Important Safety Information
Contraindication : BENDEKA is contraindicated in patients with a known hypersensitivity ( e . g ., anaphylactic and anaphylactoid reactions ) to bendamustine HCl , polyethylene glycol 400 , propylene glycol , or monothioglycerol .
Myelosuppression : Bendamustine HCl caused severe myelosuppression ( Grade 3-4 ) in 98 % of patients in the two NHL studies . Three patients ( 2 %) died from myelosuppression-related adverse reactions . Monitor leukocytes , platelets , hemoglobin ( Hgb ), and neutrophils frequently . Myelosuppression may require dose delays and / or subsequent dose reductions if recovery to the recommended values has not occurred by the fi rst day of the next scheduled cycle .
Infections : Infection , including pneumonia , sepsis , septic shock , hepatitis and death has occurred . Patients with myelosuppression following treatment with BENDEKA are more susceptible to infections . Patients treated with bendamustine HCl are at risk for reactivation of infections including ( but not limited to ) hepatitis B , cytomegalovirus , Mycobacterium tuberculosis , and herpes zoster . Patients should undergo appropriate monitoring , prophylaxis , and treatment measures prior to administration .
Anaphylaxis and Infusion Reactions : Infusion reactions to bendamustine HCl have occurred commonly in clinical trials . Symptoms include fever , chills , pruritus , and rash . In rare instances severe anaphylactic and anaphylactoid reactions have occurred , particularly in the second and subsequent cycles of therapy . Monitor clinically and discontinue drug for severe ( Grade 3-4 ) reactions . Ask patients about symptoms suggestive of infusion reactions after their fi rst cycle of therapy . Consider measures to prevent severe reactions , including antihistamines , antipyretics , and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions .
Tumor Lysis Syndrome : Tumor lysis syndrome associated with bendamustine HCl has occurred . The onset tends to be within the fi rst treatment cycle with bendamustine HCl and , without intervention , may lead to acute renal failure and death . Preventive measures include vigorous hydration and close monitoring of blood chemistry , particularly potassium and uric acid levels . There may be an increased risk of severe skin toxicity when bendamustine HCl and allopurinol are administered concomitantly .
Skin Reactions : Fatal and serious skin reactions have been reported with bendamustine HCl and include , toxic skin reactions , [ Stevens- Johnson Syndrome ( SJS ), toxic epidermal necrolysis ( TEN ), and drug reaction with eosinophilia and systemic symptoms ( DRESS )], bullous exanthema and rash . Events occurred when bendamustine HCl was given as a single agent and in combination with other anticancer agents or allopurinol . Where skin reactions occur , they may be progressive and increase in severity with further treatment . Monitor patients with skin reactions closely . If skin reactions are severe or progressive , withhold or discontinue BENDEKA .
Hepatotoxicity : Fatal and serious cases of liver injury have been reported with bendamustine HCl . Combination therapy , progressive disease or reactivation of hepatitis B were confounding factors in some patients . Most cases were reported within the fi rst three months of starting therapy . Monitor liver chemistry tests prior to and during BENDEKA therapy .
Other Malignancies : There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with bendamustine HCl , including myelodysplastic syndrome , myeloproliferative disorders , acute myeloid leukemia , and bronchial carcinoma . The association with BENDEKA has not been determined .