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  • Ribomustin
    / Astellas


    Active Ingredient

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    5 X 25 mg

    partial basket chart 65545 18516

    Vial

    1 X 100 mg

    partial basket chart 67336 18518

    Vial

    5 X 100 mg

    partial basket chart 65550 18517

    Related information


    Dosage

    For intravenous infusion over 30 – 60 min: Infusion must be administered under the supervision of a physician qualified and experienced in the use of chemotherapeutic agents. Poor bone marrow function is related to increased chemotherapy-induced haematological toxicity. Treatment should not be started if leukocyte and/or platelet values dropped to < 3,000/μl or < 75,000/μl, respectively. Monotherapy for chronic lymphocytic leukaemia 100 mg/m² body surface area bendamustine hydrochloride on days 1 and 2; every 4 weeks. Monotherapy for indolent non-Hodgkin’s lymphomas refractory to rituximab 120 mg/m² body surface area bendamustine hydrochloride on days 1 and 2; every 3 weeks. Treatment should be terminated or delayed if leukocyte and/or platelet values dropped to < 3,000/μl or < 75,000/μl, respectively. Treatment can be continued after leukocyte values have increased to > 4,000/μl and platelet values to > 100,000/μl. The leukocyte and platelet Nadir is reached after 14-20 days with regeneration after 3-5 weeks. During therapy free intervals strict monitoring of the blood count is recommended. In case of non-haematological toxicity dose reductions have to be based on the worst CTC grades in the preceding cycle. A 50% dose reduction is recommended in case of CTC grade 3 toxicity. An interruption of treatment is recommended in case of CTC grade 4 toxicity.If a patient requires a dose modification the individually calculated reduced dose must be given on day 1 and 2 of the respective treatment cycle.
    Hepatic impairment: On the basis of pharmacokinetic data, no dose adjustment is necessary in patients with mild hepatic impairment (serum bilirubin < 1.2mg/dl). A 30% dose reduction is recommended in patients with moderate hepatic impairment (serum bilirubin 1.2 – 3.0 mg/dl). No data is available in patients with severe hepatic impairment (serum bilirubin values of > 3.0 mg/dl).
    Renal impairment: On the basis of pharmacokinetic data, no dose adjustment is necessary in patients with a creatinine clearance of > 10 ml/min. Experience in patients with severe renal impairment is limited.
    Paediatric patients: There is no experience in children and adolescents with drug.
    Elderly patients: There is no evidence that dose adjustments are necessary in elderly patients.
    See prescribing information for full details.                 


    Indications

    First-line treatment of chronic lymphocytic leukaemia (Binet stage B or C) in patients for whom fludarabine combination chemotherapy is not appropriate. Indolent non-Hodgkin’s lymphomas as monotherapy in patients, who have progressed during or within 6 months following treatment with rituximab or a rituximab containing regimen.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients. Breast-feeding. Severe hepatic impairment (serum bilirubin > 3.0 mg/dl) Jaundice. Severe bone marrow suppression and severe blood count alterations (leukocyte and/or platelet values dropped to < 3,000/μl or < 75,000/μl, respectively). Major surgery less than 30 days before start of treatment. Infections, especially involving leukocytopenia. Yellow fever vaccination.       


    Special Precautions

    Myelosuppression: Patients treated with bendamustine hydrochloride may experience myelosuppression. In the event of treatmentrelated myelosuppression, leukocytes, platelets, haemoglobin, and neutrophils must be monitored at least weekly. Prior to the initiation of the next cycle of therapy, the following parameters are recommended: Leukocyte and/or platelet values > 4,000/μl or > 100,000/μl, respectively.
    Infections: Infection, including pneumonia and sepsis, has been reported. In rare cases, infection has been associated with hospitalization, septic shock and death. Patients with neutropenia and/or lymphopenia following treatment with bendamustine hydrochloride are more susceptible to infections. Patients with myelosuppression following bendamustine hydrochloride treatment should be advised to contact a physician if they have symptoms or signs of infection, including fever or respiratory symptoms.
    Skin reactions: A number of skin reactions have been reported. These events have included rash, toxic skin reactions and bullous exanthema. Some events occurred when bendamustine hydrochloride was given in combination with other anticancer agents, so the precise relationship is uncertain. Where skin reactions occur, they may be progressive and increase in severity with further treatment. If skin reactions are progressive, bendamustine should be withheld or discontinued. For severe skin reactions where a relationship to bendamustine hydrochloride is suspected, treatment should be discontinued.
    Patients with cardiac disorders: During treatment with bendamustine hydrochloride the concentration of potassium in the blood must be closely monitored and potassium supplement must be given when K+ <3,5 mEq/l, and ECG measurement must be performed.
    Nausea/ vomiting: An antiemetic may be given for the symptomatic treatment of nausea and vomiting.
    Tumour lysis syndrome: Tumour lysis syndrome associated with bendamustine treatment has been reported in patients in clinical trials. The onset tends to be within 48 hours of the first dose of bendamustine and, without intervention, may lead to acute renal failure and death. Preventive measures include adequate volume status, close monitoring of blood chemistry, particularly potassium and uric acid levels. The use of allopurinol during the first one to two weeks of bendamustine therapy can be considered but not necessarily as standard. However, there have been a few cases of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis reported when bendamustine and allopurinol are administered concomitantly.
    Anaphylaxis: Infusion reactions to bendamustine hydrochloride have occurred commonly in clinical trials. Symptoms are generally mild and include fever, chills, pruritus and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred. Patients must be asked about symptoms suggestive of infusion reactions after their first cycle of therapy. Measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids must be considered in subsequent cycles in patients who have previously experienced infusion reactions. Patients who experienced Grade 3 or worse allergic-type reactions were typically not re-challenged.
    Contraception: Bendamustine hydrochloride is teratogenic and mutagenic. Women should not become pregnant during treatment. Male patients should not father a child during and up to 6 months after treatment. They should seek advice about sperm conservation prior to treatment with bendamustine hydrochloride because of possible irreversible infertility.
    Extravasation: An extravasal injection should be stopped immediately. The needle should be removed after a short aspiration. Thereafter the affected area of tissue should be cooled. The arm should be elevated. Additional treatments like the use of corticosteroids are not of clear benefit.
    See prescribing information for full details.


    Side Effects

    Hematological adverse reactions (leukopenia, thrombopenia), dermatologic toxicities (allergic reactions), constitutional symptoms (fever), gastro-intestinal symptoms (nausea, vomiting).
    See prescribing information for full details.


    Drug interactions

    No in-vivo interaction studies have been performed. When bendamustine is combined with myelosuppressive agents, the effect of bendamustine and/or the coadministered medicinal products on the bone marrow may be potentiated. Any treatment reducing the patient’s performance status or impairing bone marrow function can increase the toxicity of bendamustine. Combination of bendamustine with cyclosporine or tacrolimus may result in excessive immunosuppression with risk of lymphoproliferation. Cytostatics can reduce antibody formation following live-virus vaccination and increase the risk of infection which may lead to fatal outcome. This risk is increased in subjects who are already immunosuppressed by their underlying disease. Bendamustine metabolism involves cytochrome P450 (CYP) 1A2 isoenzyme. Therefore, potential for interaction with CYP1A2 inhibitors such as fluvoxamine, ciprofloxacin, acyclovir, cimetidine exists.


    Pregnancy and Lactation

    Pregnancy: Women of childbearing potential must use effective methods of contraception both before and during the therapy. There are insufficient data from the use of this drug in pregnant women.
    Lactation: It is not known whether bendamustine passes into the breast milk, therefore, this drug is contraindicated during breast-feeding. Breast-feeding must be discontinued during treatment with this drug.
    See prescribing information for full details.                 


    Overdose

    After application of a 30 min infusion of bendamustine once every 3 weeks the maximum tolerated dose (MTD) was 280 mg/m². Cardiac events of CTC grade 2 which were compatible with ischaemic ECG changes occurred which were regarded as dose limiting. In a subsequent study with a 30 min infusion of bendamustine at day 1 and 2 every 3 weeks the MTD was found to be 180 mg/m2. The dose limiting toxicity was grade 4 thrombocytopenia. Cardiac toxicity was not dose limiting with this schedule.
    Counter measures: There is no specific antidote. Bone marrow transplantation and transfusions (platelets, concentrated erythrocytes) may be made or haematological growth factors may be given as effective countermeasures to control haematological side-effects. Bendamustine hydrochloride and its metabolites are dialyzable to a small extent.
    See prescribing information for full details.                 


    Important notes

    Compatibility: This medicinal product must not be mixed with other medicinal products except: sodium chloride 9 mg/ml (0.9%) solution for injection and then administered by intravenous infusion. Aseptic technique is to be used.
    Administration: The solution is administered by intravenous infusion over 30-60 min. The vials are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
    Shelf life: 3 years. The powder should be reconstituted immediately after opening of the vial. The reconstituted concentrate should be diluted immediately with 0.9% sodium chloride solution.
    Solution for infusion: After reconstitution and dilution, chemical and physical stability has been demonstrated for 3.5 hours at 25ºC and 2 days at 2ºC to 8ºC in polyethylene bags. From a microbiological point of view, the solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
    See prescribing information for full details.


    Manufacturer
    Haupt Pharma GmbH
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