Lenalidomide

Oral
Myelodysplastic syndrome
Adult: For the treatment of transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with an isolated deletion 5q (del 5q) cytogenic abnormality: Initially, 10 mg once daily on days 1-21 of repeated 28-day cycles. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<30 (requiring dialysis)	Initially, 2.5 mg once daily given after dialysis.
<30 (not requiring dialysis)	Initially, 2.5 mg once daily.
30-50	Initially, 5 mg once daily.

Oral
Multiple myeloma
Adult: Newly diagnosed patients not eligible for transplant: With dexamethasone: Initial: 25 mg once daily on days 1-21 of repeated 28-day cycles. Alternative: 25 mg once daily on days 1-14 of each 21-day cycle may be combined with bortezomib and dexamethasone for up to 8, 21-day cycles, then 25 mg once daily on days 1-21 of repeated 28-day cycles with dexamethasone. Alternative: 10 mg once daily on days 1-21 of repeated 28-day cycles for up to 9 cycles with melphalan and prednisone. Patients who complete 9 cycles/unable to complete the combined therapy are given a monotherapy of 10 mg once daily on days 1-21 of repeated 28-day cycles. Newly diagnosed patients who have undergone autologous stem cell transplantation: Monotherapy: Initial: 10 mg once daily on days 1-28 of repeated 28-day cycles. After 3 cycles, may be increased to 15 mg once daily if tolerated. Patients who received at least 1 prior therapy: With dexamethasone: Initial: 25 mg once daily on days 1-21 of repeated 28-day cycles.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<30 (requiring dialysis)	Initially, 5 mg once daily given after dialysis.
<30 (not requiring dialysis)	Initially, 7.5 mg once daily, or 15 mg every other day.
30-50	Initially, 10 mg once daily, may be increased to 15 mg once daily after 2 cycles if patient does not respond but tolerates treatment.

Oral
Mantle cell lymphoma
Adult: As monotherapy in patients with relapsed or refractory cases: Initially, 25 mg once daily on days 1-21 of repeated 28-day cycles. Continue until disease progression or unacceptable toxicity occurs. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<30 (requiring dialysis)	Initially, 5 mg once daily given after dialysis.
<30 (not requiring dialysis)	Initially, 7.5 mg once daily, or 15 mg every other day.
30-50	Initially, 10 mg once daily, may be increased to 15 mg once daily after 2 cycles if patient does not respond but tolerates treatment.

Oral
Marginal zone lymphoma
Adult: For the treatment of patients with previously treated cases in combination with rituximab: Initially, 20 mg once daily on days 1-21 of repeated 28-day cycles for up to 12 cycles. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<30 (requiring dialysis)	Initially, 5 mg once daily given after dialysis.
<30 (not requiring dialysis)	Initially, 5 mg once daily.
30-60	Initially, 10 mg once daily, may be increased to 15 mg once daily after 2 cycles if patient has tolerated the treatment.

Oral
Follicular lymphoma
Adult: For the treatment of patients with previously treated cases in combination with rituximab: Initially, 20 mg once daily on days 1-21 of repeated 28-day cycles for up to 12 cycles. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<30 (requiring dialysis)	Initially, 5 mg once daily given after dialysis.
<30 (not requiring dialysis)	Initially, 5 mg once daily.
30-60	Initially, 10 mg once daily, may be increased to 15 mg once daily after 2 cycles if patient has tolerated the treatment.

Cap: May be taken with or without food. Swallow whole, do not break/chew/open.

Pregnancy and lactation.

Patients with known risk factors for thromboembolism (e.g. prior thrombosis, smoking, hypertension, hyperlipidaemia); high tumour burden, elevated liver enzymes at baseline, pre-existing viral liver disease, or previously infected with hepatitis B virus (HBV). Not indicated for the treatment of chronic lymphocytic leukaemia. Renal impairment. Elderly. Patient Counselling This drug may cause fatigue, dizziness, somnolence, vertigo, and blurred vision, if affected, do not drive or operate machinery. Female patients of childbearing potential must commit to either abstaining continuously from sexual intercourse or using 2 reliable birth control methods for at least 4 weeks before, during (including dosage interruptions), and at least 4 weeks after discontinuation of therapy. Male patients should use condoms during treatment (including dosage interruptions), and for 7 days after stopping the treatment if partner is pregnant or of childbearing potential. Do not donate sperm (during therapy) or blood (during and for at least 7 days following treatment cessation). Do not open or crush capsules; if the powder comes in contact with your skin, wash it immediately with water. Monitoring Parameters Perform pregnancy test 10-14 days and 24 hours prior to treatment initiation, weekly during the 1st 4 weeks of therapy, then every 2-4 weeks through 4 weeks following treatment discontinuation. Monitor CBC with differential as clinically indicated. Obtain serum creatinine, LFTs, thyroid function tests; ECG as clinically indicated. Assess for signs and symptoms of infection, thromboembolism, secondary malignancies, tumour lysis syndrome, tumour flare reaction, and dermatologic effects.

Significant: Bone marrow suppression (e.g. neutropenia, thrombocytopenia), venous and arterial thromboembolic events, cardiac failure, peripheral neuropathy, second primary malignancies, tumour flare reaction, impaired stem cell mobilisation, thyroid disorders (e.g. hypo- and hyperthyroidism), CNS effects (e.g. dizziness, fatigue). Blood and lymphatic system disorders: Anaemia, leucopenia, febrile neutropenia, lymphopenia, pancytopenia, haemolytic anaemia. Cardiac disorders: Atrial fibrillation, bradycardia, chest pain. Ear and labyrinth disorders: Deafness, tinnitus, vertigo. Eye disorders: Cataract, blurred vision, reduced visual acuity. Gastrointestinal disorders: Diarrhoea, vomiting, nausea, constipation, abdominal pain, gastroenteritis, dry mouth, dysgeusia, dyspepsia. General disorders and administration site conditions: Asthenia, pyrexia, oedema. Infections and infestations: Pneumonia, neutropenic infection, sepsis. Injury, poisoning and procedural complications: Fall, contusion. Investigations: Abnormal LFTs, weight decreased, increased blood alkaline phosphatase. Metabolism and nutrition disorders: Hypokalaemia, dehydration, hypo-/hyperglycaemia, decreased appetite, hyponatraemia, hypocalcaemia. Musculoskeletal and connective tissue disorders: Muscle spasms, myalgia, arthralgia. Nervous system disorders: Headache, paraesthesia, tremor. Psychiatric disorders: Depression, insomnia. Renal and urinary disorders: UTI, urinary retention, renal failure. Reproductive system and breast disorders: Erectile dysfunction. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, rhinorrhoea, lower and upper respiratory tract infection, influenza, sinusitis, rhinitis, nasopharyngitis, bronchitis. Skin and subcutaneous tissue disorders: Rash, dry skin, pruritus, night sweats. Vascular disorders: Hypo-/hypertension, epistaxis, syncope.
Potentially Fatal: Severe cutaneous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS); tumour lysis syndrome, hepatic failure, viral reactivation, progressive multifocal leukoencephalopathy (PML).

Symptoms: Pruritus, rash, increased liver transaminases, thrombocytopenia, and neutropenia. Management: Symptomatic and supportive treatment.

May increase risk of thrombosis with erythropoietic agents, or other agents that increases its risk (e.g. hormone replacement therapy, combined oral contraceptive pills). Increased plasma exposure of digoxin. Increased risk of rhabdomyolysis with statins.

May diminish therapeutic effects with echinacea. Reduced extent of absorption with high-fat and high-calorie meals. Lab Interference:

Lenalidomide is a thalidomide analogue with antiangiogenic, antineoplastic, immunomodulatory, and pro-erythropoietic properties. It selectively inhibits proinflammatory cytokines secretion; enhances cell-mediated immunity by stimulating the proliferation of anti-CD3 stimulated T cells, which leads to increased interleukin-2 (IL-2) and interferon-γ secretion; inhibits trophic signals to angiogenic factors in cells. It induces cell cycle arrest and cell death to inhibit the growth of myeloma, myelodysplastic, and lymphoma tumour cells.
Absorption: Rapidly absorbed from the gastrointestinal tract. Reduced extent of absorption with high-fat and high-calorie meals. Time to peak plasma concentration: 0.5-6 hours (in MDS or myeloma patients).
Distribution: Present in semen (small amounts). Plasma protein binding: Approx 30%.
Metabolism: Undergoes limited metabolism to form 5-hydroxy-lenalidomide and N-acetyl-lenalidomide.
Excretion: Via urine (approx 82% as unchanged drug). Elimination half-life: 3-5 hours.

Oral: Store between 20-25°C.

Immunological Chemotherapy

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