Lenalidomide Eurodrug

Monotherapy for maintenance treatment of adults w/ newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation. Combination therapy w/ dexamethasone, or bortezomib & dexamethasone, or melphalan & prednisone for adults w/ previously untreated multiple myeloma who are not eligible for transplant. In combination w/ dexamethasone for multiple myeloma in adults who have received at least 1 prior therapy. Monotherapy for adults w/ transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated w/ isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. Monotherapy for adults w/ relapsed or refractory mantle cell lymphoma. In combination w/ rituximab (anti-CD20 Ab) for adults w/ previously treated follicular lymphoma (Grade 1-3a).

Newly diagnosed multiple myeloma In combination w/ dexamethasone until disease progression in patient not eligible for transplant: Initially 25 mg once daily on days 1-21 of repeated 28-day cycle & dexamethasone 40 mg once daily on days 1, 8, 15 & 22 of repeated 28-day cycle. Continue until disease progression or intolerance. In combination w/ bortezomib & dexamethasone followed by lenalidomide & dexamethasone until disease progression in patient not eligible for transplant: Initial treatment (Lenalidomide in combination w/ bortezomib & dexamethasone): 25 mg orally once daily on days 1-14 of each 21-day cycle in combination w/ bortezomib (given as 1.3 mg/m² SC inj twice wkly on days 1, 4, 8 & 11 of each 21-day) & dexamethasone. Recommended duration: Up to eight 21-day treatment cycles (24 wk of initial treatment). Continued treatment (Lenalidomide in combination w/ dexamethasone until disease progression): 25 mg once daily on days 1-21 of repeated 28-day cycle in combination w/ dexamethasone. Continue treatment until disease progression or unacceptable toxicity. In combination w/ melphalan & prednisone followed by lenalidomide maintenance in patient not eligible for transplant: Initially 10 mg once daily on days 1-21 of repeated 28-day cycle for up to 9 cycles, melphalan 0.18 mg/kg on days 1-4 of repeated 28-day cycle, prednisone 2 mg/kg on days 1-4 of repeated 28-day cycle. Patient who complete 9 cycles or those unable to complete combination therapy due to intolerance Monotherapy: 10 mg once daily on days 1-21 of repeated 28-day cycle given until disease progression. Patients who have undergone autologous stem cell transplantation Initially 10 mg once daily continuously (on days 1-28 of repeated 28-day cycle) given until disease progression or intolerance. May increase dose to 15 mg once daily after 3 cycles of tolerated maintenance treatment. Multiple myeloma w/ at least 1 prior therapy Initially 25 mg once daily on days 1-21 of repeated 28-day cycle & dexamethasone 40 mg orally once daily on days 1-4, 9-12, & 17-20 of each 28-day cycle for 1^st 4 cycles of therapy & then 40 mg once daily on days 1-4 every 28 days. Myelodysplastic syndromes Initially 10 mg once daily on days 1-21 of repeated 28-day cycle. Mantle cell lymphoma Initially 25 mg orally once daily on days 1-21 of repeated 28-day cycle. Follicular lymphoma Initially 20 mg once daily on days 1-21 of repeated 28-day cycle for up to 12 cycles & rituximab 375 mg/m² IV every wk in cycle 1 (days 1, 8, 15, & 22) & day 1 of every 28-day cycle for cycles 2-5. Dose adjustment: Elderly >75 yr In combination w/ dexamethasone: Start 20 mg dexamethasone once daily on days 1, 8, 15 & 22 of each 28-day treatment cycle. Multiple myeloma Moderate renal impairment (CrCl ≤30 to <50 mL/min) 10 mg once daily, may escalate dose to 15 mg once daily after 2 cycles if patient is not responding to treatment. Severe renal impairment (CrCl <30 mL/min, not requiring dialysis) 7.5 mg once daily or 15 mg every other day, ESRD (CrCl <30 mL/min, requiring dialysis) 5 mg once daily. Administer following dialysis on dialysis days. Myelodysplastic syndromes Moderate renal impairment (CrCl ≤30 to <50 mL/min) Initially 5 mg once daily (days 1-21 of repeated 28-day cycle), 1^st dose level reduction: 2.5 mg once daily (days 1-28 of repeated 28-day cycle), 2^nd dose level reduction: 2.5 mg once every other day (days 1-28 of repeated 28-day cycle), severe renal impairment (CrCl <30 mL/min, not requiring dialysis) Initially 2.5 mg once daily (days 1-21 of repeated 28-day cycle), 1^st dose level reduction: 2.5 mg every other day (days 1-28 of repeated 28-day cycle), 2^nd dose level reduction: 2.5 mg twice/wk (days 1-28 of repeated 28-day cycle), ESRD (CrCl <30 mL/min, requiring dialysis) Administer following dialysis on dialysis days. Initially 2.5 mg once daily (days 1-21 of repeated 28-day cycle), 1^st dose level reduction: 2.5 mg every other day (days 1-28 of repeated 28-day cycle), 2^nd dose level reduction: 2.5 mg twice/wk (days 1-28 of repeated 28-day cycle). Follicular lymphoma Moderate renal impairment (CrCl ≤30 to <60 mL/min) 10 mg once daily, may escalate dose to 15 mg once daily after 2 cycles if patient is not responding to treatment.

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

Hypersensitivity. Women of childbearing potential. Pregnancy.

Allergic reactions including angioedema, anaphylactic reaction & severe cutaneous reactions including SJS, TEN & DRESS. Permanently discontinue treatment if progressive multifocal leukoencephalopathy (PML) is confirmed. Discontinue & do not resume treatment in case of angioedema, anaphylactic reaction, Grade 4 rash, exfoliative or bullous rash, or if SJS, TEN or DRESS is suspected. Discontinue treatment in patients w/o at least minor erythroid response w/in 4 mth of therapy initiation; for other Grade 3 or 4 toxicities & restart at next dose level only when toxicity resolved to ≤ Grade 2. Discontinue treatment & start anticoagulation therapy if patient experiences any thromboembolic events. Temporarily hold or permanently discontinue treatment if cases of herpes zoster reactivation occur resulting in disseminated, meningitis, or ophth herpes zoster. Withhold treatment in patients w/ Grade 3 or 4 tumour flare reaction & initiate therapy w/ NSAIDs, corticosteroids &/or narcotic analgesics. Interrupt treatment in patients w/ Grade 2-4 clinical tumour lysis syndrome (TLS); for other forms of skin reaction. Suspend further dosing if PML is suspected until it has been excluded. Not to be given in patients w/ history of severe rash associated w/ thalidomide treatment. Not recommended in patients w/ high tumour burden if alternative treatment options are available. Not to donate blood during therapy or for at least 7 days following discontinuation of therapy. Closely monitor patients w/ known risk factors for thromboembolism including prior thrombosis & minimize all modifiable risk factors (eg, smoking, HTN, & hyperlipidaemia); high tumour burden prior treatment especially during 1st cycle or dose-escalation; known risk factors for infections; signs & symptoms of active HBV infection throughout therapy. Regularly monitor visual ability. MI; pulmonary HTN; neutropenia & thrombocytopenia; hypo-/hyperthyroidism; peripheral neuropathy; TLS & tumour flare reaction; acute hepatic failure, toxic hepatitis, cytolytic & cholestatic hepatitis, & mixed cytolytic or cholestatic hepatitis; abnormal LFTs; viral reactivation including serious cases of herpes zoster or HBV reactivation; PML; cataract. Increased risk of VTE (predominantly DVT & pulmonary embolism); arterial thromboembolism (predominantly MI & cerebrovascular event); early death in patients w/ high tumour burden at baseline; second primary malignancies (SPM). Patients w/ high mantle cell lymphoma International Prognostic Index at diagnosis or bulky disease (at least 1 lesion ≥7 cm in longest diameter) at baseline; previous allergic reactions w/ thalidomide; previous HBV infection, including those who are anti-HBc +ve but HBsAg -ve; previous history of thromboembolic events. Monitor baseline & ongoing thyroid function; liver function particularly when there is history of or concurrent viral liver infection or when combined w/ medicinal products known to be associated w/ liver dysfunction. Perform CBC including WBC count w/ differential count, platelet count, Hb, & haematocrit at baseline, every wk for 1st 8 wk of treatment & mthly thereafter. Monitor patients every 2 wk in cycles 3 & 4, & then at start of each cycle in mantle cell lymphoma; wkly for 1st 3 wk of cycle 1 (28 days), every 2 wk during cycles 2-4, & then at start of each cycle thereafter in follicular lymphoma; chemistry panel wkly during 1st cycle & as clinically indicated to monitor TLS. Observe for signs & symptoms of bleeding, including petechiae & epistaxis, especially in patients receiving concomitant medicinal products susceptible to induce bleeding; signs & symptoms of thromboembolism eg, shortness of breath, chest pain, arm or leg swelling. Promptly report febrile episodes. Establish HBV status before initiating treatment. Evaluate patients before & during treatment using standard cancer screening for occurrence of SPM; signs & symptoms of underlying cardiopulmonary disease prior to initiating & during therapy. Control co-morbid conditions influencing thyroid function before start of treatment. Provide vigorous IV hydration & appropriate medical management until correction of electrolyte abnormalities. Assess ability to tolerate combination therapy w/ consideration to age, ISS stage III, ECOG PS ≥2 or CrCl <60 mL/min. Not recommended to use w/ combined OCs; Cu-releasing IUD. Increased risk of infection at the time of insertion & irregular vag bleeding w/ implants & levonorgestrel-releasing intrauterine systems. Consider prophylactic antibiotics; use of growth factors in case of neutropenia. Administer prophylactic anti-thrombotics especially in patients w/ additional thrombotic risk factors; TLS prophylaxis (allopurinol, rasburicase or equiv) & oral hydration during 1st cycle wk or longer period in patients w/ TLS. Concomitant administration w/ erythropoietic agents or other agents that may increase risk of thrombosis, eg, HRT; other myelosuppressives. Not to be given in patients w/ galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Minor or moderate influence on ability to drive & use machines due to fatigue, dizziness, somnolence, vertigo & blurred vision. Hepatic impairment. Discontinue use if pregnancy occurs during treatment. Women of childbearing potential must use at least 1 effective method of contraception for at least 4 wk before, during, & until at least 4 wk after therapy & even in case of dose interruption unless patient commits to absolute & continuous abstinence confirmed on mthly basis. Perform medically supervised pregnancy test w/ min sensitivity of 25 mIU/mL during consultation, when treatment is prescribed, or in the 3 days prior to prescriber visit once patient had been using effective contraception for at least 4 wk. Repeat at least every 4 wk, including at least 4 wk after end of treatment. Male should use condom if engaged in sexual activity w/ pregnant woman or woman of childbearing potential not using effective contraception (even if man has had vasectomy), during treatment & for at least 7 days after dose interruption &/or treatment cessation. Women who are pregnant or suspect they may be pregnant should not handle blister or cap. Discontinue breastfeeding during therapy. Not to be used in childn & adolescents from birth to <18 yr. Elderly ≥75 yr; assess those w/ newly diagnosed multiple myeloma before treatment consideration.

Pneumonia, URTI, neutropenic infection, bronchitis, flu, gastroenteritis, sinusitis, nasopharyngitis, rhinitis, bacterial, viral & fungal infections (including opportunistic infections), pharyngitis; neutropenia, febrile neutropenia, thrombocytopenia, anaemia, leucopenia, lymphopenia, haemorrhagic disorder; hypokalaemia, hyper-/hypoglycaemia, hypocalcaemia, hyponatraemia, dehydration, decreased appetite & wt; paraesthesia, peripheral neuropathies, dizziness, tremor, dysgeusia, headache; cough, dyspnoea, epistaxis; diarrhoea, constipation, abdominal pain (including upper), nausea, vomiting, dyspepsia, dry mouth, stomatitis; abnormal LFTs, increased ALT & AST; rash (including allergic dermatitis), dry skin, pruritus; muscle spasms, muscular weakness, bone pain, musculoskeletal & connective tissue pain & discomfort (including back pain), pain in extremity, myalgia, arthralgia; fatigue, asthenia, pyrexia, oedema (including peripheral oedema), flu-like illness syndrome; depression, insomnia; cataract, blurred vision; venous thromboembolic events, predominantly DVT & pulmonary embolism, hypotension; renal failure (including acute); increased blood alkaline phosphatase; hypothyroidism; tumour flare. Infection, UTI, lower resp tract infection, lung infection, sepsis, bacteraemia, herpes zoster, cellulitis, infectious enterocolitis; pancytopenia, haemolytic anaemia; hypomagnesaemia, hyperuricaemia, hypercalcaemia, Fe overload, hypophosphataemia, DM, gout; peripheral sensory neuropathy, ataxia, impaired balance, syncope, neuralgia, dysaesthesia, CVA; rhinorrhoea, dysphonia, oropharyngeal pain, resp distress, hypoxia, pleuritic pain; GI haemorrhage (including rectal, haemorrhoidal & peptic ulcer haemorrhage & gingival bleeding), dysphagia, small intestinal obstruction, toothache; hepatocellular injury, hyperbilirubinaemia, cholestasis, hepatotoxicity; urticaria, hyperhidrosis, skin hyperpigmentation, eczema, erythema, night sweats; joint swelling, neck pain; chest pain, lethargy, chills, malaise; reduced visual acuity; HTN, ecchymosis, haematoma, vasculitis; haematuria, urinary retention & incontinence, acute kidney injury; increased C-reactive protein & blood bilirubin; myelodysplastic syndrome, basal cell carcinoma, AML, squamous skin cell carcinoma; deafness (including hypoacusis), tinnitus, vertigo; atrial fibrillation, bradycardia, MI (including acute), congestive cardiac failure, tachycardia, cardiac failure, myocardial ischaemia; erectile dysfunction; fall, contusion; altered mood. Hyperthyroidism; SJS, TEN & DRESS.

Increased risk of thrombosis w/ erythropoietic agents or other agents eg, HRT. Increased plasma exposure of digoxin. Increased risk of rhabdomyolysis w/ statins.

Cancer Immunotherapy

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

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