Lenalidomide Mylan

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ANNEX I  
  

SUMMARY OF PRODUCT CHARACTERISTICS  
  

  



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1.  NAME OF THE MEDICINAL PRODUCT  
 
Lenalidomide Mylan 2.5 mg hard capsules 
Lenalidomide Mylan 5 mg hard capsules 
Lenalidomide Mylan 7.5 mg hard capsules 
Lenalidomide Mylan 10 mg hard capsules 
Lenalidomide Mylan 15 mg hard capsules 
Lenalidomide Mylan 20 mg hard capsules 
Lenalidomide Mylan 25 mg hard capsules 
 
 
2.  QUALITATIVE AND QUANTITATIVE COMPOSITION  
  
Lenalidomide Mylan 2.5 mg hard capsules 
 
Each capsule contains 2.5 mg of lenalidomide 
 
Lenalidomide Mylan 5 mg hard capsules 
 
Each capsule contains 5 mg of lenalidomide 
 
Lenalidomide Mylan 7.5 mg hard capsules 
 
Each capsule contains 7.5 mg of lenalidomide 
 
Lenalidomide Mylan 10 mg hard capsules 
 
Each capsule contains 10 mg of lenalidomide 
 
Lenalidomide Mylan 15 mg hard capsules 
 
Each capsule contains 15 mg of lenalidomide 
 
Lenalidomide Mylan 20 mg hard capsules 
 
Each capsule contains 20 mg of lenalidomide 
 
Lenalidomide Mylan 25 mg hard capsules 
 
Each capsule contains 25 mg of lenalidomide 
 
For the full list of excipients, see section 6.1. 
  
  
3.  PHARMACEUTICAL FORM  
  
Hard capsule (capsule). 
 
Lenalidomide Mylan 2.5 mg hard capsules 
 
Green and white capsules, size 4, 14 mm, marked “MYLAN /LL 2.5” 
 
Lenalidomide Mylan 5 mg hard capsules 
 
White capsules, size 2, 18 mm, marked “MYLAN/LL 5” 
 



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Lenalidomide Mylan 7.5 mg hard capsules 
 
Light grey and white capsules, size 2, 18 mm, marked “MYLAN/LL7.5” 
 
Lenalidomide Mylan 10 mg hard capsules 
 
Green and light grey capsules, size 0, 22 mm, marked “MYLAN/LL 10”  
 
Lenalidomide Mylan 15 mg hard capsules 
 
White capsules, size 0, 22 mm, marked “MYLAN/LL15” 
 
Lenalidomide Mylan 20 mg hard capsules 
 
Green and white capsules, size 0, 22 mm, marked “MYLAN/LL 20” 
 
Lenalidomide Mylan 25 mg hard capsules 
 
White capsules, size 0, 22 mm, marked “MYLAN/LL 25” 
  
  
4.  CLINICAL PARTICULARS  
  
4.1  Therapeutic indications  
 
Multiple myeloma 
 
Lenalidomide Mylan as monotherapy is indicated for the maintenance treatment of adult patients with 
newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation. 
 
Lenalidomide Mylan 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. 
 
Lenalidomide Mylan in combination with dexamethasone is indicated for the treatment of multiple 
myeloma in adult patients who have received at least one prior therapy. 
 
Follicular lymphoma 
 
Lenalidomide Mylan 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  
  
Lenalidomide Mylan treatment should be supervised by a physician experienced in the use of anti-
cancer therapies. 
 
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. 



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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 
Fall to < 25 x 109/L 
Return to ≥ 50 x 109/L 

Stop lenalidomide dosing for remainder of cycleª 
Decrease by one dose level when dosing resumed  
at next cycle 

aIf 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 fall to < 0.5 x 109/L 
Return to ≥ 1 x 109/L when neutropenia is the 
only observed toxicity 

Interrupt lenalidomide treatment 
Resume lenalidomide at starting dose once daily 

Return 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 
Return to ≥ 0.5 x 109/L  

Interrupt lenalidomide treatment 
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 



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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). 
 
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 
Fall to < 30 x 109/L  
Return to ≥ 50 x 109/L 

Interrupt lenalidomide treatment 
Resume lenalidomide at dose level -1 
once daily

For each subsequent drop below 30 x 109/L 
Return to ≥ 50 x 109/L 

Interrupt lenalidomide treatment 
Resume lenalidomide at next lower dose 
level once daily

 
Absolute neutrophil count (ANC) - neutropenia 

 

When ANC Recommended coursea 
First fall to < 0.5 x 109/L  
Return to ≥ 1 x 109/L when neutropenia is the only 
observed toxicity 

Interrupt lenalidomide treatment 
Resume lenalidomide at starting dose 
once daily 

Return 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 
Return to ≥ 0.5 x 109/L 

Interrupt lenalidomide treatment 
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 

 



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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. 
 
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 coursea 
First fall to < 25 x 109/L  
Return to ≥ 25 x 109/L 

Interrupt lenalidomide treatment 
Resume lenalidomide and melphalan at 
dose level -1 

For each subsequent drop below 30 x 109/L  
Return to ≥ 30 x 109/L 

Interrupt lenalidomide treatment 
Resume lenalidomide at next lower dose 
level (dose level -2 or -3) once daily. 

 
Absolute neutrophil count (ANC)-neutropenia

 

When ANC Recommended coursea

First fall to < 0.5 x 109/L  
Return to ≥ 0.5 x 109/L when neutropenia is the 
only observed toxicity 

Interrupt lenalidomide treatment 
Resume lenalidomide at starting dose once 
daily

Return 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 x109/L  
Return to ≥ 0.5 x 109/L 

Interrupt lenalidomide treatment 
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 Absolute Neutrophil 
Count (ANC) is < 1.0 x 109/L, and/or platelet counts are < 75 x 109/L. 
 
Recommended dose 

    



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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) 
aAfter 3 cycles of lenalidomide maintenance, the dose can be increased to 15mg orally once daily if tolerated. 
 
Thrombocytopenia  
When platelets Recommended course 
Fall to < 30 x 109/L  
Return to ≥ 30 x 109/L 

Interrupt lenalidomide treatment 
Resume lenalidomide at dose level -1 once daily

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

Resume lenalidomide at next lower dose level 
once daily. 

 
Absolute neutrophile count (ANC) - neutropenia 

 

When ANC Recommended coursea

Fall to < 0.5 x 109/L  
Return to ≥ 0.5 x 109/L  

Interrupt lenalidomide treatment 
Resume lenalidomide at dose level -1 once daily 

For each subsequent drop below < 0.5 x 109/L  
Return to ≥ 0.5 x 109/L 

Interrupt lenalidomide treatment 
Resume lenalidomide at next lower dose level 
once daily. 

aAt 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 fall to < 30 x 109/L  
Return to ≥ 30 x 109/L 

Interrupt lenalidomide treatment 
Resume lenalidomide at dose level -1 



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For each subsequent drop below 30 x 109/L 
Return to ≥ 30 x 109/L 

Interrupt lenalidomide treatment 
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 fall to < 0.5 x 109/L  
Return to ≥ 0.5 x 109/L when neutropenia is the 
only observed toxicity 

Interrupt lenalidomide treatment 
Resume lenalidomide at starting dose once daily 

Return 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  
Return to ≥ 0.5 x 109/L 

Interrupt lenalidomide treatment  
Resume lenalidomide at next lower dose level 
(dose level -1, -2 or -3) once daily. Do not dose 
below 5 mg once daily. 

aAt 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.

 
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 Interrupt lenalidomide treatment and conduct 

CBC at least every 7 days 

Returns to ≥ 50 x 109/L Resume lenalidomide at next lower dose level 
(dose level -2, -3). Do not dose below dose level -
3. 

 
 
Absolute neutrophil count (ANC) - neutropenia 



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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 

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 -2, -3). Do not dose below dose 
level- 
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ª At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add G-CSF 
 
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. 
 



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Special populations 
 
Paediatric population  
Lenalidomide Mylan should not be used in children and adolescents from birth to less than 18 years 
because of safety concerns (see section 5.1). 
 
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 (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.  
 
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 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). 
 
Multiple myeloma 



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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. 
 
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. 
Lenalidomide Mylan 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  
  



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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 
 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 Lenalidomide Mylan 
or shortly after he has stopped taking Lenalidomide Mylan, he should inform his treating 



13  

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) 
 
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, 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. 



14  

 
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 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 (e.g. smoking, hypertension, and 
hyperlipidaemia). 
 
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. 
 
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 



15  

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, 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. 
 
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 haematocrit should be performed at baseline, every week for the first 8 weeks of 
lenalidomide treatment and monthly thereafter to monitor for cytopenias. 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 
 



16  

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). 
 
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). 



17  

 
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). 
 
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. 
 
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. 
 
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). 
 



18  

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). 
 
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. 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. 
 
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 Lenalidomide Mylan 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 



19  

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.  
 
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 (e.g. cough, fever, etc) thereby allowing for early 
management to reduce severity. 
 
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.  
  



20  

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 (HBV). 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.  
 
Sodium contents 
This medicinal product contains less than 1 mmol sodium (23 mg) per capsule, that is to say 
essentially ‘sodium-free’ 
 
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).  
  
Oral contraceptives  
 



21  

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 



22  

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.  
 
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%), 



23  

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%) 
 
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%), leukopenia (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).  
 



24  

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%).  
 
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 3. 
 
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 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◊ 



25  

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  
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  
 
 



26  

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^ 

 

Endocrine Disorders Common  
Hypothyroidism 

 

Metabolism and  
Nutrition  
Disorders 

Very Common  
Hypokalaemia◊,◊◊ Hyperglycaemia, 
Hypoglycaemia, Hypocalcaemia◊, 
Hyponatraemia◊, Dehydration◊◊, 

Common  
Hypokalaemia◊,◊◊,  
Hyperglycaemia,  



27  

Decreased appetite◊◊, Weight 
decreased  
Common  
Hypomagnesaemia, 
Hyperuricaemia, Hypercalcaemia+ 

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 

Respiratory,  
Thoracic and  
Mediastinal  
Disorders 

Very Common  
Dyspnoea◊,◊◊, Epistaxis^, Cough 
 
Common 

Common  
Respiratory distress◊, 
Dyspnoea◊,◊◊, Pleuritic pain◊◊ 
, Hypoxia◊◊ 



28  

Dysphonia 
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 

Renal and  
Urinary  
Disorders 

Very Common  
Renal failure (including acute)◊,◊◊  
  
Common  

Uncommon  
Renal tubular necrosis 



29  

Haematuria^, Urinary retention, 
Urinary incontinence  
  
Uncommon  
Acquired Fanconi syndrome

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 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. 
 
Table 3: 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 

Very Common 
Tumour flare^ 
 

Common 
Basal cell carcinoma^,◊ 



30  

and polyps) Common 
Squamous Cell Carcinoma of 
Skin◊,^,+ 

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 

Musculoskeletal and 
Connective Tissue 
Disorders 

Very Common 
Muscle spasms, Back pain, 
Arthralgia 
Common 

Common 
Muscular weakness, Neck pain 



31  

^see section 4.8 description of selected adverse reactions 
Algorithm applied for follicular lymphoma: 
Controlled– Phase 3 trial: 
 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) 
 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) 

 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: 
 NHL-008 ADRs- All treatment-emergent adverse events with ≥ 5.0% of subjects 
 NHL-008 Gr 3/4 ADRs- All Grade 3/4 treatment-emergent adverse events reported in ≥ 1.0% of subjects 
 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 4. 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  
  

Pain in extremity, Muscular 
weakness, 
Musculoskeletal pain, Myalgia, 
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 

 



32  

Blood and  
Lymphatic  
System Disorders 

Not Known  
Acquired haemophilia 

 

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. 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.  
 
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 



33  

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).  
  
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).  
 
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 



34  

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, 
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.  
  
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   



35  

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 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. 
 
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: Immunosuppressants, 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 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 



36  

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 five phase 3 studies in newly diagnosed 
multiple myeloma, two phase 3 studies in relapsed refractory multiple myeloma, 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.  
  
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 5 
 
Table 5: 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 



37  

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 cut-off dates: 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 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.  
 



38  

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 6. The benefit favouring RVd was 
observed regardless of eligibility for stem cell transplant. 
 
Table 6. 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 (%)   
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; Median follow-up was calculated from the date of randomization. 
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 



39  

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, multicenter, 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 acetylsalicylic acid) 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 7. 
 
Table 7: 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 
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 



40  

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 multicenter, 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.  
  
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 8:  
 
Table 8. Summary of overall efficacy data  

 MPR+R   
(N = 152) 

MPR+p  
(N = 153) 

MPp +p  
(N = 154) 

Investigator-assessed PFS − (months)      



41  

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.  
  
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.  



42  

 
Multiple myeloma with at least one prior therapy  
The efficacy and safety of lenalidomide were evaluated in two phase 3 multi-centre, 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 9 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).  
 



43  

Table 9. 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-
value b 

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.  
 
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).  
 
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. 
 



44  

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 10. 
 
Table 10: 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). 
 
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. 



45  

 
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 11: 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 lenalidomide 
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 medicinal product accumulation. In plasma, the relative exposures of the S- and R- 
enantiomers of lenalidomide are approximately 56% and 44%, respectively.  



46  

  
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 
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.  
 
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. 
  
Elderly  
 
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.  
  



47  

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 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 



48  

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 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 
 
Starch, pregelatinized 
Cellulose, microcrystalline 
Croscarmellose sodium 
Silica, colloidal anhydrous 
Sodium stearyl fumarate 
 
Capsule shell 
 
Lenalidomide Mylan 2.5 mg hard capsules and Lenalidomide Mylan 20 mg hard capsules  
Yellow iron oxide [E172] 
Titanium dioxide [E171] 
Gelatin 
Indigo carmine [E132] 
 
Lenalidomide Mylan 7.5 mg hard capsules 
Yellow iron oxide [E172] 
Black iron oxide [E172] 
Titanium dioxide [E171] 
Gelatin 
 
Lenalidomide Mylan 10 mg hard capsules  
Yellow iron oxide [E172] 
Black iron oxide [E172] 
Titanium dioxide [E172] 
Indigo carmine [E132] 
Gelatin 
 
Lenalidomide Mylan 5 mg hard capsules Lenalidomide Mylan 15 mg hard capsules Lenalidomide 
Mylan 25 mg hard capsules  
Titanium dioxide [E171] 
Gelatin 
 
 
Printing ink 
 
Shellac 
Propylene glycol [E1520] 
 



49  

Lenalidomide Mylan 2.5 mg hard capsules Lenalidomide Mylan 5 mg hard capsules Lenalidomide 
Mylan 7.5 mg hard capsules Lenalidomide Mylan 10 mg hard capsules Lenalidomide Mylan 25 mg 
hard capsules  
Black iron oxide [E172] 
Potassium hydroxide 
 
Lenalidomide Mylan 15 mg hard capsules Lenalidomide Mylan 20 mg hard capsules  
Red iron oxide [E172] 
Simeticone 
 
6.2  Incompatibilities  
 
Not applicable.  
 
6.3  Shelf life  
 
Lenalidomide Mylan 2.5 mg hard capsules  
 
15 months 
 
Lenalidomide Mylan 5 mg hard capsules, Lenalidomide Mylan 7.5 mg hard capsules, Lenalidomide 
Mylan 10 mg hard capsules, Lenalidomide Mylan 15 mg hard capsules, Lenalidomide Mylan 20 mg 
hard capsules & Lenalidomide Mylan 25 mg hard capsules 
 
2 years 
 
6.4  Special precautions for storage  
 
Do not store above 30°C 
 

6.5  Nature and contents of container  
 
 
Lenalidomide Mylan 2.5 mg hard capsules, Lenalidomide Mylan 7.5 mg hard capsules, Lenalidomide 
Mylan 20 mg hard capsules, Lenalidomide Mylan 25 mg hard capsules  
 
PVC/PCTFE/Aluminium foil blister packs containing 7 hard capsules  
 
Lenalidomide Mylan 2.5 mg hard capsules Lenalidomide Mylan 5 mg hard capsules, Lenalidomide 
Mylan 7.5 mg hard capsules, Lenalidomide Mylan 10 mg hard capsules, Lenalidomide Mylan 15 mg 
hard capsules, Lenalidomide Mylan 20 mg hard capsules Lenalidomide Mylan 25 mg hard capsules,    
 
PVC/PCTFE/Aluminium foil blister packs containing  21 hard capsules. 
 
PVC/PCTFE/Aluminium foil perforated unit dose blister packs containing 21 x 1 hard capsules. 
 
Not all pack sizes may be marketed.  
 
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. 
 



50 

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 medicinal product or waste material should be disposed of in accordance with local 
requirements. 

7. MARKETING AUTHORISATION HOLDER

Mylan Ireland Limited 
Unit 35/36 Grange Parade, 
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1490/001 
EU/1/20/1490/002 
EU/1/20/1490/003 
EU/1/20/1490/004 
EU/1/20/1490/005 
EU/1/20/1490/006 
EU/1/20/1490/007 
EU/1/20/1490/008 
EU/1/20/1490/009 
EU/1/20/1490/010 
EU/1/20/1490/011 
EU/1/20/1490/012 
EU/1/20/1490/013 
EU/1/20/1490/014 
EU/1/20/1490/015 
EU/1/20/1490/016 
EU/1/20/1490/017 
EU/1/20/1490/018 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation:  

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/.  



51 

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



52  

 
A.  MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE  
 
Name and address of the manufacturers responsible for batch release  
 
McDermott Laboratories Ltd trading as Gerard Laboratories, Ireland 
35/36 Baldoyle Industrial Estate, Grange State, Dublin 13, Ireland 
 
Mylan Hungary Kft, Hungary 
Mylan utca 1, Komárom, 2900, Hungary 
 
Mylan UK Healthcare Limited  
Building 20, Station Close, Potters Bar, EN6 1TL, United Kingdom 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.  
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING 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 (PSURs) 
The requirements for submission of PSURs 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 marketing authorisation holder (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.  

 
An updated RMP shall be submitted by {CHMP agreed deadline}.  
 

 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: 



53  

 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) Lenalidomide Mylan 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. 

3. The MAH should agree on the implementation of the patient card system in each Member 
State. 

Key elements to be included 
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 

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 Lenalidomide Mylan for healthcare 
professionals and caregivers 

 Obligations of the health care professional in relation to the prescribing of Lenalidomide 
Mylan 

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 

Lenalidomide Mylan 
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 Lenalidomide Mylan to be 

dispensed 
o Description of risk of tumour flare reaction  
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 
 After finishing treatment 

o Need to stop Lenalidomide Mylan immediately upon suspicion of pregnancy 
o Need to tell treating doctor immediately upon suspicion of pregnancy 

 Safety advice for men 



54  

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 Lenalidomide Mylan treatment 
 For at least 7 days following final dose. 

o That if his partner becomes pregnant whilst he is taking Lenalidomide Mylan or 
shortly after he has stopped taking Lenalidomide Mylan he should inform his treating 
doctor immediately 

 Requirements in the event of pregnancy 
o Instructions to stop Lenalidomide Mylan 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. 

 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 Lenalidomide Mylan 

to be dispensed 
 That the patient should not give Lenalidomide Mylan 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 Lenalidomide Mylan treatment 
 That the patient should tell their doctor about any adverse events 

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 Lenalidomide Mylan immediately upon suspicion of pregnancy 
 The need to contact their doctor immediately upon suspicion of pregnancy 

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 

contraception (even if man has had vasectomy) 
o During Lenalidomide Mylan 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 Lenalidomide Mylan treatment 
Patient Card 



55  

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 

 
 

 
  



56  

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

ANNEX III  
  

LABELLING AND PACKAGE LEAFLET  
  

    



57  

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

A. LABELLING  
  



58  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON  
 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 2.5 mg hard capsules  
lenalidomide  
 
 

2.  STATEMENT OF ACTIVE SUBSTANCE(S)  

 
Each capsule contains 2.5 mg lenalidomide.  
 
 

3.  LIST OF EXCIPIENTS  

 
 

4.  PHARMACEUTICAL FORM AND CONTENTS  

 
Hard capsule 
 
7 hard capsules 
21 hard capsules 
21 x 1 hard capsules 
 
 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION  

 
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 Lenalidomide Mylan Pregnancy Prevention Programme. 
 
 

8.  EXPIRY DATE  

 



59  

EXP 
 
 

9.  SPECIAL STORAGE CONDITIONS  

 
Do not store above 30°C 
 
 

10.  SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 

11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
 

12.  MARKETING AUTHORISATION NUMBER(S)   

 
EU/1/20/1490/001 
EU/1/20/1490/002 
EU/1/20/1490/003   
 
 

13.  BATCH NUMBER 

 
Lot 
 
 

 14.  GENERAL CLASSIFICATION FOR SUPPLY  

 
 
 

15.  INSTRUCTIONS ON USE  

 
 
 

16.  INFORMATION IN BRAILLE  
 
Lenalidomide Mylan 2.5 mg hard capsules  
 
 

17.  UNIQUE IDENTIFIER – 2D BARCODE  
 



60  

2D barcode carrying the unique identifier included. 
 
 

18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC 
SN 
NN 
 
  



61  

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
BLISTERS 

 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 2.5 mg capsules  
lenalidomide 
 
 

2.  NAME OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
 
 

3.  EXPIRY DATE  

 
EXP 
 
 

4.  BATCH NUMBER  

 
Lot 
 
 

5.  OTHER  

 
 
 
  



62  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON  
 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 5 mg hard capsules  
lenalidomide  
 
 

2.  STATEMENT OF ACTIVE SUBSTANCE(S)  

 
Each capsule contains 5 mg lenalidomide. 
 
 

3.  LIST OF EXCIPIENTS  

 
 
 

4.  PHARMACEUTICAL FORM AND CONTENTS  

 
Hard capsule 
 
21 hard capsules 
21 x 1 hard capsules 
 
 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION  

 
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 Lenalidomide Mylan Pregnancy Prevention Programme. 
 
 

8.  EXPIRY DATE  

 



63  

EXP 
 
 

9.  SPECIAL STORAGE CONDITIONS  

 
Do not store above 30°C 
 
 

10.  SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
 

11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
 

12.  MARKETING AUTHORISATION NUMBER(S)   

 
EU/1/20/1490/004 
EU/1/20/1490/005   
 
 

13.  BATCH NUMBER 

 
Lot 
 
 

14.  GENERAL CLASSIFICATION FOR SUPPLY  

 
 
 

15.  INSTRUCTIONS ON USE  

 
 
 

16.  INFORMATION IN BRAILLE  
 
Lenalidomide Mylan 5 mg hard capsules  
 
 

17.  UNIQUE IDENTIFIER – 2D BARCODE  
 



64  

2D barcode carrying the unique identifier included. 
 
 

18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC 
SN 
NN 
  



65  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
BLISTERS 

 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 5 mg capsules  
lenalidomide 
 
 

2.  NAME OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
 
 

3.  EXPIRY DATE  

 
EXP 
 
 

4.  BATCH NUMBER  

 
Lot 
 
 

5.  OTHER  

 
 
 
  



66  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON 
 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 7.5 mg hard capsules  
lenalidomide  
 
 

2.  STATEMENT OF ACTIVE SUBSTANCE(S)  

 
Each capsule contains 7.5 mg lenalidomide. 
 
 

3.  LIST OF EXCIPIENTS  

 
 
 

4.  PHARMACEUTICAL FORM AND CONTENTS  

 
Hard capsule 
 
7 hard capsules 
21 hard capsules 
21 x 1 hard capsules 
 
 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION  

 
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 Lenalidomide Mylan Pregnancy Prevention Programme. 
 
 

8.  EXPIRY DATE  



67  

 
EXP 
 
 

9.  SPECIAL STORAGE CONDITIONS  

 
Do not store above 30°C 
 
 

10.  SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
 

11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
 

12.  MARKETING AUTHORISATION NUMBER(S)   

 
EU/1/20/1490/006 
EU/1/20/1490/007 
EU/1/20/1490/008   
 
 

13.  BATCH NUMBER 

 
Lot 
 
 

14.  GENERAL CLASSIFICATION FOR SUPPLY  

 
 
 

15.  INSTRUCTIONS ON USE  

 
 
 

16.  INFORMATION IN BRAILLE  
 
Lenalidomide Mylan 7.5 mg hard capsules  
 
 



68  

17.  UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included. 
 
 

18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC 
SN 
NN 
 
  



69  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
BLISTERS 

 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 7.5 mg capsules  
lenalidomide 
 
 

2.  NAME OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
 
 

3.  EXPIRY DATE  

 
EXP 
 
 

4.  BATCH NUMBER  

 
Lot 
 
 

5.  OTHER  

 
 
 
  



70  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON  
 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 10 mg hard capsules  
lenalidomide  
 
 

2.  STATEMENT OF ACTIVE SUBSTANCE(S)  

 
Each capsule contains 10 mg lenalidomide. 
 
 

3.  LIST OF EXCIPIENTS  

 
 
 

4.  PHARMACEUTICAL FORM AND CONTENTS  

 
Hard capsule 
 
21 hard capsules 
21 x 1 hard capsules 
 
 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION  

 
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 Lenalidomide Mylan Pregnancy Prevention Programme. 
 
 

8.  EXPIRY DATE  

 



71  

EXP 
 
 

9.  SPECIAL STORAGE CONDITIONS  

 
Do not store above 30°C 
 
 

10.  SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
 

11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
 

12.  MARKETING AUTHORISATION NUMBER(S)   

 
EU/1/20/1490/009 
EU/1/20/1490/010   
 
 

13.  BATCH NUMBER 

 
Lot 
 
 

 14.  GENERAL CLASSIFICATION FOR SUPPLY  

 
 
 

15.  INSTRUCTIONS ON USE  

 
 
 

16.  INFORMATION IN BRAILLE  
 
Lenalidomide Mylan 10 mg hard capsules  
 
 

17.  UNIQUE IDENTIFIER – 2D BARCODE  
 



72  

2D barcode carrying the unique identifier included. 
 
 

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  

 
Lenalidomide Mylan 10 mg capsules  
lenalidomide 
 
 

2.  NAME OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
 
 

3.  EXPIRY DATE  

 
EXP 
 
 

4.  BATCH NUMBER  

 
Lot 
 
 

5.  OTHER  

 
 
 
  



74  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON  
 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 15 mg hard capsules  
lenalidomide  
 
 

2.  STATEMENT OF ACTIVE SUBSTANCE(S)  

 
Each capsule contains 15 mg lenalidomide. 
 
 

3.  LIST OF EXCIPIENTS  

 
 
 

4.  PHARMACEUTICAL FORM AND CONTENTS  

 
Hard capsule 
 
21 hard capsules 
21 x 1 hard capsules 
 
 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION  

 
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 Lenalidomide Mylan Pregnancy Prevention Programme. 
 
 

8.  EXPIRY DATE  

 



75  

EXP 
 
 

9.  SPECIAL STORAGE CONDITIONS  

 
Do not store above 30°C 
 
 

10.  SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
 

11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
 

12.  MARKETING AUTHORISATION NUMBER(S)   

 
EU/1/20/1490/011 
EU/1/20/1490/012   
 
 

13.  BATCH NUMBER 

 
Lot 
 
 

14.  GENERAL CLASSIFICATION FOR SUPPLY  

 
 
 

15.  INSTRUCTIONS ON USE  

 
 
 

16.  INFORMATION IN BRAILLE  
 
Lenalidomide Mylan 15 mg hard capsules  
 
 

17.  UNIQUE IDENTIFIER – 2D BARCODE  
 



76  

2D barcode carrying the unique identifier included. 
 
 

18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC 
SN 
NN 
 
  



77  

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
BLISTERS 

 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 15 mg capsules  
lenalidomide 
 
 

2.  NAME OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
 
 

3.  EXPIRY DATE  

 
EXP 
 
 

4.  BATCH NUMBER  

 
Lot 
 
 

5.  OTHER  

 
 
 
  



78  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON  
 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 20 mg hard capsules  
lenalidomide  
 
 

2.  STATEMENT OF ACTIVE SUBSTANCE(S)  

 
Each capsule contains 20 mg lenalidomide. 
 
 

3.  LIST OF EXCIPIENTS  

 
 
 

4.  PHARMACEUTICAL FORM AND CONTENTS  

 
Hard capsule 
 
7 hard capsules 
21 hard capsules 
21 x 1 hard capsules 
 
 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION  

 
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 Lenalidomide Mylan Pregnancy Prevention Programme. 
 
 

8.  EXPIRY DATE  



79  

 
EXP 
 
 

9.  SPECIAL STORAGE CONDITIONS  

 
Do not store above 30°C 
 
 

10.  SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
 

11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
 

12.  MARKETING AUTHORISATION NUMBER(S)   

 
EU/1/20/1490/013 
EU/1/20/1490/014 
EU/1/20/1490/015   
 
 

13.  BATCH NUMBER 

 
Lot 
 
 

 14.  GENERAL CLASSIFICATION FOR SUPPLY  

 
 
 

15.  INSTRUCTIONS ON USE  

 
 
 

16.  INFORMATION IN BRAILLE  
 
Lenalidomide Mylan 20 mg hard capsules  
 
 



80  

17.  UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included. 
 
 

18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC 
SN 
NN 
 
  



81  

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
BLISTERS 

 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 20 mg capsules  
lenalidomide 
 
 

2.  NAME OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
 
 

3.  EXPIRY DATE  

 
EXP 
 
 

4.  BATCH NUMBER  

 
Lot 
 
 

5.  OTHER  

 
 
 
  



82  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON  
 
 

1.  NAME OF THE MEDICINAL PRODUCT  

 
Lenalidomide Mylan 25 mg hard capsules  
lenalidomide  
 
 

2.  STATEMENT OF ACTIVE SUBSTANCE(S)  

 
Each capsule contains 25 mg lenalidomide 
 
 

3.  LIST OF EXCIPIENTS  

 
 
 

4.  PHARMACEUTICAL FORM AND CONTENTS  

 
Hard capsule 
 
7 hard capsules 
21 hard capsules 
21 x 1 hard capsules 
 
 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION  

 
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 Lenalidomide Mylan Pregnancy Prevention Programme. 
 
 

8.  EXPIRY DATE  



83  

 
EXP 
 
 

9.  SPECIAL STORAGE CONDITIONS  

 
Do not store above 30°C 
 
 

10.  SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
 

11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
 

12.  MARKETING AUTHORISATION NUMBER(S)   

 
EU/1/20/1490/016 
EU/1/20/1490/017 
EU/1/20/1490/018   
 
 

13.  BATCH NUMBER 

 
Lot 
 
 

14.  GENERAL CLASSIFICATION FOR SUPPLY  

 
 
 

15.  INSTRUCTIONS ON USE  

 
 
 

16.  INFORMATION IN BRAILLE  
 
Lenalidomide Mylan 25 mg hard capsules  
 
 



84  

17.  UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included. 
 
 

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  

 
Lenalidomide Mylan 25 mg capsules  
lenalidomide 
 
 

2.  NAME OF THE MARKETING AUTHORISATION HOLDER  

 
Mylan Ireland Limited 
 
 

3.  EXPIRY DATE  

 
EXP 
 
 

4.  BATCH NUMBER  

 
Lot 
 
 

5.  OTHER  

 
 
 
  



86  

 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

B. PACKAGE LEAFLET  
  

  



87  

Package leaflet: Information for the patient 
 

Lenalidomide Mylan 2.5 mg hard capsules 
Lenalidomide Mylan 5 mg hard capsules 

Lenalidomide Mylan 7.5 mg hard capsules 
Lenalidomide Mylan 10 mg hard capsules 
Lenalidomide Mylan 15 mg hard capsules 
Lenalidomide Mylan 20 mg hard capsules 
Lenalidomide Mylan 25 mg hard capsules 

 
lenalidomide 

 
 

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, pharmacist, or nurse.  
- 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 Lenalidomide Mylan is and what it is used for  
2. What you need to know before you take Lenalidomide Mylan  
3. How to take Lenalidomide Mylan  
4. Possible side effects  
5. How to store Lenalidomide Mylan 
6. Contents of the pack and other information  
 
 

1. What Lenalidomide Mylan is and what it is used for  
 
Lenalidomide Mylan contains the active substance ‘lenalidomide’. This medicine belongs to a group 
of medicines which affect how your immune system works.  
 
Lenalidomide Mylan is used in adults for Multiple myeloma and 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’. 
 
Newly diagnosed multiple myeloma – in patients who have had a bone marrow transplant 
Lenalidomide Mylan 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 
Lenalidomide Mylan 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’. 



88  

You will take these other medicines at the start of treatment and then continue to take Lenalidomide 
Mylan 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 
Lenalidomide Mylan is taken together with an anti-inflammatory medicine called ‘dexamethasone’. 
 
Lenalidomide Mylan 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  
 
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. 
 
Lenalidomide Mylan is taken together with another medicine called ‘rituximab’ for the treatment of 
adult patients with previously treated follicular lymphoma. 
 
How Lenalidomide Mylan works 
Lenalidomide Mylan 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 Lenalidomide Mylan   
  
You must read the package leaflet of all medicinal products to be taken in combination with 
Lenalidomide Mylan before starting treatment with Lenalidomide Mylan.  
 
Do not take Lenalidomide Mylan 
 if you are pregnant, think you may be pregnant or are planning to become pregnant, as 

Lenalidomide Mylan 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 Lenalidomide Mylan. Talk to your doctor if you are not sure.  
 
Warnings and precautions   
Talk to your doctor, pharmacist or nurse before taking Lenalidomide Mylan 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 Lenalidomide Mylan may 
cause the virus to become active again, in patients who carry the virus. This results in a 



89  

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 Lenalidomide Mylan 
 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 lenalidomide, 
tell your doctor about any change in these symptoms. 

 
 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 Lenalidomide Mylan you will have regular blood tests. This is 
because Lenalidomide Mylan 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 FL taking Lenalidomide Mylan 
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. 
 



90  

Your doctor may adjust your dose of Lenalidomide Mylan 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  
Lenalidomide Mylan 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.  
 
Other medicines and Lenalidomide Mylan 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 
medicines.  
 
This is because Lenalidomide Mylan can affect the way some other medicines work. Also, some other 
medicines can affect the way Lenalidomide Mylan 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 Lenalidomide Mylan 
 You must not take Lenalidomide Mylan if you are pregnant, as it is expected to be harmful to an 

unborn baby. 
 You must not become pregnant while taking Lenalidomide Mylan. 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 Lenalidomide Mylan, you must stop the 
treatment and inform your doctor immediately. 

 
For men taking Lenalidomide Mylan 
 If your partner becomes pregnant whilst you are taking Lenalidomide Mylan, 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 Lenalidomide Mylan, as it is not known if Lenalidomide Mylan 
passes into breast milk. 
 
Contraception 
For women taking Lenalidomide Mylan 
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 



91  

 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 Lenalidomide Mylan 
Lenalidomide Mylan 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 Lenalidomide Mylan. 
 
Lenalidomide Mylan contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially 
‘sodium-free’ 
 
 
3. How to take Lenalidomide Mylan  
 
Lenalidomide Mylan must be given to you by healthcare professionals with experience in treating 
multiple myeloma or FL. 
 
 When Lenalidomide Mylan 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 Lenalidomide Mylan is used for’). 

 When Lenalidomide Mylan is used to treat multiple myeloma in patients who have had a bone 
marrow transplant, it is taken alone 

 When Lenalidomide Mylan is used to treat follicular lymphoma, it is taken with another 
medicine called ‘rituximab’. 

 
Always take Lenalidomide Mylan exactly as your doctor has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
If you are taking Lenalidomide Mylan 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 
Lenalidomide Mylan 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 
Lenalidomide Mylan 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. 
 



92  

How much Lenalidomide Mylan to take 
Before you start treatment, your doctor will tell you: 
 how much Lenalidomide Mylan you should take 
 how much of the other medicines you should take in combination with Lenalidomide Mylan, if any  
 on what days of your treatment cycle to take each medicine. 
 
How and when to take Lenalidomide Mylan 
 swallow the capsules whole, preferably with water. 
 do not break, open or chew the capsules. If powder from a broken Lenalidomide Mylan 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 Lenalidomide Mylan 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. 
 

 
 
 
Duration of the treatment with Lenalidomide Mylan 
Lenalidomide Mylan 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 Lenalidomide Mylan than you should 
If you take more Lenalidomide Mylan than was prescribed, tell your doctor immediately. 
 
If you forget to take Lenalidomide Mylan 
If you forget to take Lenalidomide Mylan 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. 
 



93  

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4.  Possible side effects  
 
Like all medicines, Lenalidomide Mylan can cause side effects, although not everybody gets them. 
 
Stop taking Lenalidomide Mylan 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. 
 
Lenalidomide Mylan 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. 
Lenalidomide Mylan may also cause blood clots in the veins (thrombosis). 
 
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 Lenalidomide Mylan treatment. Therefore, your doctor 
should carefully evaluate the benefit and risk when you are prescribed Lenalidomide Mylan.  
 
Very common (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, tremor 
 Decreased appetite, changes 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) 



94  

 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 level (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 (may affect up to 1 in 10 people): 
 Destruction of red blood cells (haemolytic anaemia) 
 Certain types of skin tumour 
 Bleeding from 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, discolouration of your skin resulting from bleeding underneath, 

typically caused by bruising, swelling of the skin filled with blood, bruise 
 Increase in uric acid in the blood 
 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 your inner ear which leads to a 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 the liver slowed or blocked 
 Low levels of phosphate or magnesium in the blood 
 Difficulty speaking 
 Liver injury 



95  

 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 (may affect up to 1 in 100 people): 
 Bleeding within the skull 
 Circulatory problems 
 Increase in blood pressure within blood vessels that supply the lungs (pulmonary hypertension). 
 Loss of vision 
 Loss of sex drive (libido) 
 Passing large amount 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. 

 
 
Not known (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 Lenalinomide Mylan 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 



96  

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 Lenalidomide Mylan 
 
 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. 
 Do not store above 30°C. 
 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. Ask your pharmacist 

how to throw away medicines you no longer use. These measures will help protect the 
environment.  

 
 
6.  Contents of the pack and other information  
 
What Lenalidomide Mylan contains   
Lenalidomide Mylan 2.5 mg hard capsules: 
 The active substance is lenalidomide. Each capsule contains 2.5 mg of lenalidomide. 
 The other ingredients are: 

- capsule contents: pregelatinized starch, microcrystalline cellulose, sodium croscarmellose, 
colloidal anhydrous silica, sodium stearyl fumarate 

- capsule shell: gelatine, titanium dioxide [E171], yellow iron oxide [E172] and indigo carmine 
[E132] 

- printing ink: shellac, propylene glycol [E1520], potassium hydroxide and black iron oxide 
[E172].  

 
 
Lenalidomide Mylan 5 mg hard capsules: 
 The active substance is lenalidomide. Each capsule contains 5 mg of lenalidomide. 
 The other ingredients are: 

- capsule contents: pregelatinized starch, microcrystalline cellulose, sodium croscarmellose, 
colloidal anhydrous silica, sodium stearyl fumarate 

- capsule shell: titanium dioxide [E171], gelatin 
- printing ink: shellac, propylene glycol [E1520], potassium hydroxide and black iron oxide 

[E172].  
 
Lenalidomide Mylan 7.5 mg hard capsules: 
 The active substance is lenalidomide. Each capsule contains 7.5 mg of lenalidomide. 
 The other ingredients are: 

- capsule contents: pregelatinized starch, microcrystalline cellulose, sodium croscarmellose, 
colloidal anhydrous silica, sodium stearyl fumarate 

- capsule shell: yellow iron oxide [E172], titanium dioxide [E171], gelatin, 
-printing ink: shellac propylene glycol [E1520], black iron oxide [E172] and potassium 

hydroxide 
 

 
Lenalidomide Mylan 10 mg hard capsules: 
 The active substance is lenalidomide. Each capsule contains 10 mg of lenalidomide. 
 The other ingredients are: 

- capsule contents: pregelatinized starch, microcrystalline cellulose, sodium croscarmellose, 
colloidal anhydrous silica, sodium stearyl fumarate 



97  

- capsule shell: gelatine, titanium dioxide [E171], black iron oxide and yellow iron oxide 
[E172], indigo carmine[E132] 

-printing ink: shellac, propylene glycol [E1520], black iron oxide [E172]and potassium 
hydroxide 

 
 
Lenalidomide Mylan 15 mg hard capsules: 
 The active substance is lenalidomide. Each capsule contains 15 mg of lenalidomide. 
 The other ingredients are: 

- capsule contents: pregelatinized starch, microcrystalline cellulose, sodium croscarmellose, 
colloidal anhydrous silica, sodium stearyl fumarate 

- capsule shell: titanium dioxide [E171], gelatin 
-printing ink: shellac, propylene glycol [E1520], red iron oxide [E172] and simeticone 
 

Lenalidomide Mylan 20 mg hard capsules: 
 The active substance is lenalidomide. Each capsule contains 20 mg of lenalidomide. 
 The other ingredients are: 

- capsule contents: pregelatinized starch, microcrystalline cellulose, sodium croscarmellose, 
colloidal anhydrous silica, sodium stearyl fumarate 

- capsule shell: yellow iron oxide [E172], titanium dioxide, indigo carmine [E132], gelatin 
-printing ink: shellac, propylene glycol [E1520], red iron oxide [E172] and simeticone 
 

 
Lenalidomide Mylan 25 mg hard capsules: 
 The active substance is lenalidomide. Each capsule contains 25 mg of lenalidomide. 
 The other ingredients are: 

- capsule contents: pregelatinized starch, microcrystalline cellulose, sodium croscarmellose, 
colloidal anhydrous silica, sodium stearyl fumarate 

- capsule shell:  titanium dioxide [E171], gelatin 
-printing ink: shellac, propylene glycol [E1520], potassium hydroxide, and black iron oxide 

[E172]. 
 
What Lenalidomide Mylan looks like and contents of the pack  
 
Lenalidomide Mylan 2.5 mg hard capsules are green and white capsules, size 4, 14 mm, marked 
“MYLAN/LL 2.5”  
 
Lenalidomide Mylan 5 mg hard capsules are white capsules, size 2, 18 mm, marked “MYLAN/LL 5” 
 
Lenalidomide Mylan 7.5 mg hard capsules are light grey and white capsules, size 2, 18 mm, marked 
“MYLAN/LL7.5” 
 
Lenalidomide Mylan 10 mg hard capsules are green and light grey capsules, size 0, 22 mm, marked 
“MYLAN/LL 10”  
 
Lenalidomide Mylan 15 mg hard capsules are white capsules, size 0, 22 mm, marked 
“MYLAN/LL15” 
 
Lenalidomide Mylan 20 mg hard capsules are green and white capsules, size 0, 22 mm, marked 
“MYLAN/LL 20” 
 
Lenalidomide Mylan 25 mg hard capsules are white capsules, size 0, 22 mm, marked “MYLAN/LL 
25” 
 
 



98  

Lenalidomide Mylan 2.5 mg, 7.5 mg, 20 mg and 25 mg hard capsules are provided in blister packs 
containing 7 hard capsules. 
Lenalidomide Mylan 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg and 25 mg hard capsules are 
provided in blister packs containing 21 hard capsules and in perforated blister packs containing 21 x 1 
hard capsules. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
Mylan Ireland Limited 
Unit 35/36 Grange Parade,  
Baldoyle Industrial Estate 
Dublin 13, 
Ireland. 
 
Manufacturer  
 
McDermott Laboratories Ltd trading as Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange 
Road, Dublin 13, Ireland 
 
Mylan Hungary Kft, Mylan utca 1, 2900 Komárom, Hungary 
 
Mylan UK Healthcare Limited, Building 20, Station Close, Potters Bar, EN6 1TL, United Kingdom 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:  
  
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 32 (0)2 658 61 00 
 

Lietuva 
Mylan Healthcare UAB  
Tel: +370 5 205 1288 
 

България 
Майлан ЕООД 
Тел: +359 2 44 55 400 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tel: + 32 (0)2 658 61 00 
(Belgique/Belgien) 
 

Česká republika 
Mylan Healthcare CZ.s.r.o. 
Tel: + 420 222 004 400 
 

Magyarország 
Mylan EPD Kft 
Tel: + 36 1 465 2100 

Danmark 
Mylan Denmark ApS 
Tel: +45 28 11 69 32 
 

Malta 
V.J. Salomone Pharma Ltd 
Tel: + 356 21 22 01 74 
 

Deutschland 
Mylan Healthcare GmbH 
Tel: +49 800 0700 800 
 

Nederland 
Mylan BV 
Tel: +31 (0)20 426 3300 



99  

Eesti 
BGP Products Switzerland GmbH Eesti 
filiaal  
Tel: + 372 6363 052 
 

Norge 
Mylan Healthcare Norge AS 
Tel: + 47 66 75 33 00 
 

Ελλάδα  
Generics Pharma Hellas ΕΠΕ  
Τηλ:  +30 210 993 6410  
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 2418 
 

España 
Mylan Pharmaceuticals, S.L 
Tel: + 34 900 102 712 
 

Polska 
Mylan Healthcare Sp. z. o.o. 
Tel: + 48 22 546 64 00 
 

France 
Mylan S.A.S 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Tel: + 351 21 412 72 56 
 

Hrvatska 
Mylan Hrvatska d.o.o. 
Tel: +385 1 23 50 599 
  

România 
BGP Products SRL 
Tel: +40 372 579 000 
 

Ireland 
Mylan Ireland Limited 
Tel:  +353 (0) 87 1694982 

Slovenija 
Mylan Healthcare d.o.o. 
Tel: + 386 1 23 63 180 
 

Ísland 
Icepharma hf 
Tel: +354 540 8000 
 

Slovenská republika 
Mylan s.r.o. 
Tel: +421 2 32 199 100 

Italia 
Mylan Italia S.r.l. 
Tel: + 39 02 612 46921 
 

Suomi/Finland 
Mylan Finland OY 
Puh/Tel: +358 20 720 9555 
 

Κύπρος 
Varnavas Hadjipanayis Ltd. 
Τηλ: +357 2220 7700 
 

Sverige 
Mylan AB  
Tel: + 46 855 522 750 
 

Latvija 
Mylan Healthcare SIA 
Tel: +371 676 055 80 
 

United Kingdom 
Generics [UK] Ltd 
Tel: +44 1707 853000 

This leaflet was last revised in <{MM/YYYY}>.  
 
Other sources of information  
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu/. 
 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	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 USEOF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET