Venclexta

Venclexta is used to treat chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adults. It is also used in combination with azacitidine, decitabine, low-dose cytarabine, or cedazuridine + decitabine (Inqovi) to treat newly diagnosed acute myeloid leukemia (AML) in adults 75 years and older, or for adults with other medical conditions that prevent the use of standard chemotherapy. Venclexta is a tablet that is taken once daily.

Venclexta (venetoclax) is a BCL-2 inhibitor that works by blocking BCL-2, a protein that prevents cancer cells from dying naturally. CLL, SLL, and AML cancer cells overproduce BCL-2 to survive and resist chemotherapy. Venclexta is not chemotherapy; it is a targeted treatment.

Venclexta (venetoclax) gained FDA approval on April 11, 2016, and is available as a generic.

Take Venclexta exactly as your healthcare provider tells you to take it. Do not change your dose of Venclexta or stop taking Venclexta unless your healthcare provider tells you to.

When you first take Venclexta:

• You may need to take Venclexta at a hospital or clinic to be monitored for TLS.
• If you are taking Venclexta for CLL or SLL, your healthcare provider will start Venclexta at a low dose. Your dose will be slowly increased weekly over 5 weeks up to the full dose. Read the Quick Start Guide that comes with Venclexta before your first dose.
• If you are taking Venclexta for AML, your healthcare provider will start Venclexta at a low dose. Your dose will be slowly increased daily up to the full dose. Follow your healthcare provider's instructions carefully while increasing to the full dose.

Follow the instructions about drinking water described in the section above of this Guide about TLS, and also in the Quick Start Guide.

Take Venclexta 1 time a day with a meal and water at about the same time each day.

• Swallow Venclexta tablets whole with water. Do not chew or break the tablets.
• If you vomit after taking Venclexta, do not take an extra dose. Take the next dose at your usual time the next day.
• Tell your healthcare provider if you have trouble swallowing the 100 mg Venclexta tablets. Your healthcare provider may prescribe your dose in smaller tablets, or you can crush them as described below.

If you are unable to swallow Venclexta tablets whole, the tablets can be crushed:

• Crush the number of tablets needed for your prescribed dose and mix with ½ cup (4 ounces) of water, apple juice, apple sauce, or yogurt.
• Take the entire mixture right away with a meal and water.
• Do not crush more than 1 Venclexta dose at a time.
• Crushed tablets may cause yellow staining, including of the skin. Consider using disposable gloves when handling crushed tablets.

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 treatment and during treatment with Venclexta. It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have 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 have side effects. When restarting Venclexta after stopping for 1 week or longer, your healthcare provider may again check for your risk for TLS and change your dose.

Other Serious Side Effects

Venclexta may cause other serious side effects, including:

• Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta but can also be severe. Your healthcare provider will do blood tests to check your blood counts during treatment and may pause dosing.
• Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with Venclexta.

Tell your healthcare provider right away if you have a fever or any signs of infection during treatment with Venclexta.

Certain medicines must not be taken when you first start taking Venclexta and while your dose is being slowly increased because of the risk of increased tumor lysis syndrome (TLS).

• Tell your healthcare provider about all the medicines you take (see What drugs will affect Venclexta below)
• 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.
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Pregnancy

Venclexta may harm your unborn baby. If you can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Venclexta.

• Females who can become pregnant should use effective birth control during treatmentand for 30 days after the last dose of Venclexta.
• If you become pregnant or think you are pregnant, tell your healthcare provider right away.

Breastfeeding

It is not known if Venclexta passes into your breast milk. Do not breastfeed while using this medicine and for at least 1 week after your last dose.

The most common side effects of Venclexta when used in combination with obinutuzumab, rituximab, or alone in people with CLL or SLL are:

• Low white blood cell count
• Low platelet counts
• Low red blood cell counts
• Diarrhea
• Nausea
• Upper respiratory tract infection
• Cough
• Muscle and joint pain
• Tiredness
• Swelling of your arms, legs, hands, and feet.

The most common side effects of Venclexta when used in combination with azacitidine, decitabine, or low-dose cytarabine in people with AML are:

• Nausea
• Diarrhea
• Low Platelet count
• Constipation
• Low white blood cell count
• Fever with low white blood cell count
• Tiredness
• Vomiting
• Swelling of arms, legs, hands, or feet
• Fever
• Infection in the lungs
• Shortness of breath
• Bleeding
• Low red blood cell count
• Rash
• Stomach (abdominal) pain
• Infection in your blood
• Muscle and Joint Pain
• Dizziness
• Cough
• Sore throat
• Low blood pressure.

The most common side effects of Venclexta when used in combination with acalabrutinib in people with CLL or SLL are:

• Low white blood cell count
• Headache
• Diarrhea
• Muscle and bone pain
• COVID-19.

Notes:

Venclexta may cause fertility problems in males. This may affect your ability to father a child. Talk toyour healthcare provider if you have concerns about fertility

These are not all the possible side effects of Venclexta. Call your doctor for medical advice about side effects. You may report side effects to AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Venetoclax (venetoclax) works by blocking BCL-2, a protein that prevents cancer cells from dying naturally. In CLL, SLL, and AML, cancer cells overproduce BCL-2 to survive and resist chemotherapy. By binding to BCL-2, venetoclax releases death-triggering proteins, initiating a self-destruction process called apoptosis that kills the cancer cells.

Venclexta is not chemotherapy; it is a targeted treatment.

Venetoclax (venetoclax) belongs to the drug class called BCL-2 inhibitors.

Eligible patients with commercial insurance may pay as little as $0 per prescription for Venclexta + Gazyva or Venclexta + Rituxan if they qualify for the Genentech Oncology Co-pay Assistance Program.

See the Venclexta Prices, Coupons, Co-Pay Cards, & Patient Assistance for more information.

Dose of Venclexta for CLL/SLL

Venclexta dosing for CLL or SLL begins with a 5-week ramp-up (titration) phase:

• Week 1: 20 mg orally once daily
• Week 2: 50 mg orally once daily
• Week 3: 100 mg orally once daily
• Week 4: 200 mg orally once daily
• Week 5 and thereafter: 400 mg orally once daily.

Dose of Venclexta for AML

Venclexta dosing for AML begins with a 3-day or 4-day ramp-up (titration) phase:

• Day 1: 100 mg orally once daily
• Day 2: 200 mg orally once daily
• Day 3: 400 mg orally once daily
• Days 4 and beyond: In combination with azacitidine or decitabine: 400 mg orally once daily of each 28-day cycle In combination with low-dose cytarabine: 600 mg orally once daily of each 28-day cycle.

If you miss a dose of Venclexta and it has been less than 8 hours, take your dose as soon as possible. If you miss a dose and it has been more than 8 hours, skip the missed dose and take the next dose at your usual time.

If you vomit shortly after taking Venclexta, do not take another tablet. Take your next dose as scheduled the next day.

You should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking Venclexta. These products may increase the amount of Venclexta in your blood.

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. Especially tell them if you take:

• Antibiotics or antifungals
• Heart medications
• Hepatitis C or HIV medications
• Strong or moderate CYP3A inhibitors or P-gp inhibitors, such as posaconazole, clarithromycin, and ketoconazole
• Strong or moderate CYP3A inducers, such as carbamazepine, fosphenytoin, or dexamethasone
• P-gp substrates, such as apixaban, colchicine, cyclosporine, dabigatran, digoxin, edoxaban, rivaroxaban, or tacrolimus.

You should also avoid grapefruit, grapefruit products, Seville oranges, or starfruit during treatment with Venclexta because these increase your risk of side effects.

Not all possible interactions are listed here. See the Venclexta Prescribing Information for a full list of interactions.

Store Venclexta at room temperature at or below 86°F (30°C)

Keep it in its original container to protect it from moisture.

For people with CLL or SLL, keep Venclexta tablets in the original package during the first 4 weeks of treatment. Do not transfer the tablets to a different container.

Keep out of reach of children.

Active ingredient: venetoclax

Inactive ingredients: copovidone, colloidal silicon dioxide, polysorbate 80, sodium stearyl fumarate, and calcium phosphate dibasic.

Film coating (10 mg and 100 mg tablets): iron oxide yellow, polyvinyl alcohol, polyethylene glycol, talc, and titanium dioxide.

Film coating (50 mg tablets): iron oxide yellow, iron oxide red, iron oxide black, polyvinyl alcohol, talc, polyethylene glycol, and titanium dioxide.

Available as 10 mg, 50 mg, and 100 mg tablets.

Venclexta is manufactured and marketed by AbbVie Inc., North Chicago, IL 60064. It is also marketed by Genentech USA, Inc., a member of the Roche Group, South San Francisco, CA 94080-4990.