Venclexta: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Feb 27, 2023.

1. How it works

• Venclexta is a brand (trade) name for venetoclax which may be used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).
• Venclexta (venetoclax) works by binding directly to BCL-2 (B-cell lymphoma-2) which is a protein that helps determine whether cells live or die. When Venclexta binds to BCL-2 it displaces other proteins, such as BIM, which help to activate the process of apoptosis leading to programmed cell death. Cancer cells such as CLL, SLL, and AML overexpress BCL-2, which means that they have more of this protein than normal cells do. By blocking or inhibiting BCL-2, Vencelxta enables these cells to be killed.
• Venclexta belongs to the class of medicines called BCL-2 inhibitors. It may also be called a miscellaneous antineoplastic or targeted treatment.

2. Upsides

• May be used to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• May also be used in combination with azacitidine, decitabine, or low-dose cytarabine to treat newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older that have other conditions that prevent the use of intensive induction chemotherapy.
• Available as a tablet in three strengths: 10mg, 50mg, and 100mg.
• Venclexta is not chemotherapy, it is a targeted treatment that works by binding to a protein called BCL-2 which is overexpressed on cancerous cells in people with certain cancers, such as AML and CLL.
• Taken orally (by mouth) once a day. Dosing begins with a 5-week ramp-up period where the dose is gradually increased. Use the CLL/SLL Starting Pack. This helps gradually reduce cancerous cells and decreases the risk of side effects such as tumor lysis syndrome (TLS). Once the 5-week ramp-up period has been completed the recommended dosage of Venclexta is 400mg once daily.
• Should be taken with a meal (food).

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Nausea, diarrhea, thrombocytopenia, constipation, neutropenia, fatigue, vomiting, edema, fever, itch, abdominal pain, rash, anemia, and hemorrhage are the most common side effects reported. Pain, dizziness, cough, infections, and low blood pressure may also occur.
• Tumor lysis syndrome (TLS) including fatal events and kidney failure requiring dialysis has occurred in people treated with Venclexta because Venclexta can cause a rapid reduction in tumor burden. Cases have been reported within 6 to 8 hours of the first dose of Venclexta and after subsequent dose increases. The rate of TLS is much reduced in those patients who follow the 5-week dose ramp-up (2% incidence of TLS vs. 13% incidence with faster ramp-up schedules). The risk of TLS is increased in those with reduced kidney function, high tumor burden, cancer, splenomegaly, or certain medications, such as P-gp inhibitors or moderate CYP3A inhibitors. Provide appropriate prophylaxis, such as hydration and antihyperuricemics, monitor blood chemistries, and manage abnormalities appropriately.
• Grade 3 or 4 neutropenia developed in 63% to 64% of patients with CLL. Febrile neutropenia developed in 4% to 6% of patients in combination and monotherapy studies. In patients with AML baseline neutrophil counts worsened in 95% to 100% of patients treated in combination with azacitidine, decitabine, or low-dose cytarabine. Monitor CBC throughout the treatment period and withhold dosage as necessary.
• Venclexta has been associated with fatal and serious infections such as pneumonia and sepsis. Monitor patients for signs of infection and withhold Venclexta for Grade 3 and 4 infections until resolution.
• Venclexta may reduce the immune response to live vaccines, such as MMR and varicella vaccines. Do not administer live attenuated vaccines before, during, or after treatment with Venclexta until B-cell recovery occurs.
• The dosage of Venclexta needs to be reduced by 50% in severe hepatic impairment (Child-Pugh C). Monitor for adverse reactions.
• Venclexta will suppress the immune system and will reduce a person's ability to fight infection. This ability will be further compromised if the person is also taking other drugs that suppress the immune system, such as chemotherapy agents, immune-modulating therapies, or other immunosuppressants.
• May cause fetal harm if administered to pregnant women and those of childbearing potential should use effective contraception while receiving Venclexta and for 30 days after the last dose. If a woman becomes inadvertently pregnant she should advise her doctor immediately. Women should not breastfeed during treatment with Venclexta and for 7 days after the last dose. Venclexta may impair fertility in males.
• Not available as a generic.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

• Venclexta is a BCL-2 inhibitor that may be used to treat chronic lymphocytic leukemia (CLL), small cell lymphoma (SCL), or acute myeloid leukemia. It is an oral tablet that is administered once daily with an initial ramp-up dosage period to reduce the incidence of side effects such as tumor lysis syndrome (TLS). Neutropenia, nausea, diarrhea, and fatigue are common side effects.

5. Tips

• Take Venclexta exactly as directed by your healthcare provider, once a day and at approximately the same time each day. For most people, the dosage is slowly increased for the first 5 weeks (called the ramp-up period). This helps to decrease the risk of side effects. Do not increase or decrease the dosage without talking to your healthcare provider first.
• Swallow Venclexta tablets whole, do not crush, break, or chew. Take it with a meal.
• Keep Venclexta tablets in their original packaging during the first 4 weeks of treatment. Do not transfer these tablets to another container.
• If you miss or forget a dose of Venclexta and it has been less than 8 hours since the missed dose, then take the dose right away and take the next dose as usual. If it has been more than 8 hours then do not take the missed dose just wait until the next dose is due.
• If you vomit after taking your dose of Venclexta, do not take an additional dose, just wait until the next day to take your dose.
• There is a risk of tumor lysis syndrome (TLS), particularly during treatment initiation or after a dosage interruption. Report any symptoms, such as fever, chills, nausea, vomiting, confusion, shortness of breath, dark or cloudy urine, fatigue, pain, or joint discomfort to your healthcare provider immediately. Some patients at high risk for TLS may need supervision in a medical office or hospital setting.
• You should keep well hydrated while taking Venclexta and drink at least 6 to 8 glasses of water per day. Pay particular attention to keeping hydrated starting 2 days before and on the day of your first dose and then every time the dose is increased.
• Always keep your scheduled appointments with your healthcare provider and get your blood tested as instructed. Venclexta can cause changes to your blood levels, such as neutropenia (low neutrophil levels) and these must be monitored. Contact your healthcare provider immediately if you develop signs of infection such as fever, chills, muscle aches, cough, shortness of breath, runny nose, sore throat, red or painful skin or sores on your body, tiredness, or pain during urination. Ring your healthcare provider if you experience any other troublesome or unusual side effects.
• Some vaccinations may need to be avoided during treatment with Venclexta and for a few months after stopping it until B-cell recovery occurs. Take care to avoid people who are unwell and protect yourself from injury.
• Venclexta can interact with several medicines. Tell your doctor or pharmacist that you are taking Venclexta and ask them to check for drug interactions. Do not drink grapefruit juice or consume grapefruit products during treatment with Venclexta.
• Tell your doctor if you are pregnant, intending to become pregnant, or breastfeeding before being administered Venclexta as it is not suitable during pregnancy and breastfeeding. Use effective contraception while receiving Venclexta and for 30 days after the last infusion. If you inadvertently become pregnant, see your doctor immediately. Do not breastfeed during treatment with Venclexta and for one week after the last dose. Venclexta may impair fertility in males.

6. Response and effectiveness

• Continue Venclexta until disease progression or unacceptable toxicity occurs.
• Venclexta is effective for both CLL (chronic lymphocytic leukemia) and AML (acute myeloid leukemia) with trials reporting significantly more people experiencing complete remission with Venclexta in combination with other treatments compared to standard therapy. Venclexta works quickly as well, with it taking an average of one month for many people to experience a reduction in disease progression.
• For people with CLL, a trial compared Venclexta plus Obinutuzumab (V+O) to Obinutuzumab plus chlorambucil (O+C), for an average of 28 months (range 0 to 36 months). 13% of people in the V+O group experienced an event compared with 37% in the O+C group. Disease progression was experienced by 6% of people in the V+O group compared to 33% of people in the O+C group. 7% of people in the V+O group died compared with 4% in the O+C group. The overall response rate was 85% in the V+O group compared to 71% in the O+C group. Complete remission was experienced by 46% in the V+O group compared with 22% in the O+C group.
• The Murano trial compared Venclexta in combination with rituximab (VEN+R) versus bendamustine in combination with rituximab (B+R) with a median follow-up of 23.4 months. 13% experienced disease progression in the VEN + R group compared to 47% in the B+R group. 9 people (out of 194) died in the VEN + R group compared with 15 out of 195 in the B+R group. The overall response rate was 92% in the VEN + R vs 72% in the B+R group.
• When Venclexta is given as the only therapy, trials report the overall response rate to be 70% to 80% with complete remission experienced by about 6%.
• The average time to respond for people with CLL treated with Venclexta was 0.8 months (range 0.1 to 8.1 months). This is an average of 24 days. The duration of response ranged from 2.4 to 52.4 months.
• Two trials investigated how effective Venclexta was for AML in patients over the age of 75 years who weren’t able to receive intensive induction chemotherapy for one of several reasons. One trial compared Venclexta in combination with azacytidine (V+A) compared to Venclexta in combination with decitabine (V + d). Complete remission was experienced by 37% of people in the V+A group compared to 54% in the V+D group. For patients who achieved a CR, the median observed time in remission was 5.5 months (range: 0.4 to 30 months). When Venclexta was used in combination with low-dose cytarabine, 21% experienced clinical remission. The median observed time in remission was 6.0 months (range: 0.03 to 25 months).
• It took an average of one month (range 0.7 to 8.9 months) for patients with AML to experience a clinical remission in patients assigned to V+A. It took an average of 1.9 months (range 0.8 to 4.2 months) for patients to experience a clinical remission in patients assigned to V+D. It took an average of one month (range 0.8 to 9.4 months) for patients to experience a clinical remission in patients assigned to V + low-dose cytarabine.

7. Interactions

Medicines that interact with Venclexta may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Venclexta. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

More than 340 medications interact with Venclexta; most of these interactions are considered major or moderate. Common medications that may interact with Venclexta include:

• antifungals, such as itraconazole or ketoconazole
• antihistamines, such as fexofenadine or terfenadine
• antipsychotics, such as clozapine
• antiseizure medications such as carbamazepine or phenytoin
• biologics, such as adalimumab, etanercept, golimumab, or infliximab
• fingolimod or golimumab
• grapefruit juice or products
• heart medications such as captopril or diltiazem
• HIV medications, such as atazanavir, darunavir, lopinavir, nelfinavir, or zidovudine
• hormones, such as progesterone
• immunosuppressants such as azathioprine, cyclosporine, or tacrolimus
• live vaccines and some other vaccines, such as BCG, cholera, Covid-19 vaccines, measles, hepatitis b vaccines, yellow fever, or live influenza vaccines
• probiotics, such as bifidobacterium or lactobacillus
• quinidine or quinine
• rifampin or rifabutin
• strong or moderate CYP3A inhibitors or P-gp inhibitors, such as posaconazole, clarithromycin, nefazodone, amiodarone, colchicine, lansoprazole, or omeprazole.

Should not be used with bortezomib plus dexamethasone unless during a clinical trial.

Note that this list is not all-inclusive and includes only common medications that may interact with Venclexta. You should refer to the prescribing information for Venclexta for a complete list of interactions.

References

• Venclexta (venetoclax). Updated 06/2022. AbbVie Inc. https://www.drugs.com/pro/venclexta.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Venclexta only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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