Revlimid

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.

2.1 Multiple Myeloma

Multiple Myeloma

The recommended starting dose of REVLIMID is 25 mg orally once daily on Days 1-21 of repeated 28-day cycles in combination with dexamethasone. Refer to Section 14.1 for specific dexamethasone dosing. For patients > 75 years old, the starting dose of dexamethasone may be reduced [see Clinical Studies (14.1)]. Treatment should be continued until disease progression or unacceptable toxicity.

In patients who are not eligible for autologous stem cell transplantation (ASCT), treatment should continue until disease progression or unacceptable toxicity. For patients who are ASCT-eligible, hematopoietic stem cell mobilization should occur within 4 cycles of a REVLIMID-containing therapy [see Warnings and Precautions (5.11)].

Dose Adjustments for Hematologic Toxicities During Multiple Myeloma Treatment

Dose modification guidelines, as summarized in Table 1 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.

Table 1: Dose Adjustments for Hematologic Toxicities for MM

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 Resume REVLIMID at next lower dose. Do not dose below 2.5 mg daily For each subsequent drop <30,000/mcL Interrupt REVLIMID treatment Return to ≥30,000/mcL Resume REVLIMID at next lower dose. Do not dose below 2.5 mg daily

Absolute Neutrophil counts (ANC)

Neutropenia in MM

When Neutrophils Recommended Course Fall to <1000/mcL Interrupt REVLIMID treatment, follow CBC
weekly Return to ≥1,000/mcL and neutropenia is the only toxicity Resume REVLIMID at 25 mg daily or initial
starting dose Return to ≥1,000/mcL and if other toxicity Resume REVLIMID at next lower dose. Do
not dose below 2.5 mg daily For each subsequent drop <1,000/mcL Interrupt REVLIMID treatment Return to ≥1,000/mcL Resume REVLIMID at next lower dose. Do not dose below 2.5 mg daily

Other 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 Dosage and Administration (2.4)].

2.2 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 Dosage and Administration (2.4)].

2.3 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 Dosage and Administration (2.4)].

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. The recommendations for initial starting doses for patients with MDS or MCL, and MM are as follows:

Table 2: Starting Dose Adjustments for Patients with Renal Impairment in MDS or MCL Category Renal Function (Cockcroft-
Gault) Dose in 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. Table 3: Starting Dose Adjustments for Patients with Renal Impairment in MM Category Renal Function (Cockcroft-
Gault) Dose in MM Moderate Renal
Impairment CLcr 30-50 mL/min 10 mg
Every 24 hours Severe Renal Impairment CLcr < 30 mL/min (not
requiring dialysis) 15 mg
Every 48 hours End Stage Renal Disease CLcr < 30 mL/min (requiring
dialysis) 5 mg
Once daily. On dialysis
days, administer the dose
following dialysis.

Moderate renal impairment for MM: Consider escalating the dose to 15 mg after 2 cycles if the patient tolerates the 10 mg dose of lenalidomide without dose-limiting toxicity.

After initiation of REVLIMID therapy, subsequent REVLIMID dose increase or decrease is based on individual patient treatment tolerance, as described elsewhere [See Dosage and Administration (2.1-2.3)].