Category: pharmacological
Aliases: Venclexta, ABT-199
Selective Bcl-2 inhibitor (BH3 mimetic) — restores apoptosis in B-cell malignancies overexpressing Bcl-2. Indications: CLL (with rituximab or obinutuzumab), AML (with HMAs in unfit elderly). Strong CYP3A4 + P-gp substrate. Initiated with a 5-week dose ramp (20 → 50 → 100 → 200 → 400 mg) to minimize tumor lysis syndrome risk — at initiation TLS can be fatal in patients with high tumor burden. Strong CYP3A4 inhibitors are contraindicated during ramp-up. PK (Venclexta label, SS 400 mg PO qd with low-fat meal): Cmax 2.1 ± 1.1 µg/mL, AUC0-24 32.8 ± 16.9 µg·h/mL, Tmax 5-8 h (slow absorption — explains the late peak), t½ 17 h healthy (35 h severe hepatic impairment). Apparent V/F ~299 L; protein binding ~99%. Must be taken with food (F drops dramatically fasted). Required 5-week dose ramp at initiation (TLS risk).
PO: 17h