- Approval Id
- f90b075dc79e3255
- Drug Approval Emc Name
- Lenalidomide 5 mg capsules
- Drug Name
- Lenalidomide 5 mg capsules
- Company Address
- Dashwood House, 69 Old Broad Street, London, EC2M 1QS, UK
- Company Website
- https://medicalinformation.advanzpharma.com/
- Company Telephone
- +44 (0)208 588 9131
- Company Medical Info Direct Line
- +44 (0)208 588 9131
- Company Medical Info Email
- [email protected]
- Company Customer Care Direct Line
- +44 (0)208 588 9273
- Atc Code
- L04AX04
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Mercury Pharmaceuticals Ltd. Dashwood House, 69 Old Broad Street, London, EC2M 1QS, United Kingdom
- Authorisation Number
- 8. Marketing authorisation number(s) PL 12762/0638
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 28/05/2021
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Mercury Pharmaceuticals Ltd. Dashwood House, 69 Old Broad Street, London, EC2M 1QS, United Kingdom
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) PL 12762/0638
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 28/05/2021
- Instruction Composition
- 2. Qualitative and quantitative composition Each capsule contains 5 mg of lenalidomide. Excipient with known effect: Each capsule contains 107 mg of lactose Each capsule contains 0.52 mg of sodium. For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Capsule, hard A green opaque cap/light brown opaque body, capsule shell size No. 2, 17.50-18.50 mm, imprinted in black ink with “LP” on the cap and “638” on the body and filled with white powder.
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications Multiple myeloma Lenalidomide as monotherapy is indicated for the maintenance treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation. Lenalidomide 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 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 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 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. Posology Newly diagnosed multiple myeloma (NDMM) • Lenalidomide in combination with dexamethasone until disease progression in patients who are not eligible for transplant Lenalidomide treatment must not be started if the Absolute Neutrophil Count (ANC) is <1.0 x 109/L, and/or platelet counts are <50 x 109/L. Recommended dose The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1, 8, 15 and 22 of repeated 28-day cycles. Patients may continue lenalidomide and dexamethasone therapy until disease progression or intolerance. • Dose reduction steps Lenalidomidea Dexamethasonea Starting dose 25 mg 40 mg Dose level -1 20 mg 20 mg Dose level -2 15 mg 12 mg Dose level -3 10 mg 8 mg Dose level -4 5 mg 4 mg Dose level -5 2.5 mg Not applicable ª Dose reduction for both products can be managed independently. • Thrombocytopenia When platelets Recommended course Falls to <25 x 109/L Returns to ≥50 x 109/L Stop lenalidomide dosing for remainder of cycleª Decrease by one dose level when dosing resumed at next cycle ª If Dose limiting toxicity (DLT) occurs on > day15 of a cycle, lenalidomide dosing will be interrupted for at least the remainder of the current 28-day cycle. • Absolute neutrophil count (ANC) - neutropenia When ANC Recommended coursea First falls to <0.5 x 109/L Returns to ≥1 x 109/L when neutropenia is the only observed toxicity Interrupt lenalidomide treatment Resume lenalidomide at starting dose once daily Returns to ≥0.5 x 109/L when dose-dependent haematological toxicities other than neutropenia are observed Resume lenalidomide at dose level -1 once daily For each subsequent drop below <0.5 x 109/L Returns 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 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
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Other immunosuppressants. ATC code: L04AX04. Mechanism of action Lenalidomide binds directly to cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex that includes deoxyribonucleic acid (DNA) damage-binding protein 1(DDB1), cullin 4 (CUL4), and regulator of cullins 1 (Roc1). In haematopoietic cells, lenalidomide binding to cereblon recruits substrate proteins Aiolos and Ikaros, lymphoid transcriptional factors, leading to their ubiquitination and subsequent degradation resulting in cytotoxic and immunomodulatory effects. Specifically, lenalidomide inhibits proliferation and enhances apoptosis of certain haematopoietic tumour cells (including MM plasma tumour cells, follicular lymphoma tumour cells and those with deletions of chromosome 5), enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number of NK, T and NK T cells. In MDS Del (5q), lenalidomide selectively inhibits the abnormal clone by increasing the apoptosis of Del (5q) cells. The combination of lenalidomide and rituximab increases ADCC and direct tumor apoptosis in follicular lymphoma cells. The lenalidomide mechanism of action also includes additional activities such as anti-angiogenic and pro-erythropoietic properties. Lenalidomide inhibits angiogenesis by blocking the migration and adhesion of endothelial cells and the formation of microvessels, augments foetal haemoglobin production by CD34+ haematopoietic stem cells, and inhibits production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. Clinical efficacy and safety Lenalidomide efficacy and safety have been evaluated in six phase 3 studies in newly diagnosed multiple myeloma and two phase 3 studies in relapsed refractory multiple myeloma, one phase 3 study and one phase 2 study in myelodysplastic syndromes and one phase 2 study in mantle cell lymphoma and one phase 3 and one phase 3b study in iNHL as described below. Newly diagnosed multiple myeloma • Lenalidomide maintenance in patients who have undergone ASCT The efficacy and safety of lenalidomide maintenance was assessed in two phase 3 multicenter, 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 therapy 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 1
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients Capsule contents Lactose Cellulose, microcrystalline Croscarmellose sodium Magnesium stearate Capsule shell Brilliant Blue FCF (E133) Red iron oxide Yellow iron oxide Titanium dioxide Gelatin Printing ink Shellac Propylene glycol Strong ammonia solution Black iron oxide Potassium hydroxide 6.2 Incompatibilities Not applicable. 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container Carton box containing PVC/ACLAR/Al blisters of 7 capsules each. Pack size of 7 or 21 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 Capsules 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 medicinal product or waste material should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition Each capsule contains 5 mg of lenalidomide. Excipient with known effect: Each capsule contains 107 mg of lactose Each capsule contains 0.52 mg of sodium. For the full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Capsule, hard A green opaque cap/light brown opaque body, capsule shell size No. 2, 17.50-18.50 mm, imprinted in black ink with “LP” on the cap and “638” on the body and filled with white powder.
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications Multiple myeloma Lenalidomide as monotherapy is indicated for the maintenance treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation. Lenalidomide 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 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 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 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. Posology Newly diagnosed multiple myeloma (NDMM) • Lenalidomide in combination with dexamethasone until disease progression in patients who are not eligible for transplant Lenalidomide treatment must not be started if the Absolute Neutrophil Count (ANC) is <1.0 x 109/L, and/or platelet counts are <50 x 109/L. Recommended dose The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1, 8, 15 and 22 of repeated 28-day cycles. Patients may continue lenalidomide and dexamethasone therapy until disease progression or intolerance. • Dose reduction steps Lenalidomidea Dexamethasonea Starting dose 25 mg 40 mg Dose level -1 20 mg 20 mg Dose level -2 15 mg 12 mg Dose level -3 10 mg 8 mg Dose level -4 5 mg 4 mg Dose level -5 2.5 mg Not applicable ª Dose reduction for both products can be managed independently. • Thrombocytopenia When platelets Recommended course Falls to <25 x 109/L Returns to ≥50 x 109/L Stop lenalidomide dosing for remainder of cycleª Decrease by one dose level when dosing resumed at next cycle ª If Dose limiting toxicity (DLT) occurs on > day15 of a cycle, lenalidomide dosing will be interrupted for at least the remainder of the current 28-day cycle. • Absolute neutrophil count (ANC) - neutropenia When ANC Recommended coursea First falls to <0.5 x 109/L Returns to ≥1 x 109/L when neutropenia is the only observed toxicity Interrupt lenalidomide treatment Resume lenalidomide at starting dose once daily Returns to ≥0.5 x 109/L when dose-dependent haematological toxicities other than neutropenia are observed Resume lenalidomide at dose level -1 once daily For each subsequent drop below <0.5 x 109/L Returns 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 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
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Other immunosuppressants. ATC code: L04AX04. Mechanism of action Lenalidomide binds directly to cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex that includes deoxyribonucleic acid (DNA) damage-binding protein 1(DDB1), cullin 4 (CUL4), and regulator of cullins 1 (Roc1). In haematopoietic cells, lenalidomide binding to cereblon recruits substrate proteins Aiolos and Ikaros, lymphoid transcriptional factors, leading to their ubiquitination and subsequent degradation resulting in cytotoxic and immunomodulatory effects. Specifically, lenalidomide inhibits proliferation and enhances apoptosis of certain haematopoietic tumour cells (including MM plasma tumour cells, follicular lymphoma tumour cells and those with deletions of chromosome 5), enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number of NK, T and NK T cells. In MDS Del (5q), lenalidomide selectively inhibits the abnormal clone by increasing the apoptosis of Del (5q) cells. The combination of lenalidomide and rituximab increases ADCC and direct tumor apoptosis in follicular lymphoma cells. The lenalidomide mechanism of action also includes additional activities such as anti-angiogenic and pro-erythropoietic properties. Lenalidomide inhibits angiogenesis by blocking the migration and adhesion of endothelial cells and the formation of microvessels, augments foetal haemoglobin production by CD34+ haematopoietic stem cells, and inhibits production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. Clinical efficacy and safety Lenalidomide efficacy and safety have been evaluated in six phase 3 studies in newly diagnosed multiple myeloma and two phase 3 studies in relapsed refractory multiple myeloma, one phase 3 study and one phase 2 study in myelodysplastic syndromes and one phase 2 study in mantle cell lymphoma and one phase 3 and one phase 3b study in iNHL as described below. Newly diagnosed multiple myeloma • Lenalidomide maintenance in patients who have undergone ASCT The efficacy and safety of lenalidomide maintenance was assessed in two phase 3 multicenter, 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 therapy 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 1
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients Capsule contents Lactose Cellulose, microcrystalline Croscarmellose sodium Magnesium stearate Capsule shell Brilliant Blue FCF (E133) Red iron oxide Yellow iron oxide Titanium dioxide Gelatin Printing ink Shellac Propylene glycol Strong ammonia solution Black iron oxide Potassium hydroxide 6.2 Incompatibilities Not applicable. 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container Carton box containing PVC/ACLAR/Al blisters of 7 capsules each. Pack size of 7 or 21 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 Capsules 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 medicinal product or waste material should be disposed of in accordance with local requirements.
- Company Detail Path
- /organization/amdipharm-limited
