Bendamustine Kabi Dosage/Direction for Use

RECOMMENDED DOSE: Posology: Monotherapy for chronic lymphocytic leukaemia: 100 mg/m² body surface area bendamustine on days 1 and 2; every 4 weeks up to 6 cycles.
Monotherapy for indolent non-Hodgkin's lymphomas refractory to rituximab: 120 mg/m² body surface area bendamustine on days 1 and 2; every 3 weeks for at least 6 cycles (maximum 8 cycles).
Combination therapy with rituximab for first-line non-Hodgkin's lymphomas and mantle cell lymphoma: 90 mg/m² on days 1 and 2 of a 4-week cycle for up to 6 cycles.
Hepatic impairment: On the basis of pharmacokinetic data, no dose adjustment is necessary in patients with mild hepatic impairment (serum bilirubin < 1.2 mg/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: The safety and efficacy of bendamustine in children have not yet been established. Current available data is not sufficient to make a recommendation on posology.
Elderly people: There is no evidence that dose adjustments are necessary in elderly people.
MODE OF ADMINISTRATION: Method of administration: For intravenous infusion over 30 - 60 minutes.
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.
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.
For instructions on reconstitution of the medicinal product before administration, see as follows.
The powder for concentrate for solution for infusion has to be reconstituted with water for injection, diluted with sodium chloride 9 mg/ml (0.9%) solution for injection and then administered by intravenous infusion. Aseptic technique is to be used.
1. Reconstitution: Reconstitute each vial of bendamustine containing 25 mg bendamustine hydrochloride in 10 ml water for injection by shaking.
Reconstitute each vial of bendamustine containing 100 mg bendamustine hydrochloride in 40 ml water for injection by shaking.
The reconstituted concentrate contains 2.5 mg bendamustine hydrochloride per ml and appears as a clear colourless to a pale yellow solution.
2. Dilution: As soon as a clear solution is obtained (usually after 5-10 minutes) dilute the total recommended dose of bendamustine immediately with 0.9% NaCl solution to produce a final volume of about 500 ml.
Bendamustine must be diluted with 0.9% w/v NaCl solution and not with any other injectable solution.
3. 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.