Products Affected - Description

• • TheraCys intravesical injection, Sanofi Pasteur, 81 mg, vial, 1 count, NDC 49281-0880-03

Reason for the Shortage

• • Sanofi Pasteur discontinued TheraCys because of manufacturing concerns. Production will stop mid-2017, and the product will not be re-launched in the United States.[1]
  • Merck states the reason for the shortage was increased demand. Merck has Tice BCG readily available.[2]

Available Products

• • Tice BCG intravesical injection, Merck, 50 mg, single dose vial, 1 count, NDC 00052-0602-02

• • BCG live intravesical contains live attenuated mycobacteria and is labeled for the treatment and prophylaxis of carcinoma in situ of the urinary bladder.[3,4,5] BCG live intravesical is also labeled for prophylaxis of primary or recurring stage Ta or T1 papillary tumors following transurethral resection.[3,4,5]

• • BCG live is biohazardous as it contains live, attenuated mycobacteria. This poses additional safety risks both for patients and for healthcare workers handling these agents.[5,6]
  • Use additional caution when processing orders for chemotherapy drugs, especially when switching between chemotherapy agents or when processing orders for chemotherapy agents with which staff may be unfamiliar (eg, those not normally prescribed at a specific institution).[5,6]
  • Tice BCG vaccine percutaneous for tuberculosis is not a substitute for BCG live intravesical.[2]
  • Use preservative-free 0.9% sodium chloride to dilute BCG live intravesical. Avoid bacteriostatic 0.9% sodium chloride solution.[3,4,5]

• • The choice of an alternative agent must be patient-specific and based on renal function, liver function, and the neoplasm type and location. No single agent can be substituted for BCG live.[5,6,7]
  • The optimal dose, schedule and duration of BCG live therapy in non-muscle invasive bladder cancer are not fully established. Recent trials have evaluated the use of reduced (1/3 dose) dosing regimens.[8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]
  • Consult a Hematology/Oncology specialist for patient- and neoplasm-specific recommendations.
  • Refer to the ASHP Guidelines on Managing Drug Product Shortages for more guidance on developing a multidisciplinary plan when the supply must be allocated. http://www.ashp.org/DocLibrary/Policy/DrugShortages/ASHP_shortage_guide09.pdf

• 1. Sanofi Pasteur (personal communications and website). May 8, 21, and 31, June 20, July 13, August 8, September 19, November 7, 2012; January 28, March 18, May 17, July 17, September 18, December 4, 2013; January 31, March 1, June 10, July 23, December 12, 2014; January 12 and 15, February 23, March 9, April 22, June 4, August 4, September 8 and 15, November 12, and December 22, 2015; May 10, July 20, September 20, and November 15, 2016.
  2. Merck (personal communications). May 9, 21, and 31, June 20, July 13, August 8, September 19, November 7, 2012; January 28, March 18, May 17, July 17, September 23, and December 4, 2013; February 3, April 7, June 10, August 7, 15, and 22, September 11 and 23, October 7 and 13, November 4 and 20, December 12, 2014; January 12 and 15, February 23, March 27, April 27, June 15, August 4, September 4 and 30, November 9, 2015; February 1, May 10, July 11, and September 20, 2016.
  3. Sanofi Pasteur. TheraCys (BCG live intravesical) Injection, [product information]. Swiftwater, PA: Sanofi Pasteur; 2011.
  4. Merck. Tice BCG (BCG live intravesical) Injection, [product information]. West Point, PA: Merck, 2009.
  5. Beckwith MC, Tyler LS, eds. Cancer Chemotherapy Manual. St. Louis, MO: Wolters Kluwer Health Inc. 2012.
  6. Antineoplastic agents. In: McEvoy GK, ed. AHFS 2010 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists; 2010: 902-1260.
  7. Drug Facts and Comparisons Online. St. Louis, MO: Wolters Kluwer Health Inc. (http://online.factsandcomparisons.com/index.aspx). May 2012.
  8. Wood DP. Re: final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. J Urol 2014;191:348-9.
  9. Weintraub MD, Li QQ, Agarwal PK. Advances in intravesical therapy for the treatment of non-muscle invasive bladder cancer (Review). Molecular Clin Oncol 2014;2:656-60.
  10. Solsona E. Words of wisdom. Re: Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol 2014;65:847-8.
  11. Pfister C, Kerkeni W, Rigaud J, et al. Efficacy and tolerance of one-third full dose bacillus Calmette-Guerin maintenance therapy every 3 months or 6 months: Two-year results of URO-BCG-4 multicenter study. Int J Urol 2014;epub.
  12. Oddens JR, Sylvester RJ, Brausi MA, et al. The effect of age on the efficacy of maintenance bacillus calmette-guerin relative to maintenance epirubicin in patients with stage ta t1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911. Eur Urol 2014;66:694-701.
  13. Kamat AM, Witjes JA, Brausi M, et al. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer. J Urol 2014;192:305-15.
  14. Brausi M, Oddens J, Sylvester R, et al. Side effects of Bacillus Calmette-Guerin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomized phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG. Eur Urol 2014;65:69-76.
  15. Oddens J, Brausi M, Sylvester R, et al. Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol 2013;63:462-72.
  16. Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urology. 2013;64:639-53.
  17. Gontero P, Oderda M, Mehnert A, et al. The impact of intravesical gemcitabine and 1/3 dose bacillus Calmette-guerin instillation therapy of the quality of life in patients with nonmuscle invasive bladder cancer: results of a prospective, randomized Phase II trial. J Urol 2013; 190:857-62.
  18. Anastasiadis A, de Reijke TM. Best practice in the treatment of nonmuscle invasive bladder cancer. Ther Adv Urol 2012;4:13-32.
  19. Ojea A, Nogueira JL, Solsona E, et al. A multicentre, randomized prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol 2007;52:1398-406.
  20. Hall MC, Chang SS, Dalbagni G, et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol 2007;178:2314-30.
  21. Agrawal MS, Agrawal M, Bansal S, Agarwal M, Lavania P, Goyal J. The safety and efficacy of different doses of bacillus Calmette Guerin in superficial bladder transitional cell carcinoma. Urology 2007;70:1075-8.
  22. Inman BA. Re: Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial. J Urol 2006;175:1960; author reply -1.
  23. Martinez-Pineiro JA, Martinez-Pineiro L, Solsona E, et al. Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial. J Urol 2005;174:1242-7.