Lenalidomide

About Lenalidomide

• On February 22, 2017, the U.S. Food and Drug Administration approved lenalidomide for maintenance therapy in patients with multiple myeloma following autologous stem cell transplant. 
• Additionally, lenalidomide is approved for use in combination with dexamethasone for the treatment of patients with multiple myeloma, including newly diagnosed patients who are ineligible for autologous stem cell transplant. 
• Lenalidomide is also indicated for the treatment of transfusion-dependent anemia due to low- or intermediate-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality, with or without additional cytogenetic (alterations or abnormalities in the structure or number of chromosomes within cells) abnormalities.
• The mechanism of lenalidomide involves the modulation of the substrate specificity of the CRL4CRBN E3 ubiquitin ligase. In multiple myeloma, it induces the ubiquitination of IKZF1 and IKZF3 by CRL4CRBN. Subsequent proteasomal degradation of these transcription factors kills multiple myeloma cells.

Strength: 

Lenalidomide capsules are available in strengths of  2.5 mg, 5 mg, 10 mg, 15 mg, and 25 mg. 

Recommended Dosage:

Patients should be instructed to take Lenalidomide once daily at approximately the same time each day, with or without food, as directed by their healthcare provider. It’s important not to open, break, or chew the capsules, as this may affect the effectiveness of the medication. Instead, this medicine should be swallowed whole with water to ensure proper absorption and dosage delivery.

Multiple Myeloma

• The initial recommended dose of Lenalidomide is 25 mg taken once daily on Days 1-21 within each 28-day treatment cycle. 
• Dexamethasone is recommended at a dose of 40 mg taken once daily on Days 1-4, 9-12, and 17-20 for the first 4 cycles of therapy, and subsequently at 40 mg taken once daily on Days 1-4 every 28 days. 
• The treatment regimen may be adjusted based on clinical and laboratory assessments.

Myelodysplastic Syndromes: 

• The recommended initial dose of Lenalidomide is 10 mg administered daily. Adjustments to treatment are made in response to clinical and laboratory assessments.
• For patients who begin with a 10 mg dose and develop thrombocytopenia, dosage adjustments  for the medicine are determined based on your condition by your healthcare provider. 

Important:

Before initiating treatment, it’s crucial to inform your doctor about all your preexisting conditions and other relevant health histories. If you experience any adverse effects, seek medical attention immediately. Patients should be advised that if they miss a dose of Lenalidomide, they have a window of up to 12 hours after their usual dosing time to take it. However, if more than 12 hours have passed, they should skip the missed dose for that day. The following day, they should resume taking the medicine at their regular time. Patients should be cautioned against taking double doses to compensate for a missed dose.

Caution must be taken when handling Lenalidomide. The capsules should not be opened or crushed under any circumstances. In the event that powder from a capsule comes into contact with the skin, it should be promptly and thoroughly washed off with soap and water. Similarly, if the medicine comes into contact with mucous membranes, they should be thoroughly flushed with water. These precautions are essential to minimize the risk of unintended exposure and ensure safe handling of the medication.

Warnings & Precaution:

• Lenalidomide, an analog of thalidomide, has been associated with limb abnormalities in developmental monkey studies, reminiscent of the birth defects caused by thalidomide in humans. When used during pregnancy, it may lead to birth defects or fetal death.
• To mitigate these risks, it is imperative to exclude pregnancy before initiating treatment with the medicine. Females of childbearing potential must undergo two negative pregnancy tests before starting treatment and must use two reliable methods of contraception or consistently abstain from heterosexual intercourse during treatment and for four weeks after treatment cessation.
• It is also associated with hematologic toxicity, particularly neutropenia, and thrombocytopenia, necessitating dose adjustments or interruptions. Patients with del 5q myelodysplastic syndromes should have their complete blood counts monitored weekly for the first 8 weeks and monthly thereafter.
• Furthermore, there is a significantly elevated risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in multiple myeloma patients receiving the medicine with dexamethasone. Both physicians and patients should be vigilant for signs and symptoms of thromboembolism.
• Allergic reactions, including hypersensitivity, angioedema, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported with this use. In severe cases, these reactions may be fatal, necessitating discontinuation of the drug without resumption.
• Additionally, fatal instances of tumor lysis syndrome (TLS) have been reported during the treatment, particularly in patients with high tumor burden. Thus, patients at risk of TLS should be closely monitored, and appropriate precautions should be taken.
• Serious tumor flare reactions have also occurred during investigational use of this medicine for chronic lymphocytic leukemia and lymphoma.
• Moreover, higher incidences of second primary malignancies (SPM) were observed in controlled trials of multiple myeloma patients receiving the medicine. Therefore, the risk-benefit ratio of the treatment should be carefully evaluated in patients, including those with lactose intolerance, as lenalidomide capsules contain lactose.

Common Lenalidomide Side Effects:

• Thrombocytopenia
• Neutropenia
• Diarrhea
• Pruritus
• Rash
• Fatigue
• Constipation
• Nausea
• Nasopharyngitis
• Arthralgia
• Pyrexia
• Back pain
• Peripheral edema
• Cough
• Dizziness
• Headache
• Muscle cramp
• Dyspnea
• Pharyngitis
• Epistaxis

Use in Specific Population

• Lenalidomide is strictly contraindicated in pregnant women or those who may become pregnant due to the potential risk of fetal harm, as adequate studies in pregnant women are lacking. 
• Females of childbearing potential must ensure effective contraception for at least 28 days before initiating the therapy, throughout treatment, and for 28 days following therapy discontinuation. 
• The excretion of the medicine in human milk remains uncertain, and therefore, nursing mothers should weigh the importance of the medication against potential risks to the infant. 
• Safety and efficacy in pediatric patients under 18 years old have not been established, while caution is advised in geriatric patients, especially those with decreased renal function, requiring regular monitoring. 
• Although no specific dose adjustments are suggested for hepatic impairment, renal insufficiency warrants dose modification to optimize safety and efficacy, emphasizing the importance of renal function monitoring in such patients.

Storage and Handling 

Store Lenalidomide capsules at the temperature of 25°C (77°F), with excursions permitted to 15-30°C (59-86°F). Do not freeze the medicine. Keep the medicine away from pets and children. 

• 28 bottles each of 2.5 mg, 5 mg, and 10 mg. 
• 21 bottles each of 15 mg and 25 mg. 
• 100 bottles each of 2.5 mg, 5 mg, 10 mg, 15 mg and 25 mg.