.2 Neutropenia 5.3 Immunization 5.4 Embryo-Fetal Toxicity 6 ADVERSE REACTIONS
6.1 Clinical Trial Experience 7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on VENCLEXTA 7.2 Effects of VENCLEXTA on Other Drugs 8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment 8.7 Hepatic Impairment 10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology 14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are not listed. Close
1 INDICATIONS AND USAGE
VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
2 DOSAGE AND ADMINISTRATION
2.1 Patient SelectionSelect patients for the treatment of relapsed or refractory CLL with VENCLEXTA based on the presence of 17p deletions in blood specimens [see Indications and Usage (1) and Clinical Studies (14)]. Patients without 17p deletion at diagnosis should be retested at relapse because acquisition of 17p deletion can occur. Information on FDA-approved tests for the detection of 17p deletions in CLL is available at: http://www.fda.gov/CompanionDiagnostics.
2.2 Recommended Dosage Assess patient-specific factors for level of risk of tumor lysis syndrome (TLS) and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of VENCLEXTA to reduce risk of TLS [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. Administer the VENCLEXTA dose according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg as shown in Table 1. The 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS.
Instruct patients to take VENCLEXTA tablets with a meal and water at approximately the same time each day. VENCLEXTA tablets should be swallowed whole and not chewed, crushed, or broken prior to swallowing.
Table 1. Dosing Schedule for Ramp-Up Phase Week VENCLEXTA
Daily Dose
1 20 mg
2 50 mg
3 100 mg
4 200 mg
5 and beyond 400 mg
The Starting Pack provides the first 4 weeks of VENCLEXTA according to the ramp-up schedule. Once the ramp-up phase is completed, the 400 mg dose is achieved using 100 mg tablets supplied in bottles [see How Supplied/Storage and Handling (16)].
VENCLEXTA should be taken orally once daily until disease progression or unacceptable toxicity is observed.
2.3 Risk Assessment and Prophylaxis for Tumor Lysis SyndromeVENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS in the initial 5-week ramp-up phase. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase.
The risk of TLS is a continuum based on multiple factors, including tum |
