Products Affected - Description

Doxil 2 mg/mL, Janssen Products, LP
2 mg/mL, 25 mL (50 mg) vial (NDC 59676-0960-02)

Reason for the Shortage

• Janssen Products, LP is the sole supplier of doxorubicin liposomal injection and states the shortage is due to manufacturing issues. Janssen Products, LP has updates with information about the shortage on the Doxil website that is updated regularly.^1-3
• Janssen Products, LP created a new website in early-August, 2012 for the shortage of Doxil.
• Janssen is working to transition Doxil manufacturing to additional suppliers. The current solution is to use areas of the Ben Venue Laboratories facility available for production and other partners to complete the manufacturing process. This process is currently under FDA review. FDA has exercised regulatory discretion and approved three lots of 2 mg/mL 10 mL (20 mg) vials.
• 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.
• FDA is allowing temporary importation of Lipodox (doxorubicin hydrochloride liposome injection) from Sun Pharma Global FZE. The product is available as 2 mg/mL 10 mL (Lipodox™) and 25 mL (Lipodox 50™) single use vials, which contain the same active ingredient and concentration as the US doxorubicin hydrochloride liposome injection (Doxil®). Sun Pharma’s Lipodox is manufactured at an FDA inspected facility in India. The authorized distributor, Caraco Pharmaceutical Laboratories is working with FDA to make product available to wholesalers in the US. Check your wholesaler for product availability. Contact the shortage response team for further information at 888-835-2237 or fax 800-980-2237.⁴
• FDA has also posted some frequently asked questions regarding Lipodox.⁵
• FDA approved a generic version of doxorubicin liposomal injection from Sun Pharma in early-February 2013. The authorized distributor is Caraco Pharmaceutical Laboratories.
• Caraco launched generic doxorubicin liposomal injection in mid-March, 2013.⁶

Available Products

Estimated Resupply Dates

Janssen has Doxil 2 mg/mL 25 mL (50 mg) vials on long-term back order and the company cannot estimate a new production date. Three lots of the 10 mL (20 mg) vials have been released.⁴  

Implications for Patient Care

• Doxorubicin liposomal is an anthracycline glycoside agent encapsulated in liposomes. Doxil is labeled for use in adults with refractory multiple myeloma, refractory ovarian cancer, and AIDS-related Kaposi sarcoma.^7,8
• Doxil is used off-label in adults for treating refractory metastatic breast cancer.^7,8
• The imported product, Lipodox, is labeled for use in adults with refractory ovarian cancer, AIDS-related Kaposi sarcoma, or metastatic breast cancer.⁹
• Lipodox cannot be AP-rated to Doxil because it is not an FDA-approved product.⁴ However, Lipodox may be substituted with Doxil on a mg per mg basis.
• Doxorubicin liposomal is not bioequivalent to conventional doxorubicin injection. Do not substitute these products on a mg per mg basis.^8-11

Safety

• Chemotherapy agents, such as doxorubicin, pose additional safety risks both for patients and for healthcare workers handling these agents.^10,11
• 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).^10,11

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 doxorubicin liposomal.^8-11
• Evaluate the health-care system’s total supply of doxorubicin liposomal before beginning patients on combination chemotherapy regimens containing doxorubicin liposomal. If adequate supplies are not available, select an alternative regimen. The manufacturer currently recommends against initiating Doxil therapy.¹
• Lipodox cannot be AP-rated to Doxil because it is not an FDA-approved product.⁴ However, Lipodox may be substituted with Doxil on a mg per mg basis. Patients currently receiving therapy with Doxil will need a new prescription when they switch to Lipodox. The Table compares Doxil and Lipodox.
• 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
• Cytarabine Injection
• Dacarbazine Injection
• Daunorubicin Hydrochloride Injection
• Denileukin Diftitox Injection
• Doxorubicin 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. Centocor Ortho Biotech (personal communications). June 24, 2011.
2. Johnson and Johnson Distribution Center (personal communications). June 27, and July 12, 18, and 22, 2011; February 28 and December 19, 2012; January 3, February 8, and March 5, 2013.
3. Janssen Products, LP (personal communication). July 28 and 29, August 4, 5, 15, 18 and 19, September 6, 8, and 27, October 11 and 17, November 7 and 21, and December 9, 12 and 23, 2011; January 19, February 9 and 28, March 22, April 5, May 9, June 29, August 2, October 15 and 25, and November 27, 2012; January 7, March 13, April 9 and 11, 2013.
4. FDA (written communication). URGENT – Doxil® (Doxorubicin Hydrochloride Liposome Injection) Shortage Update. Available online. Accessed March 22, 2012.
5. FDA (written communication). Lipodox Importation Frequently Asked Questions. Available online. Accessed March 22, 2012.
6. Caraco (personal communication). February 7, March 4 and 19, and April 9, 2013. 
7. Doxil® (doxorubicin HCl liposome injection) for intravenous injection, [product information]. Raritan, NJ: Centocor Ortho Biotech Products, LP; 2010.
8. Drug Facts and Comparisons Online. St. Louis, MO: Wolters Kluwer Health Inc. June 2011.
9. Beckwith MC, Tyler LS, eds. Cancer Chemotherapy Manual. St. Louis, MO: Wolters Kluwer Health Inc. 2011.
10. Lipodox and Lipodox 50 (doxorubicin hydrochloride liposome injection) [product information]. Andheri, Mumbai, India: Sun Pharmaceutical; 2010. Available online. Accessed March 22, 2012.
11. Antineoplastic agents. In: McEvoy GK, ed. AHFS 2011 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists; 2011: 905-1276.
12. Lipodox (doxorubicin liposome HCl) injection. Frequently asked questions. Caraco Pharmaceutical Laboratories. Available online. Accessed March 22, 2012.
13. Material Safety Data Sheet. Lipodox (doxorubicin liposome HCl) injection. Sun Pharma. Available online. Accessed March 22, 2012.
14. HCPCS Quarterly Update. Available online. Accessed May 9, 2012.

Updated

Updated April 11, 2013 by Michelle Wheeler, PharmD, Drug Information Specialist. Created June 27, 2011, by Ginny Jones, RPh, and M. Christina Beckwith, PharmD, Drug Information Specialists. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.