Lenalidomide Dosage

Usual Adult Dose for Anemia

10 mg with water daily

Usual Adult Dose for Multiple Myeloma

25 mg/day of lenalidomide with water orally as a single 25 mg capsule on days 1 through 21 of repeated 28 day cycles.

(The recommended dose of dexamethasone is 40 mg/day on days 1 through 4, 9 through 12, and 17 through 20 of each 28 day cycle for the first 4 cycles of therapy and then 40 mg/day orally on days 1 through 4 every 28 days.)

The effects of substituting lesser strengths of lenalidomide to equal a 25 mg capsule dose is unknown.

Renal Dose Adjustments

Starting dose adjustment is recommended for patients with a creatinine clearance less than 60 mL/min. Non-dialysis patients with creatinine clearances less than 11 mL/min have not been studied. The recommendations for initial starting doses for patients with multiple myeloma (MM) and myelodysplastic syndromes (MDS) are as follows:

Moderate renal function impairment (creatinine clearance 30 to less than 60 mL/min):
Multiple Myeloma: 10 mg every 24 hours
Myelodysplastic Syndromes: 5 mg every 24 hours

Severe renal function impairment (creatinine clearance less than 30 mL/min) not requiring dialysis:
Multiple Myeloma: 15 mg every 48 hours
Myelodysplastic Syndromes: 5 mg every 48 hours

Liver Dose Adjustments

Data not available

Dose Adjustments

Dosing is continued or modified based upon clinical and laboratory findings.

ANEMIA:
Patients who are dosed initially at 10 mg and who experience thrombocytopenia should have their dosage adjusted as follows:
1) Platelet Counts
1A) If thrombocytopenia develops WITHIN 4 weeks of starting treatment at 10 mg daily
If baseline platelet count is greater than or equal to 100,000/mcL
When platelets fall to less than 50,000/mcL, then interrupt lenalidomide treatment.
When platelets return to greater than or equal to 50,000/mcL, then resume lenalidomide at 5 mg daily.

If baseline platelet counts is less than 100,000/mcL
When platelets fall to 50% of the baseline value, interrupt lenalidomide treatment.
If baseline was greater than or equal to 60,000/mcL and returns to greater than or equal to 50,000/mcL, then resume lenalidomide at 5 mg daily.
If baseline was less than or equal to 60,000/mcL and returns to greater than or equal to 30,000/mcL, then resume lenalidomide at 5 mg daily.

1B) If thrombocytopenia develops AFTER 4 weeks of starting treatment at 10 mg daily
When platelets are less than 30,000/mcL or less than 50,000/mcL with platelet transfusions, then interrupt lenalidomide treatment.
When platelets return to greater than or equal to 30,000/mcL (without hemostatic failure), then resume lenalidomide at 5 mg daily.

Patients who experience thrombocytopenia at 5 mg daily should have their dosage adjusted as follows:
1C) If thrombocytopenia develops during treatment at 5 mg daily
When platelets are less than 30,000/mcL or less than 50,000/mcL with platelet transfusions, then interrupt lenalidomide treatment.
When platelets return to greater than or equal to 30,000/mcL (without hemostatic failure), then resume lenalidomide at 5 mg every OTHER day.

Patients who are dosed initially at 10 mg and experience neutropenia should have their dosage adjusted as follows:
2) Absolute Neutrophil Counts (ANC)
2A) If neutropenia develops WITHIN 4 weeks of starting treatment at 10 mg daily
If baseline ANC is greater than or equal to 1,000/mcL
When neutrophils fall to less than 750/mcL, then interrupt lenalidomide treatment.
When neutrophils return to greater than or equal to 1,000/mcL, then resume lenalidomide at 5 mg daily.

If baseline ANC is less than 1,000/mcL
When neutrophils fall to less than 500/mcL, then interrupt lenalidomide treatment.
When neutrophils return to greater than or equal to 500/mcL, then resume lenalidomide at 5 mg daily.

2B) If neutropenia develops AFTER 4 weeks of starting treatment at 10 mg daily
When neutrophils fall to less than 500/mcL for 7 or more days or less than 500/mcL associated with fever greater than or equal to 38.5 degrees Celsius, then interrupt lenalidomide treatment.
When neutrophils return to greater than or equal to 500/mcL, then resume lenalidomide at 5 mg daily.

Patients who experience neutropenia at 5 mg daily should have their dosage adjusted as follows:
2C) If neutropenia develops during treatment at 5 mg daily
When neutrophils fall to less than 500/mcL for 7 or more days or less than 500/mcL associated with fever greater than or equal to 38.5 degrees Celsius, then interrupt lenalidomide treatment.
When neutrophils return to greater than or equal to 500/mcL, then resume lenalidomide at 5 mg every OTHER day.

MULTIPLE MYELOMA:
When platelets fall to less than 30,000/mcL, interrupt lenalidomide treatment and follow the CBC count weekly.
When platelets return to greater than or equal to 30,000/mcL, resume lenalidomide at 15 mg daily.
For each subsequent drop below 30,000/mcL interrupt lenalidomide treatment.
For each subsequent time the platelets return to greater than or equal to 30,000/mcL, resume lenalidomide at 5 mg daily less than previous dose. Do not dose below 5 mg daily.

When neutrophils fall to less than 1000/mcL, interrupt lenalidomide treatment. Add G-CSF and follow the CBC count weekly.
When neutrophils return to greater than or equal to 1000/mcL and neutropenia is the only toxicity, resume lenalidomide at 25 mg daily.
For each subsequent return to greater than or equal to 1000/mcL and if other toxicity is present, resume lenalidomide at 15 mg daily.
For each subsequent time the neutrophils drop below 1000/mcL, interrupt lenalidomide treatment.
For each subsequent return to greater than or equal to 1000/mcL, resume lenalidomide at 5 mg daily less than previous dose. Do not dose below 5 mg daily.

Precautions

Lenalidomide has been associated with significant neutropenia and thrombocytopenia. Patients on therapy should have their complete blood counts (including white blood cell count with differential, platelet count, hemoglobin, and hematocrit) monitored weekly for the first eight weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Cases of transient liver laboratory abnormalities (predominantly transaminases) have been reported. Treatment should be interrupted and may be restarted once the levels return to baseline. Successful rechallenge without recurrence of liver laboratory elevation was reported in some patients.

Lenalidomide is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

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.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Hemodialysis patients with a creatinine clearances less than 7 mL/min have not been studied. The recommendations for initial starting doses for patients with multiple myeloma (MM) and myelodysplastic syndromes (MDS) are as follows:

End stage renal disease (creatinine clearance less than 30 mL/min) requiring hemodialysis:
Multiple Myeloma: 5 mg once daily. On hemodialysis days the dose should be administered following dialysis.
Myelodysplastic Syndromes: 5 mg 3 times a week following each hemodialysis

Peritoneal dialysis patients have not been studied. The manufacturer has no dosage recommendations for patients on peritoneal dialysis.

Other Comments

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for lenalidomide. It includes a Medication Guide, elements to assure safe use, and an implementation system. Additional information is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.

The capsules should not be broken, chewed, or opened.

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