Venetoclax

Venetoclax (brand name 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. Venetoclax is a tablet that is taken once daily.

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. Venetoclax is not chemotherapy; it is a targeted treatment.

Venetoclax gained FDA approval on April 11, 2016, under the brand name Venclexta. It is also available as a generic.

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

When you first take venetoclax:

• You may need to take venetoclax at a hospital or clinic to be monitored for TLS.
• If you are taking venetoclaxa for CLL or SLL, your healthcare provider will start venetoclax 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 venetoclax before your first dose.
• If you are taking venetoclax for AML, your healthcare provider will start venetoclax 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 venetoclax 1 time a day with a meal and water at about the same time each day.

• Swallow venetoclax tablets whole with water.
• If you vomit after taking venetoclax, 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 venetoclax 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 venetoclax 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 venetoclax dose at a time.
• Crushed tablets may cause yellow staining, including of the skin. Consider using disposable gloves when handling crushed tablets.

Do not stop using this medicine without first asking your doctor.

Call your doctor at once if you have:

• Symptoms of sepsis, such as confusion, severe drowsiness, rapid breathing, and feeling very ill
• Signs of pneumonia, such as cough with yellow or green mucus, stabbing chest pain, wheezing, trouble breathing
• Low blood cell counts, such as fever, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed
• Signs of tumor cell breakdown, such as chills, joint or muscle pain, feeling tired or short of breath, fast or slow heartbeats, nausea, vomiting, dark or cloudy urine, or seizure (convulsions).

Serious Side Effects

Venetoclax can cause the following serious side effects:

• 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 of TLS and change your dose.

To make sure venetoclax is safe for you, tell your doctor 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 venetoclax 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

Venetoclax may harm an unborn baby. You may need a pregnancy test to make sure you are not pregnant. Use birth control while using venetoclax and for at least 30 days after your last dose. Tell your doctor if you become pregnant.

Breastfeeding

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

Male fertility

It may be harder for a man to get a woman pregnant while using this medicine.

Most Common Side Effects

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

• 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 venetoclax 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.

The most common side effects of venetoclax 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.

Other Serious Side Effects

Venetoclax may cause the following other serious side effects:

• Low white blood cell counts (neutropenia). Low white blood cell counts are common with venetoclax 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 venetoclax. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with venetoclax.

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

Notes:

Venetoclax 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 venetoclax. 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 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.

Venetoclax is not chemotherapy; it is a targeted treatment.

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

Venetoclax is only available as the brand Venclexta. The cost of venetoclax varies depending on your insurance plan and which pharmacy you use. Refer to our price guide page for more information about Venclexta 's cost.

You may also be eligible for a Venclexta coupon or a Venclexta copay card. Ask your doctor or pharmacist if you qualify. There is no Venclexta generic.

Dose of venetoclax for CLL/SLL

Venetoclax 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 venetoclax for AML

Venetoclax 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 venetoclax 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 venetoclax, do not take another tablet. Take your next dose as scheduled the next day.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid receiving a "live" vaccine while receiving venetoclax because the vaccine may not work as well. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles).

Grapefruit, starfruit, and Seville oranges may interact with venetoclax and cause unwanted side effects. Avoid consuming grapefruit products, starfruit, and orange marmalades.

Other drugs may interact with venetoclax and affect the blood levels of other drugs you take, which may increase side effects or make the medications less effective. Tell your pharmacist or healthcare provider about all the medicines you take, including any prescription and over-the-counter medicines, vitamins, or herbal supplements. Especially tell them if you take:

• antibiotic or antifungal medications
• heart medications
• antiviral medications to treat hepatitis C or HIV.
• strong or moderate CYP3A inhibitors or P-gp inhibitors, such as posaconazole, clarithromycin, and ketoconazole. The dosage of venetoclax will need adjusting.
• strong or moderate CYP3A inducers, such as carbamazepine, fosphenytoin, or dexamethasone. Taking these drugs at the same time as venetoclax should be avoided
• P-gp substrates, such as apixaban, colchicine, cyclosporine, dabigatran, digoxin, edoxaban, rivaroxaban, or tacrolimus. Take these medications at least 6 hours before venetoclax.

You should also avoid grapefruit, grapefruit products, Seville oranges, or starfruit during treatment with venetoclax because these prevent venetoclax from being metabolized properly and increase your risk of side effects.

Not all possible interactions are listed here. See the venetoclax prescribing information for a full list of interactions.

Store Venclexta tablets in their original container at room temperature, away from moisture and heat. Do not put the tablets into a daily pill box.

Keep out of reach of children.

Venetoclax is only available under the brand Venclexta.

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 Venclexta 10 mg, 50 mg, and 100 mg tablets.

Venetoclax 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.