nt (total bilirubin greater than 3-times the upper limit of normal). No venetoclax dosage adjustment is necessary in patients with mild or moderate hepatic impairment. The risk of adverse events may be increased in patients with moderate hepatic impairment; therefore, monitor these patients more closely for signs of toxicity during venetoclax initiation and dose titration.
Pregnancy
Venetoclax may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should be advised to avoid becoming pregnant while receiving venetoclax. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. In an embryo-fetal study in pregnant mice, post-implantation loss and decreased fetal weight were observed following venetoclax doses that resulted in drug exposures 1.2-times those reported at clinical human doses (400 mg/day). No teratogenicity occurred in mice or rabbits.
Contraception requirements, infertility, pregnancy testing, reproductive risk
Counsel patients about the reproductive risk and contraception requirements during venetoclax treatment. Pregnancy testing should be performed prior to starting venetoclax in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for at least 30 days after venetoclax therapy. Women who become pregnant while receiving venetoclax should be apprised of the potential hazard to the fetus. Venetoclax may cause infertility in male patients based on animal findings; these patients should consider sperm banking.
Breast-feeding
Women should avoid breast-feeding during venetoclax therapy due to the potential for serious adverse reactions in breastfed infants. No information is available regarding the presence of venetoclax in human milk, the effects on the breastfed infant, or the effects on milk production.
ADVERSE REACTIONS
Severe
neutropenia / Delayed / 0-41.0
hyperkalemia / Delayed / 0-20.0
anemia / Delayed / 0-18.0
thrombocytopenia / Delayed / 0-15.0
tumor lysis syndrome (TLS) / Delayed / 6.0-12.0
infection / Delayed / 0-5.0
hypokalemia / Delayed / 0-4.0
renal failure (unspecified) / Delayed / 0-3.9
hypocalcemia / Delayed / 0-3.0
hyperphosphatemia / Delayed / 0-3.0
hyperuricemia / Delayed / 0-2.0
fatigue / Early / 0-2.0
fever / Early / 0-1.0
nausea / Early / 0-1.0
diarrhea / Early / 0-1.0
vomiting / Early / 0-1.0
peripheral edema / Delayed / 0-1.0
back pain / Delayed / 0-1.0
headache / Early / 0-1.0
hemolytic anemia / Delayed / 2.0
Moderate
constipation / Delayed / 0-14.0
Mild
cough / Delayed / 0-13.0
DRUG INTERACTIONS
Alogliptin; Pioglitazone: Avoid the concomitant use of venetoclax and pioglitazone; venetoclax levels may be decreased and its efficacy reduced. Venetoclax is a CYP3A4 substrate and pioglitazone is a moderate CYP3A4 inducer. Consider alternative agents. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were decreased by 42% and 71%, respectively, following the co-administration of multiple doses of a strong CYP3A4 inducer. Use of venetoclax with a moderate CYP3A4 inducer has not been eva luated.
Amiodarone: Avoid the concomitant use of venetoclax and amiodarone; venetoclax is a substrate of CYP3A4 and P-glycoprotein (P-gp) and amiodarone is a CYP3A4 (moderate) and P-gp inhibitor. Consider alternative agents. If conc |
