Version May 2024
Note: Assess risk for tumor lysis syndrome (TLS) in all patients; administer prophylactic hydration and antihyperuricemics prior to the first venetoclax dose. TLS may also occur upon venetoclax reinitiation following therapy interruption. The ramp-up schedule/dose varies by indication. Also refer to the Azacitidine, Decitabine, Cytarabine, Obinutuzumab, or Rituximab monographs.
Acute myeloid leukemia, newly diagnosed: Adults ≥75 years of age or with comorbidities: Note: Initiate azacitidine, decitabine, or low-dose cytarabine on cycle 1, day 1. The venetoclax dose depends upon the concomitant chemotherapy agent. WBC should be <25,000/mm3 prior to initiation of venetoclax; cytoreduction prior to treatment may be required.
Day 1: Oral: 100 mg once daily.
Day 2: Oral: 200 mg once daily.
Day 3: Oral: 400 mg once daily.
Venetoclax in combination with azacitidine or decitabine: Day 4 and beyond: Oral: 400 mg once daily until disease progression or unacceptable toxicity (Ref).
Venetoclax in combination with low-dose cytarabine: Day 4 and beyond: Oral: 600 mg once daily until disease progression or unacceptable toxicity (Ref).
Tumor lysis syndrome risk assessment and p remedication : Assess patient-specific factors for TLS and provide prophylactic hydration and antihyperuricemic therapy prior to the first venetoclax dose.
WBC should be <25,000/mm3 prior to venetoclax initiation; pretreatment cytoreduction may be required.
Administer adequate hydration and antihyperuricemic agents prior to the first venetoclax dose; continue during the ramp-up phase.
Assess blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine) and correct preexisting electrolyte abnormalities prior to venetoclax initiation.
Monitor blood chemistries for TLS at pre-dose, 6 to 8 hours after each new dose during ramp-up, and 24 hours after reaching final dose.
For patients at high risk of TLS (eg, circulating blasts, high leukemia burden in the bone marrow, elevated pretreatment lactate dehydrogenase levels, reduced kidney function), consider additional TLS preventative measures, including increased laboratory monitoring and reduced initial venetoclax doses.
Chronic lymphocytic leukemia/small lymphocytic lymphoma: Note: The 5-week ramp up schedule is designed to gradually reduce tumor burden and the risk of TLS.
Week 1: Oral: 20 mg once daily.
Week 2: Oral: 50 mg once daily.
Week 3: Oral: 100 mg once daily.
Week 4: Oral: 200 mg once daily.
Week 5: Oral: 400 mg once daily.
Venetoclax monotherapy: Week 5 and thereafter: Oral: 400 mg once daily; continue until disease progression or unacceptable toxicity.
Venetoclax in combination with obinutuzumab: Note: Obinutuzumab begins on day 1 of cycle 1; initiate venetoclax on day 22 of cycle 1 according to the 5-week ramp-up schedule for chronic lymphocytic leukemia/small lymphocytic lymphoma above; ramp-up will be completed at the end of cycle 2. Cycle 3 (day 1 and beyond): Oral: 400 mg once daily until the end of cycle 12. Each cycle is 28 days (Ref).
Venetoclax in combination with rituximab: Week 5 and thereafter: Oral: 400 mg once daily; continue venetoclax until disease progression or unacceptable toxicity, for up to 24 months from day 1 (cycle 1) of rituximab; begin rituximab after receiving venetoclax at the 400 mg once daily dose for 7 days (Ref).
Venetoclax in combination with ibrutinib; fixed treatment duration in previously untreated disease (off-label combination): Note: Each cycle is 28 days. Begin ibrutinib as a single agent for 3 cycles prior to initiation of venetoclax; venetoclax is ramped up in cycle 4.
Cycle 4 (venetoclax ramp up):
Week 1: Oral: 20 mg once daily (Ref).
Week 2: Oral: 50 mg once daily (Ref).
Week 3: Oral: 100 mg once daily (Ref).
Week 4: Oral: 200 mg once daily (Ref).
Cycles 5 to 15:
Week 5 and beyond: Oral: 400 mg once daily (Ref). In one study, patients who completed 15 cycles (3 lead in ibrutinib cycles plus 12 ibrutinib/venetoclax combination cycles) were administered 1 additional ibrutinib/venetoclax cycle during which minimal residual disease status and tumor response were assessed (Ref).
Tumor lysis syndrome risk assessment and premedication: Assess patient-specific factors for TLS and provide prophylactic hydration and antihyperuricemic therapy prior to the first venetoclax dose (venetoclax causes a rapid reduction in tumor and poses a risk for TLS in the initial 5-week ramp-up phase). The risk of TLS is based on multiple factors, particularly reduced kidney function (CrCl <80 mL/minute) and tumor burden; splenomegaly may also increase the risk of TLS. Perform tumor burden assessments, including radiographic evaluation (eg, CT scan); assess blood chemistries in all patients (potassium, uric acid, phosphorus, calcium, and creatinine; changes in blood chemistries consistent with TLS requiring prompt management can occur as early as 6 to 8 hours following the first venetoclax dose and with each dose increase); correct preexisting abnormalities prior to initiation of venetoclax. Consider all patient comorbidities prior to determining prophylaxis and monitoring schedule. TLS risk may decrease as tumor burden decreases. TLS can also occur upon resumption of venetoclax following a dosage interruption; reassess TLS risk when reinitiating venetoclax following therapy interruption lasting >1 week during the ramp-up phase, or >2 weeks after ramp-up completion. Institute prophylaxis and monitoring as needed.
Low tumor burden (all lymph nodes <5 cm and absolute lymphocyte count [ALC] <25,000/mm3): Outpatient: Hydrate with 1.5 to 2 L of oral hydration and administer allopurinol or xanthine oxidase inhibitor (beginning 2 to 3 days prior to venetoclax initiation). Administer IV hydration for patients unable to tolerate oral hydration.
Medium tumor burden (any lymph node 5 to <10 cm or ALC ≥25,000/mm3): Outpatient: Hydrate with 1.5 to 2 L of oral hydration (administer IV hydration for patients unable to tolerate oral hydration; consider additional IV hydration) and administer allopurinol or xanthine oxidase inhibitor (beginning 2 to 3 days prior to venetoclax initiation).
High tumor burden (any lymph node ≥10 cm OR ALC ≥25,000/mm3 and any lymph node ≥5 cm): Inpatient: Hydrate with 1.5 to 2 L of oral hydration (administer IV hydration for patients unable to tolerate oral hydration) and 150 to 200 mL/hour IV hydration as tolerated; administer allopurinol or xanthine oxidase inhibitor (beginning 2 to 3 days prior to venetoclax initiation); consider rasburicase if baseline uric acid is elevated. Ramp-up may be completed outpatient if clinically indicated.
Mantle cell lymphoma, relapsed or refractory (off-label use):
Venetoclax monotherapy: Oral: Initial: 20 mg once daily for week 1, followed by 50 mg once daily for week 2, followed by 100 mg once daily for week 3, followed by 200 mg once daily for week 4, followed by 400 mg once daily for week 5. Week 6 and thereafter: 800 mg once daily until disease progression or unacceptable toxicity occurs or until proceeding to allogeneic stem cell transplant (Ref). Refer to protocols for further details.
Multiple myeloma, relapsed/refractory (off-label use):
With translocation t(11;14):
Venetoclax in combination with dexamethasone: Oral: 800 mg once daily; continue until disease progression or unacceptable toxicity (Ref). Refer to protocol for further information. Note: A venetoclax dose ramp-up phase has been described in some studies; refer to articles for details (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Patients with decreased kidney function (CrCl <80 mL/minute estimated using the Cockcroft-Gault formula) may require more intensive prophylaxis and monitoring to reduce the risk of tumor lysis syndrome during treatment initiation (Ref).
Altered kidney function: No dosage adjustment likely to be necessary for any degree of kidney impairment (Ref). Note: In one retrospective study, the incidence of adverse events was higher in patients with eGFR <45 mL/minute/1.73 m2; higher vigilance may be necessary in these patients (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound): Safety and efficacy data are currently limited to case reports. However, no supplemental dose or dosage adjustment likely to be necessary based on pharmacokinetic characteristics of venetoclax (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No safety or efficacy data currently exist. However, no dosage adjustment likely to be necessary based on pharmacokinetic characteristics of venetoclax (Ref).
CRRT: No safety or efficacy data currently exist. However, no dosage adjustment likely to be necessary based on pharmacokinetic characteristics of venetoclax (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No safety or efficacy data currently exist. However, no dosage adjustment likely to be necessary based on pharmacokinetic characteristics of venetoclax (Ref).
Mild or moderate impairment (Child-Pugh classes A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): Reduce the daily venetoclax dose by 50%; monitor closely for adverse reactions.
Acute myeloid leukemia: Note: Monitor blood counts frequently until cytopenias resolve. Toxicity may require venetoclax dose interruptions or permanent discontinuation.
Grade 4 neutropenia (with or without fever or infection) or grade 4 thrombocytopenia:
Occurring prior to achieving remission: Consider supportive measures, including anti-infectives and WBC growth factors, as clinically necessary. In most instances, do not interrupt treatment cycles (of venetoclax and azacitidine, decitabine, or low-dose cytarabine) due to cytopenias (prior to achieving remission). Bone marrow evaluation is recommended.
First occurrence after achieving remission and lasting at least 7 days: Delay subsequent treatment cycle (of venetoclax and azacitidine, decitabine, or low-dose cytarabine) and monitor blood counts. Once neutropenia has resolved to ≤ grade 2, resume venetoclax at the same dose in combination with azacitidine, decitabine, or low-dose cytarabine. Consider supportive measures, including anti-infectives and WBC growth factors, as clinically necessary.
Subsequent occurrences in cycles after achieving remission and lasting 7 days or longer: Delay subsequent treatment cycle (of venetoclax and azacitidine, decitabine, or low-dose cytarabine) and monitor blood counts. Once neutropenia has resolved to ≤ grade 2, resume venetoclax at the same dose and reduce the venetoclax duration by 7 days during each subsequent cycle (eg, reduce cycle from 28 days to 21 days). Consider supportive measures, including anti-infectives and WBC growth factors, as clinically necessary.
Nonhematologic toxicities, grade 3 or 4 toxicity (any occurrence): Interrupt venetoclax if not resolved with supportive measures. Resume at the same dose once toxicity is resolved to grade 1 or baseline.
Chronic lymphocytic leukemia/small lymphocytic lymphoma:
Interrupt or reduce dose for toxicities. Reassess risk for tumor lysis syndrome in patients who have had an interruption in dosing of >1 week during ramp-up or >2 weeks after completion of ramp-up (to determine if re-initiation with a reduced dose is necessary).
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Dose at interruption |
Restart dosea |
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Consider discontinuation for patients who require dose reductions to less than 100 mg for more than 2 weeks. | |
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aDuring dose escalation phase, continue the reduced dose for 1 week prior to increasing the dose. | |
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400 mg |
300 mg |
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300 mg |
200 mg |
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200 mg |
100 mg |
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100 mg |
50 mg |
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50 mg |
20 mg |
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20 mg |
10 mg |
Tumor lysis syndrome:
Blood chemistry changes or symptoms suggestive of tumor lysis syndrome (TLS): Withhold the next day's dose.
If resolved within 24 to 48 hours of the last dose: Resume at the same dose.
If blood chemistry changes require more than 48 hours to resolve: Resume at a reduced dose.
Clinical TLS (laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, and/or seizure): Withhold dose; following resolution, resume at a reduced dose.
Hematologic toxicity: Grade 3 neutropenia with infection or fever or grade 4 hematologic toxicities (except lymphopenia):
First occurrence: Interrupt treatment. Resume at the same dose once toxicity is resolved to grade 1 or baseline. Consider supportive measures, including anti-infectives and WBC growth factors, as clinically necessary.
Second and subsequent occurrences: Interrupt treatment. Resume at a lower dose level once toxicity is resolved (see dosage reduction levels in above table; a larger dose reduction may be necessary based on clinical discretion). Consider supportive measures, including anti-infectives and WBC growth factors, as clinically necessary.
Nonhematologic toxicities, Grade 3 or 4 toxicity:
First occurrence: Interrupt treatment. Resume at the same dose once toxicity is resolved to grade 1 or baseline (no dosage adjustment is necessary).
Second and subsequent occurrences: Interrupt treatment. Resume at a lower dose level once toxicity is resolved (see dosage reduction levels in above table; a larger dose reduction may be necessary based on clinical discretion).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Edema (22%)
Dermatologic: Skin rash (18%)
Endocrine & metabolic: Hyperglycemia (67%), hyperkalemia (59%), hypoalbuminemia (49%), hypocalcemia (87%), hyponatremia (40%), hypophosphatemia (45%)
Gastrointestinal: Abdominal pain (18%), constipation (16%), diarrhea (43%), nausea (42%), stomatitis (13%; grades ≥3: <1%), vomiting (16%)
Hematologic & oncologic: Anemia (33% to 71%; grades ≥3: 18% to 26%), leukopenia (89%; grades 3/4: 42%; grade 4: 11%), lymphocytopenia (11% to 74%; grades ≥3: 7% to 40%; grade 4: 9%), neutropenia (50% to 87%; grades ≥3: 45% to 63%; grade 4: 33%), thrombocytopenia (29% to 64%; grades ≥3: 20% to 31%; grade 4: 15%)
Hepatic: Increased serum aspartate aminotransferase (53%)
Nervous system: Dizziness (14%), fatigue (32%), headache (18%)
Neuromuscular & skeletal: Arthralgia (12%), musculoskeletal pain (29%)
Respiratory: Cough (22%), dyspnea (13%), lower respiratory tract infection (11%), pneumonia (14%), upper respiratory tract infection (36%)
Miscellaneous: Fever (18%)
1% to 10%:
Hematologic & oncologic: Febrile neutropenia (6%; grades ≥3: 6%), tumor lysis syndrome (5-week ramp-up phase: 2%)
Infection: Sepsis (5%)
Frequency not defined: Hematologic & oncologic: Hemolytic anemia
Concomitant use with strong CYP3A inhibitors at initiation and during ramp-up phase in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) due to the potential for increased risk of tumor lysis syndrome.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to venetoclax or any component of the formulation
Concerns related to adverse effects:
• Bone marrow suppression: Neutropenia, thrombocytopenia, and anemia may occur. Grade 3 and 4 neutropenia commonly occurred in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients receiving venetoclax, either as monotherapy or in combination with rituximab or obinutuzumab. Neutropenic fever has been reported both with monotherapy and combination therapy. When used in combination with azacitidine, decitabine, or low-dose cytarabine for acute myeloid leukemia (AML), baseline neutrophil counts worsened in almost all patients; neutropenia may occur with subsequent cycles.
• Infection: Serious and fatal infections, including pneumonia and sepsis, have occurred.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) (including fatalities and kidney failure requiring dialysis) has occurred in patients with high tumor burden when treated with venetoclax. Venetoclax may cause a rapid reduction in tumor volume and therefore a risk for TLS is present during initiation and during the ramp-up phase of treatment (as well as during reinitiation after therapy interruption in CLL/SLL). The use of the ramp-up dose, TLS prophylaxis, and monitoring reduced the rate of TLS in venetoclax monotherapy studies; a shorter ramp up (eg, 2 to 3 weeks) and higher initial doses have resulted in higher rates of TLS and related complications in patients with CLL/SLL. Changes in blood chemistries consistent with TLS may occur as early as 6 to 8 hours after the first venetoclax dose and with each dose increase and require prompt management. The risk for TLS is increased with high tumor burden, comorbidities, and type of malignancy; splenomegaly may also increase TLS risk in CLL/SLL. Reduced kidney function further increases TLS risk. The risk for TLS may decrease as tumor burden decreases. Concomitant use of strong or moderate CYP3A inhibitors or P-gp inhibitors at initiation or during ramp-up may increase the risk for TLS and requires venetoclax dosage modification.
Disease related concerns:
• Multiple myeloma: In patients with relapsed or refractory multiple myeloma, an increase in mortality was noted when venetoclax was added to bortezomib and dexamethasone (in patients without the t(11;14) translocation [Kumar 2020]). Relapsed/refractory t(11;14) multiple myeloma is an off-label use for venetoclax.
Other warnings/precautions:
• Immunizations: Live vaccinations should not be administered prior to, during, or after venetoclax treatment until B-cell recovery occurs. Vaccines may be less effective.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Venclexta: 10 mg, 50 mg, 100 mg
Tablet Therapy Pack, Oral:
Venclexta Starting Pack: Week 1: 10 mg (14); Week 2: 50 mg (7); Week 3: 100 mg (7); Week 4: 100 mg (14) (42 ea)
No
Tablet Therapy Pack (Venclexta Starting Pack Oral)
10 & 50 & 100 mg (per each): $94.15
Tablets (Venclexta Oral)
10 mg (per each): $15.27
50 mg (per each): $76.33
100 mg (per each): $152.66
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Venclexta: 10 mg, 50 mg, 100 mg
Tablet Therapy Pack, Oral:
Venclexta Starting Pack: Week 1: 10 mg (14); Week 2: 50 mg (7); Week 3: 100 mg (7); Week 4: 100 mg (14) (42 ea)
Available through specialty pharmacies and distributors. Further information may be obtained from the manufacturer.
Oral: Administer with a meal and water at approximately the same time each day. Swallow whole; do not crush, chew, or break prior to administration.
Missed or vomited doses: If a dose is missed and it is within 8 hours of the missed usual dosing time, administer the missed dose as soon as possible and resume the normal daily dosing schedule. If it is more than 8 hours, do not administer the missed dose and resume the usual dosing schedule the next day. If the patient vomits following administration of a dose, no additional doses should be administered that day; administer the next prescribed dose at the usual time.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Venetoclax may cause teratogenicity and reproductive toxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Venclexta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208573s026lbl.pdf#page=54
Acute myeloid leukemia: Treatment of newly-diagnosed acute myeloid leukemia (in combination with azacitidine, decitabine, or low-dose cytarabine) in patients ≥75 years of age, or in patients with comorbidities that preclude use of intensive induction chemotherapy.
Chronic lymphocytic leukemia/small lymphocytic lymphoma: Treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma in adults.
Mantle cell lymphoma, relapsed/refractory; Multiple myeloma, relapsed/refractory, t(11;14)
Venetoclax may be confused with vandetanib, vemurafenib, venlafaxine, vismodegib, vorinostat
Venclexta may be confused with venlafaxine
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bitter Orange: May increase the serum concentration of Venetoclax. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Venetoclax. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Venetoclax. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Digoxin: Venetoclax may increase the serum concentration of Digoxin. Management: Avoid concomitant use of venetoclax and digoxin if possible. If combined, administer digoxin at least 6 hours before venetoclax to minimize the potential for an interaction. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Elacestrant: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider therapy modification
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Futibatinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Venetoclax. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Posaconazole: May increase the serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider therapy modification
Pretomanid: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sparsentan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Star Fruit: May increase the serum concentration of Venetoclax. Risk X: Avoid combination
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Warfarin: Venetoclax may increase the serum concentration of Warfarin. Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Administration with a low-fat meal (~512 kilocalories; 25% fat calories, 60% carbohydrate calories, and 15% protein calories) increased exposure by ~3.4-fold and administration with a high-fat meal (~753 kilocalories; 55% fat calories, 28% carbohydrate calories, and 17% protein calories) increased exposure by ~5.1- to 5.3-fold, compared to fasting. Management: Administer with a meal.
Coadministration with grapefruit products, Seville oranges, and/or Star Fruit may increase venetoclax plasma concentrations. Management: Avoid concomitant administration with grapefruit products, Seville oranges, and Star Fruit.
Verify pregnancy status prior to initiating venetoclax treatment in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 30 days after the final venetoclax dose.
Based on the mechanism of action and data from animal reproduction studies, venetoclax is expected to cause fetal harm if administered during pregnancy.
Guidance is available for the management of acute myeloid leukemia during pregnancy (Ali 2015). A case report describes use of venetoclax in a pregnant patient refractory to recommended treatment (Karagiannis 2021).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).
It is not known if venetoclax is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 week after the last venetoclax dose.
Avoid grapefruit products, Seville oranges, and Star Fruit.
CBC with differential (throughout treatment); blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine). Evaluate pregnancy status prior to treatment in patients who could become pregnant. Assess tumor burden, including radiographic evaluation (eg, CT scan), for tumor lysis syndrome (TLS) risk evaluation. Monitor for signs/symptoms of infection. Monitor for adverse reactions in patients with hepatic impairment. Monitor adherence.
Blood chemistry monitoring in acute myeloid leukemia: Assess and correct preexisting abnormalities prior to therapy initiation; monitor blood chemistries for TLS prior to first dose, 6 to 8 hours after each new dose during ramp-up, and 24 hours after reaching the final dose. Increased monitoring may be necessary in patients at high risk for TLS.
Blood chemistry monitoring based on tumor burden/TLS risk in chronic lymphocytic leukemia/small lymphocytic lymphoma:
Low risk (all lymph node <5 cm and absolute lymphocyte count [ALC] <25,000/mm3) or medium risk (any lymph node 5 to <10 cm or ALC ≥25,000/mm3): Prior to first dose, 6 to 8 hours, and 24 hours after first 20 mg and 50 mg dose, and prior to each subsequent initial ramp up dose.
High risk (any lymph node ≥10 cm OR ALC ≥25,000/mm3 and any lymph node ≥5 cm): Prior to first dose, 4, 8, 12, and 24 hours after first 20 mg and 50 mg dose, and prior to plus 6 to 8 hours and 24 hours after each subsequent initial ramp up dose.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Venetoclax has cytotoxic activity in tumor cells which overexpress BCL-2. Venetoclax selectively inhibits the anti-apoptotic protein BCL-2, which is overexpressed in chronic lymphocytic leukemia (CLL) cells and acute myeloid leukemia (AML) cells. BCL-2 mediates tumor cell survival and has been associated with chemotherapy resistance. Venetoclax binds directly to the BCL-2 protein, displacing pro-apoptotic proteins and restoring the apoptotic process.
Distribution: Vdss: 256 to 321 L
Protein binding: Highly bound to plasma proteins
Metabolism: Hepatic, predominantly via CYP3A; the major metabolite is M27 (has BCL-2 inhibitory activity)
Half-life, elimination: ~26 hours
Time to peak: 5 to 8 hours
Excretion: Feces (>99.9%; ~21% as unchanged drug); Urine (<0.1%)
Hepatic function impairment: Following a single 50 mg venetoclax dose, systemic exposure (AUC0 to inf) was 2.7-fold higher in subjects with severe impairment (Child-Pugh class C), compared to subjects with normal hepatic function.
Race/ethnicity: Based on a study in patients with acute myeloid leukemia enrolled from Asian countries, venetoclax exposure was 63% higher in patients of East-Asian ethnicity (Chinese, Japanese, South Korean, and Taiwanese).
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