Lenalidomide

In this article, we will discuss about Lenalidomide (Dosage). So, let’s get started.

Lenalidomide

Indications

Multiple Myeloma

Lenalidomide (REVLIMID®) in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy.

Myelodysplastic Syndromes

Lenalidomide (REVLIMID®) is indicated for the treatment of patients with transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion S4 cytogenetic abnormality with or without additional cytogenetic abnormalities.

Dosage

Lenalidomide (REVLIMID®) should be taken orally at about the same time each day, either with or without food. Lenalidomide (REVLIMID®) capsules should be swallowed whole with water.

Multiple Myeloma

The recommended starting dose of Lenalidomide (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-duy eyele for the first 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 summarised below, are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade
3 or 4 toxicity judged to be related to lenalidomide

Platelet counts

Thrombocytopenia in MM

When Platelets – Recommended Course

Fall to <30,000 mcL – Interrupt Lenalidomide (REVLIMID®) treatment, follow CBC weekly

Return to ≥30,000 mcL – Restart Lenalidomide (REVLIMID®) at 15 mg daily

For each subsequent drop <30,000 mcL – Interrupt Lenalidomide (REVLIMID®) treatment

Return to ≥30,000 mcL – Resume Lenalidomide (REVLIMID®) 3 mg less than the previous dose Do not dose below 5mg daily

Absolute Neutrophil counts (ANC)

Neutropenia in MM

When Neutrophils – Recommended Course

Fall to <1000 mcL – lnterrupt Lenalidomide (REVLIMID®) Treatment, add G-CSF, follow CBC weekly

Return to ≥1000/mcL and neutropenia is the only toxicity – Resume Lenalidomide (REVLIMID®) at 25 mg daily

Return to ≥1000/mcL and if other toxicity – Resume Lenalidomide (REVLIMID®) 15 mg daily

For each subsequent drop <1000/mcL – Interrupt Lenalidomide (REVLIMID®) treatment

Return to ≥1000/mcL – Resume Lenalidomide (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 Lenalidomide (REVLIMID®) hold treatment and restart at next lower dose level when toxicity has resolved to ≤ Grade 2.

Starting Dose Adjustment for Renal Impairment in MM

Since Lenalidomide (REVLIMID®) is primarily excreted unchanged by the kidney, adjustments to the starting dose of Lenalidomide (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 nonmalignant conditions Lenalidomide (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 multiple myeloma (MM) are as follows:

Starting Dose Adjustment for Renal Impairment in Multiple Myelona (Days 1-21 of each 28 day cycle)

Category – Renal Function (Cockcroft-Gault) – Dose

Moderate Renal Impairment – CLcr 30-60 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.

After initiation of Lenalidomide (REVLIMID®) therapy, subsequent Lenalidomide (REVLIMID®) dose modification should be based on individual patient treatment tolerance.

Myelodysplastic Syndrome

The recommende starting dose of Lenalidomide (REVLIMID®) 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 doses 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 Lenalidomide (REVLIMID®) treatment

Return to >50,000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily

If baseline <100,000/mcL

When Platelets – Recommended Course

Fall to 50% of the baseline value – Interrupt Lenalidomide (REVLIMID®) treatment

If baseline ≥60,000 mcL and returns to ≥50.000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily

If baseline <60,000/mcL and returns to ≥30,000/mcL – Resume Lenalidomide (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 Lenalidomide (REVLIMID®) treatment

Return to ≥30,000/mcL (without hemostatic failure) – Resume Lenalidomide (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 Lenalidomide (REVLIMID®) treatment

Return to ≥30,000 mcL (without hemostatic failure) – Resume Lenalidomide (REVLIMID®) at 25 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 ≥1000/mcL

When Neutrophils – Recommended Course

Fall to <750 mcL – Interrupt Lenalidomide (REVLIMID®) treatment

Return to ≥1000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily

If baseline ANC <1000/mcL

When Neutrophils – Recommended Course

Fall to <500 mcL – Interrupt Lenalidomide (REVLIMID®) treatment

Retum to ≥500/mcL – Resume Lenalidomide (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 27 days or <500/mcL associated with fever (≥38.5°C) – Interrupt Lenalidomide (REVLIMID®) treatment

Return to ≥500/mcL – Resume Lenalidomide (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 27 days or <500/mcL (associated with fever ≥38.5°C) – Interrupt Lenalidomide (REVLIMID®) treatment

Return to ≥500/mcL – Resume Lenalidomide (REVLIMID®) 25 mg daily

Other Grade 3/4 Toxicities in MDS

For other Grade 3/4 toxicities judged to be related to Lenalidomide (REVLIMID®), hold treatment and restart at next lower dose level when toxicity has resolved to ≤Grade 2.

Starting Dose Adjustment for Renal Impairment in MDS:

Since Lenalidomide (REVLIMID®) is primarily excreted unchanged by the kidney, adjustments to the starting dose of Lenalidomide (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, Lenalidomide (REVLIMID®) starting dose adjustment is recommended for patients with CLcr<60 mL/min. Non-dialysis patients with creatitine clearances less than 11 mL/min and 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 myelodysplastic syndromes (MDS) are as follows:

Starting Dose Adjustment For Renal Impairment in Myelodysplastic Syndromes (Days 1 – 28 of each day cycle)

Category – Renal Function (Cockcroft-Gault) – Dose

Moderate Renal Impairment – CLcr 30-60 mL/min – 5 mg every 24 hours

Severe Renal Impairment – CLcr <30 mL/min (not requiring dialysis) – 2.5 mg every 24 hours

End Stage Renal Disease – CLcr < 30 mL/min (requiring dialysis) – 2.5 mg once daily. On dialysis days administer the dose following dialysis

After initiation of Lenalidomide (REVLIMID®) therapy, subsequent Lenalidomide (REVLIMID®) dose modification should be based on individual patient treatment tolerance.

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