Lenalidomide; Uses, Dosage, Side Effects, Drug Interactions

Lenalidomide is a thalidomide analog with potential antineoplastic activity. Lenalidomide inhibits TNF-alpha production, stimulates T cells, reduces serum levels of the cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and inhibits angiogenesis. This agent also promotes G1 cell cycle arrest and apoptosis of malignant cells.

Lenalidomide is immunomodulatory and antineoplastic agents that are used in the therapy of multiple myeloma. Both agents are associated with a low rate of serum aminotransferase elevations during therapy and both have been implicated in causing rare instances of clinically apparent liver injury which can be severe.

Lenalidomide is a derivative of thalidomide introduced in 2004. It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic treatment. Lenalidomide has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS). Along with several other drugs developed in recent years, lenalidomide has significantly improved overall survival in myeloma (which formerly carried a poor prognosis), although toxicity remains an issue for users. It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic modality, but has also shown efficacy in the hematological disorders known as the myelodysplastic syndromes.

Mechanism of Action of Lenalidomide

The mechanism of action of lenalidomide remains to be fully characterized, however, it has been demonstrated that lenalidomide inhibits the expression of cyclooxygenase-2 (COX-2), but not COX-1, in vitro. In vivo, it induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity. Lenalidomide inhibits the secretion of pro-inflammatory cytokines and increases the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. Lenalidomide inhibits cell proliferation with varying effectiveness (IC50s) in some but not all cell lines. Lenalidomide is effective in inhibiting growth of Namalwa cells (a human B cell lymphoma cell line with a deletion of one chromosome 5) but is much less effective in inhibiting the growth of KG-1 cells (human myeloblastic cell line, also with a deletion of one chromosome 5) and other cell lines without chromosome 5 deletions. Lenalidomide does not prolong the QTc interval.

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Indications of Lenalidomide

Multiple Myeloma
Anemia
Lymphoma
Mantle cell lymphoma
Myelodysplastic diseases
Mantle cell lymphoma
Multiple myeloma
Myelodysplastic syndrome
Refractory chronic lymphocytic leukemia
Refractory diffuse large B Cell lymphoma
Light chain amyloidosis

Contra-Indications of Lenalidomide

Hodgkin’s lymphoma
Overactive thyroid gland
Hypothyroidism
Severely decreased Platelets
Heart attack
Lung embolism
Obstruction of a blood vessel by a blood clot
Blood clot in a deep vein of the extremities
Liver problems
Pregnancy
A mother who is producing milk and breastfeeding
Severely decreased levels of neutrophils in the blood
Acute thromboembolic stroke
Therapy-related acute Leukemia
Chronic kidney disease stage 3A (moderate)
Chronic kidney disease stage 3B (moderate)
Chronic kidney disease stage 4 (severe)
Chronic kidney disease stage 5 (failure)

Dosage of Lenalidomide

Strengths: 2.5 mg; 5 mg; 10 mg; 15 mg; 20 mg; 25 mg

Myelodysplastic Disease

10 mg orally once a day

Duration of Therapy: Treatment is continued or modified based upon clinical and laboratory findings.

Multiple Myeloma

In combination with dexamethasone: 25 mg orally once a day on Days 1 to 21 of repeated 28-day cycles
Maintenance therapy following autologous hematopoietic stem cell transplantation (auto-HSCT): 10 mg once a day continuously (Days 1 to 28 of repeated 28-day cycles) for 3 cycles, then increase to 15 mg once a day if tolerated.

Duration of Therapy (both indications) – Until disease progression or unacceptable toxicity.

Lymphoma

25 mg orally once a day on Days 1 to 21 of repeated 28-day cycles.
Duration of Therapy Until disease progression or unacceptable toxicity; treatment is continued, modified, or discontinued based upon clinical and laboratory findings.

Side Effects of Lenalidomide

The most common

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More common

Fast or irregular heartbeat
fever
Back pain
dizziness
headache
increased cough
Acid or sour stomach
decreased appetite
Agitation
chest congestion
chest pain
cold sweats
confusion
decreased sexual ability or desire
heartburn
pain or tenderness around the eyes and cheekbones
problems with urinating

Less common

Abnormal dreams
change in sense of taste
congestion
discouragement, feeling sad, or empty
drugged feeling
fast or irregular breathing
feeling of unreality
headache, severe and throbbing
increased appetite
itching of the vagina or genital area
itching, pain, redness, or swelling of the eye or eyelid
lack of emotion
loss of interest or pleasure

Drug Interactions of Lenalidomide

Lenalidomide may interact with following drugs ,supplyments & may decrease the efficacy of drugs

antipsychotic medications (e.g., chlorpromazine, haloperidol, olanzapine, quetiapine, risperidone)
barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
beta-blockers (e.g., carvedilol, metoprolol, propranolol)
bupropion
captopril
celecoxib
clopidogrel
abatacept
bisphosphonates (e.g., alendronate, risedronate)
canakinumab
clozapine
diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, nateglinide, rosiglitazone)
domperidone
glucosamine
heparin
ketoconazole
losartan
low molecular weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
macrolide antibiotics (e.g., clarithromycin, erythromycin)
MAO inhibitors (e.g., linezolid, moclobemide, phenelzine, selegiline, tranylcypromine)
mirabegron
multivitamins/minerals
muscle relaxants (e.g., baclofen, cyclobenzaprine, methocarbamol, orphenadrine, tizanidine)
nonsteroidal anti-inflammatory medications (NSAIDs; diclofenac, ibuprofen, naproxen)
omega-3 fatty acids
estrogens and progestins (such as those found in birth control pills and hormone replacement therapies)
tocilizumab
trastuzumab
pentoxifylline
quinolone antibiotics (e.g., levofloxacin, moxifloxacin)
seizure medications (e.g., carbamazepine, clobazam, felbamate, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide)
serotonin/norepinephrine reuptake inhibitors (SNRIs e.g., desvenlafaxine, duloxetine, venlafaxine)
other selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, sertraline)
5-HT3 antagonists (e.g., granisetron, ondansetron)
tamsulosin
tapentadol
thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
tramadol
tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine, desipramine)
tyrosine kinase inhbitors (e.g., imatinib, lapatinib, pazopanib, sunitinib)
vitamin E
warfarin

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Pregnancy & Lactation of Lenalidomide

FDA Pregnancy Category X

Pregnancy

This medication must not be used during pregnancy because of the potential for it to cause serious birth defects. Women who take lenalidomide must use 2 methods of birth control during treatment with lenalidomide and for at least 4 weeks after treatment has stopped. Your doctor may ask you to do a pregnancy test before starting lenalidomide. If you become pregnant while taking lenalidomide, contact your doctor immediately.

Men who take lenalidomide must use a latex condom during sexual encounters with women who can become pregnant. They must continue to use a condom for at least 4 weeks after treatment has stopped.

Lactation

The safety of taking lenalidomide while breastfeeding has not been determined. It is not known if lenalidomide passes into breast milk. Because a baby may be seriously harmed if exposed to this medication, breastfeeding mothers should not use this medication.