Venetoclax

What is Venetoclax?

Venetoclax (Venclexta) is a BCL-2 inhibitor used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).

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What are the uses of this medicine?

This medicine is 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.

How does this medicine work?

• Venetoclax (ven et' oh klax) is a small molecule inhibitor of BCL-2, an intracellular protein that inhibits apoptosis.
• BCL2 is overexpressed in cancer cells, particularly in chronic lymphocyte leukemia (CLL).
• Overexpression of BCL2 increases cancer cell survival and increases resistance to chemotherapy.
• Venetoclax binds directly to BCL2 and blocks its antiapoptotic activity, leading to programmed cell death in the malignant B cells.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• use strong CYP3A inhibitors (eg: itraconazole, ketoconazole, clarithromycin) at initiation and during ramp-up phase.

What drug interactions can this medicine cause?

• Concomitant use with a strong CYP3A inhibitor at initiation and during the ramp-up phase in patients with CLL/SLL is contraindicated.
• Avoid grapefruit products, Seville oranges, and starfruit during treatment with Venclexta, as they contain inhibitors of CYP3A.
• Avoid concomitant use of Venclexta with strong CYP3A inducers or moderate CYP3A inducers.
• Adjust dosage of Venclexta while using with Strong or moderate CYP3A inhibitors or P-gp inhibitors.
• Avoid concomitant use of Venclexta with a P-gp substrate. If a concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before Venclexta.

Is this medicine FDA approved?

• It was approved for use in the United States in 2016.

How should this medicine be used?

• Provide prophylaxis for tumor lysis syndrome.

Recommended Dosage:

Recommended Dosage for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphomaː

• Administer Venclexta according to the 5-week ramp-up dosing schedule to the recommended dosage of 400 mg orally once daily as shown below:

	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

Recommended Dosage for Acute Myeloid Leukemiaː 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 below:

	Venclexta
Oral Daily Dose
Day 1	100 mg
Day 2	200 mg
Day 3	400 mg
Days 4 and beyond	400 mg orally once daily of each 28-day cycle
in combination with
azacitidine or decitabine	600 mg orally once daily of each 28-day cycle
in combination with
low-dose cytarabine

Dosage Modifications for Patients with Severe Hepatic Impairmentː

• Reduce the Venclexta once daily dose by 50% for patients with severe hepatic impairment.

Administration

• 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.
• Take Venclexta 1 time a day with a meal and water at about the same time each day.
• Swallow Venclexta tablets whole. Do not chew, crush, or break the tablets.
• 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 of Venclexta and it has been more than 8 hours, skip the missed dose and take the next dose at your usual time.
• If you vomit after taking Venclexta, do not take an extra dose. Take the next dose at your usual time the next day.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 10 mg, 50 mg, 100 mg

This medicine is available in fallowing brand namesː

• Venclexta

What side effects can this medication cause?

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

• 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 in combination with azacitidine, or decitabine, or low–dose cytarabine in people with AML include:

• 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 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

Venclexta can cause serious side effects, including:

• Low white blood cell count (neutropenia)
• Infections

What special precautions should I follow?

• 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.
• Tumor lysis syndrome (TLS), including fatal events and renal failure requiring dialysis, has occurred in patients treated with Venclexta. Premedicate with anti-hyperuricemics and ensure adequate hydration. Employ more intensive measures (intravenous hydration, frequent monitoring, hospitalization) as overall risk increases.
• Neutropenia may occur. Monitor blood counts. Interrupt dosing and resume at same or reduced dose. Consider supportive care measures.
• Fatal and serious infections, such as pneumonia and sepsis, have occurred in patients treated with Venclexta. Monitor for signs and symptoms of infection and treat promptly. Withhold for Grade 3 and 4 infection until resolution and resume at same or reduced dose.
• Do not administer live attenuated vaccines prior to, during, or after treatment with Venclexta until B-cell recovery.
• Venclexta may cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.
• Treatment of patients with multiple myeloma with Venclexta in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

What to do in case of emergency/overdose?

Management for overdosage:

• There is no specific antidote for Venclexta.
• For patients who experience overdose, closely monitor and provide appropriate supportive treatment.
• Based on venetoclax large volume of distribution and extensive protein binding, dialysis is unlikely to result in significant removal of venetoclax.

Can this medicine be used in pregnancy?

• There are no available data on Venclexta use in pregnant women to inform a drug-associated risk.

Can this medicine be used in children?

• The safety and effectiveness of Venclexta have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

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

The 10 mg and 100 mg coated tablets also include: iron oxide yellow, polyvinyl alcohol, polyethylene glycol, talc, and titanium dioxide. The 50 mg coated tablets also include: iron oxide yellow, iron oxide red, iron oxide black, polyvinyl alcohol, talc, polyethylene glycol, and titanium dioxide.

Who manufactures and distributes this medicine?

Manufactured and Marketed by:

• AbbVie Inc.
• North Chicago

Marketed by:

• Genentech USA, Inc.
• A Member of the Roche Group
• South San Francisco

What should I know about storage and disposal of this medication?

• Store Venclexta at or below 86°F (30°C).
• 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 Venclexta and all medicines out of reach of children.

• Dailymed label info on Venetoclax
• FDA Venetoclax

Venetoclax Resources
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