ed fetal body weight at 150 mg/kg/day (maternal exposures approximately 1.2 times the human AUC exposure at the recommended dose of 400 mg daily). No teratogenicity was observed in either the mouse or the rabbit.
8.2 LactationRisk Summary
There are no data on the presence of VENCLEXTA in human milk, the effects of VENCLEXTA on the breastfed child, or the effects of VENCLEXTA on milk production. Because many drugs are excreted in human milk and because the potential for serious adverse reactions in breastfed infants from VENCLEXTA is unknown, advise nursing women to discontinue breastfeeding during treatment with VENCLEXTA.
8.3 Females and Males of Reproductive PotentialVENCLEXTA may cause fetal harm [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)].
Pregnancy Testing
Females of reproductive potential should undergo pregnancy testing before initiation of VENCLEXTA [see Use in Specific Populations (8.1)].
Contraception
Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for at least 30 days after the last dose [see Use in Specific Populations (8.1)].
Infertility
Based on findings in animals, male fertility may be compromised by treatment with VENCLEXTA [see Nonclinical Toxicology (13.1)].
8.4 Pediatric UseSafety and effectiveness have not been established in pediatric patients.
8.5 Geriatric UseOf the 106 patients with previously treated CLL with 17p deletion who were eva luated for efficacy, 57% were ≥65 years of age and 17% were ≥75 years of age.
Of the 240 patients with previously treated CLL eva luated for safety from 3 open-label trials, 58% were ≥65 years of age and 17% were ≥75 years of age.
No overall differences in safety and effectiveness were observed between older and younger patients.
8.6 Renal ImpairmentPatients with reduced renal function (CrCl <80 mL/min) are at increased risk of TLS. These patients may require more intensive prophylaxis and monitoring to reduce the risk of TLS when initiating treatment with VENCLEXTA [see Dosage and Administration (2.3, 2.4)].
No specific clinical trials have been conducted in subjects with renal impairment. Less than 0.1% of radioactive VENCLEXTA dose was detected in urine. No dose adjustment is needed for patients with mild or moderate renal impairment (CrCl ≥30 mL/min) based on results of the population pharmacokinetic analysis [see Clinical Pharmacology (12.3)]. A recommended dose has not been determined for patients with severe renal impairment (CrCl <30 mL/min) or patients on dialysis.
8.7 Hepatic ImpairmentNo specific clinical trials have been conducted in subjects with hepatic impairment, however human mass balance study showed that venetoclax undergoes hepatic elimination. Although no dose adjustment is recommended in patients with mild or moderate hepatic impairment based on results of the population pharmacokinetic analysis [see Clinical Pharmacology (12.3)], a trend for increased adverse events was observed in patients with moderate hepatic impairment; monitor these patients more closely for signs of toxicity during the initiation and dose ramp-up phase. A recommended dose has not been determined for patients with severe hepatic impairment.
10 OVERDOSAGE
There is no specific antidote for VENCLEXTA. For patients who experience overdose, closely monitor and provide appropriate supportive treatment; during ramp-up phase interrupt VENCLEXTA and monitor care |
