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.
Indications of Lenalidomide
- Multiple Myeloma
- 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
- 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
- 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
- 10 mg orally once a day
Duration of Therapy: Treatment is continued or modified based upon clinical and laboratory findings.
- 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.
- 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
- Upper respiratory tract infection
- Chest pain
- A headache
- Joint painPain
- Nausea and vomiting
- Severe stomach ache
- epigastric pain,
- a headache,
- fainting, fast or pounding heartbeats.
- Fast or irregular heartbeat
- Back pain
- increased cough
- Acid or sour stomach
- decreased appetite
- chest congestion
- chest pain
- cold sweats
- decreased sexual ability or desire
- pain or tenderness around the eyes and cheekbones
- problems with urinating
- Abnormal dreams
- change in sense of taste
- 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)
- bisphosphonates (e.g., alendronate, risedronate)
- diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, nateglinide, rosiglitazone)
- low molecular weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- MAO inhibitors (e.g., linezolid, moclobemide, phenelzine, selegiline, tranylcypromine)
- 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)
- 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)
- thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
- tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine, desipramine)
- tyrosine kinase inhbitors (e.g., imatinib, lapatinib, pazopanib, sunitinib)
- vitamin E
FDA Pregnancy Category X
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.
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.