Advertisement

Midazolam Injections

[06 August 2015]

Products Affected - Description

Midazolam Injection, Akorn
1 mg/mL, 10 mL vials, 10 count (NDC 17478-0523-10)
1 mg/mL, 2 mL vials, 10 count (NDC 17478-0523-02)
1 mg/mL, 5 mL vial, 25 count (NDC 17478-0523-55)
5 mg/mL, 1 mL vials, 10 count (NDC 17478-0524-01)
5 mg/mL, 2 mL vials, 10 count (NDC 17478-0524-02)
5 mg/mL, 5 mL vials, 10 count (NDC 17478-0524-05)

Midazolam injection, Caraco
5 mg/mL, 5 mL vial, 10 count (NDC 57664-0634-44) - discontinued
 
Midazolam Injection, Fresenius Kabi
1 mg/mL, 5 mL vial, 25 count (NDC 63323-0411-25)
5 mg/mL, 10 mL vial, 10 count (NDC 63323-0412-10)
5 mg/mL, 2 mL vial, 25 count (NDC 63323-0412-02)

Midazolam injection, Sagent
1 mg/mL, 10 mL vial, 10 count (NDC 25021-0660-10)
1 mg/mL, 2 mL preservative-free vial, 10 count (NDC 25021-0655-02)
1 mg/mL, 5 mL preservative-free vial, 10 count (NDC 25021-0655-05)
5 mg/mL, 10 mL vial, 10 count (NDC 25021-0661-10)
5 mg/mL, 2 mL preservative-free vial, 10 count (NDC 25021-0656-02)
 
Midazolam Injection, The Medicines Company
1 mg/mL, 10 mL vial, 10 count (NDC 65293-0412-10) - discontinued
1 mg/mL, 2 mL vial, 25 count (NDC 65293-0411-25) - discontinued
1 mg/mL, 5 mL vial, 25 count (NDC 65293-0416-25) - discontinued
5 mg/mL, 1 mL vial, 25 count (NDC 65293-0417-25) - discontinued
5 mg/mL, 10 mL vial, 10 count (NDC 65293-0415-10) - discontinued
5 mg/mL, 2 mL vial, 10 count (NDC 65293-0413-10) - discontinued
5 mg/mL, 5 mL vial, 10 count (NDC 65293-0414-10) - discontinued
 
Midazolam injection, Wockhardt
1 mg/mL, 5 mL vial, 10 count (NDC 64679-0762-02)
5 mg/mL, 10 mL vial, 10 count (NDC 64679-0763-04)

Reason for the Shortage

  • West-Ward acquired Baxter’s midazolam injection products in May, 2011.1
  • Ben Venue stopped production in its plant in Bedford, Ohio and closed in 2014.2
  • Hospira has midazolam injection available.3
  • Fresenius Kabi had midazolam on shortage due to increased demand..4
  • Due to low demand, Akorn is focusing on other medications that are in greater need of supply.5
  • Sagent has midazolam on shortage due to manufacturing delay.6
  • Caraco has discontinued all midazolam presentations.7
  • Caraco discontinued two midazolam presentations in 2014.7
  • FDA imposed an import ban in mid-2013 on several Wockhardt products including midazolam injection.8
  • Medicines Company is no longer carrying midazolam injection.9
  • BD RX introduced midazolam injection in 2014.10

Available Products

Midazolam injection, Akorn
5 mg/mL, 10 mL vial, 10 count (NDC 17478-0524-10)
 
Midazolam Injection, BD Rx
1 mg/mL, 2 mL prefilled syringe, 24 count (NDC 76045-0001-20)
5 mg/mL, 1 mL prefilled syringe, 24 count (NDC 76045-0002-10)
5 mg/mL, 2 mL prefilled syringe, 24 count (NDC 76045-0003-20)
Midazolam Injection, Fresenius Kabi
1 mg/mL, 10 mL vial, 10 count (NDC 63323-0411-10)
1 mg/mL, 2 mL vial, 25 count (NDC 63323-0411-12)
5 mg/mL, 1 mL fill in 2 mL vial, 25 count (NDC 63323-0412-25)
5 mg/mL, 5 mL vial, 10 count (NDC 63323-0412-05)
 
Midazolam Injection, Hospira
1 mg/mL, 10 mL vial, 10 count (NDC 00409-2587-05)
1 mg/mL, 2 mL preservative-free Luer-lock syringe, 10 count (NDC 00409-2306-62)
1 mg/mL, 2 mL preservative-free iSecure syringe, 10 count (NDC 00409-2306-12)
1 mg/mL, 2 mL preservative-free vial, 25 count (NDC 00409-2305-17)
1 mg/mL, 5 mL preservative-free vial, 10 count (NDC 00409-2305-05)
5 mg/mL, 1 mL preservative-free Luer-Lock syringe, 10 count (NDC 00409-2307-60)
5 mg/mL, 1 mL preservative-free vial, 10 count (NDC 00409-2308-01)
5 mg/mL, 10 mL vial, 10 count, 10 count (NDC 00409-2596-05)
5 mg/mL, 2 mL preservative-free vial, 10 count (NDC 00409-2308-02)
5 mg/mL, 5 mL vial, 10 count, 10 count (NDC 00409-2596-03)
 
Midazolam injection, Sagent
5 mg/mL, 1 mL preservative-free vial, 10 count (NDC 25021-0656-01)
5 mg/mL, 5 mL vial, 10 count (NDC 25021-0661-05)
 
Midazolam Injection, West-Ward
1 mg/mL, 10 mL vial, 10 count (NDC 00641-6056-10)
1 mg/mL, 2 mL latex-free vial, 10 count (NDC 00641-6057-10)
1 mg/mL, 2 mL vial, 25 count (NDC 00641-6057-25)
1 mg/mL, 5 mL vial, 10 count (NDC 00641-6059-10)
5 mg/mL, 1 mL vial, 10 count (NDC 00641-6061-10)
5 mg/mL, 1 mL vial, 25 count (NDC 00641-6061-25)
5 mg/mL, 10 mL vial, 10 count (NDC 00641-6060-10)
5 mg/mL, 2 mL vial, 10 count (NDC 00641-6063-10)
5 mg/mL, 2 mL vial, 25 count (NDC 00641-6063-25)

Estimated Resupply Dates

  • Presentations are available from multiple suppliers.
  • Akorn has many midazolam presentations on back order and the company cannot estimate a release date.5
  • Fresenius Kabi has midazolam 1 mg/mL 5 mL vials on back order and the company estimates a release date in early-August 2015. Midazolam 5 mg/mL 10 mL vials are on back order and the company estimates a release date of mid-September 2015. Midazolam 5 mg/mL 2 mL vials are on back order and the company cannot estimate a release date.4
  • Sagent has midazolam 1 mg/mL 2 mL, 5 mL and 10 mL vials and 5 mg/mL 2 mL vials on back order and the company cannot estimate a release date.6
  • Wockhardt has all midazolam presentations on back order and the company cannot estimate a release date.8

Implications for Patient Care

Midazolam injection is labeled as monotherapy or combination therapy for sedation, amnesia, relief of anxiety and induction of anesthesia in patients undergoing surgery or diagnostic, therapeutic, or endoscopic procedures.11 Midazolam administered by continuous infusion is labeled for sedation in patients requiring mechanical ventilation.11

Midazolam is also available as 2 mg/mL oral syrup.12 Midazolam oral syrup is labeled for relief of anxiety, sedation, and amnesia prior to induction of anesthesia or endoscopic, diagnostic, or therapeutic procedures in pediatric patients. Midazolam oral syrup is not labeled for use in adults.12

Alternative Agents & Management

  • During this shortage, use alternative injectable benzodiazepines.
  • Consider midazolam oral syrup for pediatric patients. Typical doses of oral midazolam range from 0.25 mg/kg to 1 mg/kg in children 6 months to 15 years old. The onset of action following oral administration is 10 to 20 minutes.12
  • Ravitskiy et al 13 evaluated midazolam 2 mg/mL oral syrup for the treatment of perioperative anxiety in healthy adults undergoing Mohs surgery. Midazolam 10 mg oral syrup was safe and effective in this study.13 Data evaluating midazolam oral syrup for use in adults in other settings are lacking.
  • There are no direct dosage conversions between the benzodiazepines because each has a distinct pharmacokinetic profile dictating the agent’s therapeutic use and dosing.14
  • Lorazepam injection is also on shortage.14
  • Institutions may consider reserving injectable benzodiazepines for initial treatment of status epilepticus, as no other well established injectable therapeutic options are available for this indication. Diazepam rectal gel may be an alternative for some patients.15-19
Table 1. Pharmacokinetics of Injectable Benzodiazepines20,21,22,23,24
 

Agent

Onset of Action
Intravenous (min)

Onset of Action
Intramuscular (min)

Duration of Action
Intravenous (hours)

Duration of Action
Intramuscular (hours)

Half-life (hours)

Active Metabolites

Diazepam

1 to 5

Intramuscular administration results
in slow and erratic absorption

0.3 to 0.5

Intramuscular administration results
 in slow and erratic absorption

20 to 120

Yes

Lorazepam

5 to 20

15 to 30

6 to 8

6 to 8

8 to 15

No

Midazolam

1 to 5

5 to 15

< 2a

2a

3 to 11

Yes

 
a The pharmacologic effect of midazolam may last up to 6 hours in some patients.

Related Shortages

References

  1. West-Ward (personal communications). September 13, October 14, November 4 and 28, December 9 and 14, 2011; January 20, February 4, 10, and 27, April 3 and 6, May 7 and 23, July 3, August 6 and 31, October 4, and November 7, 2012; January 21, March 6 and 22, April 23, May 1 and 31, June 25, July 3, August 9, September 5, October 12, November 4, and December 6, 2013; January 17, and 31, February 27, March 3, 14, and 28, April 11 and 25, May 2 and 23, June 25, August 1 and 13, September 3 and 22, November 12, December 1 and 10, 2014; January 9 and 28, March 4 and 11, April 27, May 13 and 27, June 17, and July 1 and 29, 2015.
  2. Bedford (personal communications and website). August 6 and 17, September 1 and 28, October 18, November 2 and 29, December 16, 2010; and January 4 and 19, February 9, March and 30, June 1, 14, and 23, July 12, August 3, 10, and 25, September 15, October 6 and 26, November 4, 7, and 23, December 2, 2011; January 9, February 16, April 5, May 24, June 5, July 3 and 13, August 2, 9, and 30, and October 2, 2012; January 23, March 6 and 25, April 23, May 1 and 29, June 25, July 3, August 1 and 7, September 5, October 1, November 4, and December 2, 2013; January 22, February 27, March 4 and 19, April 8 and 14, May 27, June 25, and August 4, 2014. 
  3. Hospira (personal communications). August 6, September 1 and 29, October 11, 18, and 31, November 3, 15, and 29, and December 15, 2010; and January 4 and 19, February 7, March 1 and 30, May 31, June 13 and 21, July 11, August 2 and 23, September 13, October 20 and 31, November 22, December 13, 16, and 27, 2011; January 23 and 31, February 8 and 27, April 2, May 7, 10, and 24, June 11, July 3, August 6 and 13, September 5 and 17, October 2, November 2 and 7, December 4 and 19, 2012; January 2 and 19, February 6, March 6 and 25, April 12 and 23, May 1, June 4 and 25, July 3, August 8 and 15, September 5 and 13, October 9, November 4 and 13, December 9, 2013; January 16 and 24, February 5 and 27, March 5, 20, and 31, April 14 and 29, May 27, June 26, August 4 and 18, September 8, November 14, December 1, 2014; January 9 and 29, March 9, April 29, May 15, June 1 and 17, July 13, and August 4, 2015.
  4. Fresenius Kabi (personal communications). August 17, September 1 and 30, October 18, November 2 and 15, December 1 and 15, 2010; and January 5 and 19, February 9, March 1 and 30, May 18, June 1 and 22, July 11, August 3 and 24, September 16, October 6, November 2 and 23, December 9, 2011; January 17, February 28, April 5, May 1, 7, and 23, June 5, July 3 and 5, August 10 and 13, September 5 and 18, October 2, November 2 and 7, and December 4 and 19, 2012; January 19, March 6 and 22, April 18, May 1 and 29, June 4 and 25, July 3, August 5 and 9, September 5, 12, and 18, October 10, November 4, December 6 and 16, 2013; January 16 and 21, February 4, 27, and 28, March 25 and 28, April 15 and 30, May 6 and 21, June 20, August 4 and 14, September 5, November 12, December 1, 2014; January 9 and 26, March 3 and 11, April 27, May 13, June 1 and 17, July 9, and August 5, 2015.
  5. Akorn (personal communications). July 6, August 10 and 16, September 5, and October 5 and 30, 2012; March 18, April 18, May 1, June 4 and 25, July 3, September 5, October 8, November 4, December 10, 2013; February 5, March 3, April 14, May 27, June 26, August 4, September 8, December 1, 2014; January 9, February 25, May 13 and 28, July 14, and August 6, 2015.
  6. Sagent (personal communications). April 4, May 7 and 21, July 2, August 9, 13, and 27, September 20, October 5, and November 7, 2012; January 22, March 6 and 25, April 15, May 1 and 28, June 25, July 3 and 8, August 8, 15, and 28, September 12, October 14, November 8, and December 5, 2013; and January 23, February 27, March 19 and 26, April 14 and 24, May 7 and 22, June 19, August 1 and 15, September 4, November 13, December 3, 12, and 22, 2014; January 9 and 29, March 5 and 12, and April 27, May 14 and 28, June 11, and July 9 and 30, 2015.
  7. Caraco (personal communications). September 14, October 2, and December 19, 2012; January 23, March 6 and 25, June 7, August 15, October 8, November 4, and December 9, 2013; and February 4 and 27, June 23, August 4, November 3, 2014; February 25 and April 27, and June 1, 2015.
  8. Wockhardt (personal communications). September 9, October 8, November 4, and December 10, 2013; and January 22, 2014.
  9. The Medicines Company (personal communications). February 27, April 30, June 23, September 8, November 13, 2014; February 25, April 27, and June 17, 2015.
  10. BD Rx (personal communications). December 12, 2014; January 12 and April 27, 2015. 
  11. Midazolam injection prescribing information. Lake Forest, IL: Hospira, Inc., September 2009.
  12. Midazolam syrup prescribing information. Princeton, NJ: Ranbaxy Pharmaceuticals Inc., October 2009.
  13. Ravitskiy L, Phillips PK, Roenigk RK and Weaver AL et al. The use of oral midazolam for perioperative anxiolysis of healthy patients undergoing Mohs surgery: Conclusions from randomized controlled and prospective studies. Journal of the American Academy of Dermatology. February 2011;64(2):310-22.
  14. American Society of Health-System Pharmacists. Drug Shortage Resource Center available at http://www.ashp.org/shortages. Accessed on December 14, 2011.
  15. Aminoff MJ, Greenberg DA, Simon RP, eds. Clinical Neurology. 6th ed. New York, NY: Lange Medical BooksMcGraw-Hill; 2005.
  16. Meierkord H, Boon P, Engelsen B, et al. EFNS guideline on the management of status epilepticus in adults. Eur J Neurol. Mar 2010;17(3):348-355.
  17. Millikan D, Rice B, Silbergleit R. Emergency treatment of status epilepticus: current thinking. Emerg Med Clin North Am. Feb 2009;27(1):101-113, ix.
  18. Rabinstein AA. Management of status epilepticus in adults. Neurol Clin. Nov 2010;28(4):853-862.
  19. Rowland LP, ed. Merritt's Neurology. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
  20. McEvoy, G. K., E. K. Snow, et al., Eds. (2011). AHFS DI (Lexi-Comp Online). Bethesda, MD, American Society of Health-System Pharmacists.
  21. Wickersham, R. M., K. K. Novak, et al., Eds. (2010). Drug Facts and Comparisons (eFacts). St. Louis, MO, Wolters Kluwer Health, Inc.
  22. Baughman, V. L., J. Golembiewski, et al., Eds. (2010). Anesthesiology and Critical Care Drug Handbook. Hudson, OH, Lexi-Comp.
  23. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill. Am J Health-Syst Pharm. 2002;59:150-178.
  24. Mosby’s Drug Consult 2006. St Louis, MO: Elsevier-Mosby; 2006.

Updated

Updated August 6, 2015 by Jane Chandramouli, PharmD, Drug Information Specialist. Created December 14, 2011, by Kristen Jefferies, PharmD, Drug Information Specialist. Copyright 2015, 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.

« Back to Drug Shortage Product Bulletins

Advocacy Activity
Get the latest updates on ASHP's advocacy activity on drug shortages.
Advertisement