DESCRIPTION
Mechanism of Action
• Mechanism of action is not fully characterized.
• Immunomodulatory drug (IMid) that stimulates T-cell proliferation
as well as IL-2 and IFN-g production.
• Inhibition of TNF-a and IL-6 synthesis and down modulation of cell
surface adhesion molecules similar to thalidomide.
• May exert antiangiogenic effect by inhibition of basic fibroblast
growth (bFBG) and vascular endothelial growth factor (VEGF) and
through as yet undefined mechanisms.
• Overcomes cellular drug resistance to thalidomide.
Mechanism of Resistance
None characterized to date.
Absorption
Lenalidomide is rapidly absorbed following oral administration with peak
plasma concentrations at 60–90 minutes post ingestion. Coadministration
with food does not alter the extent of absorption (AUC) but does reduce
maximal plasma concentration (Cmax) by 36%.
Distribution
Not well characterized.
Metabolism
Lenalidomide does not appear to be metabolized or induced by the cytochrome
P450 pathway. Approximately 66% of an administered dose is
excreted unchanged in the urine. The elimination half-life of the drug is
approximately 3 hours.
Indications
1. FDA-approved for the treatment of low- or intermediate-1-risk myelodysplastic
syndromes (MDS) associated with the deletion 5q (del 5q) cytogenetic
abnormality with or without additional cytogenetic abnormalities.
2. FDA-approved for the treatment of multiple myeloma in combination
with dexamethasone for patients who have received at least one
prior therapy.
3. FDA-approved for the treatment of mantle cell lymphoma in patients
whose disease has relapsed or progressed after two prior therapies,
one of which included bortezomib.
Dosage Range
1. Myelodysplastic syndrome: 10 mg PO daily.
2. Multiple myeloma: 25 mg PO daily on days 1–21 and 40 mg dexamethasone
PO on days 1–4, 9–12, and 17–20 of a 28-day cycle. An
alternative regimen is to use 40 mg dexamethasone PO on days 1, 8,
15, and 22 of a 28-day cycle.
3. Mantle cell lymphoma: 25 mg PO daily on days 1–21 of a 28-day cycle.
Drug Interactions
None well characterized to date.
Special Considerations
1. Pregnancy category X. Lenalidomide is a thalidomide analog, a
known human teratogen that causes severe or life-threatening birth
defects. As such, women who are pregnant or who wish to become
pregnant should not take lenalidomide. Severe fetal malformations
can occur if even one capsule is taken by a pregnant woman. All
women should have a baseline b-human chorionic gonadotropin
(b-HCG) before starting lenalidomide therapy. Women of reproductive
age must have two negative pregnancy tests before starting
 therapy: one should be 10 to 14 days before therapy is begun, and the
second should be 24 hours before therapy.
2. All women of childbearing potential should practice two forms of
birth control throughout therapy with lenalidomide: one highly
effective form (intrauterine device, hormonal contraception [patch,
implant, pill, injection], partner’s vasectomy, or tubal ligation)
and€one additional barrier method (latex condom, diaphragm, or
cervical cap). It is strongly recommended that these precautionary€
measures be taken 1 month before initiation of therapy, continued
while on therapy, and continued at least 1 month after therapy
is discontinued.
3. Lenalidomide is only available under a special restricted distribution
program called “RevAssistSM.” Only prescribers and pharmacists registered
with the RevAssistSM program are able to prescribe and dispense
the drug. Lenalidomide should only be dispensed to those
patients who are registered and meet all the conditions of the
RevAssistSM program.
4. Breastfeeding while on therapy should be avoided, as it remains
unknown if lenalidomide is excreted in breast milk.
5. Men taking lenalidomide must use latex condoms for every sexual
encounter with a woman of childbearing potential, as the drug may
be present in semen.
6. Patients taking lenalidomide should not donate blood or semen
while receiving treatment, and for at least 1 month after stopping
this drug.
7. Monitor complete blood counts while on therapy as lenalidomide has
hematologic toxicity, especially in patients with del 5q MDS.
8. Use with caution in patients with impaired renal function, as the risk
of toxicity may be greater.
9. There is a significantly increased risk of thromboembolic complications,
including deep venous thrombosis (DVT) and pulmonary
embolism (PE), especially in myeloma patients treated with
lenalidomide and dexamethasone. Prophylaxis with low-molecular
weight heparin or aspirin (325 mg PO qd) can help prevent
and/or reduce this risk.
Toxicity 1
Potentially severe or fatal teratogenic effects.
Toxicity 2
Myelosuppression with neutropenia and thrombocytopenia that is usually
reversible.
Toxicity 3
Increased risk of thromboembolic complications, such as DVT and PE.
Toxicity 4
Nausea/vomiting, diarrhea, and constipation are most common GI side
effects.
Toxicity 5
Neurotoxic side effects are rare with almost no sedation.
Toxicity 6
Increased risk for second primary tumors, including acute myeloid
leukemia, solid tumors, and myelodysplastic syndrome.
SPECIFICATION
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