Veneta 50 mg (Venetoclax INN 10mg, 50mg & 100mg Tablet)

Description

Composition: Veneta-10: Each film coated tablet contains Venetoclax INN 10mg.
Veneta-50: Each film coated tablet contains Venetoclax INN 50mg.
Veneta-100: Each film coated tablet contains Venetoclax INN 100mg.
Pharmacology:
Pharmacodynamics: Cardiac Electrophysiology: The effect of multiple doses of
Venetoclax up to 1200 mg once daily (2 times the maximum approved recommended
dosage) on the QTc interval was evaluated in an open-label, single-arm trial in 176 patients
with previously treated hematologic malignancies. Venetoclax had no large effect on QTc
interval (i.e., >20 ms) and there was no relationship between Venetoclax exposure and
change in QTc interval.
Pharmacokinetics: Absorption: Maximum plasma concentration was reached 5 to 8 hours
following multiple oral administration under fed conditions. Effect of Food: Administration
with a low-fat meal (approximately 512 kilocalories, 25% fat calories, 60% carbohydrate
calories, and 15% protein calories) increased Venetoclax exposure by approximately 3.4-fold
and administration with a high-fat meal (approximately 753 kilocalories, 55% fat calories,
28% carbohydrate calories, and 17% protein calories) increased Venetoclax exposure by
5.1-to 5.3-fold compared with fasting conditions. Distribution: Venetoclax is highly bound to
human plasma protein with unbound fraction in plasma <0.01 across a concentration range of 1-30 micromolar (0.87-26 mcg/mL). The mean blood-to-plasma ratio was 0.57. The apparent volume of distribution (Vdss/F) of Venetoclax ranged from 256-321 L in patients. Elimination: The terminal elimination half-life was approximately 26 hours. Metabolism: Venetoclax is predominantly metabolized by CYP3A in vitro. The major metabolite identified in plasma, M27, has an inhibitory activity against BCL-2 that is at least 58-fold lower than Venetoclax in vitro and its AUC represented 80% of the parent AUC. Excretion: After single oral dose of radiolabeled [14C]-Venetoclax 200 mg to healthy subjects, >99.9% of the dose
was recovered in feces (21% as unchanged) and <0.1% in urine within 9 days.
Indications:
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Venetoclax is indicated
for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small
lymphocytic lymphoma (SLL). Acute Myeloid Leukemia: Venetoclax is indicated in
combination with Azacitidine, or Decitabine, or low-dose Cytarabine for the treatment of
newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have
comorbidities that preclude use of intensive induction chemotherapy.
Dosage & administration:
Important Safety Information: 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 Venetoclax to reduce risk of TLS