Lenalid 5/Lenalid 10/Lenalid 15/Lenalid 25

Each capsule contains 5 mg, 10 mg, 15 mg or 25 mg of Lenalidomide.
Lenalidomide 5 mg capsules: White/White size "2" capsules printed with NAT on cap and 5 mg on body of the capsule, contains off-white to pale yellow coloured powder.
Lenalidomide 10 mg capsules: Green/Yellow size "2" capsules printed with NAT on cap and 10 mg on body of the capsule, contains off-white to pale yellow coloured powder.
Lenalidomide 15 mg capsules: Blue/White size "2" capsules printed with NAT on cap and 15 mg on body of the capsule, contains off-white to pale yellow coloured powder.
Lenalidomide 25 mg capsules: White/White size "2" capsules printed with NAT on cap and 25 mg on body of the capsule, contains off-white to pale yellow coloured powder.
Excipients/Inactive Ingredients: Each capsule contains lactose anhydrous. The additional composition of the different capsule strengths is provided in the table as follows. (See Table 1.)

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Pharmacology: Pharmacodynamics: In healthy volunteers, multiple dosing with lenalidomide appeared to have an effect upon the immune response. The highest dose was 200 mg/day. Dosing occurred once on the morning of Days 1 and 8 and twice daily on Days 2 to 7 inclusive. Statistically significant dose-related decrease in both CD4 and CD8 blood counts was observed from Day 4 onwards. For CD4 counts, the magnitude of the decreases was relatively constant (approximately 300/mm³) on Days 4, 6 and 8, with values approaching 433/mm³. The decrease in mean CD8 counts were up to 242/mm³ on Day 8, with levels still considerably lower than the baseline value at the post-study assessment.
Electrocardiography: A double-blind, randomised, placebo- and active-controlled, single-dose, four-period crossover study was performed to investigate the effects of lenalidomide 10 mg and 50 mg on ECG parameters in healthy male subjects (N=52). Lenalidomide at 10 mg and 50 mg single doses was not observed to affect the QTcF interval, the QRS duration, the PR interval, or heart rate in a treatment related manner.
Multiple Myeloma: Treatment with lenalidomide in MM patients is associated with the induction of antiproliferative effects and apoptosis in malignant myeloma cells due to direct antitumor activity, the alteration of the bone marrow microenvironment, and immune modulation.
Myelodysplastic Syndromes: Treatment with lenalidomide in MDS patients is associated with apoptosis of dysplastic cells in the bone marrow of these patients. Whether long-term lenalidomide therapy affects the CD4 and CD8 counts in MDS patients is not yet known.
Pharmacokinetics: The pharmacokinetics of lenalidomide were evaluated in a single-blind, placebo-controlled, ascending single oral-dose study (see Table 2 as follows). Single oral doses of 5, 20, 50, 100, 200 and 400 mg were administered in the fasted state. Nineteen subjects entered the study and 15 completed the study. (See Table 2.)

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No formal bioavailability studies were performed in humans.
The pharmacokinetics of lenalidomide were evaluated in MDS subjects who received a single 10 mg dose of lenalidomide or multiple doses of lenalidomide (see Table 3 as follows) (see Table 3).

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Geometric mean (CV%) data are presented for all parameters; AUC = area under the concentration versus time curve from time zero to 5 hours; Cmax = maximum concentration; t1/2,z = terminal half-life.
Absorption: Lenalidomide, in healthy volunteers, is rapidly absorbed following oral administration with maximum plasma concentrations occurring between 0.625 and 1.5 hours post-dose. Co-administration with food does not alter the extent of absorption (AUC) but does reduce the maximal plasma concentration (Cmax) by 36%. The pharmacokinetic disposition of lenalidomide is linear. Cmax and AUC increase proportionately with increases in dose. Multiple dosing at the recommended dose-regimen does not result in drug accumulation.
In MM patients maximum plasma concentrations occurred between 0.5 and 4.0 hours post-dose both on Days 1 and 28. AUC and Cmax values increase proportionally with dose following single and multiple doses. Exposure (AUC) in multiple myeloma patients was 57% higher than in healthy male volunteers.
In patients with low- or intermediate-1-risk MDS, a single 10 mg oral dose of lenalidomide is rapidly absorbed with the Cmax observed at around 1 hour post-dose. There is no accumulation of lenalidomide in plasma with multiple does at 10 mg per day. The mean exposure (AUC∞) in MDS patients is approximately 57% higher than healthy male subjects, possibly related to reduced renal function associated with the MDS disease state and secondary to increased age in this patient population. In two subjects with 30 ≤CrCL <50 mL/min, the 5-hour exposure (AUC) on Day 14 was increased by more than 70%, compared with the subjects with CrCL >80 mL/min.
Distribution: In vitro (14C)-lenalidomide binding to plasma proteins is approximately 23-29%.
Lenalidomide is present in semen (<0.01% of the dose) after the administration of 25 mg/day. Lenalidomide is undetectable in the semen of healthy volunteers three days after discontinuation of the drug.
Metabolism: Lenalidomide is not a substrate of hepatic metabolic enzymes in vitro. Unchanged lenalidomide is the predominant circulating component in vivo in humans. Two identified metabolites are hydroxy-lenalidomide and N-acetyl-lenalidomide; each constitutes less than 5% of parent levels in circulation.
In vitro in human liver preparations lenalidomide does not undergo oxidative (cytochrome P450) or conjugative metabolism. Non-enzymatic hydrolysis of lenalidomide occurs in aqueous media and plasma. In vitro lenalidomide does not inhibit or induce cytochrome P450 enzymes, suggesting that clinically relevant drug-drug interactions with cytochrome P450 substrates are unlikely.
Excretion: In healthy volunteers, approximately two-thirds of lenalidomide is eliminated unchanged through urinary excretion. The process exceeds the glomerular filtration rate and therefore active secretion may have some contribution in the overall renal excretion of lenalidomide. Lenalidomide is a weak substrate, but not an inhibitor of P-glycoprotein, suggesting that drug-drug interactions are unlikely with P-glycoprotein substrates and inhibitors.
In MDS patients, urinary excretion of unchanged lenalidomide in 24 hours post-dose averages approximately 65% of the administered dose.
At recommended doses (5 to 25 mg/day), half-life in plasma is approximately 3 hours in healthy volunteers and ranged from 3 to 5 hours in patients with multiple myeloma or MDS.
Special Populations and Conditions: Pediatrics: No pharmacokinetic (PK) data are available in patients below the age of 18 years.
Geriatrics: No dedicated clinical studies have been conducted to evaluate pharmacokinetics of lenalidomide in the elderly. Population PK analyses included patients with ages ranging from 39 to 85 years old, of which 40.8 % were older than 65 years of age, and show that age does not influence the disposition of lenalidomide.
Gender: Based on a population PK analysis of pooled PK dataset containing 147 patients (M/F, 102/45) gender has no effect on lenalidomide pharmacokinetics.
Race: Based on PK studies in Asian patients, there are no clinically relevant differences in the lenalidomide PK parameters when compared to PK parameters obtained in Caucasian patients.
Hepatic Insufficiency: Population PK analyses included patients with mild hepatic impairment (N=16, total bilirubin >1.0 to ≤1.5 x ULN or AST >ULN) and show that mild hepatic impairment does not influence the disposition of lenalidomide. There are no data available for patients with moderate to severe hepatic impairment.
Renal Insufficiency: The pharmacokinetics of lenalidomide were studied in patients with renal impairment due to nonmalignant conditions. In this study, 5 patients with mild renal function impairment (CrCL 56-74 mL/min), 6 patients with moderate renal function impairment (CrCL 33-46 mL/min), 6 patients with severe renal function impairment (CrCL 17-29 mL/min), and 6 patients with end stage renal disease requiring dialysis were administered a single oral 25 mg dose of lenalidomide. As a control group comparator, 7 healthy subjects of similar age with normal renal function (CrCL 83-145 mL/min) were also administered a single oral 25 mg dose of lenalidomide. The pharmacokinetic parameters of lenalidomide were similar in patients with mild impairment and healthy subjects. Patients with moderate and severe renal impairment had a 3-fold increase in half-life and up to 75% decrease in clearance compared to healthy subjects. Patients with end stage renal disease on hemodialysis had an approximately 4.5-fold increase in half-life and an 80% decrease in clearance compared to healthy subjects. Approximately 30% of the drug in the body was removed by a 4-hour dialysis session.
Mean AUC∞ was increased by 137%, 274% and 372% in patients with moderate, severe and end stage renal disease, respectively, as compared to that of normal and mild groups combined (n=12). Renal impairment had no effect on oral absorption (Cmax and tmax).
After a single 10 mg dose of lenalidomide in MDS patients with mild renal impairment, the drug exposure (AUC∞) was increased by 55% and the apparent total clearance was reduced by 35% compared to those observed in MDS patients with normal renal function.
In two MDS patients with moderate renal impairment, lenalidomide exposure after multiple doses was increased to a greater degree (Cmax increased by 41-51% and AUC5 by (74-95%) while renal clearance was decreased by 65-92%. A starting dose adjustment is recommended for MDS patients with moderate renal impairment.

Lenalidomide (Lenalid) capsules is used with dexamethasone to treat patients with multiple myeloma who are not eligible for stem cell transplant. Multiple myeloma is a cancer of plasma cells. Plasma cells are found in the bone marrow. Plasma cells produce a protein called antibodies. Some antibodies can attack and kill disease-causing germs. Patients with this type of cancer may have low blood cell counts and immune problems giving them a higher chance for getting infections such as pneumonia. The bones can be affected leading to bone pain and breaks (fractures). Lenalidomide (Lenalid) capsules works in multiple ways within the bone marrow to stop or slow the growth of cancerous myeloma cells.
Lenalid 5/Lenalid 10: Lenalidomide (Lenalid) capsule is used in the treatment of patients who require blood transfusions due to myelodysplastic syndromes (MDS) with a chromosome problem in which part of chromosome 5 is missing. This type of MDS is known as deletion 5q MDS.
The details of how LENALIDOMIDE works in deletion 5q MDS are still being studied. When patients with deletion 5q MDS are treated with Lenalidomide (Lenalid) capsules, abnormal cells in their bone marrow are often eliminated and replaced by normal-appearing cells. Lenalidomide (Lenalid) capsule can also directly stimulate the production of red blood cells by the bone marrow. These effects can improve anemia, and reduce or eliminate the need for transfusions in patients with MDS.

Take Lenalidomide (Lenalid) capsules exactly as prescribed.
Swallow Lenalidomide (Lenalid) capsules whole with water once a day. The patient should try to take it at about the same time each day.
Do not break, chew, or open the capsules.
It is important to remember that if the patient is being assisted with the medication, females who could become pregnant, or who plan to become pregnant can handle Lenalidomide (Lenalid) capsules if they are using latex gloves.
Lenalid 5/Lenalid 10/Lenalid 15/Lenalid 25: Multiple Myeloma: Starting dose: 25 mg daily on days 1-21 of 28 day cycles in combination with dexamethasone.
The doctor may change the dosage during treatment, and will continue therapy as long as the patient is responding to and tolerating Lenalidomide (Lenalid) capsules.
The patient will have regular blood tests during treatment with Lenalidomide (Lenalid) capsules. Patient should have their blood tested once every week during the first 2 cycles (8 weeks) of treatment, every 2 weeks during the third cycle, and at least monthly after that. The healthcare provider may adjust the patient dose of Lenalidomide (Lenalid) capsules or interrupt the treatment based on the results of the patient blood tests and, on the patient, general condition.
Lenalid 5/Lenalid 10: Myelodysplastic Syndrome: Starting dose: 10 mg daily on days 1-21 of 28-day cycles.
The doctor may change the dosage during treatment, and will decide the total duration of therapy that the patient needs. If the patient doesn't respond within 4 months of starting Lenalidomide (Lenalid) capsules, the doctor may decide to stop the treatment. It all depends on the response of the patient to the treatment.
The patient will have regular blood tests during treatment with Lenalidomide (Lenalid) capsules. Patient should have their blood tested every week during their first 8 weeks of treatment, and at least monthly after that. The healthcare provider may adjust the dose of Lenalidomide (Lenalid) capsules or interrupt the treatment based on the results of the blood tests and on the patient general condition.

If the patient has taken too much Lenalidomide (Lenalid) capsules, contact a healthcare professional, hospital emergency department immediately, even if there are no symptoms.
Missed Dose: If less than 12 hours have passed since missing a dose, take the dose. If more than 12 hours have passed since missing a dose at the normal time, do not take the dose. Take the next dose at the normal time on the following day. Do not take 2 doses at the same time.

Do not take Lenalidomide (Lenalid) capsules if: Patient is pregnant.
Patient is at risk of becoming pregnant.
Patient becomes pregnant during Lenalidomide (Lenalid) capsules treatment.
Patient is breastfeeding.
Lenalidomide (Lenalid) capsules can cause an increased risk of death in people who have chronic lymphocytic leukemia (CLL). Do not take Lenalidomide (Lenalid) capsules if patient has CLL.
Patient is allergic to lenalidomide, pomalidomide or thalidomide or any of the other ingredients in Lenalidomide (Lenalid) capsules. Lenalidomide (Lenalid) capsules contains lactose.
Lenalid 5/Lenalid 10: Myelodysplastic Syndromes: Lenalidomide (Lenalid) capsules treatment should not be started in patients whose platelet levels are less than 50 x 10⁹/L.

Serious side effects may occur with the use of Lenalidomide (Lenalid) capsules and could include: Birth defects (deformed babies) or death of an unborn baby and spontaneous abortion.
Decrease in the production of blood cells resulting in very low levels of white blood cells (neutropenia) and of platelets (thrombocytopenia).
Blood clots in the veins (Deep Vein Thrombosis), in the lung (Pulmonary Embolism), and in the arteries (heart attacks and stroke). Use of a blood thinner medication is recommended to reduce the risk.
Liver problems. Treatment with Lenalidomide (Lenalid) capsules may lead to a higher risk of liver problems which may cause death.
Severe allergic reaction called anaphylaxis.

Before administration of Lenalidomide (Lenalid) capsules be advised if patients: are pregnant or are planning to get pregnant; are breastfeeding; have kidney problems; have liver problems; have blood problems; have or have had heart problems (irregular heart beat, heart attack); smoke, have high blood pressure or high cholesterol levels; have had previous viral infection including herpes zoster infection (shingles) and/or hepatitis B virus infection (a viral infection of the liver); have had organ transplantation.
Lenalidomide (Lenalid) capsules may cause birth defects. In order to take this drug patient must meet the following conditions: Females who can get pregnant: Discuss contraception (birth control) with the healthcare provider.
Use at least two effective methods of contraception at the same time.
Use these two effective methods of contraception: For at least 4 weeks before starting Lenalidomide (Lenalid) capsules treatment; During interruptions of Lenalidomide (Lenalid) capsules treatment; During Lenalidomide (Lenalid) capsules treatment; For at least 4 weeks after stopping Lenalidomide (Lenalid) capsules treatment.
Patient must have two negative pregnancy tests before starting treatment: The first 7-14 days prior to starting treatment; The second within 24 hours of starting treatment.
Patient must have negative pregnancy tests during treatment: Once weekly for the first 4 weeks; Once every 4 weeks (or once every 2 weeks if patient period is irregular) for the duration of treatment and during treatment interruption.
Patient must have a final pregnancy test 4 weeks after stopping Lenalidomide (Lenalid) capsules.
Males: Lenalidomide is present in the sperm of males who take this drug. Should use a condom every time they have sexual intercourse with a woman who is pregnant or can get pregnant. This must be done even if they have undergone a successful vasectomy. The condom must be used while: Patient is taking Lenalidomide (Lenalid) capsules; During interruptions of treatment; For 4 weeks after stopping Lenalidomide (Lenalid) capsules.
They should not donate sperm while taking Lenalidomide (Lenalid) capsules and for 4 weeks after stopping Lenalidomide (Lenalid) capsules.
Patient should inform their sexual partner who can get pregnant that: They are taking Lenalidomide (Lenalid) capsules; There is a risk of birth defects, stillbirths, and spontaneous abortions if a fetus is exposed to their sperm; Patient must use a condom.
The patient should contact their doctor immediately if they think that their female partner becomes pregnant while they are taking Lenalidomide (Lenalid) capsules.
All Patients: Lenalidomide (Lenalid) capsules may cause birth defects and any method of birth control can fail. They should contact their doctor immediately if they think they or their female partner may be pregnant. They should also contact their doctor if they miss their period or experience unusual menstrual bleeding.
Patient should not give blood while they are taking Lenalidomide (Lenalid) capsules and for 4 weeks after stopping Lenalidomide (Lenalid) capsules.
Patient should not share Lenalidomide (Lenalid) capsules with other people.
Lenalidomide (Lenalid) capsules is not recommended for use in children under 18 years of age.
Lenalid 5/Lenalid 10: Myelodysplastic syndromes: Second cancers such as skin cancers, blood cancers, and solid tumor cancers have been reported in a small number of patients while taking lenalidomide or after treatment with lenalidomide is completed. Patients should talk to their doctors if they have any concerns about their own increased risk of having other cancers.

Lenalid 5/Lenalid 10/Lenalid 15/Lenalid 25: Multiple Myeloma: Like all medicines, Lenalidomide (Lenalid) capsules can have side effects. The following are the most commonly reported side effects (≥10%): Very Common: chest and other infections, tiredness/lethargy, fever, muscle weakness, joint pain and muscle cramps, pain, abdominal pain, difficulty breathing/breathlessness, hard stools/difficult to pass, difficulty sleeping, diarrhea, bleeding from gums or other sites, numbness/abnormal sensations, dizziness, swelling of arms or legs, cough, cloudy (cataracts) or blurred vision, headache, nausea, skin rash, back pain, loss of appetite, weight loss, frequent hunger with excessive thirst and urination, taste altered, heart palpitations/awareness of abnormal heart rhythm, chest pain, swelling, mouth pain, general feeling of discomfort or uneasiness, sore throat, shaking, confusion, weight gain, depression, arm pain with arm or leg swelling, vomiting, reduced sense of touch, irritability, "pins and needles" in hands and feet, heartburn.
The following are commonly reported side effects (≥1% and <10%): Common: bruise, increased sweating, dry skin, inflammation mouth, frequent urination, high blood pressure (headache), hoarse voice, dry mouth, stuffy nose, itchy skin, lightheadedness or dizziness, dehydration (dry mouth, excessive thirst, dark yellow urine), mood changes, hiccups, flatulence, runny nose, swelling face, skin redness, dizziness or fainting, muscle spasm, fever with shaking, face redness, balance impaired, canker sores, loose stools, bone pain, skin cancer, skin discoloration, decreased urination, hot flashes, painful urination, toothache, hair loss, increased tears, skin lesions, skin wound, decreased sex drive, nervousness, difficulty moving limbs, walking or speaking (stroke), dry eye, eye redness, fall, hives, memory impairment, difficulty swallowing, eye itch, rash, ringing in ears, allergic reaction, bedsores, blood in urine, deafness, increased hair growth, walking abnormally, increased appetite, mental status changes, non-coordinated muscle movement, painful or frequent urination, pale skin, urgent need to urinate, wheezing, wound.
The patient has to inform doctor or pharmacist if they experience a side effect which is not listed previously or any of the listed side effects that bother them or does not go away. (See Table 4.)

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These are not all the possible side effects possible with the use of Lenalidomide (Lenalid) capsules. Patient should ask the healthcare provider or pharmacist for more information.
Lenalid 5/Lenalid 10: Myelodysplastic Syndromes: Like all medicines, Lenalidomide (Lenalid) capsules can have side effects. The following are the most commonly reported side effects (≥10%): Very Common: decrease in white blood cells, decrease in platelets, diarrhea, itchy skin, rash, tiredness, nausea, infection of the nasal passages, constipation, joint pain, back pain, swelling of arms and/or legs, fever, cough, dizziness, difficulty breathing, headache, decrease in red blood cells, muscle cramp, infection of the pharynx, upper respiratory tract infection, nose bleed, lack or loss of strength, dry skin, abdominal pain, pain in arm or leg, urinary tract infection, pneumonia, loss of appetite, decrease in blood potassium level, swelling, bronchitis, difficulty sleeping, sinus infection, vomiting, night sweats, muscle pain.
The following are commonly reported side effects (≥1% and <10%): Common: fall, pain, increased sweating, bruise, upper abdominal pain, loose stools, arm and/or leg swelling, acquired decreased thyroid activity, high blood pressure, difficult or painful urination, dry mouth, toothache, allergy (rhinitis), flu, decreased sensitivity to stimulation, ruptured blood vessels, skin redness, chest pain, rigors, foot pain, distortion of sense of taste, loss of sensation in limbs, decrease in blood magnesium level, weight loss, infection under the skin, depression, skin lesion, flatulence, sensation of pricking, tingling, or creeping on the skin, heart palpitations, acute leukemia, hair loss, ear pain, dry eye, eye redness, eye pain.
The patient has to inform doctor or pharmacist if they experience a side effect which is not listed previously or any of the listed side effects that bother them or does not go away. (See Table 5.)

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These are not all the possible side effects possible with the use of Lenalidomide (Lenalid) capsules. Patient should ask the healthcare provider or pharmacist for more information.

Patient should inform the healthcare providers about all the medicines they take including prescription and non-prescription medicines, vitamins and herbal supplements. It is possible that Lenalidomide (Lenalid) capsules and other medicines may affect each other causing serious side effects.
Drugs that may interact with Lenalidomide (Lenalid) capsules include: Digoxin, Hormonal Replacement Therapy, and Hormonal Contraception (estrogens and progestins).

Instructions and special precautions for handling and disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store Lenalidomide (Lenalid) capsules at temperature not exceeding 30°C.

Cancer Immunotherapy

L04AX04 - lenalidomide ; Belongs to the class of other immunosuppressants.

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