Products Affected - Description

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

Reason for the Shortage

• • Because of increased global demand, and as the only source of BCG Live (Intravesical) in the United States and many other countries, Merck anticipates supply constraints for Tice BCG in 2019. To minimize disruption to patient care and address the current imbalance between supply and increased global demand, Tice BCG will be under allocation when demand exceeds production plans and available inventory.

Available Products

• • There are no presentations available

• • Merck has Tice BCG on allocation.

• • BCG live intravesical contains live attenuated mycobacteria and is labeled for the treatment and prophylaxis of carcinoma in situ of the urinary bladder. BCG live intravesical is also labeled for prophylaxis of primary or recurring stage Ta or T1 papillary tumors following transurethral resection.[2-3]

• • 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.[3-4]
  • 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).[3-4]
  • 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.[2-3]

• • 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.[3-5]
  • 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.[6-21]
  • Several urologic associations created recommendations on how to manage the shortage in patients with non-muscle invasive bladder cancer (NMIBC). These included alternatives for treatment, rationing dosing, or administering reduced doses. The recommendations can be found at: https://www.bcan.org/wp-content/uploads/2019/02/BCAN-Letter-Re-BCG-Shortage-for-Web.pdf.
  • 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. https://www.ashp.org/-/media/assets/policy-guidelines/docs/guidelines/managing-drug-product-shortages.ashx

• 1. Merck (personal communications and website). January 15, 2019.
  2. Merck. Tice BCG (BCG live intravesical) Injection, [product information]. Whitehouse Station, NJ: Merck, 2018.
  3. Beckwith MC, Tyler LS, eds. Cancer Chemotherapy Manual. St. Louis, MO: Wolters Kluwer Health Inc. 2012.
  4. Antineoplastic agents. In: McEvoy GK, ed. AHFS 2010 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists; 2010: 902-1260.
  5. Lexicomp Online, Lexi-Drugs Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2019; January 24, 2019.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Anastasiadis A, de Reijke TM. Best practice in the treatment of nonmuscle invasive bladder cancer. Ther Adv Urol 2012;4:13-32.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.