Treatment considerations for special populations
Use of TREANDA in patients with renal impairment
- In a population pharmacokinetic analysis of TREANDA in patients receiving 120 mg/m2,
there was no meaningful effect of renal impairment (CrCL 40-80 mL/min, N=31) on
the pharmacokinetics of TREANDA
- TREANDA has not been studied in patients with CrCL <40 mL/min
- No formal studies assessing the impact of renal impairment on the pharmacokinetics
of TREANDA have been conducted
- In preclinical studies, approximately 90% of TREANDA administered was recovered
primarily in the feces
Use of TREANDA in patients with hepatic impairment
ULN=upper limit of normal; AST=aspartate aminotransferase; ALP=alkaline phosphatase; ALT=alanine aminotransferase.
- In a population pharmacokinetic analysis of TREANDA in patients receiving 120
mg/m2, there was no meaningful effect of mild (total bilirubin ≤ULN, AST ≥ULN to
2.5 x ULN, and/or ALP ≥ULN to 5.0 x ULN, N=26) hepatic impairment on the pharmacokinetics
of TREANDA
- TREANDA has not been studied in patients with moderate or severe hepatic impairment
- No formal studies assessing the impact of hepatic impairment on the pharmacokinetics
of TREANDA have been conducted
Concomitant CYP1A2 inhibitors or inducers have the potential to affect the exposure
of TREANDA
- TREANDA is primarily metabolized via hydrolysis
- Active metabolites of TREANDA, gamma-hydroxy bendamustine (M3) and N-desmethyl-bendamustine
(M4), are formed via cytochrome P450 CYP1A2
- Use caution or consider alternative treatments when used with concomitant CYP1A2
inhibitors/inducers
- Inhibitors of CYP1A2 include fluvoxamine and ciprofloxacin
- Inducers of CYP1A2 include omeprazole and smoking
- No formal clinical assessments of pharmacokinetic drug-drug interactions between
TREANDA and other drugs have been conducted
Indications
TREANDA is indicated for the treatment of patients with chronic lymphocytic leukemia
(CLL). Efficacy relative to first-line therapies other than chlorambucil has not
been established.
TREANDA is indicated for the treatment of patients with indolent B-cell non-Hodgkin’s
lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab
or a rituximab-containing regimen.
Important Safety Information
- Serious adverse reactions, including myelosuppression, infections, infusion reactions
and anaphylaxis, tumor lysis syndrome, skin reactions including SJS/TEN, other malignancies,
and extravasation, have been associated with TREANDA. Some reactions, such as myelosuppression,
infections, and SJS/TEN (when TREANDA was administered concomitantly with allopurinol
and other medications known to cause SJS/TEN), have been fatal. Patients should
be monitored closely for these reactions and treated promptly if any occur
- Adverse reactions may require interventions such as decreasing the dose of TREANDA,
or withholding or delaying treatment
- TREANDA is contraindicated in patients with a known hypersensitivity to bendamustine
or mannitol. Women should be advised to avoid becoming pregnant while using TREANDA
- The most common non-hematologic adverse reactions associated with TREANDA (frequency ≥30%) were nausea, fatigue, vomiting, diarrhea, and pyrexia. The most common hematologic abnormalities associated with TREANDA (frequency ≥15%) were lymphopenia, leukopenia, anemia, neutropenia, and thrombocytopenia
TO REPORT SIDE EFFECTS: Contact us at 1-800-896-5855 or usmedinfo@cephalon.com
