Source: Marketing Authorisation Holder Revision Year: 2022 Publisher: Janssen-Cilag (New Zealand) Ltd, Auckland, NEW ZEALAND, Telephone: 0800 800 806, Fax: (09) 588 1398, Email: medinfo@janau.jnj.com
First line treatment of Chronic Lymphocytic Leukaemia (Binet stage B or C).
Previously untreated indolent Non-Hodgkin’s Lymphoma and Mantle Cell Lymphoma.
RIBOMUSTIN should be used in combination with rituximab in CD20 positive patients.
Relapsed/Refractory indolent Non-Hodgkin’s lymphoma.
For intravenous infusion over 30-60 minutes (see section 6.6).
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 × 109/L or <75 × 109/L, respectively (see section 4.4).
100 mg/m² body surface area bendamustine hydrochloride on days 1 and 2; every 4 weeks, for up to 6 cycles.
120 mg/m² body surface area bendamustine hydrochloride on days 1 and 2; every 3 weeks, for at least 6 cycles.
90 mg/m² on days 1 and 2 of a 4-week cycle for up to 6 cycles.
Treatment should be terminated or delayed if leukocyte and/or platelet values dropped to <3 × 109/L or <75 × 109/L, respectively. Treatment can be continued after leukocyte values have increased to >4 × 109/L and platelet values to >100 × 109/L.
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 (see section 4.4).
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.
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) (see section 4.3).
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.
There is no experience in children and adolescents with bendamustine.
There is no evidence that dose adjustments are necessary in elderly patients.
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.
Reconstitute each vial of RIBOMUSTIN containing 25 mg bendamustine hydrochloride in 10 ml water for injection by shaking.
Reconstitute each vial of RIBOMUSTIN 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 solution.
As soon as a clear solution is obtained (usually after 5-10 minutes) dilute the total recommended dose of RIBOMUSTIN immediately with 0.9% NaCl solution to produce a final volume of about 500 ml.
RIBOMUSTIN must be diluted with 0.9% NaCl solution and not with any other injectable solution.
The solution is administered by intravenous infusion over 30-60 min.
The maximum single dose of bendamustine received in clinical studies was 280 mg/m² body surface area.
Three out of the four patients treated with 280 mg/m² experienced ECG changes which were regarded as dose-limiting toxicities on days 7 and 21. These changes included prolonged QT (1 patient), displaced ST and T waves (2 patients) and left interior fascicle block (1 patient).
There is no specific antidote for bendamustine overdosage. Supportive therapy should be given when needed.
For advice on the management of overdose please contact the National Poisons Centre on 0800 POISON (0800 764766)
Unopened vials: 36 months.
The powder should be reconstituted immediately after opening of the vial. The reconstituted concentrate should be diluted immediately with 0.9% sodium chloride solution.
Reconstituted solution: After reconstitution and dilution, chemical and physical stability has been demonstrated for 3.5 hours at 25°C/ 60%RH and 2 days at 2°C to 8°C in polyethylene bags.
Unopened vials: Store below 25°C. Keep the container in the outer carton in order to protect from light.
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 section 6.3
RIBOMUSTIN is supplied in Type I brown glass vials of 26 ml or 60 ml with rubber stopper and an aluminum flip-off cap.
26 mL-vials contain 25 mg bendamustine hydrochloride; supplied in cartons containing 1 vial.
60 mL-vials contain 100 mg bendamustine hydrochloride; supplied in cartons containing 1 vial.
The vials are for single use only.
Not all presentations may be marketed.
When handling RIBOMUSTIN, inhalation, skin contact or contact with mucous membranes should be avoided (wear gloves and protective clothes). Contaminated body parts should be carefully rinsed with water and soap, the eye should be rinsed with physiological saline solution. If possible it is recommended to work on special safety workbenches (laminar flow) with liquid impermeable, absorbing disposable foil. Pregnant personnel should be excluded from handling cytostatics.
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. See section 4.2.
The vials are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
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