VENCLYXTO can cause rapid reduction in tumour, and thus, poses a risk for TLS in the initial 5-week dose-titration phase in all patients with CLL, regardless of tumour burden and other patient characteristics. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Assess patient-specific factors for level of TLS risk and provide prophylactic hydration and anti-hyperuricaemics to patients prior to first dose of VENCLYXTO to reduce risk of TLS.¹

The table below describes the recommended TLS prophylaxis and monitoring during VENCLYXTO treatment based on tumour burden determination from clinical trial data. In addition, all patient comorbidities should be considered for risk-appropriate prophylaxis and monitoring, either outpatient or in hospital.¹

Recommended TLS prophylaxis based on tumour burden in patients with CLL.¹

Adapted from VENCLYXTO Summary of Product Characteristics.¹

^aInstruct patients to drink water daily starting 2 days before and throughout the dose-titration phase, specifically prior to and on the days of dosing at initiation and each subsequent dose increase. Administer intravenous hydration for any patient who cannot tolerate oral hydration.
^bStart allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of venetoclax.
^cEvaluate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time.
^dAt subsequent dose increases, monitor blood chemistries at 6 to 8 hours and at 24 hours for patients who continue to be at risk of TLS.

Adapted from VENCLYXTO Summary of Product Characteristics.^1
*Clinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or seizures and/or sudden death.
^**The modified dose should be continued for 1 week before increasing the dose.
For patients who have had a dosing interruption lasting more than 1 week during the first 5 weeks of dose-titration or more than 2 weeks after completing the dose-titration phase, TLS risk should be reassessed to determine if restarting at a reduced dose is necessary (e.g., all or some levels of the dose-titration).
Consider discontinuing VENCLYXTO for patients who require dose reductions to less than 100 mg for more than 2 weeks.

Adapted from VENCLYXTO Summary of Product Characteristics.^1
*Consider using G-CSF if clinically indicated.
^**The modified dose should be continued for 1 week before increasing the dose.
^†Adverse reactions were graded using NCI CTCAE version 4.0.
For patients who have had a dosing interruption lasting more than 1 week during the first 5 weeks of dose-titration or more than 2 weeks after completing the dose-titration phase, TLS risk should be reassessed to determine if restarting at a reduced dose is necessary (e.g., all or some levels of the dose-titration).
Consider discontinuing VENCLYXTO for patients who require dose reductions to less than 100 mg for more than 2 weeks. 

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the VENCLYXTO SmPC.

In patients with CLL, concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase (see sections 4.2 and 4.5 of the VENCLYXTO SmPC).

In all patients, concomitant use of preparations containing St. John’s wort (see sections 4.4 and 4.5 of the VENCLYXTO SmPC).

Interactions

VENCLYXTO is predominantly metabolised by CYP3A.

Agents that may alter VENCLYXTO plasma concentrations:

• CYP3A inhibitors
• P-gp and BCRP inhibitors
• CYP3A inducers
• Azithromycin
• Gastric acid reducing agents
• Bile acid sequestrants

Agents that may have their plasma concentrations altered by VENCLYXTO

• Warfarin
• Substrates of P-gp, BCRP, and OATP1B1

See SmPC for full details on managing interactions.