,◊◊, Constipation◊, Abdominal pain◊◊, 

Nausea, Vomiting,◊◊, Dyspepsia, Dry mouth, 

Stomatitis 

 

Common 

Gastrointestinal haemorrhage (including rectal 

haemorrhage, haemorrhoidal haemorrhage, 

peptic ulcer haemorrhage and gingival 

bleeding)^ ,◊◊, Dysphagia 

 

Uncommon 

Colitis, Caecitis  

Common 

Gastrointestinal haemorrhage^,◊,◊◊, 

Small intestinal obstruction◊◊, 

Diarrhoea◊◊, Constipation◊, 

Abdominal pain◊◊, Nausea, 

Vomiting◊◊ 

Hepatobiliary 

Disorders 

Very Common 

Alanine aminotransferase increased, Aspartate 

aminotransferase increased 

 

Common 

Hepatocellular injury◊◊, Abnormal liver 

function tests◊, Hyperbilirubinaemia 

 

Uncommon 

Hepatic failure^ 

Common 

Cholestasis◊, Hepatotoxicity, 

Hepatocellular injury◊◊, Alanine 

aminotransferase increased, 

Abnormal liver function tests◊ 

 

Uncommon 

Hepatic failure^ 

Skin and 

Subcutaneous 

Tissue Disorders 

Very Common 

Rashes◊◊, Pruritus 

 

Common 

Urticaria, Hyperhidrosis, Dry skin, Skin 

hyperpigmentation, Eczema, Erythema 

 

Uncommon 

Drug rash with eosinophilia and systemic 

symptoms◊◊, Skin discolouration, 

Photosensitivity reaction 

Common 

Rashes◊◊ 

 

Uncommon 

Drug rash with eosinophilia and 

systemic symptoms◊◊ 

 

Musculoskeletal 

and Connective 

Tissue Disorders 

Very Common 

Muscular weakness◊◊, Muscle spasms, Bone 

pain◊, Musculoskeletal and connective tissue 

pain and discomfort (including back pain◊,◊◊), 

Pain in extremity, Myalgia, Arthralgia◊ 

 

Common 

Joint swelling 

Common 

Muscular weakness◊◊, Bone pain◊, 

Musculoskeletal and connective 

tissue pain and discomfort 

(including back pain◊,◊◊) 

 

Uncommon 

Joint swelling 



 31 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

Renal and Urinary 

Disorders 

Very Common 

Renal failure (including acute)◊ ,◊◊ 

 

Common 

Haematuria^, Urinary retention, Urinary 

incontinence 

 

Uncommon 

Acquired Fanconi syndrome 

Uncommon 

Renal tubular necrosis 

Reproductive 

System and Breast 

Disorders 

Common 

Erectile dysfunction 

 

General Disorders 

and 

Administration 

Site Conditions 

Very Common 

Fatigue◊,◊◊, Oedema (including peripheral 

oedema), Pyrexia◊,◊◊, Asthenia, Influenza like 

illness syndrome (including pyrexia, cough, 

myalgia, musculoskeletal pain, headache and 

rigors) 

 

Common 

Chest pain◊,◊◊, Lethargy 

Very Common 

Fatigue◊,◊◊ 

 

Common 

Oedema peripheral, Pyrexia◊,◊◊, 

Asthenia 

Investigations Very Common 

Blood alkaline phosphatase increased 

 

Common 

C-reactive protein increased 

 

Injury, Poisoning 

and Procedural 

Complications 

Common 

Fall, Contusion^ 

 

◊◊Adverse reactions reported as serious in clinical trials in patients with NDMM who had received lenalidomide in combination with bortezomib and 
dexamethasone  

^See section 4.8 description of selected adverse reactions 
◊ Adverse reactions reported as serious in clinical trials in patients with multiple myeloma treated with lenalidomide in combination with 

dexamethasone, or with melphalan and prednisone 

+ Applies to serious adverse drug reactions only 
* Squamous skin cancer was reported in clinical trials in previously treated myeloma patients with lenalidomide/dexamethasone compared to controls 

** Squamous cell carcinoma of skin was reported in a clinical trial in newly diagnosed myeloma patients with lenalidomide/dexamethasone compared 

to controls 
 

Tabulated summary from monotherapy  

The following tables are derived from data gathered during the main studies in monotherapy for 

myelodysplastic syndromes and mantle cell lymphoma. 

 

Table 3. ADRs reported in clinical trials in patients with myelodysplastic syndromes treated with 

lenalidomide# 

System Organ Class / 

Preferred Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Infections and 

Infestations 

Very Common 

Bacterial, viral and fungal infections 

(including opportunistic infections)◊ 

Very Common 

Pneumonia◊ 

 

Common 

Bacterial, viral and fungal infections 

(including opportunistic infections)◊, 

Bronchitis 



 32 

System Organ Class / 

Preferred Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Blood and Lymphatic 

System Disorders 

Very Common 

Thrombocytopenia^,◊, Neutropenia^,◊,  

Leucopenia 

Very Common 

Thrombocytopenia^,◊, Neutropenia^,◊, 

Leucopenia 

 

Common 

Febrile neutropenia^,◊  

Endocrine Disorders Very Common 

Hypothyroidism 

 

Metabolism and 

Nutrition Disorders 

Very Common 

Decreased appetite 

 

Common 

Iron overload, Weight decreased 

Common 

Hyperglycaemia◊, Decreased appetite 

Psychiatric Disorders  Common 

Altered mood◊,~ 

Nervous System 

Disorders 

Very Common 

Dizziness, Headache 

 

Common 

Paraesthesia 

 

Cardiac Disorders  Common 

Acute myocardial infarction^,◊, Atrial 

fibrillation◊, Cardiac failure◊  

Vascular Disorders Common 

Hypertension, Haematoma 

Common 

Venous thromboembolic events, 

predominantly deep vein thrombosis 

and pulmonary embolism^,◊ 

Respiratory, Thoracic 

and Mediastinal 

Disorders 

Very Common 

Epistaxis^ 

 

Gastrointestinal 

Disorders 

Very Common 

Diarrhoea◊, Abdominal pain (including 

upper), Nausea, Vomiting, Constipation 

 

Common 

Dry mouth, Dyspepsia 

Common 

Diarrhoea◊, Nausea, Toothache 

Hepatobiliary 

Disorders 

Common 

Abnormal liver function tests  

Common 

Abnormal liver function tests  

Skin and Subcutaneous 

Tissue Disorders 

Very Common 

Rashes, Dry Skin, Pruritus  

Common 

Rashes, Pruritus 

Musculoskeletal and 

Connective Tissue 

Disorders 

Very Common 

Muscle spasms, Musculoskeletal pain 

(including back pain◊ and pain in 

extremity), Arthralgia, Myalgia  

Common 

Back pain◊ 

Renal and Urinary 

Disorders 

 Common 

Renal failure◊ 

General Disorders and 

Administration Site 

Conditions 

Very Common 

Fatigue, Peripheral oedema, Influenza 

like illness syndrome (including 

pyrexia, cough, pharyngitis, myalgia, 

musculoskeletal pain, headache) 

Common 

Pyrexia 

Injury, Poisoning and 

Procedural 

Complications 

 Common 

Fall 

^see section 4.8 description of selected adverse reactions 
◊Adverse events reported as serious in myelodysplastic syndromes clinical trials 



 33 

~Altered mood was reported as a common serious adverse event in the myelodysplastic syndromes phase 3 study; it was not reported as a Grade 3 or 

4 adverse event  

Algorithm applied for inclusion in the SmPC: All ADRs captured by the phase 3 study algorithm are included in the EU SmPC. For these ADRs, an 

additional check of the frequency of the ADRs captured by the phase 2 study algorithm was undertaken and, if the frequency of the ADRs in the 

phase 2 study was higher than in the phase 3 study, the event was included in the EU SmPC at the frequency it occurred in the phase 2 study. 

# Algorithm applied for myelodysplastic syndromes: 

• Myelodysplastic syndromes phase 3 study (double-blind safety population, difference between lenalidomide 5/10mg and placebo by initial 
dosing regimen occurring in at least 2 subjects)  

o All treatment-emergent adverse events with ≥ 5% of subjects in lenalidomide and at least 2% difference in proportion between 
lenalidomide and placebo 

o All treatment-emergent Grade 3 or 4 adverse events in 1% of subjects in lenalidomide and at least 1% difference in proportion 
between lenalidomide and placebo 

o All treatment-emergent serious adverse events in 1% of subjects in lenalidomide and at least 1% difference in proportion 
between lenalidomide and placebo 

• Myelodysplastic syndromes phase 2 study 
o All treatment-emergent adverse events with ≥ 5% of lenalidomide treated subjects 
o All treatment-emergent Grade 3 or 4 adverse\events in 1% of lenalidomide treated subjects 
o All treatment-emergent serious adverse events in 1% of lenalidomide treated subjects 

 

Table 4. ADRs reported in clinical trials in patients with mantle cell lymphoma treated with 

lenalidomide 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Infections and 

Infestations 

Very Common 

Bacterial, viral and fungal infections 

(including opportunistic infections)◊, 

Nasopharyngitis, Pneumonia◊ 

 

Common 

Sinusitis 

Common 

Bacterial, viral and fungal infections 

(including opportunistic infections)◊, 

Pneumonia◊ 

Neoplasms 

Benign, 

Malignant and 

Unspecified (incl 

cysts and polyps) 

Common 

Tumour flare reaction 

Common 

Tumour flare reaction, Squamous skin 

cancer^,◊, Basal cell carcinoma^,◊ 

Blood and 

Lymphatic 

System Disorders 

Very Common 

Thrombocytopenia^, Neutropenia^,◊, 

Leucopenia◊, Anaemia◊ 

 

Common 

Febrile neutropenia^,◊ 

Very Common 

Thrombocytopenia^, Neutropenia^,◊, 

Anaemia◊ 

 

Common 

Febrile neutropenia^,◊, Leucopenia◊ 

Metabolism and 

Nutrition 

Disorders 

Very Common 

Decreased appetite, Weight decreased, 

Hypokalaemia 

 

Common 

Dehydration◊ 

Common 

Dehydration◊, Hyponatraemia, 

Hypocalcaemia 

Psychiatric 

Disorders 

Common 

Insomnia 

 

Nervous System 

Disorders 

Common 

Dysgeuesia, Headache, neuropathy 

peripheral 

Common 

Peripheral sensory neuropathy, Lethargy 

Ear and 

Labyrinth 

Disorders 

Common 

Vertigo 

 

Cardiac 

Disorders 

 Common 

Myocardial infarction (including acute)^,◊, 

Cardiac failure  

Vascular 

Disorders 

Common 

Hypotension◊ 

Common 

Deep vein thrombosis◊, pulmonary 

embolism^,◊, Hypotension◊ 



 34 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Respiratory, 

Thoracic and 

Mediastinal 

Disorders 

Very Common 

Dyspnoea◊ 

Common 

Dyspnoea◊ 

Gastrointestinal 

Disorders 

Very Common 

Diarrhoea◊, Nausea◊, Vomiting◊, 

Constipation 

 

Common 

Abdominal pain◊ 

Common 

Diarrhoea◊, Abdominal pain◊, Constipation 

Skin and 

Subcutaneous 

Tissue Disorders 

Very Common 

Rashes (including dermatitis allergic), 

Pruritus 

 

Common 

Night sweats, Dry skin  

Common 

Rashes 

Musculoskeletal 

and Connective 

Tissue Disorders 

Very Common 

Muscle spasms, Back pain 

 

Common 

Arthralgia, Pain in extremity, Muscular 

weakness◊ 

Common 

Back pain, Muscular weakness◊, Arthralgia, 

Pain in extremity 

Renal and 

Urinary 

Disorders 

 Common 

Renal failure◊ 

General 

Disorders and 

Administration 

Site Conditions 

Very Common 

Fatigue, Asthenia◊, Peripheral oedema, 

Influenza like illness syndrome 

(including pyrexia◊, cough) 

 

Common 

Chills 

Common 

Pyrexia◊, Asthenia◊, Fatigue 

^see section 4.8 description of selected adverse reactions 
◊Adverse events reported as serious in mantle cell lymphoma clinical trialsAlgorithm applied for mantle cell lymphoma: 

• Mantle cell lymphoma controlled phase 2 study 
o All treatment-emergent adverse events with ≥ 5% of subjects in lenalidomide arm and at least 2% difference in proportion 

between lenalidomide and control arm 

o All treatment-emergent Grade 3 or 4 adverse events in ≥1% of subjects in lenalidomide arm and at least 1.0% difference in 
proportion between lenalidomide and control arm 

o All Serious treatment-emergent adverse events in ≥1% of subjects in lenalidomide arm and at least 1.0% difference in 
proportion between lenalidomide and control arm 

• Mantle cell lymphoma single arm phase 2 study 
o All treatment-emergent adverse events with ≥ 5% of subjects 
o All Grade 3 or 4 treatment-emergent adverse events reported in 2 or more subjects 
o All Serious treatment-emergent adverse events reported in 2 or more subjects 

 

Tabulated summary for combination therapy in FL 

The following table is derived from data gathered during the main studies (NHL-007 and NHL-008) using 

lenalidomide in combination with rituximab for patients with follicular lymphoma. 

 



 35 

Table 5: ADRs reported in clinical trials in patients with follicular lymphoma treated with 

lenalidomide in combination with rituximab 

System Organ Class / 

Preferred Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Infections and 

Infestations 

Very Common 

Upper respiratory tract infection  

 

Common 

Pneumonia◊, Influenza, Bronchitis, 

Sinusitis, Urinary tract infection  

Common 

Pneumonia◊, Sepsis◊, Lung infection, 

Bronchitis, Gastroenteritis, Sinusitis, 

Urinary tract infection, Cellulitis◊ 

 

Neoplasms Benign, 

Malignant and 

Unspecified (incl cysts 

and polyps) 

Very Common 

Tumour flare^ 

 

Common 

Squamous Cell Carcinoma of Skin◊,^,+ 

Common 

Basal cell carcinoma^,◊ 

Blood and Lymphatic 

System Disorders 

Very Common 

Neutropenia^,◊, Anaemia◊, 

Thrombocytopenia^, Leucopenia** 

Lymphopenia*** 

 

Very Common 

Neutropenia^,◊ 

 

Common 

Anaemia◊, Thrombocytopenia^, 

Febrile neutropenia◊, Pancytopenia, 

Leucopenia**, Lymphopenia*** 

Metabolism and 

Nutrition Disorders 

Very Common 

Decreased appetite, Hypokalaemia 

 

Common 

Hypophosphataemia, Dehydration 

 

Common 

Dehydration, Hypercalcaemia◊, 

Hypokalaemia, Hypophosphataemia, 

Hyperuricaemia 

Psychiatric Disorders Common 

Depression, Insomnia  

 

Nervous System 

Disorders 

Very Common 

Headache, Dizziness  

 

Common 

Peripheral sensory neuropathy, 

Dysgeusia  

Common 

Syncope 

Cardiac Disorders Uncommon 

Arrhythmia◊ 

 

Vascular Disorders Common 

Hypotension 

Common 

Pulmonary embolism^,◊, Hypotension 

Respiratory, Thoracic 

and Mediastinal 

Disorders 

Very Common 

Dyspnoea◊, Cough, 

Common 

Oropharyngeal pain, Dysphonia 

Common 

Dyspnoea◊ 

Gastrointestinal 

Disorders 

Very Common 

Abdominal pain◊, Diarrhoea, 

Constipation, Nausea, Vomiting, 

Dyspepsia 

 

Common 

Upper abdominal pain, Stomatitis, Dry 

mouth 

Common 

Abdominal pain◊, Diarrhoea, 

Constipation, Stomatitis 

Skin and Subcutaneous 

Tissue Disorders 

Very Common 

Rash*, Pruritus  

 

Common 

Dry skin, Night sweats, Erythema 

Common 

Rash*, Pruritus  



 36 

System Organ Class / 

Preferred Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Musculoskeletal and 

Connective Tissue 

Disorders 

Very Common 

Muscle spasms, Back pain, Arthralgia  

 

Common 

Pain in extremity, Muscular weakness, 

Musculoskeletal pain, Myalgia, Neck 

pain 

Common 

Muscular weakness, Neck pain 

Renal and Urinary 

Disorders 

 Common 

Acute kidney injury◊ 

General Disorders and 

Administration Site 

Conditions 

Very Common 

Pyrexia, Fatigue, Asthenia, Peripheral 

oedema 

 

Common 

Malaise, Chills 

Common 

Fatigue, Asthenia 

Investigations Very Common 

Alanine aminotransferase increased  

 

Common 

Weight decreased, Blood Bilirubin 

increased 

 

^see section 4.8 description of selected adverse reactions 

Algorithm applied for follicular lymphoma: 

Controlled– Phase 3 trial:  

o NHL-007 ADRs- All treatment-emergent AEs with ≥ 5.0% of subjects in lenalidomide/rituximab arm and at least 2.0% higher 
frequency (%) in Len arm compared to control arm - (Safety population) 

o NHL-007 Gr 3/4 ADRs- All Grades 3 or Grade 4 treatment-emergent AEs with at least 1.0% subjects in 
lenalidomide/rituximab arm and at least 1.0% higher frequency in lenalidomide arm compared to control arm - (safety 

population) 

o NHL-007 Serious ADRs- All serious treatment-emergent AEs with at least 1.0% subjects in lenalidomide/rituximab arm and at 
least 1.0% higher frequency in lenalidomide/rituximab arm compared to control arm - (safety population) 

FL single arm - phase 3 trial: 

o NHL-008 ADRs- All treatment-emergent adverse events with ≥ 5.0% of subjects  
o NHL-008 Gr 3/4 ADRs- All Grade 3/4 treatment-emergent adverse events reported in ≥ 1.0% of subjects  
o NHL-008 Serious ADRs- All serious treatment-emergent adverse events reported in ≥ 1.0% of subjects  

◊Adverse events reported as serious in follicular lymphoma clinical trials 
+ Applies to serious adverse drug reactions only 

* Rash includes PT of rash and rash maculo-papular 
**Leucopenia includes PT leucopenia and white blood cell count decreased 

***Lymphopenia includes PT lymphopenia and lymphocyte count decreased 
 

Tabulated summary of post-marketing adverse reactions 

In addition to the above adverse reactions identified from the pivotal clinical trials, the following table is 

derived from data gathered from post-marketing data.  

 

Table 6. ADRs reported in post-marketing use in patients treated with lenalidomide 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Infections and 

Infestations 

Not Known 

Viral infections, including herpes zoster and 

hepatitis B virus reactivation 

Not Known 

Viral infections, including herpes 

zoster and hepatitis B virus 

reactivation 

Neoplasms Benign, 

Malignant and 

Unspecified (incl 

cysts and polyps) 

 Rare 

Tumour lysis syndrome 

 

Blood and 

Lymphatic System 

Disorders 

Not Known 

Acquired haemophilia 

 



 37 

System Organ 

Class / Preferred 

Term 

All ADRs/Frequency Grade 3−4 ADRs/Frequency 

 

Immune System 

Disorders 

Rare 

Anaphylactic reaction^ 

 

Not Known 

Solid organ transplant rejection 

 

Rare 

Anaphylactic reaction^ 

 

Endocrine 

Disorders 

Common 

Hyperthyroidism 

 

Respiratory, 

Thoracic and 

Mediastinal 

Disorders 

Uncommon 

Pulmonary hypertension 

Rare 

Pulmonary hypertension  

 

Not Known 

Interstitial pneumonitis 

 

Gastrointestinal 

Disorders 

 Not Known 

Pancreatitis, Gastrointestinal 

perforation (including 

diverticular, intestinal and large 

intestine perforations)^ 

 

Hepatobiliary 

Disorders 

Not Known 

Acute hepatic failure^, Hepatitis toxic^, 

Cytolytic hepatitis^, Cholestatic hepatitis^, 

Mixed cytolytic/cholestatic hepatitis^ 

Not Known 

Acute hepatic failure^, Hepatitis 

toxic^ 

Skin and 

Subcutaneous 

Tissue Disorders 

 Uncommon 

Angioedema 

 

Rare 

Stevens-Johnson Syndrome^, 

Toxic epidermal necrolysis^ 

 

Not Known 

Leukocytoclastic vasculitis, Drug 

Reaction with Eosinophilia and 

Systemic Symptoms^ 

 
^see section 4.8 description of selected adverse reactions 
 

Description of selected adverse reactions 

Teratogenicity 

Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active 

substance that causes severe life-threatening birth defects. In monkeys, lenalidomide induced malformations 

similar to those described with thalidomide (see sections 4.6 and 5.3). If lenalidomide is taken during 

pregnancy, a teratogenic effect of lenalidomide in humans is expected. 

 

Neutropenia and thrombocytopenia 

• Newly diagnosed multiple myeloma: patients who have undergone ASCT treated with lenalidomide 
maintenance 

Lenalidomide maintenance after ASCT is associated with a higher frequency of Grade 4 neutropenia 

compared to placebo maintenance (32.1% vs 26.7% [16.1% vs 1.8% after the start of maintenance treatment] 

in CALGB 100104 and 16.4% vs 0.7% in IFM 2005-02, respectively). Treatment-emergent AEs of 

neutropenia leading to lenalidomide discontinuation were reported in 2.2% of patients in CALGB 100104 

and 2.4% of patients in IFM 2005-02, respectively. Grade 4 febrile neutropenia was reported at similar 

frequencies in the lenalidomide maintenance arms compared to placebo maintenance arms in both studies 



 38 

(0.4% vs 0.5% [0.4% vs 0.5% after the start of maintenance treatment] in CALGB 100104 and 0.3% vs 0% 

in IFM 2005-02, respectively). 

 

Lenalidomide maintenance after ASCT is associated with a higher frequency of Grade 3 or 4 

thrombocytopenia compared to placebo maintenance (37.5% vs 30.3% [17.9% vs 4.1% after the start of 

maintenance treatment] in CALGB 100104 and 13.0% vs 2.9% in IFM 2005-02, respectively). 

 

• Newly diagnosed multiple myeloma patients who are not eligible for transplant receiving 
lenalidomide in combination with bortezomib and dexamethasone 

Grade 4 neutropenia was observed in the RVd arm to a lesser extent than in the Rd comparator arm (2.7% vs 

5.9%) in the SWOG S0777 study. Grade 4 febrile neutropenia was reported at similar frequencies in the RVd 

arm compared to the Rd arm (0.0% vs 0.4%).  

 

Grade 3 or 4 thrombocytopenia was observed in the RVd arm to a greater extent than in the Rd comparator 

arm (17.2 % vs 9.4%). 

 

• Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with 
lenalidomide in combination with dexamethasone 

The combination of lenalidomide with dexamethasone in newly diagnosed multiple myeloma patients is 

associated with a lower frequency of Grade 4 neutropenia (8.5% in Rd and Rd18, compared with MPT 

(15%). Grade 4 febrile neutropenia was observed infrequently (0.6% in Rd and Rd18 compared with 0.7% in 

MPT). 

 

The combination of lenalidomide with dexamethasone in newly diagnosed multiple myeloma patients is 

associated with a lower frequency of Grade 3 and 4 thrombocytopenia (8.1% in Rd and Rd18) compared 

with MPT (11.1%). 

 

• Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with 
lenalidomide in combination with melphalan and prednisone 

The combination of lenalidomide with melphalan and prednisone in newly diagnosed multiple myeloma 

patients is associated with a higher frequency of Grade 4 neutropenia (34.1% in MPR+R/MPR+p) compared 

with MPp+p (7.8%). There was a higher frequency of Grade 4 febrile neutropenia observed (1.7% in 

MPR+R/MPR+p compared to 0.0% in MPp+p).  

 

The combination of lenalidomide with melphalan and prednisone in newly diagnosed multiple myeloma 

patients is associated with a higher frequency of Grade 3 and Grade 4 thrombocytopenia (40.4% in 

MPR+R/MPR+p) compared with MPp+p (13.7%).  

 

• Multiple myeloma: patients with at least one prior therapy 
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). Grade 4 febrile neutropenia episodes were observed 

infrequently (0.6% in lenalidomide/dexamethasone-treated patients compared to 0.0% in 

placebo/dexamethasone treated patients). 

 

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). 

 

• Myelodysplastic syndromes patients 
In myelodysplastic syndromes patients, lenalidomide is associated with a higher incidence of Grade 3 or 4 

neutropenia (74.6% in lenalidomide-treated patients compared with 14.9% in patients on placebo in the 

phase 3 study). Grade 3 or 4 febrile neutropenia episodes were observed in 2.2% of lenalidomide-treated 

patients compared with 0.0% in patients on placebo). Lenalidomide is associated with a higher incidence of 

Grade 3 or 4 thrombocytopenia (37% in lenalidomide-treated patients compared with 1.5% in patients on 

placebo in the phase 3 study). 

 



 39 

• Mantle cell lymphoma patients 
In mantle cell lymphoma patients, lenalidomide is associated with a higher incidence of Grade 3 or 4 

neutropenia (43.7% in lenalidomide-treated patients compared with 33.7% in patients in the control arm in 

the phase 2 study). Grade 3 or 4 febrile neutropenia episodes were observed in 6.0% of lenalidomide-treated 

patients compared with 2.4% in patients on control arm.  

 

• Follicular lymphoma patients 
The combination of lenalidomide with rituximab in follicular lymphoma is associated with a higher rate of 

grade 3 or grade 4 neutropenia (50.7% in lenalidomide/rituximab treated patients compared with 12.2% in 

placebo/rituximab treated patients). All grade 3 or 4 neutropenia were reversible through dose interruption, 

reduction and/or supportive care with growth factors. Additionally, febrile neutropenia was observed 

infrequently (2.7% in lenalidomide/rituximab treated patients compared with 0.7% in placebo/rituximab 

treated patients).   

 

Lenalidomide in combination with rituximab is also associated with a higher incidence of grade 3 or 

4 thrombocytopenia (1.4% in lenalidomide/rituximab treated patients compared to 0% in placebo/rituximab 

patients).  

 

Venous thromboembolism 

An increased risk of DVT and PE is associated with the use of the combination of lenalidomide with 

dexamethasone in patients with multiple myeloma, and to a lesser extent in patients treated with 

lenalidomide in combination with melphalan and prednisone or in patients with multiple myeloma, 

myelodysplastic syndromes and mantle cell lymphoma treated with lenalidomide monotherapy (see 

section 4.5).  

Concomitant administration of erythropoietic agents or previous history of DVT may also increase 

thrombotic risk in these patients. 

 

Myocardial infarction 

Myocardial infarction has been reported in patients receiving lenalidomide, particularly in those with known 

risk factors. 

 

Haemorrhagic disorders 

Haemorrhagic disorders are listed under several system organ classes: Blood and lymphatic system 

disorders; nervous system disorders (intracranial haemorrhage); respiratory, thoracic and mediastinal 

disorders (epistaxis); gastrointestinal disorders (gingival bleeding, haemorrhoidal haemorrhage, rectal 

haemorrhage); renal and urinary disorders (haematuria); injury, poisoning and procedural complications 

(contusion) and vascular disorders (ecchymosis). 

 

Allergic reactions and severe skin reactions 

 

Cases of allergic reactions  including angioedema, anaphylactic reaction and severe cutaneous reactions 

including SJS, TEN and DRESS have been reported with the use of lenalidomide. A possible cross-reaction 

between lenalidomide and thalidomide has been reported in the literature. Patients with a history of severe 

rash associated with thalidomide treatment should not receive lenalidomide (see section 4.4). 

 

Second primary malignancies 

In clinical trials in previously treated myeloma patients with lenalidomide/dexamethasone compared to 

controls, mainly comprising of basal cell or squamous cell skin cancers. 

 

Acute myeloid leukaemia  

• Multiple myeloma 
Cases of AML have been observed in clinical trials of newly diagnosed multiple myeloma in patients taking 

lenalidomide treatment in combination with melphalan or immediately following HDM/ASCT (see section 

4.4). This increase was not observed in clinical trials of newly diagnosed multiple myeloma in patients 

taking lenalidomide in combination with dexamethasone compared to thalidomide in combination with 

melphalan and prednisone. 

 



 40 

• Myelodysplastic syndromes 
Baseline variables including complex cytogenetics and TP53 mutation are associated with progression to 

AML in subjects who are transfusion dependent and have a Del (5q) abnormality (see section 4.4). The 

estimated 2-year cumulative risk of progression to AML were 13.8% in patients with an isolated Del (5q) 

abnormality compared to 17.3% for patients with Del (5q) and one additional cytogenetic abnormality and 

38.6% in patients with a complex karyotype. 

In a post-hoc analysis of a clinical trial of lenalidomide in myelodysplastic syndromes, the estimated 2-year 

rate of progression to AML was 27.5 % in patients with IHC-p53 positivity and 3.6% in patients with IHC-

p53 negativity (p=0.0038). In the patients with IHC-p53 positivity, a lower rate of progression to AML was 

observed amongst patients who achieved a transfusion independence (TI) response (11.1%) compared to a 

non-responder (34.8%).  

 

Hepatic disorders 

The following post-marketing adverse reactions have been reported (frequency unknown): acute hepatic 

failure and cholestasis (both potentially fatal), toxic hepatitis, cytolytic hepatitis, mixed cytolytic/cholestatic 

hepatitis. 

 
Rhabdomyolysis 

Rare cases of rhabdomyolysis have been observed, some of them when lenalidomide is administered with a 

statin. 

 
Thyroid disorders  

Cases of hypothyroidism and cases of hyperthyroidism have been reported (see section 4.4 Thyroid 

disorders). 

 

Tumour flare reaction and tumour lysis syndrome 

In study MCL-002, approximately 10% of lenalidomide-treated patients experienced TFR compared to 0% 

in the control arm. The majority of the events occurred in cycle 1, all were assessed as treatment-related, and 

the majority of the reports were grade 1 or 2. Patients with high MIPI at diagnosis or bulky disease (at least 

one lesion that is ≥ 7 cm in the longest diameter) at baseline may be at risk of TFR. In study MCL-002, TLS 

was reported for one patient in each of the two treatment arms. In the supportive study MCL-001, 

approximately 10% of subjects experienced TFR; all report were grade 1 or 2 in severity and all were 

assessed as treatment-related. The majority of the events occurred in cycle 1. There were no reports of TLS 

in study MCL-001 (see section 4.4). 

 

In study NHL-007, TFR was reported in 19/146 (13.0%) of patients in the lenalidomide/rituximab arm 

versus 1/148 (0.7%) patients in the placebo/rituximab arm. Most TFRs (18 out of 19) reported in the 

lenalidomide/rituximab arm occurred during first two cycles of treatment. One FL patient in the 

lenalidomide/rituximab arm experienced a Grade 3 TFR event versus no patients in the placebo/rituximab 

arm. In study NHL-008, 7/177 (4.0%) of FL patients experienced TFR; (3 reports were Grade 1 and 4 reports 

were Grade 2 severity); while 1 report was considered serious. In study NHL-007, TLS occurred in 2 FL 

patients (1.4%) in the lenalidomide/rituximab arm and no FL patients in the placebo/rituximab arm; neither 

patient had a Grade 3 or 4 event. TLS occurred in 1 FL patient (0.6%) in study NHL-008. This single event 

was identified as a serious, Grade 3 adverse reaction. For study NHL-007 no patients had to discontinue 

lenalidomide/rituximab therapy due to TFR or TLS. 

 

Gastrointestinal disorders 

Gastrointestinal perforations have been reported during treatment with lenalidomide. Gastrointestinal 

perforations may lead to septic complications and may be associated with fatal outcome. 

 
Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 41 

4.9 Overdose 

 

There is no specific experience in the management of lenalidomide overdose in patients, although in dose-

ranging studies some patients were exposed to up to 150 mg, and in single-dose studies, some patients were 

exposed to up to 400 mg. The dose limiting toxicity in these studies was essentially haematological. In the 

event of overdose, supportive care is advised. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Other immunosuppressants. ATC code: L04AX04. 

 

Mechanism of action 

Lenalidomide binds directly to cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex 

that includes deoxyribonucleic acid (DNA) damage-binding protein 1(DDB1), cullin 4 (CUL4), and 

regulator of cullins 1 (Roc1). In haematopoietic cells, lenalidomide binding to cereblon recruits substrate 

proteins Aiolos and Ikaros, lymphoid transcriptional factors, leading to their ubiquitination and subsequent 

degradation resulting in direct cytotoxic and immunomodulatory effects. 

 

Specifically, lenalidomide inhibits proliferation and enhances apoptosis of certain haematopoietic tumour 

cells (including MM plasma tumour cells, follicular lymphoma tumour cells and those with deletions of 

chromosome 5), enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number 

of NK, T and NK T cells. In MDS Del (5q), lenalidomide selectively inhibits the abnormal clone by 

increasing the apoptosis of Del (5q) cells. 

The combination of lenalidomide and rituximab increases ADCC and direct tumor apoptosis in follicular 

lymphoma cells. 

The lenalidomide mechanism of action also includes additional activities such as anti-angiogenic and pro-

erythropoietic properties. Lenalidomide inhibits angiogenesis by blocking the migration and adhesion of 

endothelial cells and the formation of microvessels, augments foetal haemoglobin production by CD34+ 

haematopoietic stem cells, and inhibits production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by 

monocytes. 

 

Clinical efficacy and safety 

Lenalidomide efficacy and safety have been evaluated in six phase 3 studies in newly diagnosed multiple 

myeloma, two phase 3 studies in relapsed refractory multiple myeloma, one phase 3 study and one phase 2 

study in myelodysplastic syndromes and one phase 2 study in mantle cell lymphoma and one phase 3 and 

one phase 3b study in iNHL as described below. 

 

Newly diagnosed multiple myeloma 

• Lenalidomide maintenance in patients who have undergone ASCT 
The efficacy and safety of lenalidomide maintenance was assessed in two phase 3 multicentre, randomised, 

double-blind 2-arm, parallel group, placebo-controlled studies: CALGB 100104 and IFM 2005-02 

 

CALGB 100104 

Patients between 18 and 70 years of age with active MM requiring treatment and without prior progression 

after initial treatment were eligible. 

 

Patients were randomised 1:1 within 90-100 days after ASCT to receive either lenalidomide or placebo 

maintenance. The maintenance dose was 10 mg once daily on days 1-28 of repeated 28-day cycles (increased 

up to 15 mg once daily after 3 months in the absence of dose-limiting toxicity), and treatment was continued 

until disease progression. 

 

The primary efficacy endpoint in the study was progression free survival (PFS) from randomisation to the 

date of progression or death, whichever occurred first; the study was not powered for the overall survival 

endpoint. In total 460 patients were randomised: 231 patients to Lenalidomide and 229 patients to placebo. 

The demographic and disease-related characteristics were balanced across both arms. 



 42 

 

The study was unblinded upon the recommendations of the data monitoring committee after surpassing the 

threshold for a preplanned interim analysis of PFS. After unblinding, patients in the placebo arm were 

allowed to cross over to receive lenalidomide before disease progression. 

 

The results of PFS at unblinding, following a preplanned interim analysis, using a cut-off of 17 December 

2009 (15.5 months follow up) showed a 62% reduction in risk of disease progression or death favouring 

lenalidomide (HR = 0.38; 95% CI 0.27, 0.54; p <0.001). The median overall PFS was 33.9 months (95% CI 

NE, NE) in the lenalidomide arm versus 19.0 months (95% CI 16.2, 25.6) in the placebo arm.  

 

The PFS benefit was observed both in the subgroup of patients with CR and in the subgroup of patients who 

had not achieved a CR. 

 

The results for the study, using a cut-off of 1 February 2016, are presented in Table 7. 

 

Table 7 Summary of overall efficacy data 

 Lenalidomide 

(N = 231) 

Placebo 

(N = 229) 

Investigator-assessed PFS   

Mediana PFS time, months (95% CI)b 56.9 (41.9, 71.7) 29,4 (20.7, 35.5) 

HR [95% CI]c; p-valued 0.61 (0.48, 0.76); <0.001 

PFS2e   

Mediana PFS2 time, months (95% CI) b 80.2 (63.3, 101.8) 52.8 (41.3, 64.0) 

HR [95% CI]c ; p-valued 0.61 (0.48, 0.78); <0.001 

Overall survival   

Mediana OS time, months (95% CI)b 111.0 (101.8, NE) 84.2 (71.0, 102.7) 

8-year survival rate, % (SE) 60.9 (3.78) 44.6 (3.98) 

HR [95% CI]c ; p-valued 0.61 (0.46, 0.81); <0.001 

Follow-up   

Medianf (min, max), months: all surviving patients 81.9 (0.0, 119.8) 81.0 (4.1, 119.5) 
CI = confidence interval; HR = hazard ratio; max = maximum; min = minimum; NE = not estimable; OS = overall survival; PFS = progression-free 

survival;  
a The median is based on the Kaplan-Meier estimate. 
b The 95% CI about the median. 
c Based on Cox proportional hazards model comparing the hazard functions associated with the indicated treatment arms. 
d The p-value is based on the unstratified log-rank test of Kaplan-Meier curve differences between the indicated treatment arms. 
e Exploratory endpoint (PFS2). Lenalidomide received by subjects in the placebo arm who crossed over prior to PD upon study unblinding was not 

considered as a second-line therapy. 
f Median follow-up post-ASCT for all surviving subjects. 

Data cuts: 17 Dec 2009 and 01 Feb 2016 

 

IFM 2005-02 

Patients aged < 65 years at diagnosis who had undergone ASCT and had achieved at least a stable disease 

response at the time of hematologic recovery were eligible. Patients were randomised 1:1 to receive either 

lenalidomide or placebo maintenance (10 mg once daily on days 1-28 of repeated 28-day cycles increased up 

to 15 mg once daily after 3 months in the absence of dose-limiting toxicity) following 2 courses of 

lenalidomide consolidation (25 mg/day, days 1-21 of a 28-day cycle). Treatment was to be continued until 

disease progression. 

 

The primary endpoint was PFS defined from randomisation to the date of progression or death, whichever 

occurred first; the study was not powered for the overall survival endpoint. In total 614 patients were 

randomised: 307 patients to lenalidomide and 307 patients to placebo. 

 

The study was unblinded upon the recommendations of the data monitoring committee after surpassing the 

threshold for a preplanned interim analysis of PFS. After unblinding, patients receiving placebo were not 

crossed over to lenalidomide therapy prior to progressive disease. The lenalidomide arm was discontinued, 

as a proactive safety measure, after observing an imbalance of SPMs (see Section 4.4). 

 

The results of PFS at unblinding, following a preplanned interim analysis, using a cut-off of 7 July 2010 

(31.4 months follow up) showed a 48% reduction in risk of disease progression or death favouring 



 43 

lenalidomide (HR = 0.52; 95% CI 0.41, 0.66; p <0.001). The median overall PFS was 40.1 months (95% CI 

35.7, 42.4) in the lenalidomide arm versus 22.8 months (95% CI 20.7, 27.4) in the placebo arm. 

 

The PFS benefit was less in the subgroup of patients with CR than in the subgroup of patients who had not 

achieved a CR. 

 

The updated PFS, using a cut-off of 1 February 2016 (96.7 months follow up) continues to show a PFS 

advantage: HR = 0.57 (95% CI 0.47, 0.68; p < 0.001). The median overall PFS was 44.4 months (39.6, 52.0) 

in the lenalidomide arm versus 23.8 months (95% CI 21.2, 27.3) in the placebo arm. For PFS2, the observed 

HR was 0.80 (95% CI 0.66, 0.98; p = 0.026) for lenalidomide versus placebo. The median overall PFS2 was 

69.9 months (95% CI 58.1, 80.0) in the lenalidomide arm versus 58.4 months (95% CI 51.1, 65.0) in the 

placebo arm. For OS, the observed HR was 0.90 (95% CI 0.72, 1.13; p = 0.355) for lenalidomide versus 

placebo. The median overall survival time was 105.9 months (95% CI 88.8, NE) in the lenalidomide arm 

versus 88.1 months (95% CI 80.7, 108.4) in the placebo arm. 

 

• Lenalidomide in combination with bortezomib and dexamethasone in patients who are not eligible 
for stem cell transplantation 

The SWOG S0777 study evaluated the addition of bortezomib to a foundation of lenalidomide and 

dexamethasone, as initial treatment, followed by continued Rd until disease progression, in patients with 

previously untreated multiple myeloma who are either ineligible for transplant or eligible for transplant with 

no plan to undertake immediate transplant.  
 
Patients in the lenalidomide, bortezomib and dexamethasone (RVd) arm received lenalidomide 25 mg/day 

orally on days 1-14, intravenous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, and dexamethasone 20 

mg/day orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of repeated 21-day cycles for up to eight 21-day cycles (24 

weeks). Patients in the lenalidomide and dexamethasone (Rd) arm received lenalidomide 25 mg/day orally on 

days 1-21, and dexamethasone 40 mg/day orally on days 1, 8, 15, and 22 of repeated 28-day cycles for up to 

six 28-day cycles (24 weeks). Patients in both arms took continued Rd: lenalidomide 25 mg/day orally on 

days 1-21 and dexamethasone 40 mg/day orally on days 1, 8, 15, and 22 of repeated 28-day cycles. 

Treatment was to be continued until disease progression. 

 

The primary efficacy endpoint in the study was progression free survival (PFS). In total 523 patients were 

enrolled into the study, with 263 patients randomised to RVd and 260 patients randomised to Rd. The 

demographics and disease-related baseline characteristics of the patients were well balanced between arms.  

 

The results of PFS, as assessed by IRAC, at the time of the primary analysis, using a cut-off of 05 November 

2015 (50.6 months follow up) showed a 24% reduction in risk of disease progression or death favouring RVd 

(HR = 0.76; 95% CI 0.61, 0.94; p = 0.010). The median overall PFS was 42.5 months (95% CI 34.0, 54.8) in 

the RVd arm versus 29.9 months (95% CI 25.6, 38.2) in the Rd arm. The benefit was observed regardless of 

eligibility for stem cell transplant. 

 

The results for the study, using a cut-off of 01 December 2016, where the median follow-up time for all 

surviving subjects was 69.0 months, are presented in Table 8. The benefit favouring RVd was observed 

regardless of eligibility for stem cell transplant. 

 

Table 8. Summary of overall efficacy data 

 Initial treatment 

RVd 

(3-week cycles  8) 

(N = 263) 

Rd 

(4-week cycles  6) 

(N = 260) 

IRAC-assessed PFS (months) 

Mediana PFS time, months (95% CI)b 41.7 (33.1, 51.5) 29.7 (24.2, 37.8) 

HR [95% CI]c; p-valued 0.76 (0.62, 0.94); 0.010 

Overall survival (months) 

Mediana OS time, months (95% CI)b 89.1 (76.1, NE) 67.2 (58.4, 90.8) 

HR [95% CI]c; p-valued 0.72 (0.56, 0.94); 0.013 

Response – n (%) 



 44 

 Initial treatment 

RVd 

(3-week cycles  8) 

(N = 263) 

Rd 

(4-week cycles  6) 

(N = 260) 

Overall response: CR, VGPR, or PR 199 (75.7) 170 (65.4) 

≥ VGPR 153 (58.2) 83 (31.9) 

Follow-up (months) 

Mediane (min, max): all patients 61.6 (0.2, 99.4) 59.4 (0.4, 99.1) 
CI = confidence interval; HR = hazard ratio; max = maximum; min = minimum; NE = not estimable; OS = overall survival; PFS = progression-free 

survival. 
a The median is based on Kaplan-Meier estimate. 
b Two-sided 95% CI about the median time. 
c Based on unstratified Cox proportional hazards model comparing hazard functions associated with treatment arms (RVd:Rd). 
d The p-value is based on unstratified log-rank test. 
e Median follow-up was calculated from the date of randomization. 

Data cutoff date = 01 Dec 2016. 

 

Updated OS results, using a cut-off of 01 May 2018 (84.2 months median follow-up for surviving subjects) 

continue to show an OS advantage favouring RVd: HR = 0.73 (95% CI 0.57, 0.94; p=0.014). The proportion 

of subjects alive after 7 years was 54.7% in the RVd arm versus 44.7% in the Rd arm. 

 

• Lenalidomide in combination with dexamethasone in patients who are not eligible for stem cell 
transplantation 

The safety and efficacy of lenalidomide was assessed in a phase 3, multicentre, randomised, open-label, 

3-arm study (MM-020) of patients who were at least 65 years of age or older or, if younger than 65 years of 

age, were not candidates for stem cell transplantation because they declined to undergo stem cell 

transplantation or stem cell transplantation is not available to the patient due to cost or other reason.The study 

(MM-020) compared lenalidomide and dexamethasone (Rd) given for 2 different durations of time (i.e., until 

progressive disease [Arm Rd] or for up to eighteen 28-day cycles [72 weeks, Arm Rd18]) to melphalan, 

prednisone and thalidomide (MPT) for a maximum of twelve 42-day cycles (72 weeks). Patients were 

randomised (1:1:1) to 1 of 3 treatment arms. Patients were stratified at randomisation by age (≤75 versus >75 

years), stage (ISS Stages I and II versus Stage III), and country. 

 

Patients in the Rd and Rd18 arms took lenalidomide 25 mg once daily on days 1 to 21 of 28-day cycles 

according to protocol arm. Dexamethasone 40 mg was dosed once daily on days 1, 8, 15, and 22 of each 

28-day cycle. Initial dose and regimen for Rd and Rd18 were adjusted according to age and renal function 

(see section 4.2). Patients >75 years received a dexamethasone dose of 20 mg once daily on days 1, 8, 15, 

and 22 of each 28-day cycle. All patients received prophylactic anticoagulation (low molecular weight 

heparin, warfarin, heparin, low-dose aspirin) during the study. 

 

The primary efficacy endpoint in the study was progression free survival (PFS). In total 1623 patients were 

enrolled into the study, with 535 patients randomised to Rd, 541 patients randomised to Rd18 and 547 

patients randomised to MPT. The demographics and disease-related baseline characteristics of the patients 

were well balanced in all 3 arms. In general, study subjects had advanced-stage disease: of the total study 

population, 41% had ISS stage III, 9% had severe renal insufficiency (creatinine clearance [CLcr] 

< 30 mL/min). The median age was 73 in the 3 arms. 

 

In an updated analysis of PFS, PFS2 and OS using a cut off of 3 March 2014 where the median follow-up 

time for all surviving subjects was 45.5 months, the results of the study are presented in Table 9: 

 

Table 9. Summary of overall efficacy data 

 Rd 

(N = 535) 

Rd18 

(N = 541) 

MPT 

(N = 547) 

Investigator-assessed PFS − (months)    

Mediana PFS time, months (95% CI)b 26.0 (20.7, 29.7) 21.0 (19.7, 22.4) 21.9 (19.8, 23.9) 

HR [95% CI]c; p-valued    

Rd vs MPT 0.69 (0.59, 0.80); <0.001 

Rd vs Rd18 0.71 (0.61, 0.83); <0.001 

Rd18 vs MPT 0.99 (0.86, 1.14); 0.866 



 45 

 Rd 

(N = 535) 

Rd18 

(N = 541) 

MPT 

(N = 547) 

PFS2e − (months)    

Mediana PFS2 time, months (95% CI)b 42.9 (38.1, 47.4) 40.0 (36.2, 44.2) 35.0 (30.4, 37.8) 

HR [95% CI]c; p-valued    

Rd vs MPT 0.74 (0.63, 0.86); <0.001 

Rd vs Rd18 0.92 (0.78, 1.08); 0.316 

Rd18 vs MPT 0.80 (0.69, 0.93); 0.004 

Overall survival (months)    

Mediana OS time, months (95% CI)b 58.9 (56.0, NE) 56.7 (50.1, NE) 48.5 (44.2, 52.0) 

HR [95% CI]c; p-valued    

Rd vs MPT 0.75 (0.62, 0.90); 0.002 

Rd vs Rd18 0.91 (0.75, 1.09); 0.305 

Rd18 vs MPT 0.83 (0.69, 0.99); 0.034 

Follow-up (months)    

Medianf (min, max): all patients 40.8 (0.0, 65.9) 40.1 (0.4, 65.7) 38.7 (0.0, 64.2) 

Myeloma responseg n (%)    

CR 81 (15.1) 77 (14.2) 51 (9.3) 

VGPR 152 (28.4) 154 (28.5) 103 (18.8) 

PR 169 (31.6) 166 (30.7) 187 (34.2) 

Overall response: CR, VGPR, or PR 402 (75.1) 397 (73.4) 341 (62.3) 

Duration of response − (months)h    

Mediana (95% CI)b 35.0 (27.9, 43.4) 22.1 (20.3, 24.0) 22.3 (20.2, 24.9) 
AMT = antimyeloma therapy; CI = confidence interval; CR = complete response; d = low-dose dexamethasone; HR = hazard ratio; 

IMWG = International Myeloma Working Group; IRAC = Independent Response Adjudication Committee; M = melphalan; max = maximum; 

min = minimum; NE = not estimable; OS = overall survival; P = prednisone; PFS = progression-free survival; PR = partial response; 

R = lenalidomide; Rd = Rd given until documentation of progressive disease; Rd18 = Rd given for ≤ 18 cycles; SE = standard error; 

T = thalidomide; VGPR = very good partial response; vs = versus. 
a   The median is based on the Kaplan-Meier estimate. 
b   The 95% CI about the median. 
c  Based on Cox proportional hazards model comparing the hazard functions associated with the indicated treatment arms. 
d  The p-value is based on the unstratified log-rank test of Kaplan-Meier curve differences between the indicated treatment arms. 
e   Exploratory endpoint (PFS2) 
f   The median is the univariate statistic without adjusting for censoring. 
g    Best assessment of adjudicated response during the treatment phase of the study (for definitions of each response category, Data cut-off 

date = 24 May 2013). 
h data cut 24 May 2013  

 

• Lenalidomide in combination with melphalan and prednisone followed by maintenance therapy in 
patients who are not eligible for transplant 

The safety and efficacy of lenalidomide was assessed in a phase 3 multicentre, randomised double blind 

3 arm study (MM-015) of patients who were 65 years or older and had a serum creatinine < 2.5 mg/dL. The 

study compared lenalidomide in combination with melphalan and prednisone (MPR) with or without 

lenalidomide maintenance therapy until disease progression, to that of melphalan and prednisone for a 

maximum of 9 cycles. Patients were randomised in a 1:1:1 ratio to one of 3 treatment arms. Patients were 

stratified at randomisation by age ( 75 vs. > 75 years) and stage (ISS; Stages I and II vs. stage III). 

 

This study investigated the use of combination therapy of MPR (melphalan 0.18 mg/kg orally on days 1 to 4 

of repeated 28-day cycles; prednisone 2 mg/kg orally on days 1 to 4 of repeated 28-day cycles; and 

lenalidomide 10 mg/day orally on days 1 to 21 of repeated 28-day cycles) for induction therapy, up to 

9 cycles. Patients who completed 9 cycles or who were unable to complete 9 cycles due to intolerance 

proceeded to maintenance therapy starting with lenalidomide 10 mg orally on days 1 to 21 of repeated 

28-day cycles until disease progression. 

 

The primary efficacy endpoint in the study was progression free survival (PFS). In total 459 patients were 

enrolled into the study, with 152 patients randomised to MPR+R, 153 patients randomised to MPR+p and 

154 patients randomised to MPp+p. The demographics and disease-related baseline characteristics of the 

patients were well balanced in all 3 arms; notably, approximately 50% of the patients enrolled in each arm 

had the following characteristics; ISS Stage III, and creatinine clearance < 60 mL/min. The median age was 

71 in the MPR+R and MPR+p arms and 72 in the MPp+p arm. 



 46 

 

In an analysis of PFS, PFS2, OS using a cut-off of April 2013 where the median follow up time for all 

surviving subjects was 62.4 months, the results of the study are presented in Table 10: 

 

Table 10. Summary of overall efficacy data 

 MPR+R  

(N = 152) 

MPR+p 

(N = 153) 

MPp +p 

(N = 154) 

Investigator-assessed PFS − (months)   

Mediana PFS time, months (95% CI) 27.4 (21.3, 35.0) 14.3 (13.2, 15.7) 13.1 (12.0, 14.8) 

HR [95% CI]; p-value  

MPR+R vs MPp+p 0.37 (0.27, 0.50); <0.001 

MPR+R vs MPR+p 0.47 (0.35, 0.65); <0.001 

MPR+p vs MPp +p 0.78 (0.60, 1.01); 0.059 

PFS2 − (months) ¤  

Mediana PFS2 time, months (95% CI) 39.7 (29.2, 48.4) 27.8 (23.1, 33.1) 28.8 (24.3, 33.8) 

HR [95% CI]; p-value  

MPR+R vs MPp+p 0.70 (0.54, 0.92); 0.009 

MPR+R vs MPR+p 0.77 (0.59, 1.02); 0.065 

MPR+p vs MPp +p 0.92 (0.71, 1.19); 0.051 

Overall survival (months)  

Mediana OS time, months (95% CI) 55.9 (49.1, 67.5) 51.9 (43.1, 60.6) 53.9 (47.3, 64.2) 

HR [95% CI]; p-value  

MPR+R vs MPp+p 0.95 (0.70, 1.29); 0.736 

MPR+R vs MPR+p 0.88 (0.65, 1.20); 0.43 

MPR+p vs MPp +p 1.07 (0.79, 1.45); 0.67 

Follow-up (months)  

Median (min, max): all patients 48.4 (0.8, 73.8) 46.3 (0.5, 71.9) 50.4 (0.5, 73.3) 

Investigator-assessed Myeloma response n 

(%) 

 

CR 30 (19.7) 17 (11.1) 9 (5.8) 

PR 90 (59.2) 99 ( 64.7) 75 (48.7) 

Stable Disease (SD) 24 (15.8) 31 (20.3) 63 (40.9) 

Response Not Evaluable (NE) 8 (5.3) 4 (2.6) 7 (4.5) 

Investigator-assessed Duration of response 

(CR+PR) − (months)     

Mediana (95% CI) 26.5 (19.4, 35.8) 12.4 (11.2, 13.9) 12.0 (9.4, 14.5) 
CI = confidence interval; CR = complete response; HR = Hazard Rate; M = melphalan; NE = not estimable; OS = overall survival; p = placebo; P = 

prednisone;  

PD = progressive disease; PR = partial response; R = lenalidomide; SD = stable disease; VGPR = very good partial response. 

ª The median is based on the Kaplan-Meier estimate 
¤ PFS2 (an exploratory endpoint) was defined for all patients (ITT) as time from randomisation to start of 3rd line antimyeloma therapy (AMT) or 

death for all randomised patients 

 

Supportive newly diagnosed multiple myeloma studies 

An open-label, randomised, multicentre, phase 3 study (ECOG E4A03) was conducted in 445 patients with 

newly diagnosed multiple myeloma; 222 patients were randomised to the lenalidomide/low dose 

dexamethasone arm, and 223 were randomised to the lenalidomide/standard dose dexamethasone arm. 

Patients randomised to the lenalidomide/standard dose dexamethasone arm received lenalidomide 

25 mg/day, days 1 to 21 every 28 days plus dexamethasone 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 

every 28 days for the first four cycles. Patients randomised to the lenalidomide/low dose dexamethasone arm 

received lenalidomide 25 mg/day, days 1 to 21 every 28 days plus low dose dexamethasone – 40 mg/day on 

days 1, 8, 15, and 22 every 28 days. In the lenalidomide/low dose dexamethasone group, 20 patients (9.1%) 

underwent at least one dose interruption compared to 65 patients (29.3%) in the lenalidomide/standard dose 

dexamethasone arm. 

 



 47 

In a post-hoc analysis, lower mortality was observed in the lenalidomide/low dose dexamethasone arm 6.8% 

(15/220) compared to the lenalidomide/standard dose dexamethasone arm 19.3% (43/223), in the newly 

diagnosed multiple myeloma patient population, with a median follow up of 72.3 weeks. 

 

However with a longer follow-up, the difference in overall survival in favour of lenalidomide/ low dose 

dexamethasone tends to decrease. 

 

Multiple myeloma with at least one prior therapy 

The efficacy and safety of lenalidomide were evaluated in two phase 3 multicentre, randomised, double-

blind, placebo-controlled, parallel-group controlled studies (MM-009 and MM-010) of lenalidomide plus 

dexamethasone therapy versus dexamethasone alone in previously treated patients with multiple myeloma. 

Out of 353 patients in the MM-009 and MM-010 studies who received lenalidomide/dexamethasone, 45.6% 

were aged 65 or over. Of the 704 patients evaluated in the MM-009 and MM-010 studies, 44.6% were aged 

65 or over. 

 

In both studies, patients in the lenalidomide/dexamethasone (len/dex) group took 25 mg of lenalidomide 

orally once daily on days 1 to 21 and a matching placebo capsule once daily on days 22 to 28 of each 

28-day cycle. Patients in the placebo/dexamethasone (placebo/dex) group took 1 placebo capsule on days 1 

to 28 of each 28-day cycle. Patients in both treatment groups took 40 mg of dexamethasone orally once daily 

on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy. The dose of 

dexamethasone was reduced to 40 mg orally once daily on days 1 to 4 of each 28-day cycle after the first 

4 cycles of therapy. In both studies, treatment was to continue until disease progression. In both studies, dose 

adjustments were allowed based on clinical and laboratory finding. 

 

The primary efficacy endpoint in both studies was time to progression (TTP). In total, 353 patients were 

evaluated in the MM-009 study; 177 in the len/dex group and 176 in the placebo/dex group and, in total, 

351 patients were evaluated in the MM-010 study; 176 in the len/dex group and 175 in the placebo/dex 

group. 

 

In both studies, the baseline demographic and disease-related characteristics were comparable between the 

len/dex and placebo/dex groups. Both patient populations presented a median age of 63 years, with a 

comparable male to female ratio. The ECOG performance status was comparable between both groups, as 

was the number and type of prior therapies. 

 

Pre-planned interim analyses of both studies showed that len/dex was statistically significantly superior 

(p < 0.00001) to dexamethasone alone for the primary efficacy endpoint, TTP (median follow-up duration of 

98.0 weeks). Complete response and overall response rates in the len/dex arm were also significantly higher 

than the placebo/dex arm in both studies. Results of these analyses subsequently led to an unblinding in both 

studies, in order to allow patients in the placebo/dex group to receive treatment with the len/dex 

combination. 

 

An extended follow-up efficacy analysis was conducted with a median follow-up of 130.7 weeks. Table 11 

summarises the results of the follow-up efficacy analyses – pooled studies MM-009 and MM-010. 

 

In this pooled extended follow-up analysis, the median TTP was 60.1 weeks (95% CI: 44.3, 73.1) in patients 

treated with len/dex (N = 353) versus 20.1 weeks (95% CI: 17.7, 20.3) in patients treated with placebo/dex 

(N = 351). The median progression free survival was 48.1 weeks (95% CI: 36.4, 62.1) in patients treated 

with len/dex versus 20.0 weeks (95% CI: 16.1, 20.1) in patients treated with placebo/dex. The median 

duration of treatment was 44.0 weeks (min: 0.1, max: 254.9) for len/dex and 23.1 weeks (min: 0.3, max: 

238.1) for placebo/dex. Complete response (CR), partial response (PR) and overall response (CR+PR) rates 

in the len/dex arm remain significantly higher than in the placebo/dex arm in both studies. The median 

overall survival in the extended follow-up analysis of the pooled studies is 164.3 weeks (95% CI: 145.1, 

192.6) in patients treated with len/dex versus 136.4 weeks (95% CI: 113.1, 161.7) in patients treated with 

placebo/dex. Despite the fact that 170 out of the 351 patients randomised to placebo/dex received 

lenalidomide after disease progression or after the studies were unblinded, the pooled analysis of overall 

survival demonstrated a statistically significant survival advantage for len/dex relative to placebo/dex 

(HR = 0.833, 95% CI = [0.687, 1.009], p=0.045). 

 



 48 

Table 11. Summary of results of efficacy analyses as of cut-off date for extended follow-up — pooled 

studies MM-009 and MM-010 (cut-offs 23 July 2008 and 2 March 2008, respectively) 

Endpoint len/dex 

(N=353) 

placebo/dex(N=351)  

Time to event    HR [95% CI], p-valuea 

Time to progression  

Median [95% CI], weeks 

60.1 [44.3, 

73.1] 

20.1 [17.7, 20.3] 0.350 [0.287, 0.426], p < 0.001  

Progression free survival  

Median [95% CI], weeks 

48.1  

[36.4, 62.1] 

20.0 [16.1, 20.1] 0.393 [0.326, 0.473], p < 0.001  

Overall survival 

Median [95% CI], weeks 

1-year Overall survival rate 

164.3 [145.1, 

192.6] 

82% 

136.4 [113.1, 161.7] 

75% 

0.833 [0.687, 1.009], p = 0.045  

Response rate   Odds ratio [95% CI], p-valueb 

Overall response [n, %] 

Complete response [n, %] 

212 (60.1) 

58 (16.4) 

75 (21.4) 

11 (3.1) 

5.53 [3.97, 7.71], p < 0.001 

6.08 [3.13, 11.80], p < 0.001  
a Two-tailed log rank test comparing survival curves between treatment groups. 
b Two-tailed continuity-corrected chi-square test. 

 

Myelodysplastic syndromes 

The efficacy and safety of lenalidomide were evaluated in patients with transfusion-dependent anaemia due 

to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic 

abnormality, with or without additional cytogenetic abnormalities, in two main studies: a phase 3, 

multicentre, randomised, double-blind, placebo-controlled, 3-arm study of two doses of oral lenalidomide 

(10 mg and 5 mg) versus placebo (MDS-004); and a phase 2, a multicentre, single-arm, open-label study of 

lenalidomide (10 mg) (MDS-003).  

 

The results presented below represent the intent-to-treat population studied in MDS-003 and MDS-004; with 

the results in the isolated Del (5q) sub-population also shown separately. 

 

In study MDS-004, in which 205 patients were equally randomised to receive lenalidomide 10 mg, 5 mg or 

placebo, the primary efficacy analysis consisted of a comparison of the transfusion-independence response 

rates of the 10 mg and 5 mg lenalidomide arms versus the placebo arm (double-blind phase 16 to 52 weeks 

and open-label up to a total of 156 weeks). Patients who did not have evidence of at least a minor erythroid 

response after 16 weeks were to be discontinued from treatment. Patients who had evidence of at least a 

minor erythroid response could continue therapy until erythroid relapse, disease progression or unacceptable 

toxicity. Patients, who initially received placebo or 5 mg lenalidomide and did not achieve at least a minor 

erythroid response after 16 weeks of treatment were permitted to switch from placebo to 5 mg lenalidomide 

or continue lenalidomide treatment at higher dose (5 mg to 10 mg). 

 

In, study MDS-003, in which 148 patients received lenalidomide at a dose of 10 mg, the primary efficacy 

analysis consisted of an evaluation of the efficacy of lenalidomide treatments to achieve haematopoietic 

improvement in subjects with low- or intermediate-1 risk myelodysplastic syndromes. 

 

Table 12. Summary of efficacy results – studies MDS-004 (double-blind phase) and MDS-003, intent-

to-treat populationEndpoint 

 MDS-004 

N = 205 

MDS-003 

N = 148 

10 mg† 

N = 69 

5 mg†† 

N = 69 

Placebo* 

N = 67 

10 mg 

N = 148 

Transfusion Independence  

(≥ 182 days) # 

38 (55.1%) 24 (34.8%) 4 (6.0%) 86 (58.1%) 

Transfusion Independence  

(≥ 56 days) # 

42 (60.9%) 33 (47.8%) 5 (7.5%) 97 (65.5%) 

Median Time to Transfusion 

Independence (weeks) 

4.6 4.1 0.3 4.1 

Median Duration of Transfusion 

Independence (weeks) 

NR∞ 

 

NR NR 114.4 

Median Increase in Hgb, g/dL 6.4 5.3 2.6 5.6 



 49 

† Subjects treated with lenalidomide 10 mg on 21 days of 28-day cycles  

†† Subjects treated with lenalidomide 5 mg on 28 days of 28-day cycles 

* The majority of patients on placebo discontinued the double-blind treatment for lack of efficacy after 16 weeks of treatment before entering the 

open-label phase  
#Associated with an increase in Hgb of ≥ 1g/dL  

∞ Not reached (i.e. the median was not reached) 

 

In MDS-004, a significant larger proportion of patients with myelodysplastic syndromes achieved the 

primary endpoint of transfusion independence (>182 days) on lenalidomide 10 mg compared with placebo 

(55.1% vs. 6.0%). Amongst the 47 patients with an isolated Del (5q) cytogenetic abnormality and treated 

with lenalidomide 10 mg, 27 patients (57.4%) achieved red blood cell transfusion independence. 

 

The median time to transfusion independence in the lenalidomide 10 mg arm was 4.6 weeks. The median 

duration of transfusion independence was not reached in any of the treatment arms but should exceed 2 years 

for the lenalidomide-treated subjects. The median increase in haemoglobin (Hgb) from baseline in the 10 mg 

arm was 6.4 g/dL.  

 

Additional endpoints of the study included cytogenetic response (in the 10 mg arm major and minor 

cytogenetic responses were observed in 30.0% and 24.0% of subjects, respectively), assessment of Health 

Related Quality of Life (HRQoL) and progression to acute myeloid leukaemia. Results of the cytogenetic 

response and HRQoL were consistent with the findings of the primary endpoint and in favour of 

lenalidomide treatment compared to placebo. 

 

In MDS-003, a large proportion of patients with myelodysplastic syndromes achieved transfusion 

independence (>182 days) on lenalidomide 10 mg (58.1%). The median time to transfusion independence 

was 4.1 weeks. The median duration of transfusion independence was 114.4 weeks. The median increase in 

haemoglobin (Hgb) was 5.6 g/dL. Major and minor cytogenetic responses were observed in 40.9% and 

30.7% of subjects, respectively.  

 

A large proportion of subjects enrolled in MDS-003 (72.9%) and MDS-004 (52.7%) had received prior 

erythropoiesis-stimulating agents. 

 

Mantle cell lymphoma 

The efficacy and safety of lenalidomide were evaluated in patients with mantle cell lymphoma in a phase 2, 

multicentre, randomised open-label study versus single agent of investigator’s choice in patients who were 

refractory to their last regimen or had relapsed one to three times (study MCL-002). 

Patients who were at least 18 years of age with histologically-proven MCL and CT-measurable disease were 

enrolled. Patients were required to have received adequate previous treatment with at least one prior 

combination chemotherapy regimen. Also, patients had to be ineligible for intensive chemotherapy and/or 

transplant at time of inclusion in the study. Patients were randomised 2:1 to the lenalidomide or the control 

arm. The investigator’s choice treatment was selected before randomisation and consisted of monotherapy 

with either chlorambucil, cytarabine, rituximab, fludarabine, or gemcitabine. 

 

Lenalidomide was administered orally 25 mg once daily for the first 21 days (D1 to D21) of repeating 

28-day cycles until progression or unacceptable toxicity. Patients with moderate renal insufficiency were to 

receive a lower starting dose of lenalidomide 10 mg daily on the same schedule.  

 

The baseline demographic were comparable between the lenalidomide arm and control arm. Both patient 

populations presented a median age of 68.5 years with comparable male to female ratio. The ECOG 

performance status was comparable between both groups, as was the number of prior therapies. 

 

The primary efficacy endpoint in study MCL-002 was progression-free survival (PFS). 

 

The efficacy results for the Intent-to-Treat (ITT) population were assessed by the Independent Review 

Committee (IRC), and are presented in the table below. 

 



 50 

Table 13. Summary of efficacy results – study MCL-002, intent-to-treat population 

 Lenalidomide Arm Control Arm 

 N = 170 N = 84 

PFS 

PFS, mediana [95% CI]b (weeks) 

 

37.6 [24.0, 52.6] 

 

22.7 [15.9, 30.1] 

Sequential HR [95% CI]e 0.61 [0.44, 0.84] 

Sequential log-rank test, p-valuee 0.004 

Responsea, n (%)   

Complete response (CR) 8 (4.7) 0 (0.0) 

Partial response (PR) 60 (35.3) 9 (10.7) 

Stable disease (SD)b 50 (29.4) 44 (52.4) 

Progressive disease (PD) 34 (20.0) 26 (31.0) 

Not done/Missing 18 (10.6) 5 (6.0) 

ORR (CR, CRu, PR), n (%) [95% CI]c 68 (40.0) [32.58, 47.78] 9 (10.7)d [5.02, 19.37] 

p-valuee < 0.001 

CRR (CR, CRu), n (%) [95% CI]c 8 (4.7) [2.05, 9.06] 0 (0.0) [95.70, 100.00] 

p-valuee 0.043 

Duration of Response, mediana [95% CI] (weeks) 69.6 [41.1, 86.7] 45.1 [36.3, 80.9] 

Overall Survival   

HR [95% CI]c 0.89 [0.62, 1.28] 

Log-rank test, p-value 0.520 
CI = confidence interval; CRR = complete response rate; CR = complete response; CRu = complete response unconfirmed; DMC = Data Monitoring 

Committee; ITT = intent-to-treat; HR = hazard ratio; KM = Kaplan-Meier; MIPI = Mantle Cell Lymphoma International Prognostic Index; NA = not 

applicable; ORR = overall response rate; PD = progressive disease; PFS = progression-free survival; PR= partial response; SCT = stem cell 

transplantation; SD = stable disease; SE = standard error. 
a The median was based on the KM estimate. 
b Range was calculated as 95% CIs about the median survival time. 
c The mean and median are the univariate statistics without adjusting for censoring. 
d The stratification variables included time from diagnosis to first dose (< 3 years and ≥ 3 years), time from last prior systemic anti-lymphoma therapy 

to first dose (< 6 months and ≥ 6 months), prior SCT (yes or no), and MIPI at baseline (low, intermediate, and high risk).  
e Sequential test was based on a weighted mean of a log-rank test statistic using the unstratified log-rank test for sample size increase and the 

unstratified log-rank test of the primary analysis. The weights are based on observed events at the time the third DMC meeting was held and based on 

the difference between observed and expected events at the time of the primary analysis. The associated sequential HR and the corresponding 95% CI 

are presented. 

 

In study MCL-002 in the ITT population, there was an overall apparent increase in deaths within 20 weeks in 

the lenalidomide arm 22/170 (13%) versus 6/84 (7%) in the control arm. In patients with high tumour 

burden, corresponding figures were 16/81 (20%) and 2/28 (7%) (see section 4.4). 

 

Follicular lymphoma 

AUGMENT - CC-5013-NHL-007  

The efficacy and safety of lenalidomide in combination with rituximab versus rituximab plus placebo was 

evaluated in patients with relapsed/refractory iNHL including FL in a phase 3, multicentre, randomised, 

double- blind controlled study (CC-5013-NHL-007 [AUGMENT]). 

 

A total of 358 patients who were at least 18 years of age with histologically confirmed MZL or Grade 1, 2 or 

3a FL (CD20+ by flow cytometry or histochemistry) as assessed by the investigator or local pathologist were 

randomised in a 1:1 ratio. Subjects had been previously treated with at least one prior systemic 

chemotherapy, immunotherapy or chemoimmunotherapy. 

 

Lenalidomide was administered orally 20 mg once daily for the first 21 days of repeating 28-day cycles for 

12 cycles or until unacceptable toxicity. The dose of rituximab was 375 mg/m2 every week in Cycle 1 (days 

1, 8, 15, and 22) and on day 1 of every 28-day cycle from cycles 2 through 5. All dosage calculations for 

rituximab were based on the patient’s body surface area (BSA), using actual patient weight. 

 

The demographic and disease-related baseline characteristics were similar across the 2 treatment groups. 

 

The primary objective of the study was to compare the efficacy of lenalidomide in combination with 

rituximab to rituximab plus placebo in subjects with relapsed/refractory FL Grade 1, 2 or 3a or MZL. 

Efficacy determination was based upon PFS as the primary endpoint, as assessed by the IRC using the 2007 

International Working Group (IWG) criteria but without positron emission tomography (PET).  



 51 

 

The secondary objectives of the study were to compare the safety of lenalidomide in combination with 

rituximab versus rituximab plus placebo. Further secondary objectives were to compare the efficacy of 

rituximab plus lenalidomide versus rituximab plus placebo using the following other parameters of efficacy: 

Overall response rate (ORR), CR rate, and duration of response (DoR) by IWG 2007 without PET and OS. 

 

Results from the overall population including FL and MZL showed that at a median follow up of 

28.3°months, the study met its primary endpoint of PFS with a hazard ratio (HR) (95% confidence interval 

[CI]) of 0.45 (0.33,0.61) p-value < 0.0001. The efficacy results from the follicular lymphoma population are 

presented in Table 14. 

 

Table 14: Summary of follicular lymphoma efficacy data- Study CC-5013-NHL-007 

 FL 

(N = 295) 

 Lenalidomide and Rituximab  

(N = 147) 

Placebo and Rituximab  

(N = 148) 

Progression-free survival (PFS) (EMA Censoring Rules) 

Median PFS a (95% CI) (months) 39.4 

 (25.1, NE) 

13.8  

(11.2, 16.0) 

HR [95% CI] 0.40 (0.29, 0.55)b 

p-value < 0.0001c 

Objective responsed (CR +PR), n (%) 

 (IRC, 2007  IWGRC) 

 95 % CIf 

118 (80.3) 

(72.9, 86.4) 

82 (55.4) 

(47.0, 63.6) 

Complete responsed, n (%)  

(IRC, 2007  

IWGRC) 

95 % CIf 

51 (34.7) 

(27.0, 43.0) 

29 (19.6) 

(13.5, 26.9) 

Duration of responsed (median) 

(months) 

 95% CI a 

36.6  

(24.9, NE) 

15.5 

(11.2, 25.0) 

Overall Survivald,e (OS) 

OS rate at 2 years 

% 

139 (94.8) 

(89.5, 97.5) 

127 (85.8) 

(78.5, 90.7) 

HR [95% CI]  0.45 (0.22, 0.92)b 

Follow-up   

Median duration of follow-up (min, 

max) (months) 
29.2 

(0.5, 50.9) 

27.9 

(0.6, 50.9) 
ª Median estimate from Kaplan-Meier analysis 
b Hazard ratio and its confidence interval were estimated from unstratified Cox proportional hazard model. 
c P-value from log-rank test  
d Secondary and exploratory endpoints are not α-controlled 
e With a median follow up of 28.6 months, there were 11 deaths in the R2 arm and 24 deaths in the Control Arm. 
f Exact confidence interval for binomial distribution. 

 

Follicular lymphoma for patients refractory to Rituximab 

MAGNIFY - CC-5013-NHL-008   

A total of 232 subjects who were at least 18 years of age with histologically confirmed FL (Grade 1, 2, 3a or 

MZL), as assessed by the investigator or local pathologist, were enrolled into the initial treatment period with 

12 cycles of lenalidomide plus rituximab. Subjects who achieved CR/CRu, PR, or SD by the end of the 

induction treatment period were randomised to enter the maintenance treatment period. All enrolled subjects 

must have previously been treated with at least one prior systemic antilymphoma therapy. In contrast to 

study NHL-007, the NHL-008 study included patients who were refractory to rituximab (no response or 

relapsed within 6 months of rituximab treatment or who were double-refractory to rituximab and 

chemotherapy). 



 52 

 

During the induction treatment period, lenalidomide 20 mg was given on Days 1-21 of repeated 28-day 

cycles for up to 12 cycles or until unacceptable toxicity, or withdrawal of consent or disease progression. The 

dose of rituximab was 375 mg/m2 every week in Cycle 1 (Days 1, 8, 15, and 22) and on Day 1 of every other 

28-day cycle (cycles 3, 5, 7, 9, and 11) up to 12 cycles therapy. All dosage calculations for rituximab were 

based on the patient body surface area (BSA) and actual weight. 

 

The data presented are based on an interim analysis focusing on the single-arm induction treatment period.. 

Efficacy determinations are based on ORR by best response as the primary endpoint, using a modification of 

the 1999 International Working Group Response Criteria (IWGRC). The secondary objective was to evaluate 

other parameters of efficacy, such as DoR. 

 

Table 15: Summary of overall efficacy data (InductionTreatment Period) - Study CC-5013-NHL-008 

 All Subjects FL Subjects 

 

Total 

N=187 a 

Rituximab 

Refractory: 

Yes 

N=77 

Rituximab 

Refractory: 

No 

N=110 

Total 

N=148 

Rituximab 

Refractory: 

Yes 

N=60 

Rituximab 

Refractory: 

No 

N=88 

ORR, n (%)  

(CR+CRu+PR) 

127 (67.9) 45 (58.4) 82 (75.2) 104 (70.3) 35 (58.3) 69 (79.3) 

CRR, n (%)  

(CR+Cru) 

79 (42.2) 27 (35.1) 52 (47.7) 62 (41.9) 20 (33.3) 42 (48.3) 

Number of Responders N=127 N=45 N=82 N=104 N=35 N=69 

% of Subjects with DoR b 

≥ 6 months (95% CI) c 

93.0 

(85.1, 96.8) 

90.4 

(73.0, 96.8) 

94.5 

(83.9, 98.2) 

94.3 

(85.5, 97.9) 

96.0 

(74.8, 99.4) 

93.5 

(81.0, 97.9) 

% of Subjects with DoR b 

≥ 12 months (95% CI) c 

79.1 

(67.4, 87.0) 

73.3 

(51.2, 86.6) 

82.4 

(67.5, 90.9) 

79.5 

(65.5, 88.3) 

73.9 

(43.0, 89.8) 

81.7 

(64.8, 91.0) 

CI = confidence interval; DOR = duration of response; FL = follicular lymphoma 
a Primary Analysis Population for this study is induction efficacy evaluable (IEE) population. 
b Duration of response is defined as the time (months) from the initial response (at least PR) to documented disease progression or death, whichever 

occurs first. 
c Statistics obtained from Kaplan-Meier method. 95% CI is based on Greenwood formula. 

Notes: The analysis is only performed for subjects who have achieved PR or better after the first dose date of induction therapy and prior to any 

Maintenance Period treatment and any subsequent anti-lymphoma therapy in Induction Period. Percentage is based on the total number of responders. 

 

Paediatric population 

The European Medicines Agency (EMA) has granted a product-specific waiver for Revlimid that applies to 

all subsets of the paediatric population for mature B-cell neoplasm conditions. (see section 4.2 for 

information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Lenalidomide has an asymmetric carbon atom and can therefore exist as the optically active forms S(-) and 

R(+). Lenalidomide is produced as a racemic mixture. Lenalidomide is generally more soluble in organic 

solvents but exhibits the greatest solubility in 0.1N HCl buffer. 

 

Absorption 

Lenalidomide is rapidly absorbed following oral administration in healthy volunteers, under fasting 

conditions, with maximum plasma concentrations occurring between 0.5 and 2 hours post-dose. In patients, 

as well as in healthy volunteers, the maximum concentration (Cmax) and area-under-the-concentration time 

curve (AUC) increase proportionally with increases in dose. Multiple dosing does not cause marked 



 53 

medicinal product accumulation. In plasma, the relative exposures of the S- and R- enantiomers of 

lenalidomide are approximately 56% and 44%, respectively. 

 

Co-administration with a high-fat and high-calorie meal in healthy volunteers reduces the extent of 

absorption, resulting in an approximately 20% decrease in area under the concentration versus time curve 

(AUC) and 50% decrease in Cmax in plasma. However, in the main multiple myeloma and myelodysplastic 

syndromes registration trials where the efficacy and safety were established for lenalidomide, the medicinal 

product was administered without regard to food intake. Thus, lenalidomide can be administered with or 

without food. 

 

Population pharmacokinetic analyses indicate that the oral absorption rate of lenalidomide is similar among 

MM, MDS and MCL patients. 

 

Distribution 

In vitro (14C)-lenalidomide binding to plasma proteins was low with mean plasma protein binding at 23% 

and 29% in multiple myeloma patients and healthy volunteers, respectively. 

 

Lenalidomide is present in human semen (< 0.01% of the dose) after administration of 25 mg/day and the 

medicinal product is undetectable in semen of a healthy subject 3 days after stopping the substance (see 

section 4.4). 

 

Biotransformation and elimination 

Results from human in vitro metabolism studies indicate that lenalidomide is not metabolised by cytochrome 

P450 enzymes suggesting that administration of lenalidomide with medicinal products that inhibit 

cytochrome P450 enzymes is not likely to result in metabolic medicinal product interactions in humans. In 

vitro studies indicate that lenalidomide has no inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6, 

CYP2E1, CYP3A, or UGT1A1. Therefore, lenalidomide is unlikely to cause any clinically relevant 

medicinal product interactions when co-administered with substrates of these enzymes. 

 

In vitro studies indicate that lenalidomide is not a substrate of human breast cancer resistance protein 

(BCRP), multidrug resistance protein (MRP) transporters MRP1, MRP2, or MRP3, organic anion 

transporters (OAT) OAT1 and OAT3, organic anion transporting polypeptide 1B1 (OATP1B1), organic 

cation transporters (OCT) OCT1 and OCT2, multidrug and toxin extrusion protein (MATE) MATE1, and 

organic cation transporters novel (OCTN) OCTN1 and OCTN2. 

 

In vitro studies indicate that lenalidomide has no inhibitory effect on human bile salt export pump (BSEP), 

BCRP, MRP2, OAT1, OAT3, OATP1B1, OATP1B3, and OCT2. 

 

A majority of lenalidomide is eliminated through urinary excretion. The contribution of renal excretion to 

total clearance in subjects with normal renal function was 90%, with 4% of lenalidomide eliminated in 

faeces. 

 

Lenalidomide is poorly metabolized as 82% of the dose is excreted unchanged in urine. Hydroxy-

lenalidomide and N-acetyl-lenalidomide represent 4.59% and 1.83% of the excreted dose, respectively. The 

renal clearance of lenalidomide exceeds the glomerular filtration rate and therefore is at least actively 

secreted to some extent. 

 

At doses of 5 to 25 mg/day, half-life in plasma is approximately 3 hours in healthy volunteers and ranges 

from 3 to 5 hours in patients with multiple myeloma, myelodysplastic syndromes or mantle cell lymphoma. 

 

Older people 

No dedicated clinical studies have been conducted to evaluate pharmacokinetics of lenalidomide in the 

elderly. Population pharmacokinetic analyses included patients with ages ranging from 39 to 85 years old 

and indicate that age does not influence lenalidomide clearance (exposure in plasma). Because elderly 

patients are more likely to have decreased renal function, care should be taken in dose selection and it would 

be prudent to monitor renal function. 

 



 54 

Renal impairment 

The pharmacokinetics of lenalidomide was studied in subjects with renal impairment due to nonmalignant 

conditions. In this study, two methods were used to classify renal function: the urinary creatinine clearance 

measured over 24 hours and the creatinine clearance estimated by Cockcroft-Gault formula. The results 

indicate that as renal function decreases (< 50 mL/min), the total lenalidomide clearance decreases 

proportionally resulting in an increase in AUC. The AUC was increased by approximately 2.5, 4 and 5-fold 

in subjects with moderate renal impairment, severe renal impairment, and end-stage renal disease, 

respectively, compared to the group combining subjects with normal renal function and subjects with mild 

renal impairment. The half-life of lenalidomide increased from approximately 3.5 hours in subjects with 

creatinine clearance > 50 mL/min to more than 9 hours in subjects with reduced renal function < 50 mL/min. 

However, renal impairment did not alter the oral absorption of lenalidomide. The Cmax was similar between 

healthy subjects and patients with renal impairment. Approximately 30% of the medicinal product in the 

body was removed during a single 4-hour dialysis session. Recommended dose adjustments in patients with 

impaired renal function are described in section 4.2. 

 

Hepatic impairment  

Population pharmacokinetic analyses included patients with mild hepatic impairment (N=16, total bilirubin 

>1 to ≤1.5 x ULN or AST > ULN) and indicate that mild hepatic impairment does not influence 

lenalidomide clearance (exposure in plasma). There are no data available for patients with moderate to severe 

hepatic impairment.  

 

Other intrinsic factors  

Population pharmacokinetic analyses indicate that body weight (33- 135 kg), gender, race and type of 

haematological malignancy (MM, MDS or MCL) do not have a clinically relevant effect on lenalidomide 

clearance in adult patients.  

 

5.3 Preclinical safety data 

 

An embryofoetal development study has been conducted in monkeys administered lenalidomide at doses 

from 0.5 and up to 4 mg/kg/day. Findings from this study indicate that lenalidomide produced external 

malformations including non-patent anus and malformations of upper and lower extremities (bent, shortened, 

malformed, malrotated and/or absent part of the extremities, oligo and/or polydactyly) in the offspring of 

female monkeys who received the active substance during pregnancy.  

 

Various visceral effects (discoloration, red foci at different organs, small colourless mass above atrio-

ventricular valve, small gall bladder, malformed diaphragm) were also observed in single foetuses. 

 

Lenalidomide has a potential for acute toxicity; minimum lethal doses after oral administration were > 2000 

mg/kg/day in rodents. Repeated oral administration of 75, 150 and 300 mg/kg/day to rats for up to 26 weeks 

produced a reversible treatment-related increase in kidney pelvis mineralisation in all 3 doses, most notably 

in females. The no observed adverse effect level (NOAEL) was considered to be less than 75 mg/kg/day, and 

is approximately 25-fold greater than the human daily exposure based on AUC exposure. Repeated oral 

administration of 4 and 6 mg/kg/day to monkeys for up to 20 weeks produced mortality and significant 

toxicity (marked weight loss, reduced red and white blood cell and platelet counts, multiple organ 

haemorrhage, gastrointestinal tract inflammation, lymphoid, and bone marrow atrophy). Repeated oral 

administration of 1 and 2 mg/kg/day to monkeys for up to 1 year produced reversible changes in bone 

marrow cellularity, a slight decrease in myeloid/erythroid cell ratio and thymic atrophy. Mild suppression of 

white blood cell count was observed at 1 mg/kg/day corresponding to approximately the same human dose 

based on AUC comparisons. 

 

In vitro (bacterial mutation, human lymphocytes, mouse lymphoma, Syrian Hamster Embryo cell 

transformation) and in vivo (rat micronucleus) mutagenicity studies revealed no drug related effects at either 

the gene or chromosomal level. Carcinogenicity studies with lenalidomide have not been conducted. 

 

Developmental toxicity studies were previously conducted in rabbits. In these studies, rabbits were 

administered 3, 10 and 20 mg/kg/day orally. An absence of the intermediate lobe of the lung was observed at 

10 and 20 mg/kg/day with dose dependence and displaced kidneys were observed at 20 mg/kg/day. Although 



 55 

it was observed at maternotoxic levels they may be attributable to a direct effect. Soft tissue and skeletal 

variations in the foetuses were also observed at 10 and 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Capsule contents 

Anhydrous lactose  

Microcrystalline cellulose  

Croscarmellose sodium 

Magnesium stearate 

 

Capsule shell 

Revlimid 2.5 mg/ 10 mg/ 20 mg hard capsules 

Gelatin 

Titanium dioxide (E171) 

Indigo carmine (E132) 

Yellow iron oxide (E172) 

 

Revlimid 5 mg/ 25 mg hard capsules 

Gelatin 

Titanium dioxide (E171) 

 

Revlimid 7.5 mg hard capsules 

Gelatin 

Titanium dioxide (E171) 

Yellow iron oxide (E172) 

 

Revlimid 15 mg hard capsules 

Gelatin 

Titanium dioxide (E171) 

Indigo carmine (E132) 

 

Printing ink 

Shellac 

Propylene glycol (E1520) 

Black iron oxide (E172) 

Potassium hydroxide 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

3 years. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 

 

Polyvinylchloride (PVC) / Polychlorotrifluoroethylene (PCTFE) / Aluminium foil blisters containing 7 hard 

capsules.  

 



 56 

Revlimid 2.5 mg/ 5 mg/ 7.5 mg/ 10 mg/ 15 mg/ 20 mg/ 25 mg hard capsules 

Pack size of 7 or 21 capsules. Not all pack sizes may be available. 

 

6.6 Special precautions for disposal and other handling 

 

Capsules should not be opened or crushed. If powder from lenalidomide makes contact with the skin, the 

skin should be washed immediately and thoroughly with soap and water. If lenalidomide makes contact with 

the mucous membranes, they should be thoroughly flushed with water. 

 

Healthcare professionals and caregivers should wear disposable gloves when handling the blister or capsule. 

Gloves should then be removed carefully to prevent skin exposure, placed in a sealable plastic polyethylene 

bag and disposed of in accordance with local requirements. Hands should then be washed thoroughly with 

soap and water. Women who are pregnant or suspect they may be pregnant should not handle the blister or 

capsule (see section 4.4). 

 

Any unused product or waste material should be returned to the pharmacist for safe disposal in accordance 

with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

Revlimid 2.5 mg hard capsules 

EU/1/07/391/005 

EU/1/07/391/007 

 

Revlimid 5 mg hard capsules 

EU/1/07/391/001 

EU/1/07/391/008 

 

Revlimid 7.5 mg hard capsules 

EU/1/07/391/006 

EU/1/07/391/012 

 

Revlimid 10 mg hard capsules 

EU/1/07/391/002 

EU/1/07/391/010 

 

Revlimid 15 mg hard capsules 

EU/1/07/391/003 

EU/1/07/391/011 

 

Revlimid 20 mg hard capsules 

EU/1/07/391/009 

EU/1/07/391/013 

 

Revlimid 25 mg hard capsules 

EU/1/07/391/004 

EU/1/07/391/014 

 



 57 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 14 June 2007 

Date of latest renewal: 16 February 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines Agency: 

http://www.ema.europa.eu/. 

 



 58 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



 59 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturers responsible for batch release 

 

Celgene Distribution B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING THE SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 

 

• Periodic Safety Update Reports 
The requirements for submission of periodic safety update reports for this medicinal product are set out in 

the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 

and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE 

OF THE MEDICINAL PRODUCT  

 

• Risk Management Plan (RMP) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed 

RMP presented in module 1.8.2 of the Marketing Authorisation and any agreed subsequent updates of the 

RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information being 
received that may lead to a significant change to the benefit/risk profile or as the result of an 

important (pharmacovigilance or risk minimisation) milestone being reached. 

 

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 

time. 

 

• Additional risk minimisation measures 
1. The MAH shall agree the details of a controlled distribution system with the National Competent 

Authorities and must implement such programme nationally to ensure that: 

• Prior to launch, all doctors who intend to prescribe Revlimid and all pharmacists who may dispense 
Revlimid receive a direct healthcare professional communication as described below. 

• Prior to prescribing (and where appropriate, and in agreement with the national competent authority, 
prior to dispensing) all healthcare professionals who intend to prescribe (and dispense) Revlimid are 

provided with a physician information pack containing the following: 

o Educational health care professional’s kit 
o Educational brochures for patients 
o Patient cards 
o Summary of product characteristics (SmPC) and package leaflet and labelling. 

 

2. The MAH shall implement a pregnancy prevention programme (PPP) in each Member State. Details of 
the PPP should be agreed with the National Competent Authorities in each Member State and put in 

place prior to the launch of the product. 

 



 60 

3. The MAH should agree the final text of the Direct Healthcare Professional Communication and the 
physician information pack contents with the National Competent Authority in each Member State and 

ensure that the materials contain the key elements as described below. 

 

4. The MAH should agree on the implementation of the patient card system in each Member State. 
 

5. The MAH should also agree with each Member State: 

• The details of the implementation of the MDS Post-Authorisation Safety Study (MDS PASS) 
 

Key elements to be included 

 

Direct Healthcare Professional Communications 

 

The Direct Healthcare Professional Communication prior to launch shall consist of two parts: 

• A core text as agreed by the CHMP. 

• National specific requirements agreed with the National Competent Authority regarding: 
o Distribution of the product 
o To ensure that all appropriate measures have been performed prior to Revlimid being 

dispensed 

 

The Educational Healthcare Professional’s Kit 

 

The Educational Health Care Professional’s Kit shall contain the following elements: 

• Brief background on lenalidomide and its licensed indication 

• Posology 

• Maximum duration of treatment prescribed according to the approved indications dosing regimens 
o 4 weeks treatment for women with childbearing potential 
o 12 weeks treatment for men and women without childbearing potential 

• The need to avoid foetal exposure due to teratogenicity of lenalidomide in animals and the expected 
teratogenic effect of lenalidomide in humans including a summary of the results of study CC-5013-

TOX-004 

• Guidance on handling the blister or capsule of Revlimid for healthcare professionals and caregivers 

• Obligations of the health care professional in relation to the prescribing of Revlimid 
o Need to provide comprehensive advice and counselling to patients 
o That patients should be capable of complying with the requirements for the safe use of 

Revlimid 

o Need to provide patients with appropriate patient educational brochure and patient card 

• Safety advice relevant to all patients 
o Disposal of unwanted medicine 
o Local country specific arrangements for a prescription for Revlimid to be dispensed 
o Description of risk of tumour flare reaction in MCL patients 
o Description of the risk of progression to AML in MDS patients including incidence rates 

from clinical trials 

o Description of risk of SPM 

• Description of the PPP and categorisation of patients based on sex and childbearing potential 
o Algorithm for implementation of PPP 
o Definition of women of childbearing potential (WCBP) and actions the physician should 

take if unsure 

• Safety advice for women of childbearing potential 
o The need to avoid foetal exposure 
o Description of the PPP 
o Need for adequate contraception (even if woman has amenorrhoea) and definition of 

adequate contraception 

o Pregnancy test regime 
▪ Advice on suitable tests 
▪ Before commencing treatment 
▪ During treatment based on method of contraception 



 61 

▪ After finishing treatment 
o Need to stop Revlimid immediately upon suspicion of pregnancy 
o Need to tell treating doctor immediately upon suspicion of pregnancy 

• Safety advice for men 
o The need to avoid foetal exposure 
o The need to use condoms if sexual partner is pregnant or a WCBP not using effective 

contraceptions (even if man has had a vasectomy) 

▪ During Revlimid treatment 
▪ For at least 7 days following final dose. 

o That if his partner becomes pregnant whilst he is taking Revlimid or shortly after he has 
stopped taking Revlimid he should inform his treating doctor immediately 

• Requirements in the event of pregnancy 
o Instructions to stop Revlimid immediately upon suspicion of pregnancy, if female patient 
o Need to refer to physician specialised or experienced in dealing with teratology and its 

diagnosis for evaluation and advice 

o Local contact details for reporting of any suspected pregnancy 
o Pregnancy reporting form 

• Check list for physicians ensuring that patients receive the appropriate counselling concerning the 
treatment, contraceptive methods and pregnancy prevention appropriate for their sex and 

childbearing status at treatment initiation. 

• Details on the MDS PASS emphasizing that prior to prescribing Revlimid, the healthcare 
professionals should enroll MDS patients into the PASS. 

• Adverse event reporting forms 
 

Educational Brochures for patients 

 

The Educational brochures for patients should be of 3 types: 

• Brochure for women patients of childbearing potential 

• Brochure for women patients who are not of childbearing potential 

• Brochure for male patients 
 

All patient brochures should contain the following elements: 

• That lenalidomide is teratogenic in animals and is expected to be teratogenic in humans 

• Description of the patient card and its necessity 

• Disposal of unwanted medicine  

• Guidance on handling lenalidomide for patients, caregivers and family members 

• National or other applicable specific arrangements for a prescription for Revlimid to be dispensed 

• That the patient should not give Revlimid to any other person 

• That the patient should not donate blood during therapy (including during dose interruptions) and for 
at least 7 days after discontinuation of Revlimid treatment 

• That the patient should tell their doctor about any adverse events 

• That a study is being conducted to collect information regarding the safety of the medicinal product 
and to monitor its appropriate use; and that MDS patients should be included in the study prior to the 

start of the treatment with Revlimid 

 

The following information should also be provided in the appropriate brochure: 

 

Brochure for women patients with childbearing potential 

• The need to avoid foetal exposure 

• Description of the PPP 

• Need for adequate contraception and definition of adequate contraception 

• Pregnancy test regime 
o Before commencing treatment 
o During treatment, at least every 4 weeks except in case of confirmed tubal sterilisation 
o After finishing treatment 

• The need to stop Revlimid immediately upon suspicion of pregnancy 

• The need to contact their doctor immediately upon suspicion of pregnancy 



 62 

 

Brochure for male patients 

• The need to avoid foetal exposure 

• The need to use condoms if sexual partner is pregnant or a WCBP not using effective contraceptions 
(even if man has had vasectomy) 

o During Revlimid treatment 
o For at least 7 days following final dose 

• That if his partner becomes pregnant he should inform his treating doctor immediately 

• That he should not donate semen or sperm during therapy (including during dose interruptions) and 
at least for 7 days after discontinuation of Revlimid treatment 

 

Patient Card 

 

The patient card shall contain the following elements: 

• Verification that appropriate counselling has taken place 

• Documentation of childbearing status potential 

• Pregnancy test dates and results 
 

• Obligation to conduct post-authorisation measures 
 

The MAH shall complete, within the stated timeframe, the below measures: 

 

Description Due date 

Post-authorisation non-interventional, safety studies of patients 

with myelodysplastic syndromes (MDS) treated with 

lenalidomide to gather safety data on the use of lenalidomide in 

MDS patients and monitor off-label use (CC-5013-MDS-010 and 

CC-5013-MDS-012). 

Annual safety updates with PSURs 

 

Final report of study results:  

• CC-5013-MDS-010, Q1 2023 
• CC-5013-MDS-012, Q3 2023 

A post-authorisation non-interventional, safety study of 

transplant-ineligible patients with newly diagnosed multiple 

myeloma (NDMM) treated with lenalidomide to gather safety 

data on the use of lenalidomide in NDMM patients. 

Annual safety updates with PSURs 

 

Final report of study results: 01 

December 2025 

 



 63 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 

 



 64 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 



 65 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 2.5 mg hard capsules 

lenalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 2.5 mg lenalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

21 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Risk of severe birth defects. Do not use while pregnant or breastfeeding. 

You must follow the Revlimid Pregnancy Prevention Programme. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 66 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

Return unused medicines to the pharmacist. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/391/007 7 hard capsules 

EU/1/07/391/005 21 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revlimid 2.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



 67 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 2.5 mg hard capsules 

lenalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 68 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 5 mg hard capsules 

lenalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 5 mg lenalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

21 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Risk of severe birth defects. Do not use while pregnant or breastfeeding. 

You must follow the Revlimid Pregnancy Prevention Programme. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 69 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

Return unused medicines to the pharmacist. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/391/008 7 hard capsules 

EU/1/07/391/001 21 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revlimid 5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



 70 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 5 mg hard capsules 

lenalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 71 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 7.5 mg hard capsules 

lenalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 7.5 mg lenalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

21 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Risk of severe birth defects. Do not use while pregnant or breastfeeding. 

You must follow the Revlimid Pregnancy Prevention Programme. 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 72 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

Return unused medicines to the pharmacist. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/391/012 7 hard capsules 

EU/1/07/391/006 21 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revlimid 7.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



 73 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 7.5 mg hard capsules 

lenalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 74 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 10 mg hard capsules 

lenalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 10 mg lenalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

21 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Risk of severe birth defects. Do not use while pregnant or breastfeeding. 

You must follow the Revlimid Pregnancy Prevention Programme. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 75 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

Return unused medicines to the pharmacist.  

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/391/010 7 hard capsules 

EU/1/07/391/002 21 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revlimid 10 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



 76 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 10 mg hard capsules 

lenalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 77 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 15 mg hard capsules 

lenalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 15 mg lenalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

21 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Risk of severe birth defects. Do not use while pregnant or breastfeeding. 

You must follow the Revlimid Pregnancy Prevention Programme. 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 78 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

Return unused medicines to the pharmacist. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/391/011 7 hard capsules 

EU/1/07/391/003 21 hard capsules 

 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revlimid 15 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 



 79 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 15 mg hard capsules 

lenalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 80 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 20 mg hard capsules 

lenalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 20 mg lenalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

21 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Risk of severe birth defects. Do not use while pregnant or breastfeeding. 

You must follow the Revlimid Pregnancy Prevention Programme. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 81 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

Return unused medicines to the pharmacist. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/391/013 7 hard capsules 

EU/1/07/391/009 21 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revlimid 20 mg 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



 82 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 20 mg hard capsules 

lenalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 83 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 25 mg hard capsules 

lenalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 25 mg lenalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

21 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Risk of severe birth defects. Do not use while pregnant or breastfeeding. 

You must follow the Revlimid Pregnancy Prevention Programme. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 84 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

Return unused medicines to the pharmacist. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/391/014 7 hard capsules 

EU/1/07/391/004 21 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revlimid 25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



 85 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revlimid 25 mg hard capsules 

lenalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 



 86 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 87 

Package leaflet: Information for the patient 

 

Revlimid 2.5 mg hard capsules 

Revlimid 5 mg hard capsules 

Revlimid 7.5 mg hard capsules 

Revlimid 10 mg hard capsules 

Revlimid 15 mg hard capsules 

Revlimid 20 mg hard capsules 

Revlimid 25 mg hard capsules 

 

lenalidomide 

 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 

report side effects. 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 

- If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Revlimid is and what it is used for 

2. What you need to know before you take Revlimid 

3. How to take Revlimid 

4. Possible side effects 

5. How to store Revlimid 

6. Contents of the pack and other information 

 

 

1. What Revlimid is and what it is used for 

 

What Revlimid is 

Revlimid contains the active substance ‘lenalidomide’. This medicine belongs to a group of medicines which 

affect how your immune system works. 

 

What Revlimid is used for 

Revlimid is used in adults for: 

• Multiple myeloma 

• Myelodysplastic syndromes 

• Mantle cell lymphoma 

• Follicular lymphoma 
 

Multiple myeloma 

Multiple myeloma is a type of cancer which affects a certain kind of white blood cell, called the plasma cell. 

These cells collect in the bone marrow and divide, becoming out of control. This can damage the bones and 

kidneys.  

 

Multiple myeloma generally cannot be cured. However, the signs and symptoms can be greatly reduced or 

disappear for a period of time. This is called a ‘response’. 

 



 88 

Newly diagnosed multiple myeloma – in patients who have had a bone marrow transplant 

Revlimid is used on its own as a maintenance therapy after patients have recovered enough following a bone 

marrow transplant. 

 

Newly diagnosed multiple myeloma – in patients who cannot have a bone marrow transplant 

Revlimid is taken with other medicines. These may include: 

• a chemotherapy medicine called ‘bortezomib’ 

• an anti-inflammatory medicine called ‘dexamethasone’ 

• a chemotherapy medicine called ‘melphalan’ and 

• an immunosuppressant medicine called ‘prednisone’.  
You will take these other medicines at the start of treatment and then continue to take Revlimid on its own. 

 

If you are aged 75 years or older or have moderate to severe kidney problems - your doctor will check you 

carefully before starting treatment. 

 

Multiple myeloma – in patients who have had treatment before 

Revlimid is taken together with an anti-inflammatory medicine called ‘dexamethasone’.  

 

Revlimid can stop the signs and symptoms of multiple myeloma getting worse. It has also been shown to 

delay multiple myeloma from coming back following treatment.  

 

Myelodysplastic syndromes (MDS) 

MDS are a collection of many different blood and bone marrow diseases. The blood cells become abnormal 

and do not function properly. Patients can experience a variety of signs and symptoms including a low red 

blood cell count (anaemia), the need for a blood transfusion, and be at risk of infection. 

 

Revlimid is used alone to treat adult patients who have been diagnosed with MDS, when all of the following 

apply: 

• you need regular blood transfusions to treat low levels of red blood cells (‘transfusion-dependent 
anaemia’) 

• you have an abnormality of cells in the bone marrow called an ‘isolated deletion 5q cytogenetic 
abnormality’. This means your body does not make enough healthy blood cells 

• other treatments have been used before, are not suitable or do not work well enough. 
 

Revlimid can increase the number of healthy red blood cells that the body produces by reducing the number 

of abnormal cells:  

• this can reduce the number of blood transfusions needed. It is possible that no transfusions will be 
needed. 

 

Mantle cell lymphoma (MCL) 

MCL is a cancer of part of the immune system (the lymph tissue). It affects a type of white blood cell called 

‘B-lymphocytes’ or B-cells. MCL is a disease where B-cells grow in an uncontrolled way and build up in the 

lymph tissue, bone marrow or blood. 

 

Revlimid is used alone to treat adult patients who have previously been treated with other medicines. 

 

Follicular lymphoma (FL) 

FL is a slow growing cancer that affects the B-lymphocytes. These are a type of white blood cells that help 

your body fight infection. When you have FL, too many of these B-lymphocytes may collect in your blood, 

bone marrow, lymph nodes and spleen. 

 

Revlimid is taken together with another medicine called ‘rituximab’ for the treatment of adult patients with 

previously treated follicular lymphoma. 



 89 

 

How Revlimid works 

Revlimid works by affecting the body’s immune system and directly attacking the cancer. It works in a 

number of different ways: 

• by stopping the cancer cells developing 

• by stopping blood vessels growing in the cancer 

• by stimulating part of the immune system to attack the cancer cells. 
 

 

2. What you need to know before you take Revlimid 

 

You must read the package leaflet of all medicinal products to be taken in combination with Revlimid 

before starting treament with Revlimid. 

 

Do not take Revlimid: 

• if you are pregnant, think you may be pregnant or are planning to become pregnant, as Revlimid is 
expected to be harmful to an unborn child (see section 2, ‘Pregnancy, breast-feeding and 

contraception – information for women and men’). 

• if you are able to become pregnant, unless you follow all the necessary measures to prevent you from 
becoming pregnant (see section 2, ‘Pregnancy, breast-feeding and contraception – information for 

women and men’). If you are able to become pregnant, your doctor will record with each prescription 

that the necessary measures have been taken and provide you with this confirmation. 

• if you are allergic to lenalidomide or any of the other ingredients of this medicine listed in section 6. If 
you think you may be allergic, ask your doctor for advice. 

 

If any of these apply to you, do not take Revlimid. Talk to your doctor if you are not sure. 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Revlimid if: 

• you have had blood clots in the past - you have an increased risk of developing blood clots in the veins 
and arteries during treatment 

• you have any signs of an infection, such as a cough or fever  

• you have or have ever had previous viral infection, particularly: hepatitis B infection, varicella zoster, 
HIV. If you are in doubt, talk to your doctor. Treatment with Revlimid may cause the virus to become 

active again, in patients who carry the virus. This results in a recurrence of the infection. Your doctor 
should check whether you have ever had hepatitis B infection 

• you have kidney problems - your doctor may adjust your dose of Revlimid 

• you have had a heart attack, have ever had a blood clot, or if you smoke, have high blood pressure or 
high cholesterol levels 

• you have had an allergic reaction whilst taking thalidomide (another medicine used to treat multiple 
myeloma) such as rash, itching, swelling, dizziness or trouble breathing 

• you have experienced in the past a combination of any of the following symptoms: widespread rash, red 
skin, high body temperature, flu-like symptoms, liver enzyme elevations, blood abnormalities 

(eosinophilia), enlarged lymph nodes – these are signs of a severe skin reaction called Drug Reaction 

with Eosinophilia and Systemic Symptoms which is also known as DRESS or drug hypersensitivity 

syndrome. (see also section 4 “Possible side effects”). 

 

If any of the above apply to you, tell your doctor, pharmacist or nurse before starting treatment. 

 

At any time during or after your treatment, tell your doctor or nurse immediately if you:  

• experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in 
the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of 

sensation, memory loss or confusion. These may all be symptoms of a serious and potentially fatal brain 

condition known as progressive multifocal leukoencephalopathy (PML). If you had these symptoms 

prior to treatment with Revlimid, tell your doctor about any change in these symptoms.  



 90 

• experience shortness of breath, tiredness, dizziness, pain in the chest, a faster heartbeat, or swelling in 
the legs or ankles. These may be symptoms of a serious condition known as pulmonary hypertension 

(see section 4). 

 

Tests and checks 

Before and during the treatment with Revlimid you will have regular blood tests. This is because Revlimid 

may cause a fall in the blood cells that help fight infection (white blood cells) and help the blood to clot 

(platelets).  

Your doctor will ask you to have a blood test: 

• before treatment  

• every week for the first 8 weeks of treatment 

• then at least every month after that. 
 

You may be evaluated for signs of cardiopulmonary problems before and during the treatment with 

lenalidomide. 

 

For patients with MDS taking Revlimid 

If you have MDS, you may be more likely to get a more advanced condition called acute myeloid leukaemia 

(AML). In addition, it is not known how Revlimid affects the chances of you getting AML. Your doctor may 

therefore do tests to check for signs which may better predict the likelihood of you getting AML during your 

treatment with Revlimid. 

 

For patients with MCL taking Revlimid 

Your doctor will ask you to have a blood test: 

• before treatment 

• every week for the first 8 weeks (2 cycles) of treatment 

• then every 2 weeks in cycles 3 and 4 (see section 3 ‘Treatment cycle’ for more information) 

• after this it will happen at the start of each cycle and 

• at least every month. 
 

For patients with FL taking Revlimid 

Your doctor will ask you to have a blood test: 

• before treatment  

• every week for the first 3 weeks (1 cycle) of treatment 

• then every 2 weeks in cycles 2 to 4 (see Section 3 ‘Treatment cycle’ for more information) 

• After this it will happen at the start of each cycle and 

• at least every month. 
 

Your doctor may check if you have a high total amount of tumour throughout the body, including your bone 

marrow. This could lead to a condition where the tumours break down and cause unusual levels of chemicals 

in the blood which can lead to kidney failure (this condition is called ‘Tumour Lysis Syndrome’).  

 

Your doctor may check you for changes to your skin such as red spots or rashes. 

 

Your doctor may adjust your dose of Revlimid or stop your treatment based on the results of your blood tests 

and on your general condition. If you are newly diagnosed, your doctor may also assess your treatment based 

on your age and other conditions you already have. 

 

Blood donation 

You should not donate blood during treatment and for at least 7 days after the end of treatment. 

 

Children and adolescents 

Revlimid is not recommended for use in children and adolescents under 18 years. 

 

Elderly and people with kidney problems 

If you are aged 75 years or older or have moderate to severe kidney problems - your doctor will check you 

carefully before starting treatment. 



 91 

 

Other medicines and Revlimid 

Tell your doctor or nurse if you are taking or have recently taken any other medicines. This is because 

Revlimid can affect the way some other medicines work. Also, some other medicines can affect the way 

Revlimid works. 

 

In particular, tell your doctor or nurse if you are taking any of the following medicines: 

• some medicines used to prevent pregnancy such as oral contraceptives, as they may stop working 

• some medicines used for heart problems – such as digoxin 

• some medicines used to thin the blood – such as warfarin. 
 

Pregnancy, breast-feeding and contraception - information for women and men 

 

Pregnancy  

For women taking Revlimid 

• You must not take Revlimid if you are pregnant, as it is expected to be harmful to an unborn baby.  

• You must not become pregnant while taking Revlimid. Therefore you must use effective methods of 
contraception if you are a woman of childbearing potential (see ‘Contraception’). 

• If you do become pregnant during your treatment with Revlimid, you must stop the treatment and inform 
your doctor immediately. 

 

For men taking Revlimid 

• If your partner becomes pregnant whilst you are taking Revlimid, you should inform your doctor 
immediately. It is recommended that your partner seeks medical advice. 

• You must also use effective methods of contraception (see ‘Contraception’). 
 

Breast-feeding 

You must not breast-feed when taking Revlimid, as it is not known if Revlimid passes into breast milk. 

 

Contraception 

For women taking Revlimid 

Before starting the treatment, ask your doctor if you are able to become pregnant, even if you think this is 

unlikely. 

 

If you are able to become pregnant  

• you will have pregnancy tests under the supervision of your doctor (before every treatment, at least every 
4 weeks during treatment, and at least 4 weeks after the treatment has finished) except where it has been 

confirmed that the fallopian tubes have been severed and sealed, to stop eggs from reaching the uterus 

(tubal sterilisation) 

AND 

• you must use effective methods of contraception for at least 4 weeks before starting treatment, during 
treatment, and until at least 4 weeks after stopping treatment. Your doctor will advise you on appropriate 

methods of contraception. 

 

For men taking Revlimid 

Revlimid passes into human semen. If your female partner is pregnant or able to become pregnant, and she 

does not use effective methods of contraception, you must use condoms during treatment and for at least 7 

days after the end of treatment, even if you have had a vasectomy. 

 

Driving and using machines 

Do not drive or operate machines if you feel dizzy, tired, sleepy, have vertigo or blurred vision after taking 

Revlimid. 

 

Revlimid contains lactose 

Revlimid contains lactose. If you have been told by your doctor that you have intolerance to some sugars, 

contact your doctor before taking this medicine. 

 



 92 

 

3. How to take Revlimid 

 

Revlimid must be given to you by healthcare professionals with experience in treating multiple myeloma, 

MDS, MCL or FL. 

• When Revlimid is used to treat multiple myeloma in patients who cannot have a bone marrow transplant 
or have had other treatments before, it is taken with other medicines (see section 1 ‘What Revlimid is 

used for’).  

• When Revlimid is used to treat multiple myeloma in patients who have had a bone marrow transplant or 
to treat patients with MDS or MCL, it is taken alone. 

• When Revlimid is used to treat follicular lymphoma, it is taken with another medicine called ‘rituximab’.  

 

Always take Revlimid exactly as your doctor has told you. Check with your doctor or pharmacist if you are 

not sure. 

 

If you are taking Revlimid in combination with other medicines, you should refer to the package leaflets for 

these medicines for further information on their use and effects. 

 

Treatment cycle 

Revlimid is taken on certain days over 3 weeks (21 days).  

• Every 21 days is called a ‘treatment cycle’. 

• Depending on the day of the cycle, you will take one or more of the medicines. However, on some days 
you do not take any of the medicines. 

• After completing every 21-day cycle, you should start a new ‘cycle’ over the next 21 days.  
OR 

Revlimid is taken on certain days over 4 weeks (28 days).  

• Every 28 days is called a ‘treatment cycle’. 

• Depending on the day of the cycle, you will take one or more of the medicines. However, on some days 
you do not take any of the medicines. 

• After completing every 28-day cycle, you should start a new ‘cycle’ over the next 28 days.  
 

How much Revlimid to take 

Before you start treatment, your doctor will tell you: 

• how much Revlimid you should take 
• how much of the other medicines you should take in combination with Revlimid, if any 
• on what days of your treatment cycle to take each medicine. 
 

How and when to take Revlimid 

• swallow the capsules whole, preferably with water.  

• do not break, open or chew the capsules. If powder from a broken Revlimid capsule makes contact with 
the skin, wash the skin immediately and thoroughly with soap and water. 

• healthcare professionals, caregivers and family members should wear disposable gloves when handling 
the blister or capsule. Gloves should then be removed carefully to prevent skin exposure, placed in a 

sealable plastic polyethylene bag and disposed of in accordance with local requirements. Hands should 

then be washed thoroughly with soap and water. Women who are pregnant or suspect they may be 

pregnant should not handle the blister or capsule. 

• the capsules can be taken either with or without food. 

• you should take Revlimid at about the same time on the scheduled days. 
 

Taking this medicine 

To remove the capsule from the blister: 

• press only one end of the capsule out to push it through the foil 

• do not put pressure on the centre of the capsule, as this can cause it to break. 
 



 93 

 
 

Duration of the treatment with Revlimid 

Revlimid is taken in treatment cycles, each cycle lasting 21 or 28 days (see above ‘Treatment cycle’). You 

should continue the cycles of treatment until your doctor tells you to stop. 

 

If you take more Revlimid than you should 

If you take more Revlimid than was prescribed, tell your doctor immediately. 

 

If you forget to take Revlimid 

If you forget to take Revlimid at your regular time and: 

• less than 12 hours have passed - take your capsule immediately. 

• more than 12 hours have passed - do not take your capsule. Take your next capsule at the usual time the 
next day. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 

4. Possible side effects 

 

Like all medicines, Revlimid can cause side effects, although not everybody gets them.  

 

Stop taking Revlimid and see a doctor straight away if you notice any of the following serious side 

effects – you may need urgent medical treatment: 

• Hives, rashes, swelling of eyes, mouth or face, difficulty breathing, or itching, which may be symptoms 
of serious types of allergic reactions called angioedema and anaphylactic reaction. 

• A serious allergic reaction that may begin as a rash in one area but spread with extensive loss of skin 
over the whole body (Stevens-Johnson syndrome and/or toxic epidermal necrolysis). 

• Widespread rash, high body temperature, liver enzyme elevations, blood abnormalities (eosinophilia), 
enlarged lymph nodes and other body organs involvement (Drug Reaction with Eosinophilia and 

Systemic Symptoms which is also known as DRESS or drug hypersensitivity syndrome). See also 

section 2. 

 

Tell your doctor straight away if you notice any of the following serious side effects: 

• Fever, chills, sore throat, cough, mouth ulcers or any other symptoms of infection including within the 
bloodstream (sepsis) 

• Bleeding or bruising in the absence of injury 

• Chest pain or leg pain 

• Shortness of breath 

• Bone pain, muscle weakness, confusion or tiredness that might be due to high level of calcium in the 
blood.  

 

Revlimid may reduce the number of white blood cells that fight infection and also the blood cells which help 

the blood to clot (platelets) which may lead to bleeding disorders such as nosebleeds and bruising.  

Revlimid may also cause blood clots in the veins (thrombosis). 

 



 94 

Other side effects 

It is important to note that a small number of patients may develop additional types of cancer, and it is 

possible that this risk may be increased with Revlimid treatment. Therefore your doctor should carefully 

evaluate the benefit and risk when you are prescribed Revlimid. 

 

Very common side effects (may affect more than 1 in 10 people): 

• A fall in the number of red blood cells which may cause anaemia leading to tiredness and weakness 

• Rashes, itching  

• Muscle cramps, muscle weakness, muscle pain, muscle aches, bone pain, joint pain, back pain, pain in 
the extremities 

• Generalised swelling including swelling of your arms and legs 

• Weakness, tiredness 

• Fever and flu like symptoms including fever, muscle ache, headache, earache, cough and chills 

• Numbness, tingling or burning sensation to the skin, pains in hands or feet, dizziness, tremorDecreased 
appetite, change in the way things taste 

• Increase in pain, tumour size or redness around the tumour 

• Weight loss 

• Constipation, diarrhoea, nausea, vomiting, stomach pain, heartburn  

• Low levels of potassium or calcium and/or sodium in the blood 

• Thyroid functioning less than it should be 

• Leg pain (which could be a symptom of thrombosis), chest pain or shortness of breath (which may be a 
symptom of blood clots in the lungs, called pulmonary embolism) 

• Infections of all types, including infection of the sinuses that surround the nose, infection of the lung 
and the upper respiratory tract 

• Shortness of breath 

• Blurred vision 

• Clouding of your eye (cataract) 

• Kidney problems which include kidneys not working properly or not being able to maintain normal 
function 

• Abnormal liver test results 

• Increase in liver test results 

• Changes to a protein in the blood that can cause swelling of the arteries (vasculitis) 

• Increases in your blood sugar levels (diabetes) 

• Decreases in your blood sugar levels 

• Headache 

• Nosebleed 

• Dry skin 

• Depression, mood change, difficulty sleeping 

• Cough 

• A fall in blood pressure 

• A vague feeling of bodily discomfort, feeling bad 

• Sore inflamed mouth, dry mouth 

• Dehydration 
 

Common side effects (may affect up to 1 in 10 people): 

• Destruction of red blood cells (haemolytic anaemia)  

• Certain types of skin tumour 

• Bleeding of the gums, stomach, or bowels 

• Increased blood pressure, slow, fast or irregular heart beat 

• Increase in the amount of a substance which results from normal and abnormal breakdown of red blood 
cells 

• Increase in a type of protein that indicates inflammation in body 

• Darkening of your skin, discoloration of your skin resulting from bleeding underneath, typically caused 
by bruising, swelling of skin filled with blood, bruise 

• Increase in uric acid in the blood 



 95 

• Skin eruptions, redness of skin, cracking, flaking or peeling skin, hives 

• Increased sweating, night sweats 

• Difficulty swallowing, sore throat, difficulty with voice quality or voice changes 

• Runny nose 

• Production of much more or much less urine than usual or the inability to control when to urinate  

• Passing blood in the urine 

• Shortness of breath especially when lying down (which may be a symptom of heart failure) 

• Difficulty getting an erection 

• Stroke, fainting, vertigo (problem with inner ear which leads to feeling that everything is spinning), 
temporary loss of consciousness 

• Chest pain spreading to the arms, neck, jaw, back or stomach, feeling sweaty and breathless, feeling 
sick or vomiting, which may be symptoms of a heart attack (myocardial infarction) 

• Muscle weakness, lack of energy 

• Neck pain, chest pain 

• Chills 

• Joint swelling 

• Bile flow from liver slowed or blocked 

• Low levels of phosphate or magnesium in the blood 

• Difficulty speaking 

• Liver injury 

• Impaired balance, difficulty moving  

• Deafness, ringing in the ears (tinnitus) 

• Nerve pain, unpleasant abnormal sensation especially to touch 

• An excess of iron in the body 

• Thirst 

• Confusion 

• Toothache 

• Fall which may result in injury 
 

Uncommon side effects (may affect up to 1 in 100 people): 

• Bleeding within the skull  

• Circulatory problems 

• Loss of vision 

• Loss of sex drive (libido) 

• Passing large amounts of urine with bone pain and weakness, which may be symptoms of a kidney 
disorder (Fanconi syndrome) 

• Yellow pigmentation to the skin, mucus membrane or eyes (jaundice), pale coloured stools, dark 
coloured urine, skin itch, rash, pain or swelling of the stomach – these may be symptoms of injury to 

the liver (hepatic failure) 

• Stomach pain, bloating, or diarrhoea, which may be symptoms of inflammation in the large intestine 
(called colitis or caecitis) 

• Damage to the cells of the kidney (called renal tubular necrosis) 

• Changes to the colour of your skin, sensitivity to sunlight 

• Tumour lysis syndrome - metabolic complications that can occur during treatment of cancer and 
sometimes even without treatment. These complications are caused by the break-down products of 

dying cancer cells and may include the following: changes to blood chemistry; high potassium, 

phosphorus, uric acid, and low calcium consequently leading to changes in kidney function, heart beat, 

seizures, and sometimes death. 

• Increase in blood pressure within blood vessels that supply the lungs (pulmonary hypertension). 
 



 96 

Not known side effects (frequency cannot be estimated from the available data): 

• Sudden, or mild but worsening pain in the upper stomach and/or back, which remains for a few days, 
possibly accompanied by nausea, vomiting, fever and a rapid pulse – these symptoms may be due to 

inflammation of the pancreas. 

• Wheezing, shortness of breath or a dry cough, which may be symptoms caused by inflammation of the 
tissue in the lungs. 

• Rare cases of muscle breakdown (muscle pain, weakness or swelling) which can lead to kidney 

problems (rhabdomyolysis) have been observed, some of them when Revlimid is administered with a 

statin (a type of cholesterol lowering medicines). 

• A condition affecting the skin caused by inflammation of small blood vessels, along with pain in the 
joints and fever (leukocytoclastic vasculitis). 

• Breakdown of the wall of the stomach or gut. This may lead to very serious infection. Tell your doctor 
if you have severe stomach pain, fever, nausea, vomiting, blood in your stool, or changes in bowel 

habits. 

• Viral infections, including herpes zoster (also known as ‘shingles’, a viral disease that causes a painful 
skin rash with blisters) and recurrence of hepatitis B infection (which can cause yellowing of the skin 

and eyes, dark brown-colored urine, right-sided stomach pain, fever and feeling nauseous or being sick). 

• Rejection of solid organ transplant (such as kidney, heart). 
 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5. How to store Revlimid 

 

• Keep this medicine out of the sight and reach of children. 

• Do not use this medicine after the expiry date, which is stated on the blister and on the carton after 
‘EXP’. The expiry date refers to the last day of that month. 

• This product does not require any special storage conditions. 

• Do not use this medicine if you notice any damage or signs of tampering to the pack. 

• Do not throw away any medicines via wastewater or household waste. Please return unused medicines 
to your pharmacist. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Revlimid contains 

 

Revlimid 2.5 mg hard capsules: 

• The active substance is lenalidomide. Each capsule contains 2.5 mg of lenalidomide. 

• The other ingredients are: 
- capsule contents: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose 

sodium and magnesium stearate 

- capsule shell: gelatine, titanium dioxide (E171), indigo carmine (E132) and yellow iron oxide 
(E172) 

- printing ink: shellac, propylene glycol (E1520), potassium hydroxide and black iron oxide 
(E172). 

 

Revlimid 5 mg hard capsules: 

• The active substance is lenalidomide. Each capsule contains 5 mg of lenalidomide. 

• The other ingredients are: 
- capsule contents: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose 

sodium and magnesium stearate 

- capsule shell: gelatine and titanium dioxide (E171) 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 97 

- printing ink: shellac, propylene glycol (E1520), potassium hydroxide and black iron oxide 
(E172). 

 

Revlimid 7.5 mg hard capsules: 

• The active substance is lenalidomide. Each capsule contains 7.5 mg of lenalidomide. 

• The other ingredients are: 
- capsule contents: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose 

sodium and magnesium stearate 

- capsule shell: gelatine, titanium dioxide (E171) and yellow iron oxide (E172) 
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide and black iron oxide 

(E172). 

 

Revlimid 10 mg hard capsules: 

• The active substance is lenalidomide. Each capsule contains 10 mg of lenalidomide. 

• The other ingredients are: 
- capsule contents: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose 

sodium and magnesium stearate 

- capsule shell: gelatine, titanium dioxide (E171), indigo carmine (E132) and yellow iron oxide 
(E172) 

- printing ink: shellac, propylene glycol (E1520), potassium hydroxide and black iron oxide 
(E172). 

 

Revlimid 15 mg hard capsules: 

• The active substance is lenalidomide. Each capsule contains 15 mg of lenalidomide. 

• The other ingredients are: 
- capsule contents: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose 

sodium and magnesium stearate 

- capsule shell: gelatine, titanium dioxide (E171) and indigo carmine (E132) 
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide and black iron oxide 

(E172). 

 

Revlimid 20 mg hard capsules: 

• The active substance is lenalidomide. Each capsule contains 20 mg of lenalidomide. 

• The other ingredients are: 
- capsule contents: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose 

sodium and magnesium stearate 

- capsule shell: gelatine and titanium dioxide (E171), indigo carmine (E132) and yellow iron oxide 
(E172) 

- printing ink: shellac, propylene glycol (E1520), potassium hydroxide and black iron oxide 
(E172). 

 

Revlimid 25 mg hard capsules: 

• The active substance is lenalidomide. Each capsule contains 25 mg of lenalidomide. 

• The other ingredients are: 
- capsule contents: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose 

sodium and magnesium stearate 

- capsule shell: gelatine and titanium dioxide (E171) 
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide and black iron oxide 

(E172). 

 

What Revlimid looks like and contents of the pack 

 

Revlimid 2.5 mg hard capsules are blue-green/white, with ‘REV 2.5 mg’ written on them. 

The capsules are provided in packs. Each pack contains one or three blisters, each blister with seven 

capsules. This gives a total of 7 or 21 capsules per pack. 

 



 98 

Revlimid 5 mg hard capsules are white, with ‘REV 5 mg’ written on them. 

The capsules are provided in packs. Each pack contains one or three blisters, each blister with seven 

capsules. This gives a total of 7 or 21 capsules per pack. 

 

Revlimid 7.5 mg hard capsules are pale yellow/white, with ‘REV 7.5 mg’ written on them. 

The capsules are provided in packs. Each pack contains one or three blisters, each blister with seven 

capsules. This gives a total of 7 or 21 capsules per pack. 

 

Revlimid 10 mg hard capsules are blue-green/pale yellow, with ‘REV 10 mg’ written on them. 

The capsules are provided in packs. Each pack contains one or three blisters, each blister with seven 

capsules. This gives a total of 7 or 21 capsules per pack. 

 

Revlimid 15 mg hard capsules are pale blue/white, with ‘REV 15 mg’ written on them. 

The capsules are provided in packs. Each pack contains one or three blisters, each blister with seven 

capsules. This gives a total of 7 or 21 capsules per pack. 

 

Revlimid 20 mg hard capsules are blue-green/pale blue, with ‘REV 20 mg’ written on them. 

The capsules are provided in packs. Each pack contains one or three blisters, each blister with seven 

capsules. This gives a total of 7 or 21 capsules per pack. 

 

Revlimid 25 mg hard capsules are white, with ‘REV 25 mg’ written on them. 

The capsules are provided in packs. Each pack contains one or three blisters, each blister with seven 

capsules. This gives a total of 7 or 21 capsules per pack. 

 

 

Marketing Authorisation Holder 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 

Manufacturer 

Celgene Distribution B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands 

 

This leaflet was last revised in 

 

Other sources of information: 

 

Detailed information on this medicine is available on the website of the European Medicines Agency: 

http://www.ema.europa.eu/. 

 

There are also links to other websites about rare diseases and treatments. 

http://www.ema.europa.eu/


 99 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX IV 

 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE 

MARKETING AUTHORISATION(S) 

 



 100 

Scientific conclusions 

 

Taking into account the PRAC Assessment Report on the PSUR(s) for lenalidomide, the scientific 

conclusions of CHMP are as follows:  

 

In view of the large number of cases of pulmonary hypertension collected in the cumulative review, 

including cases with a suggestive chronology and positive dechallenge, and considering that there is a 

plausible mechanism of action and a possible class effect, the PRAC considers that a causal relationship 

between lenalidomide and pulmonary hypertension is plausible. The PRAC concluded that the product 

information of products containing lenalidomide should be amended accordingly. 

 

The CHMP agrees with the scientific conclusions made by the PRAC. 

 

Grounds for the variation to the terms of the marketing authorisation(s) 

On the basis of the scientific conclusions for lenalidomide the CHMP is of the opinion that the benefit-risk 

balance of the medicinal product(s) containing lenalidomide is unchanged subject to the proposed changes 

to the product information 

 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING THE SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)