CONCLUSION

Despite IV bicarbonate shortages, HDMTX can be administered safely with the implementation of several PO alkalization regimens for urinary alkalization. Our analysis is the largest prospective look at a PO alkalization method. While it has been attempted to decrease time to MTX administration, time to urine parameters, and ultimately length of stay, PO regimens do not appear to impact these objectives unless the oral alkalization regimen has been started prior to admission.16 Further prospective trials should be undertaken to establish the safety and efficacy of alternative PO alkalization regimens.

Disclosure

Preliminary data for this manuscript have been published online in the abstract only format (https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.e18804). Dr Michael Keng is a member for the Advisory Board for Agios, outside the submitted work.The authors report no other conflicts of interest in this work. 


Daniel R. Reed,1 Eric J. Pierce,2 Jeremy M. Sen,3 Michael K. Keng1

1Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; 2Department of Medicine, University of Virginia, Charlottesville, VA, USA; 3Department of Pharmacy Services, University of Virginia, Charlottesville, VA, USA

Correspondence: Michael K Keng
University of Virginia, Department of Medicine, Division of Hematology/Oncology, 1300 Jefferson Park Avenue, West Complex, Room 6009, Charlottesville, VA 22908, USA
Tel +1 434 924 4257
Fax +1 434 244 7534
Email mk2pv@virginia.edu


References

1. Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA. The pharmacology and clinical use of methotrexate. N Engl J Med. 1983;309(18):1094–1104. doi:10.1056/NEJM198311033091805

2. Bleyer WA. The clinical pharmacology of methotrexate: new applications of an old drug. Cancer. 1978;41(1):36–51. doi:10.1002/1097-0142(197801)41:1<36::aid-cncr2820410108>3.0.co;2-i

3. Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist. 2006;11(6):694–703. doi:10.1634/theoncologist.11-6-694

4. Drost SA, Wentzell JR, Giguere P, et al. Outcomes associated with reducing the urine alkalinization threshold in patients receiving high-dose methotrexate. Pharmacotherapy. 2017;37(6):684–691. doi:10.1002/phar.1935

5. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471–1482. doi:10.1634/theoncologist.2015-0164

6. Thompson CA. Sodium bicarbonate shortage found to affect hospitals’ daily operations. Am J Heal Pharm. 2017;74(16):1208–1210. doi:10.2146/news170051

7. Rouch JA, Burton B, Dabb A, et al. Comparison of enteral and parenteral methods of urine alkalinization in patients receiving high-dose methotrexate. J Oncol Pharm Pract. 2017;23(1):3–9. doi:10.1177/1078155215610914

8. Shamash J, Earl H, Souhami R. Acetazolamide for alkalinisation of urine in patients receiving high-dose methotrexate. Cancer Chemother Pharmacol. 1991;28(2):150–151.

9. Thomas DA, O’Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol. 2010;28(24):3880–3889. doi:10.1200/JCO.2009.26.9456

10. Borowitz MJ, Wood BL, Devidas M, et al. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children’s Oncology Group study AALL0232. Blood. 2015;126(8):964–971. doi:10.1182/blood-2015-03-633685

11. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179–84. doi:10.1159/000339789

12. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi:10.1159/000180580

13. Lexicomp Online. Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc; Published 2019. Available from: http://online.lexi.com. Accessed May 6, 2019.

14. Fox ER, Sweet BV, Jensen V. Drug shortages: a complex health care crisis. Mayo Clin Proc. 2014;89(3):361–373. doi:10.1016/j.mayocp.2013.11.014

15. Roy AM, Lei M, Lou U. Safety and efficacy of a urine alkalinization protocol developed for high-dose methotrexate patients during intravenous bicarbonate shortage. J Oncol Pharm Pract. 2019;1078155218821406. doi:10.1177/1078155218821406

16. Kintzel PE, Campbell AD, Yost KJ, et al. Reduced time for urinary alkalinization before high-dose methotrexate with preadmission oral bicarbonate. J Oncol Pharm Pract. 2012;18(2):239–244. doi:10.1177/1078155211426913

17. Visage R, Kaiser N, Williams M, Kim A. Oral methods of urinary alkalinization for high-dose methotrexate administration: alternatives to intravenous sodium bicarbonate during a critical drug shortage. J Pediatr Hematol Oncol. 2018. doi:10.1097/MPH.0000000000001348

18. Alrabiah Z, Luter D, Proctor A, Bates JS. Substitution of sodium acetate for sodium bicarbonate for urine alkalinization in high-dose methotrexate therapy. Am J Health Syst Pharm. 2015;72(22):1932–1934. doi:10.2146/ajhp150407

Source: Cancer Management and Research.
Originally published August 30, 2019.