All about Lidmed (Lenalidomide) capsules

Name of Medicine:- Lidmed

Composition:- Lenalidomide

Chemical Formula:- C13H13N3O3

Description:- Lidmed is an effective formulation of Lenalidomide, available as capsules in the strengths of 10mg and 25mg. 

What is Lidmed? 

Lidmed, comprising Lenalidomide, is an anti-cancer formulation used to treat certain types of cancers. This regimen works by slowing or stopping the multiplication of cancer cells in the body. It tends to target the specific proteins responsible for the growth of cancer cells. 

Clinical Relevance

It is a prescription medicine used in the treatment of patients suffering from Multiple Myeloma (MM) who have received at least one prior therapy. It is also used to treat Myelodysplastic Syndromes (MDS). In patients with MM, it is generally prescribed in combination with Dexamethasone. 

• Multiple Myeloma 

• Myelodysplastic Syndromes 

• Mantle Cell Lymphoma 

Clinical Pharmacology 

Pharmacodynamics 

In hematological malignancies, the system is deregulated within the sort of altered cytokine networks within the tumor microenvironment, defective T cell regulation of host-tumor immune interactions, and diminished NK cell activity. The active compound of Lidmed is an immunomodulatory agent with properties including antineoplastic, antiangiogenic, and anti-inflammatory. It tends to exert direct cytotoxicity by raising apoptosis and working to inhibit the proliferation of hematopoietic malignant cells. It delays tumor growth in nonclinical hematopoietic tumor models in vivo, including myeloma. Lenalidomide also works to limit the invasion or metastasis of tumor cells and inhibits angiogenesis.

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

Mechanism of Action 

Lenalidomide (Lidmed) may be a drug with a number of mechanisms of action. The compound tends to exert immunomodulating effects by altering cytokine production, regulation of T cell co-stimulation, and enhancement of the NK cell-mediated cytotoxicity. It directly works to inhibit the cullin ring E3 ubiquitin ligase complex: upon binding to a substrate adaptor of the complex known as cereblon, the compound modulates substrate specificity of the complex to recruit substrate proteins of the ligase, including Ikaros, Aiolos, and CK1α. Such substrates are then tagged for ubiquitination and subsequent proteasomal degradation. B-cell transcription factors that are essential for B-cell differentiation and survival of malignant cells ARE IKZF1 and IKZF3. IKZF3 also regulates the expression of interferon regulatory factor 4 (IRF4), which may be a transcription factor that regulates the aberrant myeloma-specific gene. The immunomodulatory actions of Lidmed capsules are often partly explained by the degradation of IKZF3 since it’s a repressor of the interleukin 2 gene (IL2): as Lenalidomide decreases the extent of IKZF3, the IL-2 assembly increases, side by side raising the proliferation of natural killer (NK), NKT cells, and CD4+ T cells. Lenalidomide inhibits the assembly of pro-inflammatory cytokines TNF-α, IL-1, IL-6, and IL-12, while elevating the assembly of anti-inflammatory cytokine IL-10. Lenalidomide acts as a T-cell co-stimulatory molecule that promotes CD3 T-cell proliferation and increases the assembly of IL-2 and IFN-γ in T lymphocytes, which reinforces NK cell cytotoxicity and ADCC. It inhibits the expression and performance of T-regulatory cells, which are often overabundant in some hematological malignancies.

Metabolism 

This compound isn’t subject to extensive hepatic metabolism including CYP enzymes and metabolism contributes to a really minor extent to the clearance of Lenalidomide in humans. Lenalidomide undergoes hydrolysis in human plasma to make 5-hydroxy-Lenalidomide and N-acetyl-Lenalidomide. The unchanged compound (Lidmed) is that the predominant circulating drug form, with metabolites accounting for fewer than five percent of the parent drug levels within the circulation.

Clinical Trials 

Lenalidomide may be a novel immunomodulatory agent with a singular dual mechanism of action: its tumoricidal effect results in direct tumor necrobiosis, and its immunomodulatory effect keeps the tumor arrested. phase III clinical trial clinical trials have demonstrated that in patients with relapsed/refractory myeloma (MM), Lenalidomide together with dexamethasone offers high clinical response rates and improved time to disease progression, PFS (progression-free survival), and OS (overall survival) in comparison with Dexamethasone alone. In patients with newly diagnosed MM, the mixture of Lenalidomide and low-dose dexamethasone prolonged survival compared with Lenalidomide and standard high-dose dexamethasone. The advantages of Lenalidomide-based treatment regimens are often optimized by initiating treatment early within the disease course, either as a frontline treatment or initially relapse. Lenalidomide is usually well tolerated; the first adverse events are myelosuppression and venous thromboembolic complications. These adverse events emerge early within the course of treatment and may be managed using standard interventions like granulocyte colony-stimulating factor, dose reduction, and thromboprophylaxis. The mixture of Lenalidomide and dexamethasone is effective and usually well-tolerated in patients with renal impairment as long as creatinine clearance level and adverse events are carefully monitored and therefore the starting dose of lenalidomide is adjusted appropriately. Early results from the phase III clinical trial indicate that in patients suffering from a newly diagnosed Multiple Myeloma, continuous Lenalidomide therapy is well tolerated and related to significant improvements in PFS, that offers a replacement treatment option for patients with Multiple Myeloma – although no OS benefit has yet been seen during this setting. Lidmed-based treatment is effective across the spectrum of Multiple Myeloma disease phases, allowing the long-term management of myeloma.

Interactions 

Drug-Drug Interactions 

• Atorvastatin:- Using Lenalidomide with atorvastatin may increase the risk of a serious condition known as rhabdomyolysis (it involves the breakdown of skeletal muscle tissue) it can also cause kidney damage in some patients. Inform your medical practitioner to receive supportive care if you experience unexplained side effects like muscle pain, tenderness, or weakness during treatment with atorvastatin. 

• Certolizumab:- This medication can increase the risk of serious bacterial infections your physician will guide you if signs and symptoms occur like – fever, chills, diarrhea, sore throat, muscle aches, and shortness of breath. 

• Estrone:- Using Lenalidomide in combination with estrone may increase the risk of dangerous blood clots and it can lead to complications such as heart attack, stroke, and pulmonary embolism (blockage of an artery in the lung). Your healthcare professional will monitor you closely because the risk can increase with age, smoking, high blood pressure, or high cholesterol.

• Lomitapide:- can cause some serious and major liver problems in order to avoid effects like – fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, and abdominal pain your physician may suggest you avoid the consumption of alcohol during the time of treatment. 

Drug-Disease Interactions

• Thromboembolic events:- Patients receiving Lenalidomide may experience thromboembolic events (deep venous thrombosis and pulmonary embolism) and arterial thrombosis. Your healthcare professional may advise you to avoid factors like – smoking, hyperlipidemia, and hypertension to minimize the risk. 

• Anemia:- This medication can cause anemia and patients with these preexisting conditions should be closely monitored by their healthcare professional to check the blood cell counts. 

• Renal impairment:- Adjustment and alteration of the dose is required in patients suffering from moderate or severe kidney-related disease. 

Drug Category

• Angiogenesis Inhibitors:- These medications stop the division and multiplication of new blood vessels that tumors need to grow in the body. They are powerful cancer-fighting agents. 

• Antineoplastic Agents:- Effective use of antineoplastic agents depends on an understanding of basic principles of cancer drug actions, toxicities, and drug handling safety.

• Immunosuppressive Agents:- These agents suppress the strength of the body’s immune system. Immunosuppressant drugs are used for the treatment of autoimmune diseases.

Dosage and Administration 

Recommended Dose:- Lidmed capsule should be administered orally with or without food every day. The capsules should be swallowed as a whole with water and should not be opened or chewed. The recommended dose of Lidmed for patients with Multiple Myeloma is 25 mg once daily on days 1-21 of 28-day cycles (repeated). 

Overdosage:- In case of an overdose, the patients might feel a number of symptoms that could cause fetal harm. Therefore, it is necessary to consult a qualified physician in order to receive supportive care and regular monitoring as per the medical condition.

Dose Adjustments:- Dose adjustments for Hematologic Toxicities during treatment of Multiple Myeloma using Lidmed capsules may be needed. These modifications depend upon the response of the body to the medicine. 

Adverse Reactions 

Some adverse reactions may occur after the administration of Lidmed capsules and even after discontinuing the use of Lidmed. However, many patients do not experience any side effects at all. This depends highly upon the patient’s medical history and the reaction of the body. The side effects of any medicine should be discussed with the doctor before starting the treatment. 

Gastrointestinal disorders may occur in some patients including diarrhea, dyspepsia (indigestion), constipation, nausea, vomiting, chest pain, abdominal pain (pain in the belly), and incontinence (involuntary leakage of urine). 

Lidmed capsules may cause rapid destruction of cancerous cells in the body. To lower your risk of dehydration and other side effects like back pain, painful urination, blood in urine, and change in the amount of urine, your doctor will recommend you to drink plenty of fluids. 

The use of Lenalidomide may lead to serious liver disease that may include reactions like nausea, vomiting (that doesn’t stop), loss of appetite, stomach pain, and yellowing eyes/skin. These effects may cause fetal or life-threatening conditions for some patients.

Severe allergic reactions such as skin rash, swelling, itching, pain, shortness of breath, and severe dizziness may occur in some patients administering Lenalidomide. Such reactions need to be monitored and discussed for proper management and prevention. 

Administration of Lidmed capsules may lead to certain signs or symptoms of a stroke including chest pain (spreading to the arms, neck, jaw, back, or stomach), feeling sweaty, shortness of breath, severe headache or confusion, and numbness. 

Certain neurological and psychological side effects may occur such as depression, mood changes, increased thirst/urination, tremors (shaking), slow/fast/irregular heartbeat, unexpected weight gain, and loss of interest. 

Warnings and Precautions

General Warnings 

• Lidmed (Lenalidomide) can pass into human semen. Males, who receive Lidmed therapy, should use a latex or synthetic condom during sexual intercourse with a pregnant female or a female having child-bearing potential. 

• It is important to make your doctor aware of any reaction/effect you experience after administering the capsules. 

• It is advised to not donate sperms during the course of Lidmed till at least 4 weeks after discontinuing the medication. 

Special Population

• Pregnant Women
  Lidmed can cause fetal harm when administered to a pregnant female. This medication is contraindicated to patients who are pregnant and planning to become pregnant. Women having child-bearing potential are advised to start using proper contraceptive measures 28 days prior to the course of Lidmed.

• Nursing Mothers
  It is not known whether Lidmed is excreted in human milk or not. Since most other medicines are excreted in breast milk, it is important to take precautions in order to avoid adverse conditions. Therefore, breastfeeding should be discontinued during the course of Lidmed. 

• Pediatric Use
  The safety and efficacy of Lidmed capsules have not been established in patients below the age of 18. 

• Geriatric Use
  In patients, aged 86 and below, Lenalidomide has been used in several clinical trials for Multiple Myeloma. Since geriatrics are more likely to develop renal impairment, regular monitoring and care may be needed. 

• Renal Impairment
  Since Lidmed is primarily excreted unchanged by the kidneys, dose adjustments should be done in order to provide appropriate drug exposure in patients suffering from moderate or severe renal impairment. 

• Hepatic Impairment
  No studies have been initiated in patients suffering from hepatic impairment. Please consult a qualified medical practitioner. 

Packaging and Storage

Lidmed is available as hard-capsules packed in high-density polyethylene bottles for oral use. Store this medicine at 20°C – 25°C; excursions permitted to 15°C – 30°C. Keep Lidmed capsules away from the reach of children and pets. Protect them from direct heat, light, and moisture. Proper care should be exercised while handling this medicine. Women who are pregnant should not handle Lidmed capsules without protection (gloves). Know the procedure to dispose of the used and expired bottles of medicines from your nearest pharmacist.