Venclexta Venetoclax 100 mg Tablet, Film Coated, 120-count

1 INDICATIONS AND USAGE VENCLEXTA is a BCL-2 inhibitor indicated: For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ( 1.1 ) In combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. ( 1.2 )

1.1Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

1.2Acute Myeloid Leukemia VENCLEXTA is indicated in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for recommended VENCLEXTA dosages. ( 2.2 , 2.3 ) Take VENCLEXTA tablets orally once daily with a meal and water. ( 2.8 ) Provide prophylaxis for tumor lysis syndrome. ( 2.1 , 2.4 )

2.1Important Safety Information Assess patient-specific factors for level of risk of tumor lysis syndrome (TLS) and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of VENCLEXTA to reduce risk of TLS [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5.1 )].

2.2Recommended Dosage for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma VENCLEXTA dosing begins with a 5-week ramp-up. The 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS. VENCLEXTA 5-week Dose Ramp-Up Schedule Administer VENCLEXTA according to the 5-week ramp-up dosing schedule to the recommended dosage of 400 mg orally once daily as shown in Table 1 .

Table 1. Dosing Schedule for 5-Week Ramp-up Phase for Patients with CLL/SLL VENCLEXTA Oral Daily Dose Week 1 20 mg Week 2 50 mg Week 3 100 mg Week 4 200 mg Week 5 and beyond 400 mg The CLL/SLL Starting Pack provides the first 4 weeks of VENCLEXTA according to the ramp-up schedule [see How Supplied/Storage and Handling ( 16 )] . In Combination with Acalabrutinib Cycle 1 Day 1: Start acalabrutinib 100 mg orally approximately every 12 hours until disease progression, unacceptable toxicity or completion of 14 cycles of treatment.

Each cycle is 28 days. Refer to the acalabrutinib prescribing information for additional dosing information. Cycle 3 Day 1: start VENCLEXTA according to the 5-week ramp-up dosing schedule (see Table 1 ).

After completing the ramp-up phase, continue VENCLEXTA at a dose of 400 mg orally once daily until disease progression, unacceptable toxicity, or until the last day of Cycle 14. In Combination with Obinutuzumab Start obinutuzumab administration at 100 mg on Cycle 1 Day 1, followed by 900 mg on Cycle 1 Day 2. Administer 1,000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for a total of 6 cycles.

Refer to the obinutuzumab prescribing information for additional dosing information. On Cycle 1 Day 22, start VENCLEXTA according to the 5-week ramp-up dosing schedule (see Table 1 ). After completing the ramp-up phase on Cycle 2 Day 28, continue VENCLEXTA at a dose of 400 mg orally once daily from Cycle 3 Day 1 until the last day of Cycle 12.

In Combination with Rituximab Start rituximab administration after the patient has completed the 5-week ramp-up dosing schedule for VENCLEXTA (see Table 1 ) and has received VENCLEXTA at the recommended dosage of 400 mg orally once daily for 7 days. Administer rituximab on Day 1 of each 28-day cycle for 6 cycles, at a dose of 375 mg/m 2 intravenously for Cycle 1 and 500 mg/m 2 intravenously for Cycles 2-6. Continue VENCLEXTA 400 mg orally once daily for 24 months from Cycle 1 Day 1 of rituximab.

Refer to the rituximab prescribing information for additional dosing information. Monotherapy The recommended dosage of VENCLEXTA is 400 mg once daily after completion of the 5-week ramp-up dosing schedule (see Table 1 ). Continue VENCLEXTA until disease progression or unacceptable toxicity.

2.3Recommended Dosage for Acute Myeloid Leukemia The recommended dosage and ramp-up of VENCLEXTA depends upon the combination agent. Follow the dosing schedule, including the 3-day or 4-day dose ramp-up, as shown in Table 2. Start VENCLEXTA administration on Cycle 1 Day 1 in combination with: Azacitidine 75 mg/m 2 intravenously or subcutaneously once daily on Days 1-7 of each 28-day cycle; OR Decitabine 20 mg/m 2 intravenously once daily on Days 1-5 of each 28-day cycle; OR Cytarabine 20 mg/m 2 subcutaneously once daily on Days 1-10 of each 28-day cycle.

Table 2. Dosing Schedule for 3- or 4-Day Ramp-up Phase in Patients with AML VENCLEXTA Oral Daily Dose Day 1 100 mg Day 2 200 mg Day 3 400 mg D…

3 DOSAGE FORMS AND STRENGTHS Table 9. VENCLEXTA Tablet Strength and Description Tablet Strength Description of Tablet 10 mg Round, biconvex shaped, pale yellow film-coated tablet debossed with “V” on one side and “10” on the other side 50 mg Oblong, biconvex shaped, beige film-coated tablet debossed with “V” on one side and “50” on the other side 100 mg Oblong, biconvex shaped, pale yellow film-coated tablet debossed with “V” on one side and “100” on the other side Tablets: 10 mg, 50 mg, 100 mg ( 3 )

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Tumor Lysis Syndrome Advise patients of the potential risk of TLS, particularly at treatment initiation, during the ramp-up phase, and with resumption after an interruption and to immediately report any signs and symptoms associated with this event (fever, chills, nausea, vomiting, confusion, shortness of breath, seizure, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle or bone pain, and/or joint discomfort) to their health care provider (HCP) for evaluation [see Warnings and Precautions ( 5.1 )] .

Advise patients to be adequately hydrated every day when taking VENCLEXTA to reduce the risk of TLS. The recommended volume is 6 to 8 glasses (approximately 56 ounces total) of water each day. Patients should drink water starting 2 days before and on the day of the first dose, and every time the dose is increased [see Dosage and Administration ( 2.4 )] .

Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests [see Dosage and Administration ( 2.4 )] . Advise patients that it may be necessary to take VENCLEXTA in the hospital or medical office setting to allow monitoring for TLS. Neutropenia Advise patients to contact their HCP immediately if they develop a fever or any signs of infection.

Advise patients of the need for periodic monitoring of blood counts [see Warnings and Precautions ( 5.2 )] . Infections Advise patients to contact their HCP immediately if they develop a fever or any signs of infection [see Warnings and Precautions ( 5.3 )] . Drug Interactions Advise patients to avoid consuming grapefruit products, Seville oranges, or starfruit during treatment with VENCLEXTA.

Advise patients that VENCLEXTA may interact with some drugs; therefore, advise patients to inform their health care provider of the use of any prescription medication, over-the-counter drugs, vitamins and herbal products [see Contraindications ( 4 ) and Drug Interactions ( 7.1 )] . Immunizations Advise patients to avoid vaccination with live vaccines because they may not be safe or effective during treatment with VENCLEXTA [see Warnings and Precautions ( 5.4 )] . Embryo-Fetal Toxicity Advise pregnant women of the potential risk to the fetus.

Advise females or reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.5 ) and Use in Specific Populations ( 8.1 )] . Advise female patients of reproductive potential to use effective contraception during therapy and for 30 days after the last dose [see Use in Specific Populations ( 8.3 )] . Lactation Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week after the last dose [see Use in Specific Populations ( 8.2 )] .

Infertility Advise males of reproductive potential that VENCLEXTA may impair fertility [see Use in Specific Populations ( 8.3 )] . Administration Advise patients to keep VENCLEXTA in original packaging or container. Advise patients to take VENCLEXTA exactly as prescribed and not to change their dose or to stop taking VENCLEXTA unless they are told to do so by their HCP.

Advise patients to take VENCLEXTA orally once daily, at approximately the same time each day, according to their HCP's instructions and that the tablets should be taken with a meal and water [see Dosage and Administration ( 2.8 )] . Advise patients to contact their HCP if they have trouble swallowing VENCLEXTA tablets. A dose in smaller sized tablets may be prescribed, or tablets may be crushed and mixed with ½ cup (4 ounces) of water, apple juice, apple sauce, or yogurt.

Take the entire dose immediately with a meal and water. Do not crush more than one dose at a time [see Dosage and Administration ( 2.8 )] . Crushed tablets may cause yellow staining, including of the skin.

Consider using disposable gloves when handling crushed tablets. Advise patients that if a…

MEDICATION GUIDE VENCLEXTA ® (ven-KLEKS-tuh) (venetoclax tablets) What is the most important information I should know about VENCLEXTA? VENCLEXTA can cause serious side effects, including: Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells.

TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS.

You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start and during treatment with VENCLEXTA. It is important to keep your appointments for blood tests.

Tell your healthcare provider right away if you get any symptoms of TLS during treatment with VENCLEXTA, including: ○ fever ○ chills ○ nausea ○ vomiting ○ confusion ○ shortness of breath ○ seizures ○ irregular heartbeat ○ dark or cloudy urine ○ unusual tiredness ○ muscle or joint pain Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS . Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you get symptoms of TLS. When restarting VENCLEXTA after stopping for 1 week or longer, your healthcare provider may again check for your risk of TLS and change your dose. See " What are the possible side effects of VENCLEXTA? " for more information about side effects.

What is VENCLEXTA? VENCLEXTA is a prescription medicine used: to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly diagnosed acute myeloid leukemia (AML) who: ○ are 75 years of age or older, or ○ have other medical conditions that prevent the use of standard chemotherapy. It is not known if VENCLEXTA is safe and effective in children.

Who should not take VENCLEXTA? People taking certain medicines during the beginning of VENCLEXTA treatment (when the dose is being slowly increased) are at increased risk of TLS. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

VENCLEXTA and other medicines may affect each other causing serious side effects. Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider. Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you: have kidney problems have liver problems have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium have a history of high uric acid levels in your blood or gout are scheduled to receive a vaccine.

You should not receive a “live vaccine” before, during, or after treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA. are pregnant or plan to become pregnant.

VENCLEXTA may harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA. Use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA.

If you become pregnant or think you are pregnant, tell your healthcare provider right away. are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment and for 1 week after the last dose…