Ribomustin Special Precautions

Myelosuppression: Patients treated with bendamustine hydrochloride may experience myelosuppression (bone marrow failure). In the event of treatment-related myelosuppression, leukocytes, platelets, hemoglobin, and neutrophils should be monitored and re-evaluated prior to initiation of the next cycle of therapy. Prior to the initiation of the next cycle of therapy, the following parameters are recommended: Leukocyte and/or platelet values > 4000/μL or > 100000/μL, respectively. Treatment-related myelosuppression may require dose adjustment and/or dose delays.
Treatment with bendamustine hydrochloride may cause prolonged lymphocytopenia (< 600/μL) and low CD4-positive T-cell (T-helper cell) counts (< 200/μL) for at least 7-9 months after the completion of treatment. Lymphocytopenia and CD4-positive T-cell depletion are more pronounced when bendamustine is combined with rituximab. Patients with lymphopenia and low CD4-positive T-cell count following treatment with bendamustine hydrochloride are more susceptible to (opportunistic) infections.
Ribomustin should not be used during severe bone marrow suppression and severe blood count alterations. See Dosage & Administration.
Infections: Serious and fatal infections, including fatal sepsis, have occurred with bendamustine treatment. These infections included bacterial (pneumonia) and opportunistic infections such as Pneumocystis Jirovecii Pneumonia (PJP), Varicella Zoster Virus (VZV) and Cytomegalovirus (CMV). Cases of progressive multifocal leukoencephalopathy (PML) including fatal ones have been reported following the use of bendamustine mainly in combination with rituximab or obinutuzumab. Patients with lymphopenia and low CD4-positive T-cell count following treatment with bendamustine hydrochloride are more susceptible to (opportunistic) infections. In case of low CD4-positive T-cell counts (<200/μL) Pneumocystis jirovecii pneumonia (PJP) prophylaxis should be considered. All patients should be monitored for respiratory signs and symptoms throughout treatment. Discontinuation of bendamustine hydrochloride should be considered if there are signs of (opportunistic) infections. Consider PML in the differential diagnosis in patients with new or worsening neurological, cognitive or behavioural signs or symptoms. If PML is suspected then appropriate evaluations should be undertaken and treatment suspended until PML is excluded.
Skin reactions: A number of skin reactions have been reported. These events have included rash, toxic skin reactions and bullous exanthema. Cases of Stevens - Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), some fatal, have also been reported. Some events of SJS and TEN occurred when bendamustine hydrochloride was administered concomitantly with allopurinol or when bendamustine hydrochloride was given in combination with other anticancer agents. Cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of bendamustine hydrochloride in combination with rituximab. Where skin reactions occur, they may be progressive and increase in severity with further treatment; therefore, patients with skin reactions should be monitored closely. If skin reactions are severe or progressive, Ribomustin 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 should be closely monitored. Potassium supplementation should be given when K⁺ <3.5 mEq/L, and ECG measurement must be performed.
Fatal cases of myocardial infarction and cardiac failure have been reported with bendamustine treatment. Patients with concurrent or history of cardiac disease should be observed closely.
Nausea, vomiting: An antiemetic may be given for the symptomatic treatment of nausea and vomiting.
Tumor lysis syndrome: Tumor lysis syndrome associated with Ribomustin treatment has been reported in patients in clinical trials. The onset tends to be within 48 hours of the first dose of Ribomustin 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 Ribomustin therapy can be considered but not necessarily as standard.
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 administration of 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 Ribomustin 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, such as the use of corticosteroids, are not of clear benefit.
Non-melanoma skin cancer: In clinical studies, an increased risk for non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) has been observed in patients treated with bendamustine containing therapies. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
Other malignancies: There are reports of secondary tumors, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia and bronchial carcinoma. The association with bendamustine therapy has not been determined.
Hepatitis B reactivation: Reactivation of hepatitis B in patients who are chronic carriers of this virus has occurred after these patients received bendamustine hydrochloride. Some cases resulted in acute hepatic failure or a fatal outcome. Patients should be tested for HBV infection before initiating treatment with bendamustine hydrochloride. Carriers of HBV who require treatment with bendamustine hydrochloride should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. See Adverse Reactions.
Effects on Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. However, ataxia, peripheral neuropathy and somnolence have been reported during treatment with Ribomustin (see Adverse Reactions). Patients should be instructed that if they experience these symptoms they should avoid potentially hazardous tasks such as driving and using machines.