Commentary
Article
Carefully Dose and Taper Venetoclax to Avoid Tumor Lysis Syndrome
Author(s):
Recent data show how to dose venetoclax (Venclexta; AbbVie, Genentech) to avoid tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Patients with low calcium levels or who have high blood levels of potassium, phosphate, or uric acid meet the criteria of laboratory TLS.1
Venetoclax prevents the B-cell leukemia/lymphoma 2 protein (BCL-2)4 from functioning.2 Normally, cells know how long they should live, but some damaged cells stay alive longer than they should. If a cell has too much BCL-2, it stays alive too long.2 By then, it is damaged and trying to constantly reproduce uncontrollably.3
A team of researchers from Canada retrospectively investigated this issue. By increasing the dose of venetoclax from 20 mg to 400 mg over 5 weeks (see Table2), the risk of adverse effects was reduced from 12.5% to no more than 10%, and possibly less.1 The patients’ median age was 70. Clinical TLS typically occurs in one-eighth of patients and, in severe cases, can result in death.1 In the study, none of the 88 patients experienced symptoms of TLS, although 2 patients had elevated blood phosphate and uric acid levels.
Table. Monotherapy Dosage in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Geriatric and non-geriatric patients should receive the same dosage.2 No dose change is needed regardless of a patient’s weight, sex, or a creatinine clearance as low as 15 mL/min. If the patient has moderate hepatic impairment, no dose adjustment is needed. However, no absorption information for patients on dialysis, pediatric patients, or end stage renal disease is available.2
There is, however, information on drug interactions. Patients must avoid coadministration of interacting drugs like colchicine.4 Colchicine’s half-life is on average 31 hours but may go up to 50 hours. Consequently, if the prescriber insists on an interacting drug’s necessity, the dose and frequency should be reduced.4
Venetoclax has 2 types of interactions. The first occurs when taking venetoclax with a moderate cytochrome 3A4 (CYP3A4) inhibitor such as diltiazem, or fluconazole.1 The second is caused by P-glycoprotein (PGP) substrates like digoxin.1
Additionally, patients must understand adverse effects and when to contact their pharmacist or other health care professional. Examples of more common adverse effects are lower red and white blood cell counts, gastrointestinal adverse effects, fatigue, and upper respiratory infections.3
REFERENCES
1. de Boer A, McCaw C, Ackman M, Leslie T, Peters A, Koshman S. Evaluating the impact of a pharmacist-led venetoclax ramp-up clinic for chronic lymphocytic leukemia patients: a retrospective chart review. J Oncol Pharm Pract. 2025;10781552251324522. doi:10.1177/10781552251324522
2. Venetoclax [prescribing information]. AbbVie Inc; April 2016. Accessed April 22, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf
3. Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9(1):47-59. doi:10.1038/nrm2308
4. Colcrys [prescribing information]. Mutual Pharmaceutical Company, Inc; July 2009. Accessed April 22, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022351lbl.pdf
