Lenalidomide

Lenalidomide Uses, Dosage, Side Effects, Food Interaction and all others data.

Lenalidomide, a thalidomide analogue, is an immunomodulatory agent w/ antiangiogenic and antineoplastic property. It inhibits proinflammatory cytokines secretion, increases interleukin-2 and interferon-γ secretion, and increases cytolytic T-cell and natural killer cell response. It also inhibits the growth of myeloma cells by inducing cell cycle arrest and cell death.

In hematological malignancies, the immune system is deregulated in the form of altered cytokine networks in the tumour microenvironment, defective T cell regulation of host-tumour immune interactions, and diminished NK cell activity. Lenalidomide is an immunomodulatory agent with antineoplastic, antiangiogenic, and anti-inflammatory properties. Lenalidomide exerts direct cytotoxicity by increasing apoptosis and inhibiting the proliferation of hematopoietic malignant cells. It delays tumour growth in nonclinical hematopoietic tumour models in vivo, including multiple myeloma. Lenalidomide also works to limit the invasion or metastasis of tumour cells and inhibits angiogenesis.

Lenalidomide also mediates indirect antitumour effects via its immunomodulatory actions: it inhibits the production of pro-inflammatory cytokines, which are implicated in various hematologic malignancies. Lenalidomide enhances the host immunity by stimulating T cell proliferation and enhancing the activity of natural killer (NK) cells. Lenalidomide is about 100–1000 times more potent in stimulating T cell proliferation than thalidomide. In vitro, it enhances antibody-dependent cell-mediated cytotoxicity (ADCC), which is even more pronounced when used in combination with rituximab. Due to its anti-inflammatory properties, lenalidomide has been investigated in the context of inflammatory and autoimmune diseases, such as amyotrophic lateral sclerosis.

Trade Name Lenalidomide
Availability Prescription only
Generic Lenalidomide
Lenalidomide Other Names Lenalidomida, Lenalidomide
Related Drugs prednisone, methotrexate, dexamethasone, rituximab, pyridoxine, Rituxan, Revlimid, cyclophosphamide, imatinib, Gleevec
Weight 10mg, 15mg, 2.5mg, 20mg, 25mg, 5mg
Type Oral capsule
Formula C13H13N3O3
Weight Average: 259.2606
Monoisotopic: 259.095691297
Protein binding

In vitro, about 30% of lenalidomide was bound to plasma proteins.

Groups Approved
Therapeutic Class Immunosuppressant
Manufacturer
Available Country United States
Last Updated: September 19, 2023 at 7:00 am
Lenalidomide
Lenalidomide

Uses

Lenalidomide is a thalidomide analogue used for the treatment of patients with:

  • Multiple myeloma (MM), in combination with dexamethasone
  • MM, as maintenance following autologous hematopoietic stem cell transplantation (auto-HSCT)
  • Transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities
  • Mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib

Limitations of Use: Lenalidomide is not used and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

Lenalidomide is also used to associated treatment for these conditions: Chronic Lymphocytic Leukemia (CLL) - Refractory, Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Multiple Myeloma (MM), Myelodysplastic Syndrome, Refractory Diffuse Large B Cell Lymphoma, Light chain amyloidosis

How Lenalidomide works

Lenalidomide is a drug with multiple mechanisms of action. Lenalidomide exerts immunomodulating effects by altering cytokine production, regulating T cell co-stimulation, and enhancing the NK cell-mediated cytotoxicity. Lenalidomide directly inhibits the cullin ring E3 ubiquitin ligase complex: upon binding to cereblon, a substrate adaptor of the complex, lenalidomide modulates substrate specificity of the complex to recruit substrate proteins of the ligase, including Ikaros (IKZF1), Aiolos (IKZF3), and CK1α. These substrates are then tagged for ubiquitination and subsequent proteasomal degradation. IKZF1 and IKZF3 are B-cell transcription factors that are essential for B-cell differentiation and survival of malignant cells. IKZF3 also regulates the expression of interferon regulatory factor 4 (IRF4), which is a transcription factor that regulates the aberrant myeloma-specific gene. The immunomodulatory actions of lenalidomide can be partly explained by the degradation of IKZF3, since it is a repressor of the interleukin 2 gene (IL2): as lenalidomide decreases the level of IKZF3, the production of IL-2 increases, thereby increasing the proliferation of natural killer (NK), NKT cells, and CD4+ T cells. Lenalidomide inhibits the production of pro-inflammatory cytokines TNF-α, IL-1, IL-6, and IL-12, while elevating the production of anti-inflammatory cytokine IL-10. Lenalidomide acts as a T-cell co-stimulatory molecule that promotes CD3 T-cell proliferation and increases the production of IL-2 and IFN-γ in T lymphocytes, which enhances NK cell cytotoxicity and ADCC. It inhibits the expression and function of T-regulatory cells, which are often overabundant in some hematological malignancies.

Lenalidomide directly exerts antitumour effects by inhibiting the proliferation and inducing apoptosis of tumour cells. Lenalidomide triggers the activation of pro-apoptotic caspase-8, enhances tumour cell sensitivity to FAS-induced apoptosis, and downregulates NF-κB, an anti-apoptotic protein. Independent of its immunomodulatory effects, lenalidomide mediates anti-angiogenic effects by inhibiting angiogenic growth factors released by tumour cells, such as vascular endothelial growth factor (VEGF), basic fibroblastic-growth factor (BFGF), and hepatocyte-growth factor. In vitro, lenalidomide inhibits cell adhesion molecules such as ICAM-1, LFA-1, β2 and β3 integrins, as well as gap-junction function, thereby preventing metastasis of malignant cells.

Dosage

Lenalidomide dosage

Multiple myeloma combination therapy: 25 mg once daily orally on Days 1-21 of repeated 28-day cycles. Refer to section 14.1 for dexamethasone dosing

Multiple myeloma maintenance therapy following autologous hematopoietic stem cell transplantation: 10 mg once daily continuously on Days 1-28 of repeated 28-day cycles

Myelodysplastic syndromes: 10 mg once daily

Mantle cell lymphoma: 25 mg once daily orally on Days 1-21 of repeated 28-day cycles

Renal impairment: Adjust starting dose based on the creatinine clearance value

Side Effects

Deep vein thrombosis, MI, pulmonary embolism; pruritus, skin hyperpigmentation, hyperhidrosis, dry skin, peripheral oedema, GI disturbances, resp distress, interstitial pneumonitis, cough, fatigue, vertigo, pyrexia, dyspnoea, pancreatitis, CVA, alopecia, electrolyte disturbances, infections (e.g. herpes and pneumonia). Eye disorders (e.g. cataracts, blurred vision, irritation and loss of vision). Musculoskeletal effects (e.g. arthralgia, myalgia, muscle cramps, myopathy and musculoskeletal pain).

Toxicity

The lowest lethal dose (LDLo) in rats is >2000 mg/kg following oral administration and >40 mg/kg following intravenous administration. The oral Lowest published toxic dose (TDLo) in humans is 9 mg/kg/4W (intermittent).

There is limited clinical experience in managing lenalidomide overdose. In single-dose studies, healthy subjects have been exposed to doses up to 400 mg. In clinical trials, the dose-limiting toxicity was neutropenia and thrombocytopenia. Toxicities associated with lenalidomide, some leading to fatality, include embryo-fetal toxicity, neutropenia, thrombocytopenia, venous (deep vein thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke), serious adverse cardiovascular reactions, second primary malignancies, hepatotoxicity, severe cutaneous reactions, tumour lysis syndrome, tumour flare reaction, hypothyroidism, and hyperthyroidism.

Precaution

Pregnancy test is required prior initiation of therapy and should commence contraceptive measures following negative result. Pregnancy test must be repeated at a regular interval during therapy. History of thrombosis; smokers; patients with HTN, hyperlipidaemia, high tumour burden. Renal impairment. Elderly.

Interaction

May increase risk of thrombosis with erythropoietic agents. May increase plasma concentration of digoxin, ketoconazole, itraconazole, ciclosporin, verapamil, quinidine, clarithromycin.

Food Interaction

  • Take at the same time every day. Skip the missed dose if it has been more than 12 hours since your regular time.
  • Take with or without food. High-fat meals decrease absorption, but not to a clinically significant extent.

Lenalidomide Disease Interaction

Moderate: renal impairment, thromboembolic events, anemia

Volume of Distribution

In healthy male subjects, the apparent volume of distribution was 75.8 ± 7.3 L.

Elimination Route

Following oral administration, lenalidomide is rapidly absorbed with high bioavailability. It has a Tmax ranging from 0.5 to six hours. Lenalidomide exhibits a linear pharmacokinetic profile, with its AUC and Cmax increasing proportionally with dose. Multiple dosing does not result in drug accumulation. In healthy male subjects, the Cmax was 413 ± 77 ng/ml and the AUCinfinity was 1319 ± 162 h x ng/ml.

Half Life

In healthy subjects, the mean half-life of lenalidomide is three hours in the clinically relevant dose range (5–50 mg). Half-life can range from three to five hours in patients with multiple myeloma, myelodysplastic syndromes, or mantle cell lymphoma.

Clearance

The renal clearance of lenalidomide exceeds the glomerular filtration rate. In healthy male subjects, the oral clearance was 318 ± 41 mL/min.

Elimination Route

Lenalidomide is eliminated predominantly via urinary excretion in the unchanged form. Following oral administration of 25 mg of radiolabeled lenalidomide in healthy subjects, about 90% of the dose (4.59% as metabolites) was eliminated in urine and 4% of the dose (1.83% as metabolites) was eliminated in feces within ten days post-dose. Approximately 85% of the dose was excreted as lenalidomide in the urine within 24 hours.

Pregnancy & Breastfeeding use

Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Contraindication

Pregnancy: Lenalidomide can cause fetal harm when administered to a pregnant female. Limb abnormalities were seen in the offspring of monkeys that were dosed with lenalidomide during organogenesis. This effect was seen at all doses tested. Due to the results of this developmental monkey study, and lenalidomide’s structural similarities to thalidomide, a known human teratogen, lenalidomide is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus

Severe Hypersensitivity Reactions: Lenalidomide is contraindicated in patients who have demonstrated severe hypersensitivity

Special Warning

Renal Impairment-

Myelodysplastic disease:

  • Moderate: 5 mg once daily.
  • Severe (not requiring dialysis): 5 mg every other day.
  • End-stage renal disease: 5 mg 3 times/wk after dialysis.

Multiple myeloma:

  • Moderate: 10 mg once daily may be increased to 15 mg once daily after 2 cycles if needed.
  • Severe (not requiring dialysis): 15 mg every other day, may be increased to 10 mg once daily if needed.
  • End-stage renal disease: 5 mg once daily after dialysis.

Storage Condition

Store at 20 to 25° C; excursions permitted to 15 to 30° C

Innovators Monograph

You find simplified version here Lenalidomide

Lenalidomide contains Lenalidomide see full prescribing information from innovator Lenalidomide Monograph, Lenalidomide MSDS, Lenalidomide FDA label

FAQ

What is Lenalidomide used for?

Lenalidomide is used to treat various types of cancers. It works by slowing or stopping the growth of cancer cells. Lenalidomide is also used to treat anemia in patients with certain blood/bone marrow disorders.

How safe is Lenalidomide?

Lenalidomide is effective and safe for the treatment of patients with relapsed multiple myeloma and very severe renal impairment.

How does Lenalidomide work?

Lenalidomide works in several ways it blocks the development of abnormal cells, prevents the growth of blood vessels within tumours and also stimulates specialised cells of the immune system to attack the abnormal cells.

What are the common side effects of Lenalidomide?

The most common side effects of Lenalidomide include:

  • diarrhea.
  • rash.
  • nausea.
  • constipation.
  • tiredness or weakness.
  • fever.
  • itching.

Is Lenalidomide safe during pregnancy?

Lenalidomide can cause severe, life-threatening birth defects or death of a baby if the mother or the father is taking this medicine at the time of conception or during pregnancy.

Is Lenalidomide safe during breastfeeding?

You should not breastfeed while using Lenalidomide.

Can I drink alcohol with Lenalidomide?

Drinking alcohol during your treatment may increase some side effects and make your medication less effective. Speak to your health care team about smoking and drinking alcohol while on treatment.

When is the best time to take Lenalidomide?

Lenalidomide can be taken at any time of the day but it is best to take it at approximately the same time each day.empty stomach either one hour before or two hours after food.

Does Lenalidomide make me sleepy?

Lenalidomide may cause fatigue at the start of treatment but can improve as the body learns to tolerate the drug.Lenalidomide may also cause anaemia.

Does Lenalidomide cause hair loss?

Hair loss could be a side effect of other medications you may be taking to treat your cancer.

What does Lenalidomide do to your body?

Lenalidomide affects the immune system. It promotes immune responses to help slow tumor growth. Lenalidomide is used to treat multiple myeloma , either in combination with another medicine or after stem cell transplant.

Does Lenalidomide lower my immune system?

Lenalidomide is known to have various effects on the immune system, which may contribute to its therapeutic effect.Lenalidomide may also alter the production and activity of cytokines  involved in the growth and survival of certain cancer cells.

Does Lenalidomide cause weight gain?

Lenalidomide can causes rapid weight gain also with other side effcts.

Can I take Lenalidomide long time ?

Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

How long can my stay on Lenalidomide?

The median duration of Lenalidomide maintenance was 21 months, with 25% of patients receiving <11 months of maintenance and 25% with treatment longer than 31 months. The treatment had been discontinued in 64.7% of the patients when the analysis was performed.

Can Lenalidomide cure multiple myeloma?

Lenalidomide works well in treating multiple myeloma.

When can I stop taking Lenalidomide?

after three years of Lenalidomide maintenance and getting a complete response, if negative, it is a good idea to stop therapy.

When can I stop taking Lenalidomide?

You should not take Lenalidomide if you have CLL unless you are participating in a controlled clinical trial.

Is Lenalidomide toxic?

Lenalidomide is the major dose-limiting toxicity, which is not the case with thalidomide.

What happens if I miss a dose of Lenalidomide?

Take the missed dose as soon as you remember. If you are more than 12 hours late, skip the missed dose. Do not take extra medicine to make up the missed dose.

Can I overdose on Lenalidomide?

If you take too much Lenalidomide or overdose, call your healthcare provider or poison control center right away.

*** Taking medicines without doctor's advice can cause long-term problems.
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