VIVIMUSTA

AbsorptionFollowing a single IV dose of bendamustine hydrochloride C max typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied.

DistributionThe protein binding of bendamustine ranged from 94-96% and was concentration independent from 1 to 50 μg/mL. The blood to plasma concentration ratios in human blood ranged from 0.84 to 0.86 over a concentration range of 10 to 100 μg/mL. The mean steady-state volume of distribution (V ss ) of bendamustine w...

14.1 Chronic Lymphocytic Leukemia (CLL) The efficacy of bendamustine hydrochloride was evaluated in an open-label, randomized, controlled multicenter trial comparing bendamustine hydrochloride to chlorambucil. The trial was conducted in 301 previously-untreated patients with Binet Stage B or C (Rai Stages I - IV) CLL requiring treatment. Need-to-treat criteria included hematopoietic insufficiency, B-symptoms, rapidly progressive disease or risk of complications from bulky lymphadenopathy. Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia, Richter’s syndrome, or transform...

The following clinically significant adverse reactions are described elsewhere in the labelling:

• Myelosuppression [see Warnings and Precautions ( 5.1 )]
• Infections [see Warnings and Precautions ( 5.2 )]
• Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions ( 5.3 )]
• Anaphylaxis and Infusion-Related Reactions [see Warnings and Precautions ( 5.4 )]
• Tumor Lysis Syndrome [see Warnings and Precautions ( 5.5 )]
• Skin Reactions [see Warnings and Precautions ( 5.6 )]
• Hepat...

VIVIMUSTA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, dehydrated alcohol, or monothioglycerol [see Warnings and Precautions ( 5.4 )] History of a hypersensitivity reaction to bendamustine, polyethylene glycol 400, dehydrated alcohol, or monothioglycerol. Reactions to bendamustine hydrochlori...

• Myelosuppression : Delay or reduce dose, and restart treatment based on ANC and platelet count recovery. ( 5.1 )
• Infections : Monitor for fever and other signs of infection or reactivation of infections and treat promptly. ( 5.2 )
• Progressive multifocal leukoencephalopathy (PML) : Monitor for new or worsening neurological, cognitive or behavioral signs or symptoms suggestive of PML. ( 5.3 )
• Anaphylaxis and Infusion-Related Reactions : Severe anaphylactic reactions have occurred. Monitor ...

7 DRUG INTERACTIONS Consider alternative therapies that are not CYP1A2 inducers or inhibitors during treatment with VIVIMUSTA. ( 7.1 ) 7.1 Effect of Other Drugs on VIVIMUSTA CYP1A2 Inhibitors The coadministration of VIVIMUSTA with CYP1A2 inhibitors may increase bendamustine plasma concentrations and may result in increased incidence of adverse reactions with VIVIMUSTA [see Clinical Pharmacology ( ...