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רבלימיד 25 מ"ג REVLIMID ® 25 MG (LENALIDOMIDE)
תרופה במרשם
תרופה בסל
נרקוטיקה
ציטוטוקסיקה
צורת מתן:
פומי : PER OS
צורת מינון:
קפסולה קשיחה : HARD CAPSULE
עלון לרופא
מינוניםPosology התוויות
Indications תופעות לוואי
Adverse reactions התוויות נגד
Contraindications אינטראקציות
Interactions מינון יתר
Overdose הריון/הנקה
Pregnancy & Lactation אוכלוסיות מיוחדות
Special populations תכונות פרמקולוגיות
Pharmacological properties מידע רוקחי
Pharmaceutical particulars אזהרת שימוש
Special Warning עלון לרופא
Physicians Leaflet
Posology : מינונים
2. DOSAGE AND ADMINISTRATION REVLIMID should be taken orally at about the same time each day, either with or without food. REVLIMID hard capsules should be swallowed whole with water. The hard capsules should not be opened, broken, or chewed. 2.1 Newly Diagnosed Multiple Myeloma 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 Counts (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 1-21 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. Dosing is continued or modified based upon clinical and laboratory findings. For patients ≥75 years of age, the starting dose of dexamethasone is 20 mg/day on days 1, 8, 15 and 22 of each 28- day treatment cycle. The recommended dose of lenalidomide for patients suffering from moderate renal impairment is 10 mg once daily. Recommended dose adjustments during treatment and restart of treatment: Dose adjustments, as summarised below, are recommended to manage grade 3 or 4 thrombocytopenia, neutropenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide. • Dose reduction steps Lenalidomide Dexamethasone 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 NA • Thrombocytopenia When platelets Recommended course Fall to < 25 x 109/L Stop lenalidomide dosing for remainder of cycleª Return to ≥ 50 x 109/L Decrease by one dose level when dosing resumed at next cycle ª If Dose Limiting Toxicity (DLT) occurs on > day15 of a cycle, lenalidomide dosing will be interrupted for at least the remainder of the current 28-day cycle. • Neutropenia When neutrophils Recommended course First fall to < 0.5 x 109/L Interrupt lenalidomide treatment Return to ≥ 1 x 109/L when neutropenia is Resume lenalidomide at Starting dose the only observed toxicity once daily Return to ≥ 0.5 x 109/L when dose- Resume lenalidomide at Dose level -1 dependent haematological toxicities other once daily than neutropenia are observed For each subsequent drop below Interrupt lenalidomide treatment < 0.5 x 109/L Return to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level once daily. In case of neutropenia, the use of growth factors in patient management should be considered. If the dose of lenalidomide was reduced for a hematologic DLT, the dose of lenalidomide may be re-introduced to the next higher dose level (up to the starting dose) at the discretion of the treating physician if continued lenalidomide / dexamethasone therapy resulted in improved bone marrow function (no DLT for at least 2 consecutive cycles and an ANC ≥1,500/µL with a platelet count ≥ 100,000/µL at the beginning of a new cycle at the current dose level). Lenalidomide in combination with melphalan and prednisone followed by maintenance monotherapy in patients who are not eligible for transplant Lenalidomide9 treatment must not be started if the ANC is < 1.5 x 109/L, and/or platelet counts are < 75 x 10 /L. Recommended dose The recommended starting dose is lenalidomide 10 mg/day orally on days 1-21 of repeated 28-day cycles for up to 9 cycles, melphalan 0.18 mg/kg orally on days 1-4 of repeated 28 day cycles, prednisone 2 mg/kg orally on days 1-4 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 alone, 10 mg/day orally on days 1-21 of repeated 28-day cycles given until disease progression. Dosing is continued or modified based upon clinical and laboratory findings. Recommended dose adjustments during treatment and restart of treatment: Dose adjustments, as summarised below, are recommended to manage grade 3 or 4 thrombocytopenia, neutropenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide. • 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 NA 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 x 109/L Interrupt lenalidomide treatment Return to ≥ 25 x 109/L Resume lenalidomide and melphalan at Dose level -1 For each subsequent drop below Interrupt lenalidomide treatment 30 x 109/L Return to ≥ 30 x 109/L Resume lenalidomide at next lower dose level (Dose level -2 or -3) once daily. • Neutropenia When neutrophils Recommended course First fall to < 0.5 x 109/Lª Interrupt lenalidomide treatment Return to ≥ 0.5 x 109/L when neutropenia Resume lenalidomide at Starting dose is the only observed toxicity once daily Return to ≥ 0.5 x 109/L when dose- Resume lenalidomide at Dose level -1 dependent haematological toxicities other once daily than neutropenia are observed For each subsequent drop below Interrupt lenalidomide treatment < 0.5 x 109/L Return to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level once daily. ªIf the subject has not been receiving G-CSF therapy, initiate G-CSF therapy. On Day 1 of next cycle, continue G-CSF as needed and maintain dose of melphalan if neutropenia was the only DLT. Otherwise, decrease by one dose level at start of next cycle. In case of neutropenia, the use of growth factors in patient management should be considered. For patients older than 75 years of age treated with lenalidomide in combination with dexamethasone, the starting dose of dexamethasone is 20 mg/day on days 1, 8, 15 and 22 of each 28-day treatment cycle. No dose adjustment is proposed for patients older than 75 years treated with lenalidomide in combination with melphalan and prednisone. 2.2 Multiple Myeloma with at least one prior therapy The recommended starting dose of REVLIMID is 25 mg once daily on days 1-21 of repeated 28- day cycles. The recommended dose of dexamethasone is 40 mg once daily on days 1-4, 9-12, and 17-20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg once daily orally on days 1-4 every 28 days. Treatment is continued or modified based upon clinical and laboratory findings. Prescribing physicians should carefully evaluate which dose of dexamethasone to use, taking into account the condition and disease status of the patient. Lenalidomide treatment must not be started if the ANC < 1,000/mcL, and/or platelet counts < 75,000/ mcL or, dependent on bone marrow infiltration by plasma cells, platelet counts < 30,000/mcL. Dose Adjustments for Hematologic Toxicities During Multiple Myeloma Treatment Dose modification guidelines, as summarized below, are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID. Platelet counts Thrombocytopenia in MM When Platelets Recommended Course Fall to <30,000/mcL Interrupt REVLIMID treatment, follow CBC weekly Return to ≥30,000/mcL Restart REVLIMID at 15 mg daily For each subsequent drop <30,000/mcL Interrupt REVLIMID treatment Return to ≥30,000/mcL Resume REVLIMID at 5 mg less than the previous dose. Do not dose below 5 mg daily Absolute Neutrophil counts (ANC) Neutropenia in MM When Neutrophils Recommended Course Fall to <1000/mcL Interrupt REVLIMID treatment, add G-CSF, follow CBC weekly Return to ≥1,000/mcL and neutropenia is the only Resume REVLIMID at 25 mg toxicity daily Return to ≥1,000/mcL and if other toxicity Resume REVLIMID at 15 mg daily For each subsequent drop <1,000/mcL Interrupt REVLIMID treatment Return to ≥1,000/mcL Resume REVLIMID at 5 mg less than the previous dose. Do not dose below 5 mg daily In case of neutropenia, the physician should consider the use of growth factors in patient management. Starting Dose Adjustment for Renal Impairment in MM: See Section 2.5 2.3 Myelodysplastic Syndromes The recommended starting dose of REVLIMID is 10 mg daily. Treatment is continued or modified based upon clinical and laboratory findings. Dose Adjustments for Hematologic Toxicities During MDS Treatment Patients who are dosed initially at 10 mg and who experience thrombocytopenia should have their dosage adjusted as follows: Platelet counts If thrombocytopenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS If baseline ≥100,000/mcL When Platelets Recommended Course Fall to <50,000/mcL Interrupt REVLIMID treatment Return to ≥50,000/mcL Resume REVLIMID at 5 mg daily If baseline <100,000/mcL When Platelets Recommended Course Fall to 50% of the baseline value Interrupt REVLIMID treatment If baseline ≥60,000/mcL and Resume REVLIMID at 5 mg daily returns to ≥50,000/mcL If baseline <60,000/mcL and Resume REVLIMID at 5 mg daily returns to ≥30,000/mcL If thrombocytopenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS When Platelets Recommended Course <30,000/mcL or <50,000/mcL Interrupt REVLIMID treatment with platelet transfusions Return to ≥30,000/mcL Resume REVLIMID at 5 mg daily (without hemostatic failure) Patients who experience thrombocytopenia at 5 mg daily should have their dosage adjusted as follows: If thrombocytopenia develops during treatment at 5 mg daily in MDS When Platelets Recommended Course <30,000/mcL or <50,000/mcL Interrupt REVLIMID treatment with platelet transfusions Return to ≥30,000/mcL Resume REVLIMID at 2.5 mg (without hemostatic failure) daily Patients who are dosed initially at 10 mg and experience neutropenia should have their dosage adjusted as follows: Absolute Neutrophil counts (ANC) If neutropenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS If baseline ANC ≥1,000/mcL When Neutrophils Recommended Course Fall to <750/mcL Interrupt REVLIMID treatment Return to ≥1,000/mcL Resume REVLIMID at 5 mg daily If baseline ANC <1,000/mcL When Neutrophils Recommended Course Fall to <500/mcL Interrupt REVLIMID treatment Return to ≥500/mcL Resume REVLIMID at 5 mg daily If neutropenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS When Neutrophils Recommended Course <500/mcL for ≥7 days or <500/mcL Interrupt REVLIMID treatment associated with fever (≥38.5°C) Return to ≥500/mcL Resume REVLIMID at 5 mg daily Patients who experience neutropenia at 5 mg daily should have their dosage adjusted as follows: If neutropenia develops during treatment at 5 mg daily in MDS When Neutrophils Recommended Course <500/mcL for ≥7 days or <500/mcL Interrupt REVLIMID associated with fever (≥38.5°C) treatment Return to ≥500/mcL Resume REVLIMID at 2.5 mg daily 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. Starting Dose Adjustment for Renal Impairment in MDS: See Section 2.5 2.4 Mantle Cell Lymphoma The recommended starting dose of REVLIMID is 25 mg/day orally on days 1-21 of repeated 28-day cycles. Dosing is continued or modified based upon clinical and laboratory findings. Dose reduction steps Starting dose 25 mg once daily on days 1-21, every 28 days Dose Level -1 20 mg once daily on days 1-21, every 28 days Dose Level -2 15 mg once daily on days 1-21, every 28 days Dose Level -3 10 mg once daily on days 1-21, every 28 days Dose Level -4 5 mg once daily on days 1-21, every 28 days Dose Level -5 2.5 mg once daily on days 1-21, every 28 days 5 mg every other day on days 1-21, every 28 days Thrombocytopenia When Platelets Recommended Course Fall to <50 x 109/L Interrupt REVLIMID treatment and conduct Complete Blood Count (CBC) at least every 7 days Return to ≥ 60 x 109/L Resume lenalidomide 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 Return 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 Neutropenia When Neutrophils Recommended Course Fall to <1 x 109/L for at least 7 days Interrupt REVLIMID OR treatment and conduct the Falls to <1 x 109/L with an associated fever (body CBC at least every 7 days temperature ≥ 38.5°C) OR Falls to <0.5 x 109/L Return 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 Interrupt REVLIMID days or drop to < 1 x 109/L with associated fever (body treatment temperature ≥ 38.5°C) or drop to < 0.5 x 109/L Returns to ≥1 x 109/L Resume REVLIMID at next lower dose level (Dose Level - 2, -3, -4, -5). Do not dose below Dose Level -5 Tumour flare reaction REVLIMID may be continued in patients with Grade 1 or 2 tumour flare reaction (TFR) without interruption or modification, at the physician’s discretion. In patients with Grade 3 or 4 TFR, withhold treatment with REVLIMID until TFR resolves to ≤ Grade 1 and patients may be treated for management of symptoms per the guidance for treatment of Grade 1 and 2 TFR. 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) or toxic epidermal necrolysis (TEN) is suspected, and should not be resumed following discontinuation from these reactions. Starting Dose Adjustment for Renal Impairment in MCL: See Section 2.5. 2.5 Starting Dose for Renal Impairment in MM, MDS or MCL Since REVLIMID is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment and in patients on dialysis. Based on a pharmacokinetic study in patients with renal impairment due to non-malignant conditions, REVLIMID starting dose adjustment is recommended for patients with CLcr < 60 mL/min. Non-dialysis patients with creatinine clearances less than 11 mL/min and dialysis patients with creatinine clearances less than 7 mL/min have not been studied. The recommendations for initial starting doses for patients with MM, MDS or MCL are as follows: Starting Dose Adjustments for Patients with Renal Impairment in MM, MDS or MCL Category Renal Function Dose in MM or Dose in MDS (Cockcroft-Gault) MCL Moderate Renal CLcr 30-60 mL/min 10 mg 5 mg Impairment Every 24 hours Every 24 hours Severe Renal CLcr < 30 mL/min 7.5 mg 2.5 mg Impairment (not requiring Every 24 hours Every 24 hours dialysis) End Stage Renal CLcr < 30 mL/min 5 mg 2.5 mg Disease (requiring dialysis) once daily. On Once daily. On dialysis dialysis days, days, administer the administer the dose following dialysis. dose following dialysis. After initiation of REVLIMID therapy, subsequent REVLIMID dose modification is based on individual patient treatment tolerance, as described elsewhere (see section 2). All patients 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) or toxic epidermal necrolysis (TEN) is suspected, and should not be resumed following discontinuation from these reactions. 3. DOSAGE FORMS AND STRENGTHS REVLIMID 2.5 mg, 5 mg, 7.5mg, 10 mg, 15 mg, 20 mg and 25 mg hard capsules will be supplied through the Revlimid RMP-PPP. REVLIMID is available in the following hard capsule strengths: 2.5 mg: White and blue-green opaque hard capsules imprinted “REV” on one half and “2.5 mg” on the other half in black ink 5 mg: White opaque hard capsules imprinted “REV” on one half and “5 mg” on the other half in black ink 7.5mg: Pale yellow/white hard capsules marked “REV 7.5 mg” 10 mg: Blue/green and pale yellow opaque hard capsules imprinted “REV” on one half and “10 mg” on the other half in black ink 15 mg: Powder blue and white opaque hard capsules imprinted “REV” on one half and “15 mg” on the other half in black ink 20 mg: Powder blue and blue-green opaque hard capsules imprinted “REV” on one half and “20 mg” on the other half in black ink 25 mg: White opaque hard capsules imprinted “REV” on one half and “25 mg” on the other half in black ink
פרטי מסגרת הכללה בסל
א. התרופה האמורה תינתן לטיפול במקרים האלה: 1. מיאלומה נפוצה ובהתקיים אחד מאלה: א. חולה שטרם קיבל טיפול למחלתו ואינו מועמד להשתלת מח עצם.הטיפול יינתן בשילוב עם Dexamethasone או בשילוב עם Dexamethasone ו-Bortezomib.ב. מונותרפיה כטיפול אחזקה במאובחן חדש לאחר השתלת מח עצם.ג. חולה שמחלתו עמידה או נשנית לאחר מיצוי קו טיפול אחד שכלל אחד מהשניים - BORTEZOMIB או THALIDOMIDE, אלא אם כן לחולה הייתה הורית נגד לאחד מהטיפולים האמורים. על אף האמור בפסקה זו הטיפול בתכשיר ייפסק בחולה העונה על אחד מאלה: 1. בחולה שמחלתו התקדמה לאחר שני מחזורי טיפול מלאים או ארבעה מחזורי טיפול חלקיים. 2. חולה שפיתח תופעות לוואי קשות לטיפול. הטיפול בתכשיר יינתן לחולה שטרם טופל ב-Lenalidomide למחלה זו. 2. תסמונת מיאלודיספלסטית ברמת חומרה low או intermediate-1 עם הפרעה ציטוגנטית מסוג deletion 5q. ב. מתן התרופה האמורה ייעשה לפי מרשם של מומחה בהמטולוגיה.
מסגרת הכללה בסל
התוויות הכלולות במסגרת הסל
התוויה | תאריך הכללה | תחום קליני | Class Effect | מצב מחלה |
---|---|---|---|---|
מיאלומה נפוצה - טיפול אחזקה במאובחנים חדשים לאחר השתלת מח עצם | ||||
מיאלומה נפוצה כקו טיפול ראשון עבור חולים שאינם מועמדים להשתלת מח עצם (בשילוב עם Dexamethasone / Bortezomib + Dexamethasone) | ||||
Myelodysplatic syndromes מסוג 5q del | ||||
מיאלומה נפוצה - קו שני | ||||
מיאלומה נפוצה - קו טיפול מתקדם (קו שלישי והלאה) |
שימוש לפי פנקס קופ''ח כללית 1994
לא צוין
תאריך הכללה מקורי בסל
03/01/2010
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