Venetoclax
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From MedlinePlus, U.S. National Library of Medicine
BCL-2 Inhibitor
Dosing in kidney impairment
Renal Impairment Due to the increased risk of TLS, patients with reduced renal function (CLcr <80 mL/min, calculated by Cockcroft-Gault formula) require more intensive prophylaxis and monitoring to reduce the risk of TLS when initiating treatment with VENCLEXTA [see Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 ) and Warnings and Precautions] .
No dose adjustment is recommended for patients with mild, moderate or severe renal impairment (CLcr ≥15 mL/min) [see Clinical Pharmacology] .
| Tumor Burden | Prophylaxis | Blood Chemistry Monitoringc,d | ||
| Hydrationa | Anti- hyperuricemicsb | Setting and Frequency of Assessments | ||
| Low | All LN <5 cm AND ALC <25 x109/L | Oral (1.5 to 2 L) | Allopurinol | OutpatientFor first dose of 20 mg and 50 mg: Pre-dose, 6 to 8 hours, 24 hours For subsequent ramp-up doses: Pre-dose |
| Medium | Any LN 5 to <10 cm OR ALC ≥25 x109/L | Oral (1.5 to 2 L) and consider additional intravenous | Allopurinol | OutpatientFor first dose of 20 mg and 50 mg: Pre-dose, 6 to 8 hours, 24 hours For subsequent ramp-up doses: Pre-dose For first dose of 20 mg and 50 mg: Consider hospitalization for patients with CLcr <80ml/min; see below for monitoring in hospital |
| High | Any LN ≥10 cm OR ALC ≥25 x109/L AND any LN ≥5 cm | Oral (1.5 to 2 L) and intravenous (150 to 200 mL/hr as tolerated) | Allopurinol; consider rasburicase if baseline uric acid is elevated | In hospital For first dose of 20 mg and 50 mg: Pre-dose, 4, 8, 12, and 24 hoursOutpatientFor subsequent ramp-up doses: Pre-dose, 6 to 8 hours, 24 hours |
| ALC = absolute lymphocyte count; CLcr = creatinine clearance; LN = lymph node. aAdminister intravenous hydration for any patient who cannot tolerate oral hydration. bStart allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of VENCLEXTA. cEvaluate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time. dFor patients at risk of TLS, monitor blood chemistries at 6 to 8 hours and at 24 hours at each subsequent ramp-up dose. | ||||
| Adverse Reaction | Occurrence | Dosage Modification |
| Tumor Lysis Syndrome | ||
| Blood chemistry changes or symptoms suggestive of TLS [see Warnings and Precautions (5.1)] | Any | Withhold the next day’s dose. If resolved within 24 to 48 hours of last dose, resume at same dose. |
| For any blood chemistry changes requiring more than 48 hours to resolve, resume at reduced dose (see Table 4). | ||
| For any events of clinical TLS,b resume at reduced dose following resolution (see Table 4). | ||
| Non-Hematologic Adverse Reactions | ||
| Grade 3 or 4 non-hematologic toxicities [see Adverse Reactions (6.1)] | 1st occurrence | Interrupt VENCLEXTA. Upon resolution to Grade 1 or baseline level, resume VENCLEXTA at the same dose. |
| 2nd and subsequent occurrences | Interrupt VENCLEXTA. Follow dose reduction guidelines in Table 4 when resuming treatment with VENCLEXTA after resolution. A larger dose reduction may occur at the discretion of the physician. | |
| Hematologic Adverse Reactions | ||
| Grade 3 neutropenia with infection or fever; or Grade 4 hematologic toxicities (except lymphopenia) [see Warnings and Precautions (5.2)] | 1st occurrence | Interrupt VENCLEXTA. Upon resolution to Grade 1 or baseline level, resume VENCLEXTA at the same dose. |
| 2nd and subsequent occurrences | Interrupt VENCLEXTA. Follow dose reduction guidelines in Table 4 when resuming treatment with VENCLEXTA after resolution. A larger dose reduction may occur at the discretion of the physician. | |
| Consider discontinuing VENCLEXTA for patients who require dose reductions to less than 100 mg for more than 2 weeks. aAdverse reactions were graded using NCI CTCAE version 4.0. bClinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or sudden death and/or seizures [see Adverse Reactions (6.1)]. | ||
Dosing in liver impairment
Dosage Modifications for Patients with Severe Hepatic Impairment Reduce the VENCLEXTA once daily dose by 50% for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more closely for adverse reactions [see Use in Specific Populations] .
Preparation and administration
Administration Instruct patients of the following: Take VENCLEXTA with a meal and water. Take VENCLEXTA at approximately the same time each day. The recommended dosage of VENCLEXTA may be delivered using any of the approved tablet strengths. For patients who are unable to swallow a VENCLEXTA tablet whole, the tablets can be crushed [see Clinical Pharmacology] .
Mix the entire dose with 120 mL (4 ounces) of water, apple juice, apple sauce, or yogurt. Take the entire dose immediately with a meal and water. Do not crush more than one dose at a time. If the patient misses a dose of VENCLEXTA within 8 hours of the time it is usually taken, instruct the patient to take the missed dose as soon as possible and resume the normal daily dosing schedule.
If a patient misses a dose by more than 8 hours, instruct the patient not to take the missed dose and resume the usual dosing schedule the next day. If the patient vomits following dosing, instruct the patient to not take an additional dose that day and to take the next prescribed dose at the usual time.
Drug interactions
Check venetoclax against a medication listLabel text (5 paragraphs)
Strong or moderate CYP3A inhibitors or P-gp inhibitors: Adjust dosage of VENCLEXTA. ( 2.6 , 7.1 ) Strong or moderate CYP3A inducers: Avoid co-administration. ( 7.1 ) P-gp substrates: Take at least 6 hours before VENCLEXTA. ( 7.2 )
7.1 Effects of Other Drugs on VENCLEXTA Strong or Moderate CYP3A Inhibitors or P-gp Inhibitors Concomitant use with a strong or moderate CYP3A inhibitor or a P-gp inhibitor increases venetoclax C max and AUC 0-INF [see Clinical Pharmacology ( 12.3 )] , which may increase VENCLEXTA toxicities, including the risk of TLS [see Warnings and Precautions ( 5.1 )] . Concomitant use with a strong CYP3A inhibitor at initiation and during the ramp-up phase in patients with CLL/SLL is contraindicated [see Contraindications ( 4 )] .
In patients with CLL/SLL taking a steady daily dosage (after ramp-up phase), consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions [see Dosage and Administration ( 2.5 , 2.6 )] . In patients with AML, adjust VENCLEXTA dosage and monitor more frequently for adverse reactions [see Dosage and Administration ( 2.5 , 2.6 )] . Resume the VENCLEXTA dosage that was used prior to concomitant use with a strong or moderate CYP3A inhibitor or a P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor [see Dosage and Administration ( 2.5 , 2.6 )] .
Avoid grapefruit products, Seville oranges, and starfruit during treatment with VENCLEXTA, as they contain inhibitors of CYP3A. Strong or Moderate CYP3A Inducers Concomitant use with a strong CYP3A inducer decreases venetoclax C max and AUC 0-INF [see Clinical Pharmacology ( 12.3 )] , which may decrease VENCLEXTA efficacy. Avoid concomitant use of VENCLEXTA with strong CYP3A inducers or moderate CYP3A inducers.
7.2 Effect of VENCLEXTA on Other Drugs Warfarin Concomitant use of VENCLEXTA increases warfarin C max and AUC 0-INF [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of bleeding. Monitor international normalized ratio (INR) more frequently in patients using warfarin concomitantly with VENCLEXTA. P-gp Substrates Concomitant use of VENCLEXTA increases C max and AUC 0-INF of P-gp substrates [see Clinical Pharmacology ( 12.3 )] , which may increase toxicities of these substrates. 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.
Contraindications
Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome [see Dosage and Administration ( 2.6 ) and Drug Interactions ( 7.1 )] . Concomitant use with strong CYP3A inhibitors at initiation and during ramp-up phase in patients with CLL/SLL is contraindicated. ( 2.6 , 4 , 7.1 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Venetoclax is an oral selective BCL-2 inhibitor and antineoplastic agent used in the therapy of refractory chronic lymphocytic leukemia (CLL). Venetoclax is associated with a low rate of transient serum enzyme elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury with jaundice. Venetoclax has potent immunosuppressive activity and may be capable of causing reactivation of hepatitis B.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. There are no available data on VENCLEXTA use in pregnant women to inform a drug-associated risk. Administration of venetoclax to pregnant mice during the period of organogenesis was fetotoxic at exposures 1.2 times the human exposure at the recommended dose of 400 mg daily based on AUC. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data In embryo-fetal development studies, venetoclax was administered to pregnant mice and rabbits during the period of organogenesis. In mice, venetoclax was associated with increased post-implantation loss and decreased fetal body weight at 150 mg/kg/day (maternal exposures approximately 1.2 times the human exposure at the recommended dose of 400 mg once daily).
No teratogenicity was observed in either the mouse or the rabbit.
Breastfeeding (LactMed)
No information is available on the use of venetoclax during breastfeeding. Because venetoclax is more than 99% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is 26 hours and it might accumulate in the infant. Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. The manufacturer recommends that breastfeeding be discontinued during vemurafenib therapy and for 1 week after the final dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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