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Methotrexate Injection

[03 April 2013]

Products Affected - Description

Methotrexate 25 mg/mL (with preservative), APP1
2 mL vial (NDC 63323-0123-02) – discontinued

Methotrexate 25 mg/mL injection, Bedford2
2 mL vial, preservative-free (NDC 55390-0031-10)
4 mL vial, preservative-free (NDC 55390-0032-10)
8 mL vial, preservative-free (NDC 55390-0033-10)
10 mL vial, preservative-free (NDC 55390-0034-10)

Methotrexate lyophilized powder for injection, Bedford2
1 gram vial (NDC 55390-0143-01)

Methotrexate 25 mg/mL injection, Mylan Institutional4
2 mL vial, preservative-free (NDC 10139-0062-02) - discontinued
40 mL preservative-free vial (NDC 10139-0062-40) - discontinued

Methotrexate 25 mg/mL injection, Sandoz5
2 mL vial, preservative-free (NDC 66758-0040-02)
10 mL vial, preservative-free (NDC 66758-0040-08)

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 many multiple products for Bedford Laboratories, a division of Ben Venue.2
  • Sandoz recalled their 2 mL and 10 mL methotrexate preservative-free vials in October, 2010. Sandoz cannot provide a reason for the current shortage.5
  • Mylan Institutional has new NDC numbers for some presentations, starting in March, 2013.4
  • Bioniche was acquired by Mylan Institutional in September, 2011.4,6

Available Products

Methotrexate lyophilized powder for injection, APP1
1 gram vial (NDC 63323-0122-50)
 
Methotrexate 25 mg/mL (with preservative), APP1
10 mL (with preservative) vial (NDC 63323-0123-10)
 
Methotrexate 25 mg/mL injection, Hospira3
2 mL (with preservative) vial (NDC 61703-0350-38)
40 mL preservative-free vial (NDC 61703-0408-41)
 
Methotrexate 25 mg/mL injection, Mylan Institutional4
2 mL vial, preservative-free (NDC 67457-0221-02)
10 mL vial, preservative-free (NDC 10139-0062-10)
40 mL preservative-free vial (NDC 67457-0221-40)
 
Methotrexate 25 mg/mL injection, Pfizer7
2 mL vial, preservative-free (NDC 00069-0146-02)
4 mL vial, preservative-free (NDC 00069-0147-02)
8 mL vial, preservative-free (NDC 00069-0181-02)
10 mL vial, preservative-free (NDC 00069-0148-01)
40 mL vial, preservative-free (NDC 00069-0149-01)
 
Methotrexate 25 mg/mL injection, Sandoz5
40 mL vial, preservative-free (NDC 66758-0041-01)

Methotrexate 25 mg/mL injection, Teva8
2 mL vial, preservative-free, package of 10 (NDC 00703-3671-03)
2 mL Novaplus vial, preservative-free, package of 10 (NDC 00703-3671-93)
4 mL vial, preservative-free (NDC 00703-3673-01)
10 mL vial, preservative-free (NDC 00703-3675-01)
10 mL Novaplus vial, preservative-free (NDC 00703-3675-91)
40 mL vial, preservative-free (NDC 00703-3678-01)

Estimated Resupply Dates

  • Bedford has methotrexate1 gram lyophilized powder for injection available in limited quantities for direct order or drop shipment after allocation approval. The product has short expiration dating. All other methotrexate presentations are on back order and the company cannot estimate a release date.2
  • Sandoz has methotrexate 25 mg/mL 2 mL and 10 mL vials temporarily unavailable and the company does not expect product in 2013.5

Implications for Patient Care

  • Methotrexate is a folic acid antimetabolite. It is labeled for both adults and children for the treatment of osteosarcoma, acute lymphoid leukemia, and lung cancer. It is labeled for use in adults in the treatment of gestational trophoblastic tumors, meningeal leukemia, breast cancer, head and neck cancer, advanced mycosis fungoides, and advanced non-Hodgkin lymphomas. It is also labeled for treatment of psoriasis and rheumatoid arthritis. It is also labeled in children for treatment of polyarticular-course juvenile rheumatoid arthritis.9-11
  • Methotrexate is used off-label for a variety of neoplastic diseases not limited to testicular carcinoma, bladder cancer, gastrointestinal cancer, and soft tissue sarcomas. It is also used off-label for nonneoplastic not limited to the prevention of graft versus host disease, ectopic pregnancy, systemic lupus erythematosus, and Crohn disease.9-11
  • Methotrexate can be used alone or in combination with other antineoplastic agents.9-11

Safety

  • Chemotherapy agents, such as methotrexate, pose additional safety risks both for patients and for healthcare workers handling these agents.9,10
  • 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).9,10

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 methotrexate.9-11
  • Reserve preservative-free methotrexate for intrathecal doses.
  • Consider reserving methotrexate injection for oncology indications.
  • Use oral methotrexate whenever possible for non-oncology indications.
  • Consider evaluating the health-care system’s total supply of methotrexate before beginning patients on combination chemotherapy regimens containing methotrexate. If adequate supplies are not available, select an alternative regimen.
  • Consult a Hematology/Oncology specialist for patient- and neoplasm-specific recommendations and other specialists for non-oncology uses.
  • 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

References

  1. APP (personal communications). November 18, December 17, 2010; February 16, March 1, April 4, June 7, July 13, August 3 and 23, September 16, October 28, November 28, 2011; February 6, 21, and 29, March 9 and 26, April 18, May 23, June 18, July 30, August 27, October 2, and December 12, 2012; January 14 and 28, February 28, and April 1, 2013.
  2. Bedford (personal communications). November 19, December 15, 2010; February 15, March 1, April 4, June 7 and 23, July 12 and 20, August 3, 10, and 25, September 2 and 14, October 24, November 28, 2011; February 6 , 15, and 28, March 12 and 22, April 13 and 20, May 21, June 18, July 13, September 25, and December 12 and 17, 2012; January 18 and 29, and March 4 and 28, 2013.
  3. Hospira (personal communications). November 18, December 14, 2010; February 14, March 1, April 5, June 6 and 21, July 12 and 18, August 2, 8, 23, and 31, September 13, October 12 and 27, November 7 and 29, 2011; February 6,12, 21, and 27, March 12 and 26, April 12 and 23, May 24, June 18, July 13 and 30, August 27, October 1, and December 12, 2012; January 4, 16 and 28, March 4, and April 1, 2013.
  4. Mylan Institutional (personal communications). August 2, 11, 23, and 31, September 14 and 27, October 12 and 28, November 8 and 23, 2011; February 8, 13, and 29, March 13, April 11 and 23, May 24, June 18, and July 13, and August 2 and 27, October 4, and December 12, 2012; January 4, 17 and 28, February 13, and March 4, and April 3, 2013.
  5. Sandoz (personal communications). November 18, December 14, 2010; February 14, March 1, April 6, June 7, August 3 and 24, September 13, October 27, November 30, December 5, 2011; February 7, 13, 16, 23 and 29, March 13, April 12 and 23, May 22, June 18, July 31, August 27, October 1, and December 12 and 18, 2012; January 3 and 28, and April 1, 2013.
  6. Bioniche (personal communications). November 19, December 16, 2010; February 16, March 1, April 7, and June 7 and 30, 2011.
  7. Pfizer (personal communications). October 10 and December 12, 2012; January 28 and March 4 and 29, 2013.
  8. Teva (personal communications). August 1 and 27, October 1, and December 12, 2012; and January 28, 2013.
  9. Beckwith MC, Tyler LS, eds. Cancer Chemotherapy Manual. St. Louis, MO: Wolters Kluwer Health Inc. 2012.
  10. Antineoplastic agents. In: McEvoy GK, ed. AHFS 2010 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists; 2011: 905-1276.
  11. Drug Facts and Comparisons Online. St. Louis, MO: Wolters Kluwer Health Inc. February, 2012.

Updated

Updated: April 3, 2013 by Jane Chandramouli, PharmD, Drug Information Specialist; March 4, 2013 by Jane Chandramouli, PharmD, Drug Information Specialist. Created February 13, 2012, by Michelle M. Wheeler, PharmD, Drug Information Specialist. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.

Disclaimer

This information is provided through the support of Novation to ASHP solely as a service to its members, which shall not use this information for their further commercial use. The content was prepared by the Drug Information Center of University of Utah. Novation, ASHP, and the University of Utah make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, which respect to such information, and specifically disclaim all such warranties. Users of this information are advised that decisions regarding the use of drugs and drug therapies are complex medical decisions and that in using this information, each user must exercise his or her own independent professional judgment. Neither Novation, ASHP nor the University of Utah assumes any liability for persons administering or receiving drugs or other medical care in reliance upon this information, or otherwise in connection with this bulletin. Neither Novation, ASHP nor University of Utah endorses or recommends the use of any drug.

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