Posology : מינונים

4.2       Posology and method of administration
Revlimid 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 REVLIMID.
• In case of neutropenia, the use of growth factors in patient management should be considered.
• If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day.

Posology
Newly diagnosed multiple myeloma (NDMM)
• REVLIMID in combination with dexamethasone until disease progression in patients who are not eligible for transplant
REVLIMID 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 REVLIMID 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 REVLIMID and dexamethasone therapy until disease progression or intolerance.

•    Dose reduction steps

REVLIMIDa   Dexamethasonea
Starting dose                                    25 mg          40 mg Dose level -1                                    20 mg          20 mg Dose level -2                                    15 mg          12 mg Dose level -3                                    10 mg           8 mg Dose level- 4                                     5 mg           4 mg Dose level -5                                    2.5 mg     Not applicable ª Dose reduction for both products can be managed independently

•    Thrombocytopenia

When platelets                                              Recommended course Falls to < 25 x 109/L                                       Stop REVLIMID dosing for remainder of cycleª
Returns to ≥ 50 x 109/L                                     Decrease by one dose level when dosing resumed at next cycle
ª If Dose limiting toxicity (DLT) occurs on > day15 of a cycle, REVLIMID dosing will be interrupted for at least the remainder of the current 28-day cycle.


•    Absolute neutrophil count (ANC) - neutropenia
When ANC                                                    Recommended courseª First falls to < 0.5 x 109/L                                Interrupt REVLIMID treatment Returns to ≥ 1 x 109/L when neutropenia                     Resume REVLIMID at starting dose is the only observed toxicity                               once daily Returns to ≥ 0.5 x 109/L when dose-                         Resume REVLIMID at dose level -1 dependent haematological toxicities other                   once daily than neutropenia are observed
For each subsequent drop below                              Interrupt REVLIMID treatment < 0.5 x 109/L
Returns to ≥ 0.5 x 109/L                                    Resume REVLIMID 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 REVLIMID.

For hematologic toxicity the dose of REVLIMID may be re-introduced to the next higher dose level (up to the starting dose) upon improvement in bone marrow function (no hematologic toxicity for at least 2 consecutive cycles: ANC ≥1,5 x 109/L with a platelet count ≥ 100 x 109/L at the beginning of a new cycle).

•   REVLIMID in combination with bortezomib and dexamethasone followed by REVLIMID and dexamethasone until disease progression in patients who are not eligible for transplant Initial treatment: REVLIMID in combination with bortezomib and dexamethasone REVLIMID 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 REVLIMID 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.


Up to eight 21-day treatment cycles (24 weeks of initial treatment) are recommended.
Revlimid                         Bortezomib                         Dexamethasone 2
25 mg once daily on Days 1-      1.3 mg/m on Days 1, 4, 8 and 20 mg once daily orally on
14 of 21-day cycles              11 of 21-day cycles                Days 1, 2, 4, 5, 8, 9, 11 and 12 of 21-day cycles

•    REVLIMID in combination with bortezomib and dexamethasone followed by REVLIMID and dexamethasone until disease progression in patients who are eligible for transplant 
Up to eight 21-day or six 28-day treatment cycles (24 weeks of initial treatment) are recommended.

Initial treatment: REVLIMID in combination with bortezomib and dexamethasone REVLIMID 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.

Revlimid                                   Bortezomib                           Dexamethasone 25 mg once daily on Days 1-14 of           1.3 mg/m on Days 1, 4, 8 and 11 of
2
20 mg once daily on Days 1, 2, 4, 5,
21-day cycles                              21-day cycles                        8, 9, 11 and 12 of 21-day cycles
OR
25 mg once daily on Days 1-21 of 1.3 mg/m2 on Days 1, 4, 8 and 11 of            20 mg once daily on Days 1-4 and 9-
28-day cycles                    28-day cycles                                  12 of 28-day cycles
• Continued treatment: Autologous stem cell transplant
For patients who proceed to autologous stem cell transplant, hematopoietic stem cell mobilization should occur within 4 cycles of initial therapy.

Continued treatment: REVLIMID in combination with dexamethasone until progression Continue REVLIMID 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
REVLIMIDa
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                           5 mg every other day
ª Dose reduction for all products can be managed independently

• Thrombocytopenia
When platelets                                                         Recommended course Falls to < 30 x 109/L                                                  Interrupt REVLIMID treatment Returns to ≥ 50 x 109/L                                                Resume REVLIMID at dose level -1 once daily For each subsequent drop below 30 x 109/L                              Interrupt REVLIMID treatment Returns to ≥ 50 x 109/L                                                Resume REVLIMID at next lower dose level once daily

• Absolute neutrophil count (ANC) - neutropenia
When ANC                                                               Recommended coursea First falls to < 0.5 x 109/L or febrile neutropenia [< 1.0 x           Interrupt REVLIMID treatment 109/L associated with fever (temperature ≥ 38.5°C)]
Returns to ≥ 1 x 109/L when neutropenia is the only                    Resume REVLIMID at starting dose once daily observed toxicity
Returns to ≥ 0.5 x 109/L when dose-dependent                           Resume REVLIMID at dose level -1 once daily haematological toxicities other than neutropenia are observed
For each subsequent drop below < 0.5 x 109/L                           Interrupt REVLIMID treatment Returns to ≥ 0.5 x 109/L                                               Resume REVLIMID 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 REVLIMID.

• REVLIMID in combination with melphalan and prednisone followed by REVLIMID maintenance in patients who are not eligible for transplant
REVLIMID 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 REVLIMID 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 REVLIMID 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
REVLIMID                        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 REVLIMID 
•    Thrombocytopenia
When platelets                                                  Recommended course First falls to < 25 x 109/L                                     Interrupt REVLIMID treatment Returns to ≥ 25 x 109/L                                         Resume REVLIMID and melphalan at dose level -1
For each subsequent drop below                                Interrupt REVLIMID treatment 30 x 109/L
Returns to ≥ 30 x 109/L                                       Resume REVLIMID at next lower dose level (dose level -2 or -3) once daily.

•    Absolute neutrophil count (ANC) - neutropenia
When ANC                                                        Recommended courseª First falls to < 0.5 x 109/L                                    Interrupt REVLIMID treatment Returns to ≥ 0.5 x 109/L when neutropenia                       Resume REVLIMID at starting dose is the only observed toxicity                                   once daily Returns to ≥ 0.5 x 109/L when dose-                             Resume REVLIMID at dose level -1 dependent haematological toxicities other                       once daily than neutropenia are observed
For each subsequent drop below                                  Interrupt REVLIMID treatment < 0.5 x 109/L
Returns to ≥ 0.5 x 109/L                                        Resume REVLIMID 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 REVLIMID.

• REVLIMID maintenance in patients who have undergone autologous stem cell transplantation (ASCT) REVLIMID maintenance should be initiated after adequate haematologic recovery following ASCT in patients without evidence of progression. REVLIMID must not be started if the ANC is < 1.0 x 109/L, and/or platelet counts are < 75 x 109/L.


Recommended dose
The recommended starting dose is REVLIMID 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 REVLIMID maintenance, the dose can be increased to 15 mg orally once daily if tolerated.

•     Dose reduction steps
Starting dose (10 mg)                     If dose increased (15 mg)a
Dose level -1                                  5 mg                                        10 mg Dose level -2                     5 mg (days 1-21 every 28 days)                            5 mg Dose level -3                             Not applicable                      5 mg (days 1-21 every 28 days) Do not dose below 5 mg (days 1-21 every 28 days) a After   3 cycles of REVLIMID maintenance, the dose can be increased to 15 mg orally once daily if tolerated.


• Thrombocytopenia
When platelets                                                                  Recommended course Falls to < 30 x 109/L                                                           Interrupt REVLIMID treatment Returns to ≥ 30 x 109/L                                                         Resume REVLIMID at dose level -1 once daily For each subsequent drop below 30 x 109/L                                       Interrupt REVLIMID treatment Returns to ≥ 30 x 109/L                                                         Resume REVLIMID at next lower dose level once daily

• Absolute neutrophil count (ANC) - neutropenia
When ANC                                                                        Recommended coursea Falls to < 0.5 x 109/L                                                          Interrupt REVLIMID treatment Returns to ≥ 0.5 x 109/L                                                        Resume REVLIMID at dose level -1 once daily For each subsequent drop below < 0.5 x 109/L                                    Interrupt REVLIMID treatment Returns to ≥ 0.5 x 109/L                                                        Resume REVLIMID 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 REVLIMID.



Multiple myeloma with at least one prior therapy
REVLIMID 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 REVLIMID is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg once daily on days 1 to 4 every 28 days.
Prescribing physicians should carefully evaluate which dose of dexamethasone to use, taking into account the condition and disease status of the patient.

•      Dose reduction steps
Starting dose                                                                                                        25 mg Dose level -1                                                                                                        15 mg Dose level -2                                                                                                        10 mg Dose level -3                                                                                                         5 mg 

• Thrombocytopenia
When platelets                                                                  Recommended course First falls to < 30 x 109/L                                                     Interrupt REVLIMID treatment Returns to ≥ 30 x 109/L                                                         Resume REVLIMID at dose level -1 For each subsequent drop below 30 x 109/L                                       Interrupt REVLIMID treatment Returns to ≥ 30 x 109/L                                                         Resume REVLIMID at next lower dose level (dose level -2 or -3) once daily. Do not dose below 5 mg once daily.

• Absolute neutrophil count (ANC) - neutropenia
When ANC                                                                        Recommended coursea First falls to < 0.5 x 109/L                                                    Interrupt REVLIMID treatment Returns to ≥ 0.5 x 109/L when neutropenia is the only                           Resume REVLIMID at starting dose once daily observed toxicity
Returns to ≥ 0.5 x 109/L when dose-dependent                                    Resume REVLIMID at dose level -1 once daily haematological toxicities other than neutropenia are observed
For each subsequent drop below < 0.5 x 109/L                                    Interrupt REVLIMID treatment Returns to ≥ 0.5 x 109/L                                                        Resume REVLIMID at next lower dose level (dose level -1, -2 or -3) once daily. Do not dose below 5 mg 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 REVLIMID.

Myelodysplastic syndromes (MDS)
REVLIMID treatment must not be started if the ANC < 0.5 x 109/L and/or platelet counts < 25 x 109/L.
Recommended dose
The recommended starting dose of REVLIMID is 10 mg orally once daily on days 1 to 21 of repeated 28-day cycles.

•      Dose reduction steps
Starting dose                         10 mg once daily on days 1 to 21 every 28 days Dose level -1                         5 mg once daily on days 1 to 28 every 28 days Dose level -2                         2.5 mg once daily on days 1 to 28 every 28 days Dose level -3                         2.5 mg every other day 1 to 28 every 28 days 
• Thrombocytopenia
When platelets                                                                  Recommended course Falls to < 25 x 109/L                                                           Interrupt REVLIMID treatment Returns to ≥ 25 x 109/L - < 50 x 109/L on at least 2                            Resume REVLIMID at next lower dose level occasions for ≥ 7 days or when the platelet count                               (dose level -1, -2 or -3) recovers to ≥ 50 x 109/L at any time

• Absolute neutrophil count (ANC) - neutropenia
When ANC                                                                        Recommended course Falls to < 0.5 x 109/L                                                          Interrupt REVLIMID treatment Returns to ≥ 0.5 x 109/L                                                        Resume REVLIMID at next lower dose level (dose level -1, -2 or -3)
Discontinuation of REVLIMID
Patients without at least a minor erythroid response within 4 months of therapy initiation, demonstrated by at least a 50% reduction in transfusion requirements or, if not transfused, a 1g/dl rise in haemoglobin, should discontinue REVLIMID treatment.

Mantle cell lymphoma (MCL)
Recommended dose
The recommended starting dose of REVLIMID is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles.

•      Dose reduction steps
Starting dose        25 mg once daily on days 1 to 21, every 28 days
Dose Level -1        20 mg once daily on days 1 to 21, every 28 days
Dose Level -2        15 mg once daily on days 1 to 21, every 28 days
Dose Level -3        10 mg once daily on days 1 to 21, every 28 days
Dose Level -4        5 mg once daily on days 1 to 21, every 28 days
Dose Level -5        2.5 mg once daily on days 1 to 21, every 28 days1 5 mg every other day on days 1 to 21, every 28 days
1-   In countries where the 2.5 mg capsule is available.


•      Thrombocytopenia
When platelets                                                  Recommended course Falls to < 50 x 109/L                                           Interrupt REVLIMID treatment and conduct Complete Blood Count
(CBC) at least every 7 days
Returns to ≥ 60 x 109/L                                         Resume REVLIMID at next lower level (dose level -1)
For each subsequent drop below 50 x 109/L                       Interrupt REVLIMID treatment and conduct the CBC at least every 7 days
Returns to ≥60 x 109/L                                          Resume REVLIMID at next lower level (dose level -2, -3, -4 or -5). Do not dose below dose level -5

•      Absolute neutrophil count (ANC) - neutropenia
When ANC                                                       Recommended course Falls to < 1 x 109/L for at least 7 days or                    Interrupt REVLIMID treatment and Falls to < 1 x 109/L with associated fever (body temperature   conduct the CBC at least every 7 ≥ 38.5°C) or                                                   days Falls to < 0.5 x 109/L

Returns to ≥ 1 x 109/L                                         Resume REVLIMID at next lower dose level (dose level –1)
For each subsequent drop below 1 x 109/L for at least 7 days   Interrupt REVLIMID treatment or drop to < 1 x 109/L with associated fever (body temperature ≥ 38.5°C) or drop to < 0.5 x 109/L
Resume REVLIMID at next lower
9
Returns to ≥1 x 10 /L                                          dose level (dose level -2, -3, -4, -5).
Do not dose below dose level -5
Follicular lymphoma (FL)
REVLIMID 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 REVLIMID 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 REVLIMID 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 REVLIMID treatment and conduct CBC at least every 7 days

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

• Absolute neutrophil count (ANC) - neutropenia
When ANC                                                                          Recommended course ª Falls < 1.0 x 109/L for at least 7 days or                                        Interrupt REVLIMID treatment and conduct CBC Falls to < 1.0 x 109/L with associated fever (body                                at least every 7 days temperature ≥ 38.5°C) or
Falls to < 0.5 x 109/L
Returns to ≥ 1.0 x 109/L                                                          Resume REVLIMID at next lower dose level (dose level -1)
For each subsequent drop below 1.0 x 109/L for at least 7                         Interrupt REVLIMID treatment and conduct CBC days or drop to < 1.0 x 109/L with associated fever (body                         at least every 7 days temperature ≥ 38.5°C) or drop to < 0.5 x 109/L

Returns to ≥1.0 x 109/L                                                           Resume REVLIMID at next lower dose level (dose level -2, -3). Do not dose below dose level-3
ª At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add G-CSF 
Mantle cell lymphoma (MCL) or follicular lymphoma (FL)

Tumour lysis syndrome (TLS)
All patients should receive TLS prophylaxis (allopurinol, rasburicase or equivalent as per institutional guidelines) and be well hydrated (orally) during the first week of the first cycle or for a longer period if clinically indicated. To monitor for TLS, patients should have a chemistry panel drawn weekly during the first cycle and as clinically indicated.
REVLIMID 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 REVLIMID. 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 REVLIMID 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 REVLIMID at next lower dose per physician’s discretion (see section 4.4).

Tumour flare reaction
At the physician’s discretion, REVLIMID 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 REVLIMID and initiate therapy with NSAIDs, corticosteroids and/or narcotic analgesics. When TFR resolves to ≤ Grade 1, restart REVLIMID 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 REVLIMID, 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.

REVLIMID interruption or discontinuation should be considered for Grade 2 or 3 skin rash. REVLIMID must be discontinued for angioedema, anaphylactic reaction, Grade 4 rash, exfoliative or bullous rash, or if Stevens- Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected, and should not be resumed following discontinuation from these reactions.

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

• Elderly
Currently available pharmacokinetic data are described in section 5.2. REVLIMID has been used in clinical trials in multiple myeloma patients up to 91 years of age, in myelodysplastic syndromes patients up to 95 years of age and in mantle cell lymphoma patients up to 88 years of age (see section 5.1).

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it would be prudent to monitor renal function.

Newly diagnosed multiple myeloma: patients who are not eligible for transplant Patients with newly diagnosed multiple myeloma aged 75 years and older should be carefully assessed before treatment is considered (see section 4.4).
For patients older than 75 years of age treated with REVLIMID 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 REVLIMID in combination with melphalan and prednisone.

In patients with newly diagnosed multiple myeloma aged 75 years and older who received REVLIMID, there was a higher incidence of serious adverse reactions and adverse reactions that led to treatment discontinuation.

REVLIMID 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 REVLIMID/dexamethasone and placebo/dexamethasone groups. No overall difference in safety or efficacy was observed between these patients and younger patients, but greater pre-disposition of older individuals cannot be ruled out.

Myelodysplastic syndromes
For myelodysplastic syndromes patients treated with REVLIMID, no overall difference in safety and efficacy was observed between patients aged over 65 and younger patients.

Mantle cell lymphoma
For mantle cell lymphoma patients treated with REVLIMID, no overall difference in safety and efficacy was observed between patients aged 65 years or over compared with patients aged under 65 years of age.

Follicular lymphoma
For follicular lymphoma patients treated with REVLIMID 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
REVLIMID is primarily excreted by the kidney; patients with greater degrees of renal impairment can have impaired treatment tolerance (see section 4.4). Care should be taken in dose selection and monitoring of renal function is advised.

No dose adjustments are required for patients with mild renal impairment and multiple myeloma, myelodysplastic syndromes, mantle cell lymphoma, or follicular lymphoma.
The following dose adjustments are recommended at the start of therapy and throughout treatment for patients with moderate or severe impaired renal function or end stage renal disease.
There are no phase 3 trial experiences with End Stage Renal Disease (ESRD) (CLcr < 30 mL/min, requiring dialysis).

Multiple myeloma
Renal function (CLcr)                                                     Dose adjustment Moderate renal impairment                                                 10 mg once daily1 (30 ≤ CLcr < 50 mL/min)
Severe renal impairment                                                   7.5 mg once daily2 (CLcr < 30 mL/min, not requiring dialysis)                                15 mg every other day End Stage Renal Disease (ESRD)                                                                      5 mg once daily. On dialysis days, (CLcr < 30 mL/min, requiring dialysis)                                                              the dose should be administered following dialysis.
1 The   dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment.
2   In countries where the 7.5 mg capsule is available.

Myelodysplastic syndromes
Renal function (CLcr)                                                                             Dose adjustment Moderate renal impairment                                              Starting dose           5 mg once daily (30 ≤ CLcr < 50 mL/min)                                                                        (days 1 to 21 of repeated 28-day cycles) Dose level -1*         2.5 mg once daily
(days 1 to 28 of repeated 28-day cycles)
Dose level -2*         2.5 mg once every other day
(days 1 to 28 of repeated 28-day cycles)
Severe renal impairment                                             Starting dose           2.5 mg once daily (CLcr < 30 mL/min, not requiring dialysis)                                                  (days 1 to 21 of repeated 28-day cycles) Dose level -1*         2.5 mg every other day
(days 1 to 28 of repeated 28-day cycles)
Dose level -2*         2.5 mg twice a week
(days 1 to 28 of repeated 28-day cycles)
End Stage Renal Disease (ESRD)                                      Starting dose           2.5 mg once daily (CLcr < 30 mL/min, requiring dialysis)                                                      (days 1 to 21 of repeated 28-day cycles) Dose level -1*         2.5 mg every other day
On dialysis days, the dose should be                                                        (days 1 to 28 of repeated 28-day cycles) administered following dialysis.                                     Dose level -2*         2.5 mg twice a week (days 1 to 28 of repeated 28-day cycles)
* Recommended dose reduction steps during treatment and restart of treatment to manage Grade 3 or 4 neutropenia or thrombocytopenia, or other Grade 3 or 4 toxicity judged to be related to REVLIMID, as described above.

Mantle cell lymphoma
Renal function (CLcr)                                                                                  Dose adjustment (days 1 to 21 of repeated
28-day cycles)
Moderate renal impairment                                                                           10 mg once daily1 (30 ≤ CLcr < 50 mL/min)
Severe renal impairment                                                                             7.5 mg once daily2 (CLcr < 30 mL/min, not requiring dialysis)                                                          15 mg every other day End Stage Renal Disease (ESRD)                                                                      5 mg once daily. On dialysis days, (CLcr < 30 mL/min, requiring dialysis)                                                              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                                                                      10 mg once daily1, 2 (30 ≤ CLcr < 60 mL/min)
Severe renal impairment                                                                        No data available3 (CLcr < 30 mL/min, not requiring dialysis)
End Stage Renal Disease (ESRD)                                                                 No data available3 (CLcr < 30 mL/min, requiring dialysis)
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 REVLIMID 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 REVLIMID therapy, subsequent REVLIMID dose modification in renally impaired patients should be based on individual patient treatment tolerance, as described above.

• Patients with hepatic impairment
REVLIMID has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations.

Method of administration
Oral use.
Revlimid capsules should be taken orally at about the same time on the scheduled days. The capsules should not be opened, broken or chewed. The capsules should be swallowed whole, preferably with water, either with or without food.

It is recommended to press only on one end of the capsule to remove it from the blister thereby reducing the risk of capsule deformation or breakage.