Pocket Drug Guide

(British Approved Name Modified, US Adopted Name, rINNM)

Drug Nomenclature

INNs in main languages (French, Latin, Russian, and Spanish):

Stability. US licensed product information for bendamustine hydrochloride states that, once reconstituted as directed and further diluted with sodium chloride 0.9%, the final infusion solution is stable for 24 hours when refrigerated (2° to 8°) or for 3 hours when stored at room temperature (15° to 30°) and exposed to light.

Adverse Effects, Treatment, and Precautions

Bendamustine commonly causes myelosuppression and doses may need to be reduced (see Uses and Administration, below); patients are therefore susceptible to infection. Other common adverse effects include gastrointestinal disturbances, fever, asthenia, fatigue, malaise, dry mouth, somnolence, cough, headache, mucosal inflammation, and stomatitis. Infusion reactions are common; symptoms include fever, chills, pruritus, and rash. Anaphylactic reactions have been reported rarely, especially during the second and subsequent cycles of therapy. Prophylactic anti-histamines, antipyretics, and corticosteroids should be considered. If severe infusion reactions occur, stopping therapy should be considered. Tumour lysis syndrome has been reported, usually within the first treatment cycle, and may lead to acute renal failure and death. Adequate volume status should be maintained and potassium and uric acid concentrations should be monitored; allopurinol may be used in patients at high risk. Skin reactions such as bullous exanthema can occur with bendamustine; therapy may need to be withheld or stopped. Worsening hypertension, including hypertensive crisis, has also occurred. Increases in creatinine concentrations and liver enzyme values have been reported; bendamustine should be used with caution in patients with renal or hepatic impairment.

Interactions

Bendamustine is extensively metabolised by cytochrome P450 isoenzyme CYP1A2. Inhibitors of CYP1A2, such as fluvoxam-ine and ciprofloxacin, may increase exposure to bendamustine. Conversely, CYP1A2 inducers, such as omeprazole, can reduce exposure to bendamustine; tobacco smoking also may increase exposure to bendamustine.

Pharmacokinetics

Bendamustine is about 95% bound to plasma proteins; data suggest it is not likely to displace nor to be displaced by highly protein-bound drugs. Bendamustine distributes freely into human red blood cells. It is mainly metabolised by hydrolysis via the cytochrome P450 isoenzyme CYP1A2. Little or no accumulation in plasma is anticipated for intravenous doses of bendamustine given on days 1 and 2 of a 28-day cycle. About 90% of the drug is eliminated, mainly via the faeces.

Uses and Administration

Bendamustine is an antineoplastic alkylating agent. It is given intravenously as the hydrochloride for the treatment of chronic lymphocytic leukaemia; it may also be used in non-Hodgkin’s lymphoma, Hodgkin’s disease, multiple myeloma, and breast cancer.

For the treatment of chronic lymphocytic leukaemia, bendamustine hydrochloride is given in a dose of 100 mg/m, in 500 mL of sodium chloride 0.9%, infused over 30 minutes on days 1 and 2 of a 28-day cycle, for up to 6 cycles.

Doses are modified if toxicity occurs; dose delays may be warranted until neutrophils and platelets have recovered to acceptable concentrations. For severe haematological or non-haemato-logical toxicity, doses should be reduced to 50 mg/m on days 1 and 2 of each cycle. If severe haematological toxicity recurs, the dose should be further reduced to 25 mg/m. Dose re-escalation in subsequent cycles may be considered.

Administration in hepatic impairment. US licensed product information states that, although no meaningful effect on the pharmacokinetics of bendamustine was seen in mild hepatic impairment, data are limited, and therefore caution should be exercised when using bendamustine in these patients. Bendamustine should not be used in moderate or severe hepatic impairment due to a lack of data.

Administration in renal impairment. US licensed product information states that, although no meaningful effect on the pharmacokinetic s of bendamustine was seen in renal impairment, data are limited, and therefore caution should be exercised in patients with mild or moderate renal impairment. Bendamustine should not be used in patients with creatinine clearance less than 40 mL/minute, due to a lack of data.

Proprietary Preparations

Germany: Ribomustin;

USA: Treanda

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