Vilena Dosage/Direction for Use

Vilena treatment should be supervised by a physician experienced in the use of anti-cancer therapies. For all indications described as follows: Dose is modified based upon clinical and laboratory findings.
Dose adjustments, during treatment and restart of treatment, are recommended to manage grade 3 or 4 thrombocytopenia, neutropenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide.
In case of neutropenia, the use of growth factors in patient management should be considered.
If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day.
Newly diagnosed multiple myeloma (NDMM): Lenalidomide in combination with dexamethasone until disease progression in patients who are not eligible for transplant: Lenalidomide treatment must not be started if the ANC is <1.0 x 10⁹/L, and/or platelet counts are <50 x 10⁹/L.
Recommended dose: The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1-21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1, 8, 15 and 22 of repeated 28-day cycles. Patients may continue lenalidomide and dexamethasone therapy until disease progression or intolerance.
Dose reduction steps: (See Table 6.)


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Thrombocytopenia: (See Table 7.)


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Neutropenia: (See Table 8.)


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For hematologic toxicity the dose of lenalidomide may be re-introduced to the next higher dose level (up to the starting dose) upon improvement in bone marrow function (no hematologic toxicity for at least 2 consecutive cycles: ANC ≥1.5 x 10⁹/L with a platelet count ≥100 x 10⁹/L at the beginning of a new cycle).
Lenalidomide in combination with melphalan and prednisone followed by lenalidomide maintenance in patients who are not eligible for transplant: Lenalidomide treatment must not be started if the ANC is <1.5 x 10⁹/L, and/or platelet counts are <75 x 10⁹/L.
Recommended dose: The recommended starting dose is lenalidomide 10 mg orally once daily on days 1 to 21 of repeated 28-day cycles for up to 9 cycles, melphalan 0.18 mg/kg orally on days 1 to 4 of repeated 28-day cycles, prednisone 2 mg/kg orally on days 1 to 4 of repeated 28-day cycles. Patients who complete 9 cycles or who are unable to complete the combination therapy due to intolerance are treated with lenalidomide monotherapy as follows: 10 mg orally once daily on days 1 to 21 of repeated 28-day cycles given until disease progression.
Dose reduction steps: (See Table 9.)


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Thrombocytopenia: (See Table 10.)


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Neutropenia: (See Table 11.)


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Multiple myeloma with at least one prior therapy: Lenalidomide treatment must not be started if the ANC <1.0 x 10⁹/L, and/or platelet counts <75 x 10⁹/L or, dependent on bone marrow infiltration by plasma cells, platelet counts <30 x 10⁹/L.
Recommended dose: The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg once daily on days 1 to 4 every 28 days.
Prescribing physicians should carefully evaluate which dose of dexamethasone to use, taking into account the condition and disease status of the patient.
Dose reduction steps: (See Table 12.)


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Thrombocytopenia: (See Table 13.)


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Neutropenia: (See Table 14.)


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Myelodysplastic syndromes (MDS): Lenalidomide treatment must not be started if the ANC <0.5 x 10⁹/L and/or platelet counts <25 x 10⁹/L.
Recommended dose: The recommended starting dose of lenalidomide is 10 mg orally once daily on days 1 to 21 of repeated 28-day cycles.
Dose reduction steps: (See Table 15.)


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Thrombocytopenia: (See Table 16.)


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Neutropenia: (See Table 17.)


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Discontinuation of lenalidomide: Patients without at least a minor erythroid response within 4 months of therapy initiation, demonstrated by at least a 50% reduction in transfusion requirements or, if not transfused, a 1g/dl rise in haemoglobin, should discontinue lenalidomide treatment.
Mantle cell lymphoma (MCL): Recommended dose: The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles.
Dose reduction steps: (See Table 18.)


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Thrombocytopenia: (See Table 19.)


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Neutropenia: (See Table 20.)


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Tumour flare reaction: Lenalidomide may be continued in patients with Grade 1 or 2 tumour flare reaction (TFR) without interruption or modification, at the physician's discretion. In patients with Grade 3 or 4 TFR, withhold treatment with lenalidomide until TFR resolves to ≤Grade 1 and patients may be treated for management of symptoms per the guidance for treatment of Grade 1 and 2 TFR.
All indications: For other grade 3 or 4 toxicities judged to be related to lenalidomide, treatment should be stopped and only restarted at next lower dose level when toxicity has resolved to ≤grade 2 depending on the physician's discretion.
Lenalidomide interruption or discontinuation should be considered for grade 2 or 3 skin rash. Lenalidomide must be discontinued for angioedema, grade 4 rash, exfoliative or bullous rash, or if Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected, and should not be resumed following discontinuation from these reactions.
Special populations: Paediatric population: Vilena should not be used in children and adolescents from birth to less than 18 years because of safety concerns.
Elderly: Currently available pharmacokinetic data are described in Pharmacology: Pharmacokinetics under Actions, Lenalidomide has been used in clinical trials in multiple myeloma patients up to 91 years of age, in myelodysplastic syndromes patients up to 95 years of age and in mantle cell lymphoma patients up to 88 years of age.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it would be prudent to monitor renal function.
Newly diagnosed multiple myeloma: patients who are not eligible for transplant: Patients with newly diagnosed multiple myeloma aged 75 years and older should be carefully assessed before treatment is considered. For patients older than 75 years of age treated with lenalidomide in combination with dexamethasone, the starting dose of dexamethasone is 20 mg once daily on days 1, 8, 15 and 22 of each 28-day treatment cycle. No dose adjustment is proposed for patients older than 75 years who are treated with lenalidomide in combination with melphalan and prednisone. In patients with newly diagnosed multiple myeloma aged 75 years and older who received lenalidomide, there was a higher incidence of serious adverse reactions and adverse reactions that led to treatment discontinuation. Lenalidomide combined therapy was less tolerated in newly diagnosed multiple myeloma patients older than 75 years of age compared to the younger population. These patients discontinued at a higher rate due to intolerance (Grade 3 or 4 adverse events and serious adverse events), when compared to patients <75 years.
Multiple myeloma: patients with at least one prior therapy: The percentage of multiple myeloma patients aged 65 or over was not significantly different between the lenalidomide/dexamethasone and placebo/dexamethasone groups. No overall difference in safety or efficacy was observed between these patients and younger patients, but greater pre-disposition of older individuals cannot be ruled out.
Myelodysplastic syndromes: For myelodysplastic syndromes patients treated with lenalidomide, no overall difference in safety and efficacy was observed between patients aged over 65 and younger patients.
Mantle cell lymphoma: For mantle cell lymphoma patients treated with lenalidomide, no overall difference in safety and efficacy was observed between patients aged 65 years or over compared with patients aged under 65 years of age.
Patients with renal impairment: Lenalidomide is primarily excreted by the kidney; patients with greater degrees of renal impairment can have impaired treatment tolerance. Care should be taken in dose selection and monitoring of renal function is advised.
No dose adjustments are required for patients with mild renal impairment and multiple myeloma, myelodysplastic syndromes or mantle cell lymphoma.
The following dose adjustments are recommended at the start of therapy and throughout treatment for patients with moderate or severe impaired renal function or end stage renal disease.
There are no phase III trial experiences with End Stage Renal Disease (ESRD) (CLcr <30 mL/min, requiring dialysis).
Multiple myeloma: (See Table 21.)


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Myelodysplastic syndromes: (See Table 22.)


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Mantle cell lymphoma: (See Table 23.)


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After initiation of lenalidomide therapy, subsequent lenalidomide dose modification in renally impaired patients should be based on individual patient treatment tolerance, as described previously.
Patients with hepatic impairment: Lenalidomide has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations.
Method of administration: Oral use.
Vilena capsules should be taken orally at about the same time on the scheduled days. The capsules should not be opened, broken or chewed. The capsules should be swallowed whole, preferably with water, either with or without food.
It is recommended to press only on one end of the capsule to remove it from the blister thereby reducing the risk of capsule deformation or breakage.