DOSAGE AND ADMINISTRATION
REVLIMID should be taken orally at about the same time each day, either with or without food. REVLIMID capsules should be swallowed whole with water. The capsules should not be opened, broken, or chewed.
Multiple Myeloma
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.
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 toxicity |
Resume REVLIMID at 25 mg 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 |
Other Grade 3 / 4 Toxicities in MM
For other Grade 3/4 toxicities judged to be related to REVLIMID, hold treatment and restart at the physician's discretion at next lower dose level when toxicity has resolved to ≤ Grade 2.
Starting Dose Adjustment for Renal Impairment in MM:
See Section 2.4
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 returns to ≥50,000/mcL |
Resume REVLIMID at 5 mg daily |
If baseline <60,000/mcL and returns to ≥30,000/mcL |
Resume REVLIMID at 5 mg daily |
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 with platelet transfusions |
Interrupt REVLIMID treatment |
Return to ≥30,000/mcL (without hemostatic failure) |
Resume REVLIMID at 5 mg daily |
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 with platelet transfusions |
Interrupt REVLIMID treatment |
Return to ≥30,000/mcL (without hemostatic failure) |
Resume REVLIMID at 2.5 mg 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 associated with fever (≥38.5°C) |
Interrupt REVLIMID treatment |
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 associated with fever (≥38.5°C) |
Interrupt REVLIMID treatment |
Return to ≥500/mcL |
Resume REVLIMID at 2.5 mg daily |
Other Grade 3 / 4 Toxicities in MDS
For other Grade 3/4 toxicities judged to be related to REVLIMID, hold treatment and restart at the physician's discretion at next lower dose level when toxicity has resolved to ≤ Grade 2.
Starting Dose Adjustment for Renal Impairment in MDS:
See Section 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 for relapsed or refractory mantle cell lymphoma. Treatment should be continued until disease progression or unacceptable toxicity.
Treatment is continued, modified or discontinued based upon clinical and laboratory findings.
Dose Adjustments for Hematologic Toxicities During MCL Treatment
Dose modification guidelines as summarized below are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicities considered to be related to REVLIMID.
Platelet counts
Thrombocytopenia during treatment in MCL
When Platelets
|
Recommended Course
|
Fall to <50,000/mcL |
Interrupt REVLIMID treatment and follow CBC weekly |
Return to ≥50,000/mcL |
Resume REVLIMID at 5 mg less than the previous dose. Do not dose below 5 mg daily |
Absolute Neutrophil counts (ANC)
Neutropenia during treatment in MCL
When Neutrophils
|
Recommended Course
|
Fall to <1000/mcL for at least 7 days OR Falls to < 1,000/mcL with an associated temperature ≥ 38.5°C OR Falls to < 500 /mcL |
Interrupt REVLIMID treatment and follow CBC weekly |
Return to ≥1,000/mcL |
Resume REVLIMID at 5 mg less than the previous dose. Do not dose below 5 mg daily |
Other Grade 3 / 4 Toxicities in MCL
For other Grade 3/4 toxicities judged to be related to REVLIMID, hold treatment and restart at the physician’s discretion at next lower dose level when toxicity has resolved to ≤ Grade 2.
Starting Dose Adjustment for Renal Impairment in MCL:
See Section 2.4.
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:
Table 1: Starting Dose Adjustments for Patients with Renal Impairment in MM, MDS or MCL
Category
|
Renal Function (Cockcroft- Gault)
|
Dose in MM or MCL
|
Dose in MDS
|
Moderate Renal Impairment
|
CLcr 30-60 mL/min |
10 mg Every 24 hours |
5 mg Every 24 hours |
Severe Renal Impairment
|
CLcr < 30 mL/min (not requiring dialysis) |
15 mg Every 48 hours |
2.5 mg Every 24 hours |
End Stage Renal Disease
|
CLcr < 30 mL/min (requiring dialysis) |
5 mg Once daily. On dialysis days, administer the dose following dialysis. |
2.5 mg Once daily. On dialysis days, administer the 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).
DOSAGE FORMS AND STRENGTHS
REVLIMID 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg and 25 mg capsules will be supplied through the REVLIMID REMS™ program.
REVLIMID is available in the following 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 capsules imprinted “REV” on one half and “5 mg” on the other half in black ink
10 mg: Blue/green and pale yellow opaque capsules imprinted “REV” on one half and “10 mg” on the other half in black ink
15 mg: Powder blue and white opaque 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 capsules imprinted “REV” on one half and “25 mg” on the other half in black ink
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