• {%brandMenuItems%}
    • {%itemName%} {%arrowSpan%}
        {%subBrandMenuItems%}
    • {%itemName%} {%arrowSpan%}
        {%productMenuItems%}
    • {%selfProduct%}
      • {%languages%}
    • This website is for UK Healthcare Professionals only

      VENCLYXTO® (venetoclax) in Acute Myeloid Leukaemia (AML)

       

      In combination with a hypomethylating agent for newly-diagnosed patients with AML who are ineligible for intensive chemotherapy1

       

       

       

      UK-VNCAML-220109 | April 2022
      1. Venclyxto Summary of Product Characteristics

      Dosing & Administration

      VENCLYXTO is administered as an oral tablet with the dose increasing daily per the 3-day ramp-up schedule1

      • VENCLYXTO should be taken with a meal and water at approximately the same time each day1
      • VENCLYXTO tablets should be swallowed whole, not chewed, crushed or broken1
      • VENCLYXTO is available in 10-mg, 50-mg, and 100-mg film-coated tablets1
      • Patients should continue to take VENCLYXTO until disease progression or unacceptable toxicity is observed1
      • Some patients may require dose interruptions and dose reductions due to adverse events1

      AZA=azacitidine; CLL=chronic lymphocytic leukaemia; IV=intravenous; SC=subcutaneous.


      RECOMMENDATIONS FOR STARTING VENCLYXTO IN SPECIAL POPULATIONS1

      Dosing considerations for patients with hepatic impairment1

      Dosing considerations for patients with renal impairment1

      CrCl=creatinine clearance; TLS=tumour lysis sydrome.

      DOSING MODIFICATIONS BASED ON DRUG-DRUG INTERACTIONS1

      Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with VENCLYXTO as they contain inhibitors of CYP3A.1

      *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

      DOSE MODIFICATIONS FOR CONCOMITANT USE OF CYP3A INHIBITORS1

      Maximum dose of VENCLYXTO when used in combination with strong CYP3A inhibitors1*

      Reduce to 100 mg or less, or by at least 75% if already modified for other reasons.1

      Maximum dose of VENCLYXTO when used in combination with moderate CYP3A inhibitors (reduce VENCLYXTO dose by at least 50%)1* 

      *Consider alternative medications.1

      AZA=azacitidine; CYP3A=cytochrome P450 3A. 

      VENCLYXTO PLUS AZA DEMONSTARATED A GENERALLY MANAGABLE ADVERSE EVENT PROFILE1,2

      MANAGEMENT OF SOME ADVERSE REACTIONS MAY REQUIRE DOSE INTERRUPTIONS OR PERMANENT DISCONTINUATION OF VENCLYXTO1

      *Grade 4 neutropenia (ANC <500/μL) with or without fever or infection; or Grade 4 thrombocytopenia (platelet count <25,000/μL).1

      Consider bone marrow evaluation to assess remission

      ANC=absolute neutrophil count; AZA=azacitidine.

      G-CSF=granulocyte-colony stimulating factor

      PROPHYLAXIS MEASURES

      Consider additional measures, including increasing laboratory monitoring and reducing VENCLYXTO starting dose for patients with risk factors for TLS, e.g. circulating blasts, high burden of leukaemia involvement in bone marrow, elevated pre-treatment LDH levels, reduced renal function.1

      RISK FACTORS AND FEATURES OF TLS1,3

      VENCLYXTO can cause rapid reduction in tumour burden and poses a risk of TLS at initiation and during the dose-titration phase1,3

      *Within 3 days before the start of therapy or up to 7 days afterward.

      If probably or definitely caused by hypocalcemia.3

      Acute kidney injury represents clinical TLS even if criteria for laboratory TLS are not satisfied.3

      In VIALE-A, the rates of reported events of laboratory or clinical
      TLS were low (1%)1,2

      • 3 of 283 patients (1%) experienced TLS
      • 1 case of clinical TLS, 2 cases of laboratory TLS 
      • All cases occurred in the VENCLYXTO plus AZA arm (during the dose-titration phase) 
      • All cases were resolved with uricosuric agents and calcium supplements without treatment interruption 

      AZA=azacitidine; LDH=lactate dehydrogenase; TLS=tumour lysis syndrome; VEN=VENCLYXTO; WBC=white blood cell count. 

       

      Dosing recommendations for patients with AML1

      3-step process for initiating and managing patients on VENCLYXTO

      *VIALE-A was a Phase 3, randomised, double-blind, placebo-controlled study comparing the efficacy and safety of VEN+AZA vs AZA alone in first-line AML patients ineligible for intensive chemotherapy. VEN+AZA reached its primary efficacy endpoints, achieving statistically significant increases in overall survival and composite complete remission rates (CR+CRi) vs AZA alone. In VIALE-A, 66.4% (190/286) patients on VEN+AZA achieved CR+CRi vs. 28.3% (41/145) patients on AZA alone (P<0.001). 43.4% of patients (124/286) on VEN+AZA achieved CR/CRi before cycle 2 compared with 7.6% (11/145) of patients on AZA alone (P<0.001).1,2

      For information on study design click here.

      AZA=azacitidine; CR=complete remission; CRi=CR with incomplete blood count recovery; CYP3A=Cytochrome P450 3A; VEN=VENCLYXTO.

       

      References

      1. VENCLYXTO Summary of Product Characteristics.
      2. DiNardo CD et al. N Engl J Med. 2020; 383(7): 617-29.
      3. Howard SC et al. N Engl J Med 2011; 364:1844–54.

       

      Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.

      Adverse events should also be reported to AbbVie on GBPV@abbvie.com

      UK-VNCAML-220116. Date of preparation: April 2022.