Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments

Clinical Therapeutics

Volumn 39, Issue 2, 2017, Pages 359-367

  Agarwal, Suresh K ^a   DiNardo, Courtney D ^b   Potluri, Jalaja ^a   Dunbar, Martin ^a   Kantarjian, Hagop M ^b   Humerickhouse, Rod A ^a   Wong, Shekman L ^a   Menon, Rajeev M ^a   Konopleva, Marina Y ^b   Salem, Ahmed Hamed ^a,c  

^a ABBVIE INC   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c African Union Organization St Abbassia   (Egypt)

Author keywords

ABT 199 GDC 0199; BCL 2; CYP3A; pharmacokinetic interaction; posaconazole; venetoclax

Indexed keywords

AZACITIDINE; DECITABINE; POSACONAZOLE; VENETOCLAX; ANTIFUNGAL AGENT; CYTOCHROME P450 3A; FUSED HETEROCYCLIC RINGS; SULFONAMIDE; TRIAZOLE DERIVATIVE;

ACUTE MYELOID LEUKEMIA; ADULT; ANEMIA; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CLINICAL ARTICLE; CLINICAL TRIAL; DIARRHEA; DRUG BIOAVAILABILITY; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG METABOLISM; DRUG TOLERABILITY; FEMALE; HUMAN; HYPERPHOSPHATEMIA; HYPOKALEMIA; MALE; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; MULTIPLE DRUG DOSE; MYCOSIS; NAUSEA; NEUTROPENIA; THROMBOCYTOPENIA; LEUKEMIA, MYELOID, ACUTE; METABOLISM; MIDDLE AGED; ORAL DRUG ADMINISTRATION; PHASE 1 CLINICAL TRIAL;

ADMINISTRATION, ORAL; ADULT; ANTIFUNGAL AGENTS; BRIDGED BICYCLO COMPOUNDS, HETEROCYCLIC; CYTOCHROME P-450 CYP3A; FEMALE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; SULFONAMIDES; TRIAZOLES;

EID: 85011039454     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2017.01.003     Document Type: Article

References (36)

1. 1 Venclexta (venetoclax) [US prescribing information]., 2016, AbbVie Inc., North Chicago, IL.
2. 2 Souers, A.J., Leverson, J.D., Boghaert, E.R., et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 19 (2013), 202–208.
3. 3 Roberts, A.W., Davids, M.S., Pagel, J.M., et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med 374 (2016), 311–322.
4. 4 Stilgenbauer, S., Eichhorst, B., Schetelig, J., et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol 17 (2016), 768–778.
5. 5 Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. [published online January 17, 2017]; http://dx.doi.org/10.1200/JCO.2016.70.4320.
6. 6 Moreau, P., Chanan-Khan, A., Roberts, A.W., et al. Safety and efficacy of venetoclax (ABT-199/GDC-0199) in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma: phase 1b results. Blood, 126, 2015, 3038.
7. 7 DiNardo, C., Pollyea, D., Pratz, K., et al. A phase 1b study of venetoclax (ABT-199/GDC-0199) in combination with decitabine or azacitidine in treatment-naive patients with acute myelogenous leukemia who are ≥ to 65 years and not eligible for standard induction therapy. Blood, 126, 2015, 327.
8. 8 Seymour JF, Ma S, Brander DM, et al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol. [published online January 12, 2017]; http://dx.doi.org/10.1016/S1470-2045(17)30012-8.
9. 9 Konopleva, M., Pollyea, D.A., Potluri, J., et al. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov 6 (2016), 1106–1117.
10. 10 de Vos, S., Swinnen, L., Kozloff, M., et al. A dose-escalation study of venetoclax (ABT-199/GDC-0199) in combination with bendamustine and rituximab in patients with relapsed or refractory non-Hodgkin׳s lymphoma. Blood, 126, 2015, 255.
11. 11 Salem, A.H., Agarwal, S.K., Dunbar, M., et al. Effect of low- and high-fat meals on the pharmacokinetics of venetoclax, a selective first-in-class BCL-2 inhibitor. J Clin Pharmacol 56 (2016), 1355–1361.
12. 12 Jones, A.K., Freise, K.J., Agarwal, S., et al. Clinical predictors of venetoclax pharmacokinetics in chronic lymphocytic leukemia and Non-Hodgkin׳s lymphoma patients: a pooled population pharmacokinetic analysis. AAPS J 18 (2016), 1192–1202.
13. 13 Liu H, Michmerhuizen MJ, Lao Y, et al. Metabolism and disposition of a novel B-cell lymphoma-2 inhibitor venetoclax in humans and characterization of its unusual metabolites. Drug Metab Dispos. [published online December 19, 2016]. https://doi.org/10.1124/dmd.116.071613.
14. 14 Freise KJ, Jones AK, Menon R, et al. Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. Hematol. Oncol. [published online December 16, 2016]; http://onlinelibrary.wiley.com/doi/10.1002/hon.2373/full.
15. 15 Freise KJ, Jones AK, Eckert D, et al. Impact of venetoclax exposure on clinical efficacy and safety in patients with relapsed or refractory chronic lymphocytic leukemia. Clin Pharmacokinet. [published online September 15, 2016]; http://link.springer.com/article/10.1007/s40262-016-0453-9.
16. 16 Freise, K.J., Dunbar, M., Jones, A.K., et al. Venetoclax does not prolong the QT interval in patients with hematological malignancies: An exposure-response analysis. Cancer Chemother Pharmacol 78 (2016), 847–853.
17. 17 Salem AH, Agarwal SK, Dunbar M, et al. Pharmacokinetics of venetoclax, a novel BCL-2 inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia or non-Hodgkin׳s lymphoma. J Clin Pharmacol. [published online August 25, 2016]; http://onlinelibrary.wiley.com/doi/10.1002/jcph.821/abstract.
18. 18 Salem AH, Hu B, Freise KJ, et al. Evaluation of the pharmacokinetic interaction between venetoclax, a selective BCL-2 inhibitor, and warfarin in healthy volunteers. Clin Drug Investig. [published online December 2, 2016]; http://link.springer.com/article/10.1007/s40261-016-0485-9.
19. 19 Agarwal, S.K., Hu, B., Chien, D., et al. Evaluation of rifampin׳s transporter inhibitory and CYP3A inductive effects on the pharmacokinetics of venetoclax, a BCL-2 inhibitor: results of a single- and multiple-dose study. J Clin Pharmacol 56 (2016), 1335–1343.
20. 20 Agarwal SK, Salem AH, Danilov AV, et al. Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL-2 inhibitor, in patients with non-Hodgkin lymphoma. Br J Clin Pharmacol. [published online November 2, 2016]; http://onlinelibrary.wiley.com/doi/10.1111/bcp.13175/full.
21. 21 Pagano, L., Caira, M., Candoni, A., et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 91 (2006), 1068–1075.
22. 22 Cornely, O.A., Maertens, J., Winston, D.J., et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356 (2007), 348–359.
23. 23 Bruggemann, R.J., Alffenaar, J.W., Blijlevens, N.M., et al. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis 48 (2009), 1441–1458.
24. 24 Vardiman, J.W., Thiele, J., Arber, D.A., et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 2009, 937–951.
25. 25 Noxafil (posaconazole) [US prescribing information]. 2014, Merck & Co., Inc., Whitehouse Station, NJ.
26. 26 Verbeke, G., Molenberghs, G., Linear Mixed Models for Longitudinal Data. 2000, Springer-Verlag, New York.
27. 27 Pollyea, D., Dinardo, C., Thirman, M., et al. Results of a phase 1b study of venetoclax plus decitabine or azacitidine in untreated acute myeloid leukemia patients ≥ 65 years ineligible for standard induction therapy. J Clin Oncol, 34, 2016 (suppl; abstr 7009).
28. 28 Kikuchi R, Shebley M, Bow DAJ, et al. In vitro characterization of drug metabolizing enzymes and transporters to enable a mechanistic drug-drug interaction assessment for venetoclax. Presented at: 11th International ISSX Meeting, June 12-16, 2016, Busan, Korea. https://issx.confex.com/issx/intl11/webprogram/Paper36597.html.
29. 29 Sansone-Parsons, A., Krishna, G., Martinho, M., et al. Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacotherapy 27 (2007), 825–834.
30. 30 Zhang, Y., Hsieh, Y., Izumi, T., et al. Effects of ketoconazole on the intestinal metabolism, transport and oral bioavailability of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor and a P450 3A, P-glycoprotein dual substrate, in male Sprague-Dawley rats. J Pharmacol Exp Ther 287 (1998), 246–252.
31. 31 Moody, D.E., Liu, F., Fang, W.B., Azole antifungal inhibition of buprenorphine, methadone and oxycodone in vitro metabolism. J Anal Toxicol 39 (2015), 374–386.
32. 32 Heredi-Szabo, K., Palm, J.E., Andersson, T.B., et al. A P-gp vesicular transport inhibition assay - optimization and validation for drug-drug interaction testing. Eur J Pharm Sci 49 (2013), 773–781.
33. 33 Lempers, V.J., van den Heuvel, J.J., Russel, F.G., et al. Inhibitory potential of antifungal drugs on ATP-binding cassette transporters P-glycoprotein, MRP1 to MRP5, BCRP, and BSEP. Antimicrob Agents Chemother 60 (2016), 3372–3379.
34. 34 Krishna, G., Moton, A., Ma, L., et al. Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers. Clin Ther 31 (2009), 286–298.
35. 35 Freise, K.J., Shebley, M., Salem, A.H., Quantitative Prediction of the Effect of CYP3A Inhibitors and Inducers on Venetoclax Pharmacokinetics Using a Physiologically Based Pharmacokinetic Model. The Journal of Clinical Pharmacology, 2017, 10.1002/jcph.858.
36. 36 Dacogen (decitabine) [US prescribing information]. 2010, Eisai Inc, Woodcliff Lake, NJ.