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Methotrexate Injection

[02 July 2014]

Products Affected - Description

Methotrexate 25 mg/mL (with preservative), Fresenius Kabi, USA (formerly APP)1
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) – NDC discontinued
40 mL preservative-free vial (NDC 10139-0062-40)– NDC discontinued
2 mL vial, preservative-free (NDC 67457-0221-02) - discontinued
10 mL vial, preservative-free (NDC 67457-0221-10) - discontinued
40 mL preservative-free vial (NDC 67457-0221-40) - discontinued


Methotrexate 25 mg/mL injection, Mylan Institutional (formerly Pfizer products)4
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)

Methotrexate 25 mg/mL injection, Sandoz5
2 mL vial, preservative-free (NDC 66758-0040-02)
10 mL vial, preservative-free (NDC 66758-0040-08)
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)
4 mL vial, preservative-free (NDC 00703-3673-01) - discontinued

Reason for the Shortage

  • Ben Venue has stopped production in its plant in Bedford, Ohio and will close in 2014. Ben Venue supplies multiple sterile injectable products for Bedford Laboratories. Supplies of product that have already been manufactured will continue to be released until inventory is depleted. Bedford Laboratories has a small number of products manufactured elsewhere that are not affected by this closure.2
  • Sandoz recalled two lots of methotrexate 40 mL preservative-free vials in May 2013 due to discover of particulate matter during routine quality control inspection.5
  • Mylan Institutional acquired methotrexate injection from Pfizer on December 6, 2013.4, 7
  • Mylan Institutional divested three presentations of methotrexate injection to Intas (Accord Healthcare) in April 2014.4,9
  • Bioniche was acquired by Mylan Institutional in September, 2011.4,6
  • Teva discontinued methotrexate 4 mL vials in October 2013 due to business reasons.8

Available Products

Methotrexate 25 mg/mL injection, Accord Healthcare9
2 mL vial, preservative-free (NDC 16729-0277-30)
10 mL vial, preservative-free (NDC 16729-0277-03)
40 mL preservative-free vial (NDC 16729-0277-35)
 
Methotrexate lyophilized powder for injection, Fresenius Kabi, USA (formerly APP)1
10 mL (with preservative) vial (NDC 63323-0123-10)
1 gram vial (NDC 63323-0122-50)
 
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 Institutional (formerly Pfizer products)4
40 mL vial, preservative-free (NDC 67457-0480-40)
 
Methotrexate 25 mg/mL injection, Teva8
10 mL vial, preservative-free (NDC 00703-3675-01)
40 mL vial, preservative-free (NDC 00703-3678-01)

Estimated Resupply Dates

  • Bedford has all methotrexate injection on back order and the company cannot estimate a release date. Ben Venue manufactured methotrexate injection for Bedford.2
  • Mylan Institutional has the methotrexate 25 mg/mL 2 mL and 4 mL vials on back order and the company cannot estimate a release date. Methotrexate 8 mL and 10 mL vials have been temporarily discontinued and the company cannot estimate a return date.4
  • Sandoz has methotrexate 25 mg/mL 2 mL and 10 mL vials temporarily unavailable and the company does not expect product in 2014. Methotrexate 40 mL vials are on back order and the company cannot estimate a release date.5
  • Teva has methotrexate 25 mg/mL 2 mL vials available in limited supply for drop shipment. Additional supplies are expected in early-July 2014.8

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.10-12
  • 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.10-12
  • Methotrexate can be used alone or in combination with other antineoplastic agents.10-12

Safety

  • Chemotherapy agents, such as methotrexate, 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 methotrexate.10-12
  • 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. Fresenius Kabi, USA (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; and January 14 and 28, February 28, April 1, May 29, June 18, July 16, September 9, November 7 and 19, and December 9 and 16, 2013; and January 18, February 5 and 28, March 28, April 30, May 12 and 30, June 3 and 17, and July 1, 2014.
  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; and January 18 and 29, March 4 and 28, May 29, June 18, July 16, September 9, October 21, and December 9 and 17, 2013; and January 21, February 5 and 26, March 31, April 14, May 12 and 27, and June 16 and 25, 2014.
  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, April 1, May 29, June 18, July 16, September 9, November 4, and December 9 and 20, 2013; and January 22, March 3 and 31, April 29, May 12, June 5 and 19, and July 2, 2014.
  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, and February 13, March 4, April 3, May 28, June 18, July 16, September 9, November 6, and December 9 and 12, 2013; and January 22, March 3 and 20, April 2 and 29, May 14 and 19, and June 2, 19, and 30, 2014.
  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, December 12 and 18, 2012; January 3 and 28, April 1, May 21, June 18, September 9, October 30, and December 9, 2013; and January 22, March 3 and 20, May 14, June 2, and July 2, 2014.
  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; and January 28, March 4 and 29, May 24, June 18, July 16, September 9, and December 9, 2013.
  8. Teva (personal communications). August 1 and 27, October 1, and December 12, 2012; and January 28 May 13, June 19, July 16, September 9, November 1, and December 9, 2013; and January 23, February 5, March 3, April 2, May 12, and June 19, 2014.
  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 July 2, 2014 by Jane Chandramouli, PharmD, Drug Information Specialist. Created February 13, 2012, by Michelle M. Wheeler, PharmD, Drug Information Specialist. Copyright 2014, 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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