This promotional website is for UK healthcare professionals involved in the care of patients with cancer. Adverse event reporting information can be found below.
UK-VNCAML-240003 | April 2024.
Dosing & TLS prophylaxis
(tumour lysis syndrome)
VENCLYXTO IS METABOLISED PRIMARILY BY CYP3A AND IS ALSO A SUBSTRATE FOR P‑GP AND BCRP
If given with other CYP3A inhibitors/inducers, P-gp or BCRP inhibitors, you may need to avoid VENCLYXTO use or reduce the dose
Concomitant use of preparations containing St. John's wort are contraindicated.1
Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with VENCLYXTO as they contain inhibitors of CYP3A.1
Please refer to SmPC for full prescribing information.
Footnotes
*This is not an exhaustive list of examples.
†The VENCLYXTO dose that was used prior to initiating the CYP3A inhibitor should be resumed 2-3 days after discontinuation of the CYP3A inhibitor.1
‡Consider alternative medication.1
BCRP=breast cancer resistance protein; CYP3A=cytochrome P450 3A; DDI=drug-drug interaction; INR=international normalised ratio;
OATP1B1=organic anion transporting polypeptide 1B1; P-gp=permeability glycoprotein.
Slide 1 of 3
Concomitant use of VENCLYXTO with strong or moderate CYP3A inhibitors increases VENCLYXTO exposure and may increase the risk for TLS at initiation and during the dose titration phase and for other toxicities1
Consider alternative medications. If a CYP3A inhibitor must be used, adjust the dose as below and monitor patients more closely for signs of toxicities. The dose may need to be further adjusted.
Maximum dose of VENCLYXTO in combination with strong CYP3A inhibitors. During steady state, reduce venclyxto dose to 100mg or less (or by at least 75% if already modified for other reasons)1*
Maximum dose of VENCLYXTO in combination with moderate CYP3A inhibitors (reduce VENCLYXTO dose by at least 50%)1*
Maximum dose of VENCLYXTO in combination with strong CYP3A inhibitors. During steady state, reduce venclyxto dose to 100mg or less (or by at least 75% if already modified for other reasons)1*
Maximum dose of VENCLYXTO in combination with moderate CYP3A inhibitors (reduce VENCLYXTO dose by at least 50%)1*
WHEN SHOULD I STOP PROPHYLAXIS WITH STRONG OR MODERATE CYP3A INHIBITORS AND WHICH VENCLYXTO DOSE SHOULD I COME BACK TO?
Stopping antifungals should be at the discretion of the clinician.
The VENCLYXTO dose that was used prior to initiating the CYP3A inhibitor should be resumed 2-3 days after discontinuation of the CYP3A inhibitor.1
Please refer to SmPC for full prescribing information.
Footnotes
*Consider alternative medications.1
†Reduce to 100 mg or less, or by at least 75% if already modified for other reasons.1
CYP3A=cytochrome P450 3A; P-gp=permeability glycoprotein.
Slide 2 of 3
Are there any drug-drug interactions (DDIs) I should be aware of?
A number of agents may have their plasma concentrations altered by VENCLYXTO1
Warfarin:1
It is recommended that the international normalised ratio be monitored closely in patients receiving warfarin.
Substrates of P-gp, BCRP:1
Co-administration of narrow therapeutic index P-gp or BCRP substrates (e.g. digoxin, dabigatran, everolimus, sirolimus) with VENCLYXTO should be avoided.
If a narrow therapeutic index P-gp or BCRP substrate must be used, it should be used with caution. For an orally administered P-gp or BCRP substrate sensitive to inhibition in the gastrointestinal tract (e.g. dabigatran exetilate), its administration should be separated from VENCLYXTO administration as much as possible to minimise a potential interaction.
Substrates of OATP1B1:1
If a statin (OATP substrate) is used concomitantly with VENCLYXTO, close monitoring of statin-related toxicity is recommended.
Please refer to the VENCLYXTO Summary of Product Characteristics for full details
Footnotes
BCRP=breast cancer resistance protein; CYP3A=cytochrome P450 3A; DDI=drug-drug interaction;
INR=international normalised ratio; OATP1B1=organic anion transporting polypeptide 1B1; P-gp=permeability glycoprotein.
Slide 3 of 3
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UK-VNCAML-240066 | April 2024.
DOES USE OF ANTIMICROBIAL PROPHYLAXIS IMPACT PATIENT OUTCOMES WITH VENCLYXTO?
Antimicrobial prophylaxis with CYP3A inhibitors was used in neutropenic patients in the VIALE-A study, with overall similar composite remission rates with VENCLYXTO dose reductions2*
OVERALL SURVIVAL
Median OS in patients receiving VEN+AZA was not statistically different regardless of use of moderate or strong CYP3A inhibitor2
ADVERSE EVENTS
Rates of discontinuation from infections were similar across all patients treated with VEN+AZA regardless of CYP3Ai use2
RESPONSES
Rates of CR+CRi as best response in the VEN+AZA arm of VIALE-A were similar with concomitant use of CYP3A inhibitor vs. no use2
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Graphs adapted from Jonas BA et al.
VIALE-A was a phase 3, randomised (2:1), placebo-controlled, trial evaluating the efficacy and safety of VEN+AZA vs. PBO+AZA in first-line adult AML patients ineligible for intensive chemotherapy. VEN+AZA acheived its primary endpoints, achieving statistically significant increases in overall survival and CR+CRi rate vs AZA alone (p<0.001 for both).3
*Neutropenic patients were defined as having an ANC <500/µL.2
ANC=absolute neutrophil count; CI=confidence interval; CR=complete remission; CRi=CR with incomplete count recovery; CYP3Ai=cytochrome P450 3A inhibitor;
OS=overall survival; VEN=VENCLYXTO.
OVERALL SURVIVAL
Median OS in patients receiving VEN+AZA was not statistically different regardless of use of moderate or strong CYP3A inhibitor2*
Adapted from Jonas BA et al.
*As noted by overlapping confidence intervals.
ADVERSE EVENTS
Rates of discontinuation from infections were similar across all patients treated with Ven+AZA regardless of CYP3A inhibitor use2*
Graph adapted from Jonas BA et al.
*Reported AEs that began within the the first 2 cycles of treatment with CYP3Ai were reported as being given for prophylaxis.
RESPONSES
Rates of CR+CRi as best response in the VEN+AZA arm of VIALE-A were similar with concomitant use of CYP3A inhibitor vs. no use2*
Graph adapted from Jonas BA et al.
*CR=absolute neutrophil count (ANC) >1,000/microlitre, platelets >100,000/microlitre, RBC transfusion independence, and bone marrow with <5% blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.
CRi=ANC ≤1,000/microlitre or platelets ≤100,000/microlitre1
