Lenalidomide Krka D.D.

Lenalidomide treatment should be supervised by a physician experienced in the use of anti-cancer therapies. 4). - 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.

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 to 21 of repeated Medicinal product no longer authorised 4 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. 5 mg Not applicable ª Dose reduction for both products can be managed independently Thrombocytopenia When platelets Recommended course Fall to < 25 x 109/L Stop lenalidomide dosing for remainder of cycleª Return to ≥ 50 x 109/L Decrease by one dose level when dosing resumed at next cycle ª If Dose limiting toxicity (DLT) occurs on > day15 of a cycle, lenalidomide dosing will be interrupted for at least the remainder of the current 28-day cycle.

5 x 109/L Interrupt lenalidomide treatment Resume lenalidomide at next lower dose level once daily. a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain the dose level of lenalidomide.

5 x 109/L with a platelet count ≥ 100 x 109/L at the beginning of a new cycle). 0 x 109/L, and/or platelet counts are < 50 x 109/L. The recommended starting dose is lenalidomide 25 mg orally once daily days 1-14 of each 21-day cycle in combination with bortezomib and dexamethasone.

3 mg/m2 body surface area) twice weekly on days 1, 4, 8 and 11 of each 21- day. 1 and the corresponding Summary of Product Characteristics. Up to eight 21-day treatment cycles (24 weeks of initial treatment) are recommended.

Summary of the safety profile Newly diagnosed multiple myeloma: patients who have undergone ASCT treated with lenalidomide maintenance A conservative approach was applied to determine the adverse reactions from CALGB 100104. The adverse reactions described in Table 1 included events reported post-HDM/ASCT as well as events from the maintenance treatment period.

A second analysis that identified events that occurred after the start of maintenance treatment suggests that the frequencies described in Table 1 may be higher than actually observed during the maintenance treatment period. In IFM 2005-02, the adverse reactions were from the maintenance treatment period only.

5%). 8%]). 0%). 5%). 0%). Multiple myeloma: patients with at least one prior therapy In two phase 3 placebo-controlled studies, 353 patients with multiple myeloma were exposed to the lenalidomide/dexamethasone combination and 351 to the placebo/dexamethasone combination.

4). 2%). 1). In the phase 2, all 148 patients were on lenalidomide treatment. In the phase 3 study, 69 patients were on lenalidomide 5 mg, 69 patients on lenalidomide 10 mg and 67 patients were on placebo during the double-blind phase of the study.

Most adverse reactions tended to occur during the first 16 weeks of therapy with lenalidomide. 4). 7%). Follicular […]

When lenalidomide is given in combination with other medicinal products, the corresponding Summary of Product Characteristics must be consulted prior to initiation of treatment. Pregnancy warning Lenalidomide is structurally related to thalidomide.

Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects. 3). If lenalidomide is taken during pregnancy, a teratogenic effect of lenalidomide in humans is expected. The conditions of the Pregnancy Prevention Programme must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential.

Criteria for women of non-childbearing potential A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria: - Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year (Amenorrhoea following cancer therapy or during breast-feeding does not rule out childbearing potential).

- Premature ovarian failure confirmed by a specialist gynaecologist. - Previous bilateral salpingo-oophorectomy, or hysterectomy. - XY genotype, Turner syndrome, uterine agenesis. Medicinal product no longer authorised 13 Counselling For women of childbearing potential, lenalidomide is contraindicated unless all of the following are met: - She understands the expected teratogenic risk to the unborn child - She understands the need for effective contraception, without interruption, at least 4 weeks before starting treatment, throughout the entire duration of treatment, and at least 4 weeks after the end of treatment - Even if a woman of childbearing potential has amenorrhea she must follow all the advice on effective contraception - She should be capable of complying with effective contraceptive measures - She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy - She understands the need to commence the treatment as soon as lenalidomide is dispensed following a negative pregnancy test - She understands the need and accepts to undergo pregnancy testing at least every 4 weeks except in case of confirmed tubal sterilisation - She acknowledges that she understands the hazards and necessary precautions associated with the use of lenalidomide.

1. - Women who are pregnant. 6).