Products Affected - Description

Reason for the Shortage

• Ben Venue voluntarily entered into a consent decree with FDA in late-January, 2013. The terms allow Ben Venue to continue to manufacture over 100 medications as long as they are compliant with the decree. FDA will continue to work with Ben Venue to ensure the products are being made with federal current good manufacturing practice requirements. Ben Venue supplies multiple products for Bedford Laboratories, a division of Ben Venue.
• Bedford issued a voluntary recall of 3 lots of cytarabine 1 gram vials in February, 2012. The company determined there was a potential increased risk for lack of sterility with these specific lots. More information can be found online.
• Bedford discontinued cytarabine 2 gram presentations in May, 2011 to concentrate on the manufacturing of other products.^1,2
• Pfizer launched cytarabine in May, 2012.⁶

Available Products

Estimated Resupply Dates

Bedford has cytarabine 100 mg and 500 mg vials on long-term back order and will not manufacture these presentations until capacity permits.^1,2

Implications for Patient Care

• Cytarabine is a pyrimidine antimetabolite. It is labeled for use as a single agent or in combination with other antineoplastic agents for a variety of leukemias including acute and chronic myelocytic leukemia, acute lymphocytic leukemia, meningeal leukemia, and erythroleukemia. Cytarabine is also labeled for use in non-Hodgkin lymphoma. These regimens are labeled for use in both adult and pediatric patients.^7-9
• Cytarabine is used off-label in adults with Hodgkin disease or undergoing hematopoietic stem cell transplantation.^7-9

Safety

• Chemotherapy agents, such as cytarabine, pose additional safety risks both for patients and for healthcare workers handling these agents.^7,8
• 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).^7,8

Alternative Agents & Management

• 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 cytarabine.^7-9
• Consider evaluating the health-care system’s total supply of cytarabine before beginning patients on combination chemotherapy regimens containing cytarabine. If adequate supplies are not available, select an alternative regimen.
• 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. 

Related Shortages

• Asparaginase Injection— No Longer Available
• Bendamustine Injection— Resolved
• Bleomycin Injection— Resolved
• Busulfan— Resolved
• Capecitabine Tablets— Resolved
• Carboplatin Solution for Injection
• Carmustine Injection— Resolved
• Cisplatin Injection— Resolved
• Cyclophosphamide Injection— Resolved
• Dacarbazine Injection
• Daunorubicin Hydrochloride Injection
• Denileukin Diftitox Injection
• Doxorubicin Injection
• Doxorubicin Liposomal Injection
• Etoposide Injection— Resolved
• Fludarabine Injection
• Fluorouracil Injection
• Gemtuzumab Ozogamicin Injection— No Longer Available
• Idarubicin Hydrochloride Injection— Resolved
• Interferon Alpha-2b, Intron A— Resolved
• Irinotecan Injection— Resolved
• Leuprolide Acetate 14-Day Kit
• Lomustine Capsules
• Mercaptopurine Tablets
• Methotrexate Injection
• Methotrexate Tablets
• Mitomycin Injection
• Paclitaxel Injection
• Pentostatin Injection
• Streptozocin For Injection— Resolved
• Thiotepa for Injection
• Tretinoin Oral Capsules— Resolved
• Vinblastine Injection
• Vincristine Injection— Resolved

1. Bedford (personal communications). May 12, June 2 and 26, July 7, 9 and 14, August 6, September 2, October 15, November 17, 2008; January 5, February 10, March 3, April 6, May 4, June 9 and 22, July 22 and 30, August 6, September 14, October 20, November 17, December 11, 2009; January 12, February 1 and 22, March 11, April 5 and 23, May 11, June 1, July 28, September 9, October 12, November 17, December 1, 17 and 20, 2010; January 6 and 19, February 1 and 17, March 1, 8 and 22, April 11, May 3, 13 and 26, June 23 and 30, July 12 and 20, August 3, September 7 and 15, October 6, 12 and 27, and November 21, 2011; June 20, July 11, and December 17, 2012; March 15 and 28, 2013.
2. Bedford (website). December 15, 2011; January 9, February 16, March 20, June 18, August 16, and November 12, 2012; March 28, 2013. 
3. Hospira (personal communications). May 12, June 2 and 26, July 7, August 6, September 2, 3, and 12, October 16, November 17, 2008; January 5, February 10, March 3, April 6, May 4, June 9 and 22, July 22 and 30, September 14, October 20, November 18, December 14, 2009; January 12, February 5 and 22, March 9, April 5 and 23, May 11, June 1, August 5, September 9, October 13 and 20, November 15, December 1 and 17, 2010, January 6 and 18, February 1, 15, and 25, March 7, 23 and 31, April 11 and 18, May 10 and 25, June 21 and 28, July 12 and 27, September 5 and 13, October 6 and 24, November 21, and December 15, 2011; January 31, February 24, March 20, June 18, July 11, August 27, and November 12, 2012; March 15, and April 1, 2013.
4. Hospira (website).  August 3, 2011; and December 17, 2012; April 2, 2013. 
5. APP (personal communications). May 12, June 2 and 26, July 7 and 9, August 6, September 2, October 15, November 17, 2008; January 5, February 10, March 3, April 6, May 4, June 9 and 22, July 22 and 29, September 14, October 20, November 18, December 11, 2009; January 12, February 1 and 22, March 10, April 5 and 23, May 11, June 2, July 22 and 28, August 4, September 13, October 13 and 15, November 18 and 19,  December 1 and 16, 2010, January 6 and 19, February 15 and 17, April 12 and 20, May 6 and 25, June 22, July 13, August 3, September 9 and 16, October 3 and 27, and December 14, 2011; January 31, February 24, March 20, June 19, July 12, November 5, and December 13, 2012; March 15 and 29, 2013.
6. Pfizer (personal communications). June 18, July 12, August 28, and November 12, and December 17, 2012; March 15 and 29, 2013.
7. Beckwith MC, Tyler LS, eds. Cancer Chemotherapy Manual. St. Louis, MO: Wolters Kluwer Health Inc. 2010.
8. Antineoplastic agents. In: McEvoy GK, ed. AHFS 2010 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists; 2010: 902-1260.
9. Drug Facts and Comparisons Online. St. Louis, MO: Wolters Kluwer Health Inc. September 2010.

Updated

Updated: April 3, 2013 by Michelle Wheeler, PharmD, Drug Information Specialist; March 15, 2013 by Leslie Jensen, PharmD, Drug Information Specialist. Created September 10, 2010, by Michelle M. Wheeler, PharmD, and M. Christina Beckwith, PharmD, Drug Information Specialists. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.