Lenalidomide (Revlimid) is an immunomodulatory drug that is closely related to thalidomide. It is used in the treatment of patients with blood-related malignancies including multiple myeloma and lymphoma.

Lenalidomide Uses:

• Follicular lymphoma:

• • It is used to treat formerly treated follicular lymphoma in adults in combination with rituximab product.
• Mantle cell lymphoma:
  • Used to treat mantle cell lymphoma which has relapsed or advanced after 2 treatments, one of which consists of bortezomib.
• Marginal zone lymphoma:
  • In adults, it is used to treat marginal zone lymphoma that has relapsed (in combination with rituximab).
• Multiple myeloma:
  • In adults it is used to treat multiple myeloma in combination with dexamethasone; autologous hematopoietic stem cell transplantation followed by upkeep treatment.
• Myelodysplastic syndromes:
  • In adults, it is used to treat transfusion-dependent anemia due to low or intermediate 1 risk myelodysplastic syndromes (MDS) associated with a deletion 5q (del 5q) cytogenetic abnormality with or without added cytogenetic anomalies.
  • Limitations of use: It is not recommended in the treatment of CLL (outside clinical trials).
• Off Label Use of Lenalidomide in Adults:
  • Multiple myeloma, newly detected.
  • Prolonged lymphocytic leukemia, relapsed or stubborn.
  • Systemic light chain amyloidosis
  • Myelodysplastic syndrome without deletion 5q
  • Diffuse large B-cell lymphoma relapsed or stubborn.

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Lenalidomide (Revlimid) Dose in Adults:

Lenalidomide (Revlimid) Dose in the treatment of relapsed or refractory Chronic lymphocytic leukemia,  (off-label):

• Oral: 10 mg one time a day starting on the 9th day of the first cycle; administer continuously in combination with cyclic rituximab.

Lenalidomide (Revlimid) Dose in the treatment of relapsed or refractory diffuse large B-cell lymphoma  (off-label):

• Oral: 25 mg one time each day for 21 days of a 28-day treatment cycle for up to 1 year.

Lenalidomide (Revlimid) Dose in the treatment of Follicular lymphoma:

• Oral: 20 mg one time each day for 21 days of a 28-day treatment cycle (in combination with rituximab) for up to 12 cycles.

Lenalidomide (Revlimid) Dose in the treatment of Mantle cell lymphoma:

• Oral: 25 mg one time each day for 21 days of a 28-day treatment cycle; continue until disease development or undesirable toxicity.

Lenalidomide (Revlimid) Dose in the treatment of Marginal zone lymphoma:

• Oral: 20 mg one time each day for 21 days of a 28-day treatment cycle (in combination with rituximab) for up to 12 cycles.

Lenalidomide (Revlimid) Dose in the treatment of Multiple myeloma:

• Oral: 25 mg one time each day for 21 days of a 28-day treatment cycle (in combination with dexamethasone [consider a lowered dexamethasone dose in patients >75 years of age]).
• In patients not qualified for autologous stem cell transplantation, continue till disease advancement or undesirable toxicity occurs; in patients qualified for transplant, hematopoietic stem cell mobilization should occur within 4 cycles of a lenalidomide-limiting treatment.

Lenalidomide (Revlimid) Dose in the maintenance treatment of Multiple myeloma (following autologous stem cell transplant):

• Oral: 10 mg one time each day (begin after adequate hematologic recovery [ANC ≥1,000/mm³ ; platelets ≥75,000/mm³]);
• continue treatment until disease advancement or undesirable toxicity occurs. If endured well, may increase the dose to 15 mg one time a day after 3 cycles (each cycle is 28 days).

• Off-label dosing:

  • 10 mg one time each day for 21 days of a 28-day treatment cycle until relapse.

Lenalidomide (Revlimid) Dose in the treatment of newly diagnosed  Multiple myeloma (off-label combination):

• Oral: 25 mg one time each day for two weeks of a 28-day cycle (in combination with daratumumab and dexamethasone) until disease advancement or undesirable toxicity occurs or
• 25 mg once daily for 2-week cycle of a 21-day cycle (in combination with bortezomib and dexamethasone) for 8 cycles or
• 25 mg once daily for 21 days of a 28-day cycle (in combination with carfilzomib and dexamethasone) for up to 8 cycles.

Lenalidomide (Revlimid) Dose in the treatment of relapsed Multiple myeloma (off-label combinations):

• Adults:

  • Oral: 25 mg one time each day for 3 weeks of a 28-day cycle (in combination with carfilzomib and dexamethasone) until disease advancement or undesirable toxicity occurs or
  • 25 mg once daily for 21 days of a 28-day cycle (in combination with daratumumab and dexamethasone) until advancement or undesirable toxicity occurs; refer to the IMWG suggestions for Dosing in kidney damage.

Lenalidomide (Revlimid) Dose in the treatment of Myelodysplastic syndrome with deletion 5q:

• Oral: 10 mg one time a day, continue until disease advancement or undesirable toxicity occurs.

Lenalidomide (Revlimid) Dose in the treatment of Myelodysplastic syndrome, lower risk, without deletion 5q (off-label):

• Oral: 10 mg one time a day.

Lenalidomide (Revlimid) Dose in the treatment of Systemic light chain amyloidosis (off-label):

• Oral: 15 mg one time a day for 3 weeks of a 28day cycle (in combination with dexamethasone).

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Use in Children:

Not indicated.

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Pregnancy Risk Category: X

• Pregnancy is not a good time to use it.
• [US Boxed Warning] Do not use lenalidomide while pregnant
• A thalidomide analog called Lenalidomide caused limb anomalies during a study in the developmental monkeys.
• Thalidomide, a human teratogen known to cause serious and life-threatening birth abnormalities in humans, is known.
• Lenalidomide can cause birth abnormalities and fetal deaths if it is administered during pregnancy.
• Before starting lenalidomide therapy for females with reproductive potential, you should have two negative pregnancy tests.
• Females with reproductive potential should use two forms or refrain from having sex for at least one month after treatment with lenalidomide.
• It is not available under the Revlimid REMS program, which strictly regulates distribution to prevent embryo-fetal exposure.
• Only treat females with reproductive potential if they can comply with the Revlimid REMS requirements
• Reproductively-competent females must not get pregnant during therapy breaks or for 4 weeks prior to therapy.
• Females who are pregnant or have not had a full hysterectomy must use one of two forms of reliable and effective contraception: IUD, tubal ligation, condoms, diaphragm or cervical cap.
• Females with reproductive potential need to have a negative pregnancy test (sensitivity at least 50 mg/mL) within one day of starting treatment.
• This is done weekly for the first four weeks and then every four weeks thereafter.
• For missed periods, abnormal pregnancy tests, or irregular menstrual flow, Lenalidomide should be stopped immediately.
• Refer the patient to a specialist in reproductive toxicology if you become pregnant while on treatment.
• Male semen also contains lenalidomide.
• Males, including those who have been vasectomized, should use condoms during sexual contact with females during treatment and during breaks.
• Condoms can also be used for up to 4 weeks after the treatment has ended.
• Male patients shouldn't donate sperm during and after treatment.
• To monitor the outcomes of females who have been exposed to lenalidomide in pregnancy and the female partners of male patients, a pregnancy exposure registry was created.
• This allows for understanding the root cause of the pregnancy.
• You can contact the pregnancy exposure registry at 1-888-423-5436
• Patients aged 12-18 years must be accompanied by a parent or legal guardian to comply with these guidelines.
• Any suspicion of fetal exposure should go to the FDA via MedWatch (1-800-FDA-1088), and Celgene Corporation (1 888-423-5436).

Use while breastfeeding

• If lenalidomide can be found in breast milk, it is not known. 
• The manufacturer does not recommend breastfeeding due to the risk of serious adverse reactions in breastfed babies.

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Lenalidomide (Revlimid) Dose in Kidney Disease:

Note: Maintain an appropriate number of treatment days per cycle based on indication and/or protocol. Further customized (increase or decrease dose) based on endurance.

• Recommended initial dose adjustment in the manufacturer's labeling:

  • Follicular lymphoma and marginal zone lymphoma:

    • CrCl >60 mL/minute: No dosage changes required.
    • CrCl 30 to 60 mL/minute: 10 mg one time a day (may increase to 15 mg once daily after 2 cycles if tolerating treatment).
    • CrCl <30 mL/minute not requiring dialysis: 5 mg one time a day.
    • CrCl <30 mL/minute requiring dialysis: 5 mg one time a day (give after dialysis on dialysis days).

  • Mantle cell lymphoma and multiple myeloma (combination therapy with dexamethasone):

    • CrCl >60 mL/minute: No dosage modifications required.
    • CrCl 30 to 60 mL/minute: 10 mg one time a day (for multiple myeloma, may increase to 15 mg one time a day after 2 cycles if tolerating treatment).
    • CrCl <30 mL/minute not requiring dialysis: 15 mg every alternate day.
    • CrCl <30 mL/minute requiring dialysis: 5 mg one time a day (give after dialysis on dialysis days).

  • Myelodysplastic syndrome and multiple myeloma (maintenance treatment after autologous stem cell transplant):

    • CrCl >60 mL/minute: No dosage changes needed.
    • CrCl 30 to 60 mL/minute: 5 mg one time a day.
    • CrCl <30 mL/minute not requiring dialysis:5 mg one time a day.
    • CrCl <30 mL/minute requiring dialysis:5 mg one time a day (give after dialysis on dialysis days).
    • Dialysis removal: ~30% removed during a 4-hour hemodialysis session.

  • The International Myeloma Working Group (IMWG) recommendations:

    • The IMWG recommends the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (preferred) or the Dietary modifications in kidney Disease (MDRD) formula to evaluate renal function estimation in multiple myeloma patients with stable serum creatinine.

    • Combination therapy with dexamethasone:

      • CrCl ≥60 mL/minute: 25 mg one time a day (no changes necessary).
      • CrCl 30 to 59 mL/minute: 10 mg one time a day (may increase to 15 mg one time a day in the absence of toxicity).
      • CrCl 15 to 29 mL/minute: 15 mg once every alternate day; may adjust to 10 mg one time a day.
      • CrCl <15 mL/minute: 5 mg one time a day.
      • ESRD on dialysis: 5 mg one time a day.

Dose in Liver disease:

There are no dosage adjustments given in the manufacturer's labeling (it has not been studied). However, lenalidomide undergoes minimal hepatic metabolism.

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May vary based on the indication.

Common Side Effects of Lenalidomide (Revlimid):

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Fatigue
  • Dizziness
  • Headache
  • Paresthesia

• Dermatologic:

  • Pruritus
  • Skin Rash
  • Xeroderma

• Endocrine & Metabolic:

  • Weight Loss
  • Hypokalemia

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Constipation
  • Gastroenteritis
  • Decreased Appetite
  • Abdominal Pain
  • Vomiting

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Neutropenia
  • Leukopenia
  • Anemia

• Infection:

  • Influenza

• Neuromuscular & Skeletal:

  • Muscle Spasm
  • Asthenia
  • Arthralgia
  • Back Pain
  • Muscle Cramps
  • Limb Pain

• Respiratory:

  • Bronchitis
  • Nasopharyngitis
  • Cough
  • Pneumonia
  • Dyspnea
  • Pharyngitis
  • Epistaxis
  • Upper Respiratory Tract Infection
  • Rhinitis
  • Sinusitis

• Miscellaneous:

  • Fever

Less Common Side Effects Of Lenalidomide (Revlimid):

• Cardiovascular:

  • Edema
  • Hypotension
  • Hypertension
  • Chest Pain
  • Palpitations
  • Deep Vein Thrombosis
  • Pulmonary Embolism
  • Cardiac Failure

• Central Nervous System:

  • Insomnia
  • Peripheral Neuropathy
  • Hypoesthesia
  • Pain
  • Myasthenia
  • Rigors
  • Chills
  • Lethargy
  • Vertigo

• Dermatologic:

  • Night Sweats
  • Diaphoresis
  • Ecchymoses
  • Erythema Of Skin
  • Cellulitis

• Endocrine & Metabolic:

  • Dehydration
  • Hypothyroidism
  • Hypomagnesemia
  • Hypocalcemia
  • Hyponatremia

• Gastrointestinal:

  • Anorexia
  • Upper Abdominal Pain
  • Xerostomia
  • Dysgeusia
  • Loose Stools
  • Oral Herpes Simplex Infection

• Genitourinary:

  • Dysuria
  • Urolithiasis

• Hematologic & Oncologic:

  • Tumor Flare
  • Bruise
  • Lymphocytopenia
  • Febrile Neutropenia
  • Pancytopenia
  • Squamous Cell Carcinoma Of Skin
  • Granulocytopenia
  • Myelodysplastic Syndrome

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Hyperbilirubinemia

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Herpes Zoster Infection
  • Infection
  • Sepsis
  • Bacteremia

• Neuromuscular & Skeletal:

  • Myalgia
  • Swelling Of Extremities
  • Musculoskeletal Pain

• Renal:

  • Renal Failure Syndrome

• Respiratory:

  • Oropharyngeal Pain
  • Dyspnea On Exertion
  • Pleural Effusion
  • Rhinorrhea
  • Pulmonary Infection
  • Hypoxia
  • Respiratory Distress
  • Respiratory Tract Infection

• Miscellaneous:

  • Physical Health Deterioration
  • Troponin Increased In Blood Specimen

Frequency of side effects not defined:

• Cardiovascular:

  • Acute Myocardial Infarction
  • Angina Pectoris
  • Arterial Thromboembolism
  • Atrial Fibrillation (Including Exacerbation)
  • Bradycardia
  • Cardiac Disorder (Aortic Disorder)
  • Cardiogenic Shock
  • Cardiomyopathy
  • Cerebral Infarction
  • Cerebrovascular Accident
  • Ischemia
  • Ischemic Heart Disease
  • Septic Shock
  • Subarachnoid Hemorrhage
  • Superficial Thrombophlebitis
  • Supraventricular Cardiac Arrhythmia
  • Supraventricular Tachycardia
  • Tachyarrhythmia
  • Thrombosis
  • Transient Ischemic Attacks
  • Venous Thromboembolism
  • Ventricular Dysfunction

• Central Nervous System:

  • Abnormal Gait
  • Aphasia
  • Cerebellar Infarction
  • Confusion
  • Depression
  • Dysarthria
  • Falling
  • Impaired Consciousness
  • Migraine
  • Spinal Cord Compression

• Dermatologic:

  • Erythema Multiforme
  • Erythematous Rash
  • Exfoliative Dermatitis
  • Follicular Rash
  • Macular Eruption
  • Maculopapular Rash
  • Papular Rash
  • Pruritic Rash
  • Pustular Rash
  • Sweet's Syndrome

• Endocrine & Metabolic:

  • Gout
  • Gouty Arthritis
  • Graves' Disease
  • Hypernatremia
  • Hypoglycemia

• Gastrointestinal:

  • Biliary Obstruction
  • Cholecystitis (May Be Acute)
  • Clostridioides Difficile Associated Diarrhea
  • Clostridioides Difficile Colitis
  • Colonic Polyps
  • Diverticulitis Of The Gastrointestinal Tract
  • Dysphagia
  • Gastritis
  • Gastrointestinal Hemorrhage
  • Gastrointestinal Pain
  • Gastrointestinal Reflux Disease
  • Infection Of Mouth
  • Inguinal Hernia (Obstructive)
  • Intestinal Obstruction (Small Intestine)
  • Intestinal Perforation
  • Irritable Bowel Syndrome
  • Ischemic Colitis
  • Lower Abdominal Pain
  • Melena
  • Pancreatitis

• Genitourinary:

  • Abscess Of Rectum And/Or Peri-Rectal Area
  • Azotemia
  • Hematuria
  • Pelvic Pain
  • Urinary Tract Infection With Sepsis

• Hematologic & Oncologic:

  • Acquired Blood Coagulation Disorder
  • Acute Leukemia
  • Basal Cell Carcinoma Of Skin
  • Bone Marrow Depression
  • Bronchogenic Carcinoma
  • Decreased Hemoglobin
  • Hemolysis
  • Hemolytic Anemia
  • Malignant Lymphoma
  • Malignant Neoplasm Of Lung
  • Myeloid Leukemia (Acute)
  • Postprocedural Hemorrhage
  • Progression Of Cancer
  • Prostate Carcinoma
  • Rectal Hemorrhage
  • Splenic Infarction
  • Warm Antibody Immunohemolytic Anemia

• Hepatic:

  • Abnormal Hepatic Function Tests (May Be Transient)
  • Hepatic Failure

• Hypersensitivity:

  • Transfusion Reaction

• Infection:

  • Fungal Infection
  • Herpes Virus Infection
  • Kidney Infection
  • Localized Infection
  • Pseudomonas Infection
  • Staphylococcal Infection

• Local:

  • Catheter Infection

• Neuromuscular & Skeletal:

  • Arthritis (Including Exacerbation)
  • Bone Fracture (Femur, Femoral Neck, Pelvis, Hip, Rib, Spinal Compression)
  • Calcium Pyrophosphate Deposition Disease
  • Neck Pain

• Otic:

  • Otic Infection

• Renal:

  • Acute Renal Failure
  • Increased Serum Creatinine

• Respiratory:

  • Acute Sinusitis
  • Chronic Obstructive Pulmonary Disease (Includes Exacerbation)
  • Interstitial Pulmonary Disease
  • Lobar Pneumonia
  • Pulmonary Edema
  • Pulmonary Infiltrates
  • Respiratory Failure
  • Wheezing

• Miscellaneous:

  • Accidental Injury (Traffic Accident)
  • Mass (Renal)
  • Nodule

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Contraindication to Lenalidomide (Revlimid):

• Severe allergic reactions to lenalidomide and any component of the formulation (eg, Stevens-Johnson syndrome or toxic epidermal Necrolysis)
• Pregnancy

Canadian labeling: Additional contraindications not in the US labeling

• In MDS patients, platelet count is 50,000/mm3
• Sensitivity to thalidomide and pomalidomide
• Females can become pregnant by being able to conceive;
• Breastfeeding
• Male patients are unable to comply with contraceptive requirements

Warnings and precautions

• Suppression of bone marrow: [US Boxed Warning]

  • Patients with hemotoxic toxicity (neutropenia or thrombocytopenia), occur in most cases. Doses may need to be decreased or delayed. Blood product support and/or growth factor may also be necessary.
  • Patients being treated for del5q myelodysplastic disorders should have their CBC checked every week for the first 8 weeks, and then at least once a month thereafter.
  • Patients being treated for multiple myeloma should monitor their CBC weekly during the first two cycles, every 2 week during cycle 3 and then monthly thereafter.
  • Monitor CBC weekly in patients receiving lenalidomide to treat mantle cell lymphoma. Then, check it every 2 weeks during the cycles 2 through 4. Monthly thereafter.
  • Monitor CBC weekly during the first 3 weeks of cycle 1, every 2 weeks thereafter in cycles 2 through 4, and monthly in patients with follicular or marginal lymphoma.
  • Be on the lookout for signs of infection, bleeding or bruising. You may need to adjust your dosage.

• CNS effects

  • This can cause dizziness and lethargy. Patients should be warned about driving or operating machinery that requires mental attention.

• Dermatologic reactions

  • Severe cutaneous reactions including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis(TEN), and drug reaction eosinophilia with systemic symptoms (DRESS) have been observed; could be fatal.
  • DRESS can manifest as a cutaneous reaction (eg. rash, exfoliative dermatologtitis), fever and/or lymphadenopathy. Systemic complications may include hepatitis or nephritis.
  • You may consider stopping treatment for grade 2 or 3 skin reactions; you should also stop treatment permanently with grade 4 rash or exfoliative or bullous eruptions.
  • Patients who have a history of thalidomide-induced grade 4 rash should not receive lenalidomide.

• Hepatotoxicity

  • Patients who have received combination dexamethasone and lenalidomide have experienced liver failure that has led to deaths. They may also have hepatocellular or cholestatic characteristics.
  • Some risk factors include liver enzymes that are higher than baseline and concomitant medication.
  • Patients with abnormal liver function should be monitored closely.
  • You may consider starting treatment again at a lower dose once you return to baseline.

• Hypersensitivity

  • There have been reports of sensitivity including angioedema or anaphylactic reactions.
  • Permanently stop using this medication if you have angioedema, anaphylaxis, or both.

• Secondary malignancy

  • When lenalidomide was used to treat multiple myeloma and MDS, second primary malignancies (SPMs) were reported.
  • The incidence of these cases may be greater if lenalidomide and an alkylating agent are combined.
  • For secondary malignancies, examine for signs and symptoms.

• Thromboembolic Events: [US Boxed Warning]

  • Multiple myeloma patients who received lenalidomide with dexamethasone combination therapy have been shown to be at increased risk of arterial and venous embombolic events due to Lenalidomide.
  • There have been cases of deep vein thrombosis, pulmonary embolism, stroke, myocardial injury, and pulmonary embolism.
  • Patients should be aware of the signs and symptoms of thromboembolism, such as chest pain, shortness of breath, arm or leg swelling, and to seek immediate medical attention if they develop.
  • It is recommended that thromboprophylaxis be used. The choice of therapy should be made based on the patient's underlying risks.
  • According to the American Society of Clinical Oncology, VTE treatment and prophylaxis should be performed for patients receiving lenalidomide with chemotherapy and/or dexamethasone.
  • Patients who are at lower risk of developing thromboprophylaxis include patients receiving chemotherapy and/or dexamethasone. For patients at higher risk, LMWH or aspirin is recommended.
  • Use caution when using estrogens and erythropoietin stimulating agents (ESAs).
  • Patients who have had a history of arterial thromboembolic episodes may be at greater risk.
  • Anticoagulant prophylaxis must be tailored and selected based on the risk of thromboembolism from the combination treatment regimen. The safest and easiest to give is recommended.

• Thyroid disorders

  • Lenalidomide has been shown to cause hypothyroidism as well as hyperthyroidism. It is important to examine your thyroid function before you start treatment, and continue it regularly.

• TumorFlare:

  • In studies of lenalidomide to treat prolonged lymphocyticleukemia (CLL), and lymphomas. Clinical presentation includes low-grade fever, pain, rash and tender lymph node swelling.
  • Patients with marginal zone lymphoma or mantle-cell lymphoma may experience tumor flare. Keep an eye on patients.
  • Clinical trials showed that most tumor flare-ups occurred in the first treatment cycle.
  • The treatment may include analgesics, corticosteroids and nonsteroidal anti-inflammatory drug (NSAIDs); a treatment pause may also be considered.

• TumourThe lysis syndrome

  • Lenalidomide has been shown to treat tumor lysis syndrome, which can lead to fatalities.
  • Patients with a high tumor burden could be at risk of developing tumor lysis syndrome. Monitor closely and implement appropriate management.

• Heart Failure:

  • The American Heart Association has stated that lenalidomide may cause myocardial damage or worsen existing myocardial dysfunction in a scientific statement (magnitude major).

• Mantle cell lymphoma

  • One study that looked at patients receiving lenalidomide as a treatment for mantle cell lymphoma showed an increase in the incidence of early mortality (within 20 week).
  • High tumor burden, high mantle cell lymphoma International Prognostic Index (MIPI) score at diagnosis and high WBC count at baseline (>=10,000/mm3) are all risk factors for early death.

• Multiple myeloma

  • Two clinical studies showed an increase in deaths in multiple myeloma patients who received pembrolizumab along with a combination of thalidomide analogs and dexamethasone.
  • The experimental arm, which contained pembrolizumab and dexamethasone and a thalidomide analog [pomalidomide and lenalidomide], was associated with myocarditis and Stevens-Johnson Syndrome. It also included pneumonia, large intestine perforation and sudden death.
  • Multiple myeloma has not been approved for PD-1 and PD-L1 blocking antibody treatment. Pembrolizumab should never be used in conjunction with a thalidomide analog or dexamethasone to treat multiple myeloma unless it is part of a clinical study.

• Renal impairment

  • Patients with kidney damage should be cautious; patients may experience increased toxicities from decreased clearance and longer half-life.
  • For kidney damage that is not dialysis-reliant or normal, starting dose adjustments are recommended.

• Stem cell mobilization

  • Use of lenalidomide (>=4 cycles), may reduce the number CD34+ cells that are collected for autologous stem-cell transplant.
  • To speed up stem cell collection, patients who are eligible for transplant should be referred by a qualified transplant center.
  • When CD34+ cells are not being collected, Cyclophosphamide may be combined with G-CSF (or G-CSF with a combination of a CXC Chemokine Receptor 4 inhibitor such as plerixafor).

Lenalidomide: Drug Interaction

Risk Factor C (Monitor therapy)
Bisphosphonate Derivatives	Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased.
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Digoxin	Lenalidomide may increase the serum concentration of Digoxin.
Erythropoiesis-Stimulating Agents	May enhance the thrombogenic effect of Lenalidomide.
Estrogen Derivatives	May enhance the thrombogenic effect of Lenalidomide.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Smallpox and Monkeypox Vaccine (Live)	Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live).
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
DexAMETHasone (Systemic)	May enhance the thrombogenic effect of Lenalidomide.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
Abatacept	Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported.
Anakinra	Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported.
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Canakinumab	Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased.
Certolizumab Pegol	Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol.
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pembrolizumab	May enhance the adverse/toxic effect of Thalidomide Analogues. Specifically, mortality may be increased when this combination is used for treatment of refractory multiple myeloma.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Rilonacept	Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Tocilizumab	May enhance the immunosuppressive effect of Anti-TNF Agents.
Upadacitinib	Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live).
Vedolizumab	Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab.

 

Monitoring parameters:

• CBC with differential
  • Patients with MCL should be monitored weekly during the first cycle and every 2 weeks during the second and fourth cycles.
  • Patients with MDS should be seen weekly for the first 8 weeks.
  • Multiple myeloma: Weekly for the first two cycles and every 2 weeks during the 3rd cycle.
  • Follicular lymphoma and marginal zone lymphoma are treated weekly in the first three weeks of cycle 1, and then every 2 weeks thereafter in cycles 2 and 4. Then, monthly thereafter.
• TSH, serum creatinine, liver function tests and thyroid function tests (TSH at baseline, then every 2 to 3-months during treatment with lenalidomide;
• ECG when clinically indicated
• You should monitor for any signs and symptoms such as infection, secondary malignancies or thromboembolism.

Females with reproductive potential

• Pregnancy test 10-14 days before treatment begins. Weekly for the first 4 weeks. Then, every 2-4 weeks, through 4 weeks.

You must ensure that you adhere to the rules.

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How to administer Lenalidomide (Revlimid)?

Take with water everyday without chewing the capsule. It can be taken with or without food.

Missed doses:

• May administer a missed dose if within 12 hours of usual dosing time.
• If more than 12 hours, patient should skip dose for that day and continue usual dosing the following day.
• Patient should not take 2 doses to make up for a missed dose.

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Mechanism of action of Lenalidomide (Revlimid):

Lenalidomide is antineoplastic and antiangiogenic. It also has immunomodulatory properties through multiple mechanisms, such as the following:

• It selectively restricts the secretion proinflammatory cytokines (potent inhibitors of TNF-alpha release).
• It increases cell-mediated immunity by stimulating the proliferation of antiCD3-stimulated T cells (resulting increased IL-2 or interferon gamma production).
• It reduces trophic signals to cells that are angiogenic and inhibits growth of lymphoma, myelodysplastic and myelodysplastic cells.

Lenalidomide is added to rubuximab, increasing antibody dependent cell-mediated Cytotoxicity in follicular and marginal lymphoma, and inducing apoptosis.

Absorption:

• Rapid

Protein binding:

• ~30%

Half-life elimination:

• 3 to 5 hours

Time, to peak, plasma:

• MDS or myeloma patients: 0.5 to 6 hours

Excretion:

• Urine (~82%; as unchanged drug)
• Hemodialysis effect: In a 4 hour haemodialysis 30% drug is cleared.
• There is 80% reduction in drug clearance in a patient who requires haemodialysis.

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International Brand Names of Lenalidomide:

• Revlimid
• Immunomide
• Ladevina
• Lenangio
• Linamide

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Lenalidomide Brand Names in Pakistan:

No Brands Available in Pakistan.