Venetoclax

Venetoclax is a prescription medicine used to treat the symptoms of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML).

• Venetoclax is available under the following different brand names: Venclexta

Adult dosage

Tablet

• 10mg
• 50mg
• 100mg

Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Adult dosage

Dose ramp-up 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 beyond: 400 mg orally once daily

 Monotherapy

• 400 mg orally once daily after completing the 5-week dose ramp-up schedule
• Continue until disease progression or unacceptable toxicity

Combination with obinutuzumab

Cycle 1

• Day 1: Obinutuzumab 100 mg IV
• Day 2: Obinutuzumab 900 mg IV
• Days 8 and 15: Obinutuzumab 1000 mg IV
• Day 22: Start venetoclax according to 5-week ramp-up schedule

Cycle 2

• Day 1: Obinutuzumab 1000 mg IV
• Day 28: After completing the ramp-up phase on Cycle 2 Day 28, continue venetoclax 400 mg once daily from Cycle 3 Day 1 until Cycle 12 Day 28

Cycles 3-6

• Day 1: Obinutuzumab 1000 mg IV
• Days 1-28: Continue venetoclax 400 mg orally once daily
• Cycles 7-12
• Days 1-28: Continue venetoclax 400 mg orally once daily

Combination with rituximab

Venetoclax

• Complete 5-week ramp-up dosing to reach 400 mg orally once daily
• Continue venetoclax 400 mg once daily for 24 months from Cycle 1 Day 1 of rituximab

Rituximab

• Initiate 375 mg/m² IV after the patient has received venetoclax 400 mg/day x 7 days (i.e., this will be Day 1 of Cycle 1)
• 500 mg/m² IV on Day 1 for Cycles 2-6

Acute Myeloid Leukemia

Adult dosage

Dose ramp-up phase

• Day 1: 100 mg orally once daily
• Day 2: 200 mg orally once daily
• Day 3: 400 mg orally once daily
• Day 4 and beyond (in combination with decitabine or azacitidine): 400 mg orally once daily
• Day 4 and beyond (in combination with low-dose cytarabine): 600 mg orally once daily
• In combination with decitabine, azacitidine, or low-dose cytarabine: Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Venetoclax include:

• diarrhea,
• nausea,
• vomiting,
• tiredness, and
• headache

Serious side effects of Venetoclax include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• easy bruising or bleeding,
• sore throat,
• fever,
• chills,
• cough,
• low back or side pain,
• painful urination,
• pink or bloody urine,
• changes in the amount of urine,
• muscle spasms,
• weakness, and
• severe dizziness.

Rare side effects of Venetoclax include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Venetoclax has severe interactions with the following drugs:
  • atazanavir
  • clarithromycin
  • cobicistat
  • conivaptan
  • darunavir
  • fosamprenavir
  • grapefruit
  • idelalisib
  • imatinib
  • indinavir
  • isoniazid
  • itraconazole
  • ketoconazole
  • levoketoconazole
  • lopinavir
  • nefazodone
  • nelfinavir
  • nicardipine
  • posaconazole
  • ritonavir
  • saquinavir
  • tipranavir
  • voriconazole
• Venetoclax has serious interactions with at least 110 other drugs.
• Venetoclax has moderate interactions with at least 21 other drugs.
• Venetoclax has minor interactions with no other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Strong CYP3A inhibitors at initiation and during the ramp-up phase

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Venetoclax?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Venetoclax?”

Cautions

• Tumor lysis syndrome (TLS), including fatal events and renal failure requiring dialysis, has occurred in previously treated CLL patients with high tumor burden when treated with venetoclax
• The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy; splenomegaly may also increase the risk of TLS in patients with CLL/SLL
• Therapy can cause a rapid reduction in tumor and thus poses a risk for TLS at initiation and during ramp-up phase in all patients, and during reinitiation after dosage interruption in patients with CLL/SLL; changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose and at each dose increase; TLS, including fatal cases, has been reported after a single 20 mg dose
• Neutropenia frequently reported; monitor complete blood cell counts throughout the treatment period
• Fatal and serious infections such as pneumonia and sepsis have occurred; monitor patients closely for signs and symptoms of infection and treat promptly; withhold therapy for Grade 3 and higher infection
• Do not administer live attenuated vaccines before, during, or after treatment until B-cell recovery occurs; safety and efficacy of immunization with live attenuated vaccines during or following therapy have not been studied; advise patients that vaccinations may be less effective
• Based on its mechanism of action and findings in animals, may cause embryofetal harm when administered to a pregnant woman
• In a randomized trial in patients with relapsed or refractory multiple myeloma, the addition of venetoclax to bortezomib plus dexamethasone resulted in increased mortality; treatment of patients with multiple myeloma with venetoclax in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials
• Drug interaction overview
  • Effects of other drugs on venetoclax
  • Venetoclax is a CYP3A substrate
  • Concomitant use with a strong or moderate CYP3A inhibitor or a P-GP inhibitor increases venetoclax plasma concentrations and toxicities, including the risk of TLS
  • Reduce dose when coadministered with P-GP or moderate CYP3A4 inhibitors
  • Avoid grapefruit products, Seville oranges, and starfruit during treatment, as they contain inhibitors of CYP3A
  • Concomitant use with a strong CYP3A inducer decreases venetoclax plasma concentrations and efficacy
  • Venetoclax effects on other drugs
  • Venetoclax has inhibition potential on P-GP substrates at therapeutic dose levels in the gut; therefore, avoid coadministration with narrow-therapeutic index P-GP substrates
  • Coadministration with warfarin increases warfarin peak plasma concentrations and AUC, which may increase the risk of bleeding; closely monitor INR; monitor international normalized ratio (INR) more frequently in patients using warfarin concomitantly

Pregnancy and Lactation

• There are no available human data on use in pregnant women; based on its mechanism of action and findings in animals, may cause embryofetal harm when administered to a pregnant woman
• Females of reproductive potential should undergo pregnancy testing before initiation

Fertility and contraception

• Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after the last dose
• Male fertility may be compromised by treatment

Lactation

• Unknown if distributed in human breast milk; advise nursing women to discontinue breastfeeding during treatment and for at least one week after the last dose