Oncology Drug Reference Sheet: Venetoclax

Category/Class

Targeted/small-molecule inhibitor of BCL-2    

Indication  

• CLL or SLL in adults
• AML when used in combination with azacitidine or decitabine or low-dose cytarabine in newly diagnosed adults at least 75 years old or who have comorbidities that prevent the use of intensive induction chemotherapy  

Dosing 

• CLL or SLL: Dosing begins with a five-week ramp up to reduce the risk of tumor lysis syndrome (TLS). If venetoclax is given as part of combination therapy, refer to the full prescribing information for dosing and schedules (https://www.rxabbvie.com/pdf/venclexta.pdf). 

CLL/SLL Dosing Ramp-Up Schedule

week	daily dose
Week 1	20 mg
Week 2	50 mg
Week 3	100 mg
Week 4	200 mg
Week 5 and beyond	400 mg

• AML: Dosing begins with a four-day ramp up, with the final dose depending on the other agent administered.

AML Dosing Ramp-Up Schedule

Day	Daily Dose
Day 1	100 mg
Day 2	200 mg
Day 3	400 mg
Day 4 and beyond	400 mg with azacytidine; 600 mg with low-dose cytarabine

• Dose adjustments may be required in patients with recurrent grade 3–4 toxicities or those who take P-gp or CYP3A inhibitors.

Administration

The oral tablets should be taken with a meal and water at the same time each day.

Adverse Reactions

Patients receiving venetoclax monotherapy experienced TLS (significant, but uncommon with ramp-up dosing, prehydration and antiuricemics), neutropenia, diarrhea, nausea, upper respiratory tract infection, fatigue, musculoskeletal pain, thrombocytopenia, edema, anemia, and febrile neutropenia. Incidence rates may vary with combination therapy.

Nursing Considerations

• Before beginning venetoclax therapy, patients should be assessed for TLS risk, as indicated by tumor burden and comorbidities. 
• To reduce TLS risk, patients should receive pro­phylactic hydration and antiuricemics before beginning treatment. 
• For the first dose, patients should have bloodwork done to monitor for TLS before, six to eight hours after, and 24 hours after the dose. Repeat the lab tests with the first increased dose on the ramp-up schedule. 
• Women of reproductive potential should have a pregnancy test before beginning treatment with venetoclax. 
• Blood counts should be monitored throughout treatment for hematologic and nonhematologic toxicities. 
• Concurrent treatment with P-gp inhibitors or strong or moderate CYP3A inhibitors can increase toxicity from venetoclax and should be avoided. Strong CYP3A inhibitors are contraindicated during treatment initiation and dose increases. After the full dose is reached, patients who must use P-gp or CYP3A inhibitors will likely need their venetoclax dose adjusted. Strong or moderate CYP3A inducers should be avoided throughout treatment.  

Patient Education

• Advise women that venetoclax can potentially harm a fetus. Women of reproductive potential should use effective contraception during and for at least 30 days after and should not breastfeed while taking venetoclax. 
• Men should be advised of the possibility of infertility and sperm banking options. 
• Patients must avoid grapefruit products, Seville oranges, and starfruit while taking venetoclax. 
• Patients should contact their oncology care providers before taking any new prescription or over-the-counter drugs. 
• Advise patients to not get live attenuated vaccines prior to, during, or after treatment with venetoclax until B-cell recovery occurs. 
• Teach patients how to monitor for and decrease the risk of infection and bleeding, including when to contact their healthcare providers. 
• Instruct patients to take venetoclax at a similar time each day with a meal and water. If they are within eight hours of a missed dose, they should take it as soon as possible. If it has been more than eight hours, they should wait until the next scheduled dose. If they vomit after taking a dose, they should not repeat the venetoclax but wait until their next scheduled dose. 

Gero-Oncology Considerations

No clinically significant differences in safety and effectiveness were found between older and younger patients who received venetoclax during clinical trials.   

Safe Handling

Venetoclax is considered a hazardous drug because of its reproductive risk. Venetoclax was found to cause embryo-fetal harm in animal studies, and testicular germ cell toxicity was seen in male animals.