Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Mylan Ireland Limited, Unit 35/36 Grange Parade, Baldoyle Industrial Estate, Dublin 13, Ireland
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.
Lenalidomide Mylan as monotherapy is indicated for the treatment of adult patients with transfusiondependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.
Lenalidomide Mylan as monotherapy is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (see sections 4.4 and 5.1).
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).
Lenalidomide Mylan treatment should be supervised by a physician experienced in the use of anti-cancer therapies.
For all indications described below:
Lenalidomide treatment must not be started if the ANC is <1.0 × 109/L, and/or platelet counts are <50 × 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 × 109/L | Stop lenalidomide dosing for remainder of cyclea |
| Return to ≥50 × 109/L | Decrease by one dose level when dosing resumed at next cycle |
a If Dose limiting toxicity (DLT) occurs on >day15 of a cycle, lenalidomide dosing will be interrupted for at least the remainder of the current 28-day cycle.
Absolute neutrophil count (ANC) neutropenia:
| When ANC | Recommended coursea |
|---|---|
| First fall to <0.5 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥1 × 109/L when neutropenia is the only observed toxicity | Resume lenalidomide at starting dose once daily |
| Return to ≥0.5 × 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 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L | Resume lenalidomide at next lower dose level once daily. |
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain the dose level of lenalidomide.
For hematologic toxicity the dose of lenalidomide may be re-introduced to the next higher dose level (up to the starting dose) upon improvement in bone marrow function (no hematologic toxicity for at least 2 consecutive cycles: ANC ≥1,5 × 109/L with a platelet count ≥100 × 109/L at the beginning of a new cycle).
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 × 109/L, and/or platelet counts are <50 × 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 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥50 × 109/L | Resume lenalidomide at dose level -1 once daily |
| For each subsequent drop below 30 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥50 × 109/L | Resume lenalidomide at next lower dose level once daily |
Absolute neutrophil count (ANC) neutropenia:
| When ANC | Recommended coursea |
|---|---|
| First fall to <0.5 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥1 × 109/L when neutropenia is the only observed toxicity | Resume lenalidomide at starting dose once daily |
| Return to ≥0.5 × 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 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L | Resume lenalidomide at next lower dose level once daily. |
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain the dose level of lenalidomide.
Lenalidomide treatment must not be started if the ANC is <1.5 × 109/L, and/or platelet counts are <75 × 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 course |
|---|---|
| First fall to <25 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥25 × 109/L | Resume lenalidomide and melphalan at dose level -1 |
| For each subsequent drop below 30 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥30 × 109/L | Resume lenalidomide at next lower dose level (dose level -2 or -3) once daily. |
Absolute neutrophil count (ANC) neutropenia:
| When ANC | Recommended courseccc |
|---|---|
| First fall to <0.5 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L when neutropenia is the only observed toxicity | Resume lenalidomide at starting dose once daily |
| Return to ≥0.5 × 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 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L | Resume lenalidomide at next lower dose level once daily. |
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 × 109/L, and/or platelet counts are <75 × 109/L.
Recommended dose:
The recommended starting dose is lenalidomide 10 mg orally once daily continuously (on days 1 to 28 of repeated 28-day cycles) given until disease progression or intolerance. After 3 cycles of lenalidomide maintenance, the dose can be increased to 15 mg orally once daily if tolerated.
Dose reduction steps:
| Starting dose (10 mg) | If dose increased (15 mg)a | |
|---|---|---|
| Dose level -1 | 5 mg | 10 mg |
| Dose level -2 | 5 mg (days 1-21 every 28 days) | 5 mg |
| Dose level -3 | Not applicable | 5 mg (days 1-21 every 28 days) |
| Do not dose below 5 mg (days 1-21 every 28 days) | ||
a After 3 cycles of lenalidomide maintenance, the dose can be increased to 15 mg orally once daily if tolerated.
Thrombocytopenia:
| When platelets | Recommended course |
|---|---|
| Fall to <30 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥30 × 109/L | Resume lenalidomide at dose level -1 once daily |
| For each subsequent drop below 30 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥30 × 109/L | Resume lenalidomide at next lower dose level once daily |
Absolute neutrophil count (ANC) neutropenia:
| When ANC | Recommended coursea |
|---|---|
| Fall to <0.5 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L | Resume lenalidomide at dose level -1 once daily |
| For each subsequent drop below <0.5 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L | Resume lenalidomide at next lower dose level once daily |
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain the dose level of lenalidomide.
Lenalidomide treatment must not be started if the ANC <1.0 × 109/L, and/or platelet counts <75 × 109/L or, dependent on bone marrow infiltration by plasma cells, platelet counts <30 × 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 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥30 × 109/L | Resume lenalidomide at dose level -1 |
| For each subsequent drop below 30 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥30 × 109/L | Resume lenalidomide at next lower dose level (dose level -2 or -3) once daily. Do not dose below 5 mg once daily. |
Absolute neutrophil count (ANC) neutropenia:
| When ANC | Recommended coursea |
|---|---|
| First fall to <0.5 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L when neutropenia is the only observed toxicity | Resume lenalidomide at starting dose once daily |
| Return to ≥0.5 × 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 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥0.5 × 109/L | Resume lenalidomide at next lower dose level (dose level -1, -2 or -3) once daily. Do not dose below 5 mg once daily. |
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 treatment must not be started if the ANC <0.5 × 109/L and/or platelet counts <25 × 109/L.
Recommended dose:
The recommended starting dose of lenalidomide is 10 mg orally once daily on days 1 to 21 of repeated 28-day cycles.
Dose reduction steps:
| Starting dose | 10 mg once daily on days 1 to 21 every 28 days |
| Dose level -1 | 5 mg once daily on days 1 to 28 every 28 days |
| Dose level -2 | 2.5 mg once daily on days 1 to 28 every 28 days |
| Dose level -3 | 2.5 mg every other day 1 to 28 every 28 days |
Thrombocytopenia:
| When platelets | Recommended course |
|---|---|
| Fall to <25 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥25 × 109/L - <50 × 109/L on at least 2 occasions for ≥7 days or when the platelet count recovers to ≥50 × 109/L at any time | Resume lenalidomide at next lower dose level (dose level -1, -2 or -3) |
Absolute neutrophil count (ANC) neutropenia:
| When ANC | Recommended course |
|---|---|
| Fall to < 0.5 × 109/L | Interrupt lenalidomide treatment |
| Return to ≥ 0.5 × 109/L | Resume lenalidomide at next lower dose level (dose level -1, -2 or -3) |
Discontinuation of lenalidomide:
Patients without at least a minor erythroid response within 4 months of therapy initiation, demonstrated by at least a 50% reduction in transfusion requirements or, if not transfused, a 1g/dl rise in haemoglobin, should discontinue lenalidomide treatment.
Recommended dose:
The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles.
Dose reduction steps:
| Starting dose | 25 mg once daily on days 1 to 21, every 28 days |
| Dose Level -1 | 20 mg once daily on days 1 to 21, every 28 days |
| Dose Level -2 | 15 mg once daily on days 1 to 21, every 28 days |
| Dose Level -3 | 10 mg once daily on days 1 to 21, every 28 days |
| Dose Level -4 | 5 mg once daily on days 1 to 21, every 28 days |
| Dose Level -5 | 2.5 mg once daily on days 1 to 21, every 28 days1 |
| 5 mg every other day on days 1 to 21, every 28 days |
1 In countries where the 2.5 mg capsule is available.
Thrombocytopenia:
| When platelets | Recommended Course |
|---|---|
| Fall to <50 × 109/L | Interrupt lenalidomide treatment and conduct Complete Blood Count (CBC) at least every 7 days |
| Return to ≥ 60 × 109/L | Resume lenalidomide at next lower level (dose level -1) |
| For each subsequent drop below 50 × 109/L | Interrupt lenalidomide treatment and conduct the CBC at least every 7 days |
| Return to ≥60 × 109/L | Resume lenalidomide at next lower level (dose level -2, -3, -4 or -5). Do not dose below dose level -5 |
Absolute neutrophil count (ANC) neutropenia:
| When ANC | Recommended Coursea |
|---|---|
| Fall to <1 × 109/L for at least 7 days or | Interrupt lenalidomide treatment and conduct the CBC at least every 7 days |
| Falls to <1 × 109/L with associated fever (body temperature ≥38.5°C) or | |
| Falls to <0.5 × 109/L | |
| Return to ≥1 × 109/L | Resume lenalidomide at next lower dose level (dose level -1) |
| For each subsequent drop below 1 × 109/L for at least 7 days or drop to <1 × 109/L with associated fever (body temperature ≥38.5°C) or drop to <0.5 × 109/L | Interrupt lenalidomide treatment |
| Returns to ≥1 × 109/L | Resume lenalidomide at next lower dose level (dose level -2, -3, -4, -5) once daily. Do not dose Below -5 |
Lenalidomide treatment must not be started if the ANC is <1 × 109/L, and/or platelet count <50 × 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 × 109/L | Interrupt lenalidomide treatment and conduct CBC at least every 7 days |
| Returns to ≥50 × 109/L | Resume at next lower dose level (dose level -1) |
| For each subsequent drop below 50 × 109/L | Interrupt lenalidomide treatment and conduct CBC at least every 7 days |
| Returns to ≥50 × 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:
| When ANC | Recommended coursea |
|---|---|
| Falls <1.0 × 109/L for at least 7 days or Falls to <1.0 × 109/L with associated fever (body temperature ≥38.5°C) or Falls to <0.5 × 109/L | Interrupt lenalidomide treatment and conduct CBC at least every 7 days |
| Returns to ≥1.0 × 109/L | Resume lenalidomide at next lower dose level (dose level -1) |
| For each subsequent drop below 1.0 × 109/L for at least 7 days or drop to <1.0 × 109/L with associated fever (body temperature ≥38.5°C) or drop to <0.5 × 109/L | Interrupt lenalidomide treatment and conduct CBC at least every 7 days |
| Returns to ≥1.0 × 109/L | Resume lenalidomide at next lower dose level (dose level -2, -3). Do not dose below dose level-3 |
a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add G-CSF
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).
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).
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, 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.
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).
Currently available pharmacokinetic data are described in section 5.2. Lenalidomide has been used in clinical trials in multiple myeloma patients up to 91 years of age, in myelodysplastic syndromes patients up to 95 years of age and in mantle cell lymphoma patients up to 88 years of age (see section 5.1).
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it would be prudent to monitor renal function.
Patients with newly diagnosed multiple myeloma aged 75 years and older should be carefully assessed before treatment is considered (see section 4.4).
For patients older than 75 years of age treated with lenalidomide in combination with dexamethasone, the starting dose of dexamethasone is 20 mg once daily on days 1, 8, 15 and 22 of each 28-day treatment cycle.
No dose adjustment is proposed for patients older than 75 years who are treated with lenalidomide in combination with melphalan and prednisone.
In patients with newly diagnosed multiple myeloma aged 75 years and older who received lenalidomide, there was a higher incidence of serious adverse reactions and adverse reactions that led to treatment discontinuation.
Lenalidomide combined therapy was less tolerated in newly diagnosed multiple myeloma patients older than 75 years of age compared to the younger population. These patients discontinued at a higher rate due to intolerance (Grade 3 or 4 adverse events and serious adverse events), when compared to patients <75 years.
Multiple myeloma: patients with at least one prior therapy:
The percentage of multiple myeloma patients aged 65 or over was not significantly different between the lenalidomide/dexamethasone and placebo/dexamethasone groups. No overall difference in safety or efficacy was observed between these patients and younger patients, but greater pre-disposition of older individuals cannot be ruled out.
Myelodysplastic syndromes:
For myelodysplastic syndromes patients treated with lenalidomide, no overall difference in safety and efficacy was observed between patients aged over 65 and younger patients.
Mantle cell lymphoma:
For mantle cell lymphoma patients treated with lenalidomide, no overall difference in safety and efficacy was observed between patients aged 65 years or over compared with patients aged under 65 years of age.
Lenalidomide is primarily excreted by the kidney; patients with greater degrees of renal impairment can have impaired treatment tolerance (see section 4.4). Care should be taken in dose selection and monitoring of renal function is advised.
No dose adjustments are required for patients with mild renal impairment and multiple myeloma, myelodysplastic syndromes or mantle cell 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 (30≤ CLcr <50 mL/min) | 10 mg once daily1 |
| Severe renal impairment (CLcr <30 mL/min, not requiring dialysis) | 7.5 mg once daily2 15 mg every other day |
| End Stage Renal Disease (ESRD) (CLcr <30 mL/min, requiring dialysis) | 5 mg once daily. On dialysis days, the dose should be administered following dialysis. |
1 The dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment.
2 In countries where the 7.5 mg capsule is available.
Myelodysplastic syndromes:
| Renal function (CLcr) | Dose adjustment | |
|---|---|---|
| Moderate renal impairment (30≤ CLcr <50 mL/min) | Starting dose | 5 mg once daily (days 1 to 21 of repeated 28-day cycles) |
| Dose level -1* | 2.5 mg once daily (days 1 to 28 of repeated 28-day cycles) | |
| Dose level -2* | 2.5 mg once every other day (days 1 to 28 of repeated 28-day cycles) | |
| Severe renal impairment (CLcr <30 mL/min, not requiring dialysis) | Starting dose | 2.5 mg once daily (days 1 to 21 of repeated 28-day cycles) |
| Dose level -1* | 2.5 mg every other day (days 1 to 28 of repeated 28-day cycles) | |
| Dose level -2* | 2.5 mg twice a week (days 1 to 28 of repeated 28-day cycles) | |
| End Stage Renal Disease (ESRD) (CLcr <30 mL/min, requiring dialysis). On dialysis days, the dose should be administered following dialysis. | Starting dose | 2.5 mg once daily (days 1 to 21 of repeated 28-day cycles) |
| Dose level -1* | 2.5 mg every other day (days 1 to 28 of repeated 28-day cycles) | |
| Dose level -2* | 2.5 mg twice a week (days 1 to 28 of repeated 28-day cycles) | |
* Recommended dose reduction steps during treatment and restart of treatment to manage grade 3 or 4 neutropenia or thrombocytopenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide, as described above.
Mantle cell lymphoma:
| Renal function (CLcr) | Dose adjustment (days 1 to 21 of repeated 28-day cycles) |
|---|---|
| Moderate renal impairment (30≤ CLcr <50 mL/min) | 10 mg once daily1 |
| Severe renal impairment (CLcr <30 mL/min, not requiring dialysis) | 7.5 mg once daily2 15 mg every other day |
| End Stage Renal Disease (ESRD) (CLcr <30 mL/min, requiring dialysis) | 5 mg once daily. On dialysis days, the dose should be administered following dialysis. |
1 The dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment.
2 In countries where the 7.5 mg capsule is available.
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.
Lenalidomide has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations.
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.
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.
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.
Do not store above 30°C.
Lenalidomide Mylan 2.5 mg hard capsules, Lenalidomide Mylan 7.5 mg hard capsules, Lenalidomide Mylan 10 mg hard capsules, Lenalidomide Mylan 20 mg hard capsules, Lenalidomide Mylan 25 mg 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:
Not all pack sizes may be marketed.
Capsules should not be opened or crushed. If powder from lenalidomide makes contact with the skin, the skin should be washed immediately and thoroughly with soap and water. If lenalidomide makes contact with the mucous membranes, they should be thoroughly flushed with water.
Healthcare professionals and caregivers should wear disposable gloves when handling the blister or capsule. Gloves should then be removed carefully to prevent skin exposure, placed in a sealable plastic polyethylene bag and disposed of in accordance with local requirements. Hands should then be washed thoroughly with soap and water. Women who are pregnant or suspect they may be pregnant should not handle the blister or capsule (see section 4.4).
Any unused product or waste material should be returned to the pharmacist for safe disposal in accordance with local requirements.
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