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Midazolam Injections

[26 June 2014]

Products Affected - Description

Midazolam Injection, Akorn
1 mg/mL, 2 mL vials, 10 count (NDC 17478-0523-02)
1 mg/mL, 5 mL vials, 25 count (NDC 17478-0523-55)
1 mg/mL, 10 mL vials, 10 count (NDC 17478-0523-10)
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)
5 mg/mL, 10 mL vials, 10 count (NDC 17478-0524-10)
 
Midazolam Injection, Bedford
1 mg/mL, 2 mL preservative-free vial, 10 count (NDC 55390-0137-02)
1 mg/mL, 5 mL preservative-free vial, 10 count (NDC 55390-0137-05)
1 mg/mL, 10 mL vial, 10 count (NDC 55390-0125-10)
5 mg/mL, 2 mL preservative-free vial, 10 count (NDC 55390-0138-02)
5 mg/mL, 1 mL preservative-free, in 2 mL vial, 10 count (NDC 55390-0138-01)
5 mg/mL, 5 mL vial, 10 count (NDC 55390-0126-05)
5 mg/mL, 10 mL vial, 10 count (NDC 55390-0126-10)
 
Midazolam injection, Caraco7
5 mg/mL, 10 mL vial (NDC 57664-0634-45)
 
Midazolam Injection, Hospira
1 mg/mL, 10 mL vial (NDC 00409-2587-05)
1 mg/mL, 2 mL preservative-free iSecure syringe (NDC 00409-2306-12)

Midazolam Injection, West-Ward1
5 mg/mL, 1 mL vial, 25 count (NDC 00641-6061-25)
 
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 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.
  • Hospira has midazolam on shortage due to manufacturing delays and demand exceeding supply due to current market conditions.3
  • Hospira discontinued midazolam 5 mg/mL 1 mL iSecure syringes in July 2011.3
  • Fresenius Kabi (formerly APP) 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
  • FDA imposed an import ban in mid-2013 on several Wockhardt products including midazolam injection.8
  • Medicines Company launched midazolam injection in early 2014.9

Available Products

Midazolam Injection, Fresenius Kabi (formerly APP)4
1 mg/mL, 2 mL vial, 25 count (NDC 63323-0411-12)
1 mg/mL, 5 mL vial, 25 count (NDC 63323-0411-25)
1 mg/mL, 10 mL vial, 10 count (NDC 63323-0411-10)
5 mg/mL, 5 mL vial, 10 count (NDC 63323-0412-05)
5 mg/mL, 2 mL vial, 25 count (NDC 63323-0412-02)
5 mg/mL, 10 mL vial, 10 count (NDC 63323-0412-10)
 
Midazolam injection, Caraco7
1 mg/mL, 2 mL vial (NDC 57664-0633-43)
5 mg/mL, 5 mL vial (NDC 57664-0634-44)
 
Midazolam Injection, Hospira3
1 mg/mL, 2 mL preservative-free Luer-lock syringe (NDC 00409-2306-62)
1 mg/mL, 5 mL preservative-free vial, 10 count (NDC 00409-2305-05)
1 mg/mL, 2 mL preservative-free vial (NDC 00409-2305-17)
1 mg/mL, Novaplus 2 mL preservative-free vial, 100 count (NDC 00409-2305-21)
1 mg/mL Novaplus 5 mL preservative-free vial (NDC 00409-2305-50)
1 mg/mL Novaplus 10 mL vial (NDC 00409-2587-53)
5 mg/mL, 1 mL preservative-free vial (NDC 00409-2308-01)
5 mg/mL, 2 mL preservative-free vial, 10 count (NDC 00409-2308-02)
5 mg/mL, 10 mL vial, 10 count (NDC 00409-2596-05)
5 mg/mL, 1 mL preservative-free Novaplus vial (NDC 00409-2308-49)
5 mg/mL, 1 mL preservative-free Luer-Lock syringe, 10 count (NDC 00409-2307-60)
5 mg/mL, 2 mL preservative-free Novaplus vial (NDC 00409-2308-50)
5 mg/mL, 5 mL vial, 10 count (NDC 00409-2596-03)
5 mg/mL, Novaplus 5 mL vial (NDC 00409-2596-52)
5 mg/mL, Novaplus 10 mL vial (NDC 00409-2596-53)     
  
Midazolam Injection, The Medicines Company9
1 mg/mL, 2 mL vial, 25 count (NDC 65293-0411-25)
1 mg/mL, 5 mL vial, 25 count (NDC 65293-0416-25)
1 mg/mL, 10 mL vial, 10 count (NDC 65293-0412-10)
5 mg/mL, 1 mL vial, 25 count (NDC 65293-0417-25)
5 mg/mL, 2 mL vial, 10 count (NDC 65293-0413-10)
5 mg/mL, 5 mL vial, 10 count (NDC 65293-0414-10)
5 mg/mL,10 mL vial, 10 count (NDC 65293-0415-10)
 
Midazolam Injection, Sagent6
1 mg/mL, 2 mL preservative-free vial (NDC 25021-0655-02)
1 mg/mL, 5 mL preservative-free vial (NDC 25021-0655-05)
1 mg/mL, 10 mL vial (NDC 25021-0660-10)
5 mg/mL, 1 mL preservative-free vial (NDC 25021-0656-01)
5 mg/mL, 2 mL preservative-free vial (NDC 25021-0656-02)
5 mg/mL, 5 mL vial (NDC 25021-0661-05)
5 mg/mL, 10 mL vial (NDC 25021-0661-10)

Midazolam Injection, West-Ward1

1 mg/mL, 10 mL vial, 10 count (NDC 00641-6056-10)
1 mg/mL, 5 mL vial, 10 count (NDC 00641-6059-10)
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)
5 mg/mL, 2 mL vial, 25 count (NDC 00641-6063-25)
5 mg/mL, 2 mL vial, 10 count (NDC 00641-6063-10)
5 mg/mL, 1 mL vial, 10 count (NDC 00641-6061-10)
5 mg/mL, 10 mL vial, 10 count (NDC 00641-6060-10)

Estimated Resupply Dates

  • Akorn has limited supplies of midazolam 1 mg/mL 5 mL vials and 5 mg/mL 10 mL vials available at wholesalers. All other midazolam presentations are on back order and the company cannot estimate a release date.5
  • Caraco has temporarily discontinued midazolam 5 mg/mL 10 mL vials and the company cannot estimate a return date.7
  • Hospira has midazolam 1 mg/mL 10 mL vials on back order with an estimated release date of October 2014. Midazolam 1 mg/mL 2 mL iSecure syringes are available in limited supply.3
  • Bedford has all midazolam presentations on long term back order and the company cannot estimate a release date. Ben Venue manufactured midazolam for Bedford.2
  • West-Ward has midazolam 5 mg/mL 1 mL vials in 25 count available with short expiration dating (August 2014).1
  • 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.10 Midazolam administered by continuous infusion is labeled for sedation in patients requiring mechanical ventilation.10

Midazolam is also available as 2 mg/mL oral syrup.11 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.11

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.11
  • Ravitskiy et al12 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.12 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.
  • Lorazepam and diazepam injection are also on shortage.13
  • 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.14-18

Table. Pharmacokinetics of Injectable Benzodiazepines19-23

Agent

Onset of Action (min)

Duration of Action (hours)

Half-life
(hours)

Active Metabolites

Intravenous

Intramuscular

Intravenous

Intramuscular

Diazepam

1–5

a

0.3–0.5

a

20–120

Yes

Lorazepam

5–20

15–30

6–8

6–8

8–15

No

Midazolam

         1–5      

 5–15

<2b

2b

3–11

Yes

a Intramuscular administration results in slow and erratic absorption.
b 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, and June 25, 2014.
  2. Bedford (personal communications). 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, and June 25, 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, and June 26, 2014.
  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, and June 20, 2014.
  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, and June 26, 2014.
  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, and June 19, 2014.
  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 and June 23, 2014.
  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, and June 23, 2014.
  10. Midazolam injection prescribing information. Lake Forest, IL: Hospira, Inc., September 2009.
  11. Midazolam syrup prescribing information. Princeton, NJ: Ranbaxy Pharmaceuticals Inc., October 2009.
  12. 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.
  13. American Society of Health-System Pharmacists. Drug Shortage Resource Center available at http://www.ashp.org/shortages. Accessed on December 14, 2011.
  14. Aminoff MJ, Greenberg DA, Simon RP, eds. Clinical Neurology. 6th ed. New York, NY: Lange Medical BooksMcGraw-Hill; 2005.
  15. 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.
  16. 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.
  17. Rabinstein AA. Management of status epilepticus in adults. Neurol Clin. Nov 2010;28(4):853-862.
  18. Rowland LP, ed. Merritt's Neurology. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
  19. McEvoy, G. K., E. K. Snow, et al., Eds. (2011). AHFS DI (Lexi-Comp Online). Bethesda, MD, American Society of Health-System Pharmacists.
  20. Wickersham, R. M., K. K. Novak, et al., Eds. (2010). Drug Facts and Comparisons (eFacts). St. Louis, MO, Wolters Kluwer Health, Inc.
  21. Baughman, V. L., J. Golembiewski, et al., Eds. (2010). Anesthesiology and Critical Care Drug Handbook. Hudson, OH, Lexi-Comp.
  22. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill. Am J Health-Syst Pharm. 2002;59:150-178.
  23. Mosby’s Drug Consult 2006. St Louis, MO: Elsevier-Mosby; 2006.

Updated

Updated June 26, 2014 by Jane Chandramouli, PharmD, Drug Information Specialist. Created December 14, 2011, by Kristen Jefferies, 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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