Venetoclax
Venetoclax. Selective Bcl-2 inhibitor (BH3 mimetic) — restores apoptosis in B-cell malignancies overexpressing Bcl-2. Indications: CLL (with… Oral half-life 17 h.
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).
PK PROVENANCE, moved here from source_label when that field was shortened to a citation that names the label revision: FDA label: Venclexta (venetoclax) — 400 mg PO qd with a low-fat meal at steady state, V/F within the label 256–321 L range. t½ 17 h is NOT the label figure (the label says ~26 h) but an interior pick from PMID:27558232; ka is derived from a verbatim Tmax 5–8 h. PK: A LABEL CITATION THAT ATTRIBUTES TO THE LABEL A NUMBER THE LABEL CONTRADICTS. The stored half-life is presented as a Venclexta label value and THE LABEL SAYS ABOUT TWENTY-SIX HOURS; the stored figure is a pick from inside a cited range, "ranged between 14.1 and 18.2 hours at different doses", and two other verbatim means exist that are neither. THE NUMBER IS KEPT AND THE ATTRIBUTION IS FIXED, because the label three exposure figures are mutually inconsistent in one compartment by a factor of 1.59 and the shorter half-life is what makes exposure close — which is precisely why it was picked. The absorption rate is the real defect: it implied a peak at 11.9 h against a verbatim "Venetoclax peak exposures were achieved at 5 to 8 hours under low-fat conditions" and under-predicted the peak roughly two-fold. The apparent volume is back-derived but LANDS INSIDE THE LABEL OWN STATED RANGE, so it is a near-miss and must not be corrected. MY ABIRATERONE COMPARISON IS REFUTED: the food effect is real and roughly four-fold, but the label MANDATES food and this record already declares the low-fat fed state, so a single fed-state parameterisation IS the clinically realised one — unlike abiraterone, where the label instruction and the food effect pull apart.
Pharmacokinetics
- Oral — t½ 17 h · F 100% · ka 0.38 h⁻¹ · Vd 299 L
Sources: PMID:27558232