Products Affected - Description

Reason for the Shortage

• West-Ward acquired Baxter’s midazolam injection products in May, 2011. NDC codes began changing for these products in early, 2012.¹
• Bedford has midazolam on shortage due to manufacturing delays. Bedford anticipates full availability of each presentation the company reintroduces to market.²
• Ben Venue voluntarily entered into a consent decree with FDA in late-January 2013 which allows Ben Venue to manufacture over 100 medications as long as they are compliant with the decree. Ben Venue supplies multiple products for Bedford Laboratories, a division of Ben Venue.²
•  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
• APP has midazolam on shortage due to increased demand.⁴
• Akorn launched midazolam injection in July, 2012. The company is focusing production on specific midazolam presentations to help meet the demands of the current shortage.⁵

Available Products

Estimated Resupply Dates

• Akorn is not currently manufacturing midazolam 1 mg/mL 2 mL vials in 25 count, 1 mg/mL 5 mL vials in 10 count, or 5 mg/mL 1 m vials in 25 count in order to focus production on other presentations. The company cannot estimate a release date for these products.⁵
• APP has midazolam 5 mg/mL 10 mL vials on back order and the company estimates a release date in mid- to late-July, 2013.⁴
• Caraco has midazolam 5 mg/mL 10 mL vials on back order and the company cannot estimate a release date.
• Hospira has midazolam 1 mg/mL 2 mL preservative free, 5 mL preservative free, and 10 mL Novaplus vials are on back order until June 2013. Midazolam 5 mg/mL 10 mL multi-dose vials and 10 mL Novaplus multi-dose vials are on back order and the company estimates a release date of mid- to late- June 2013. Midazolam 5 mg/mL preservative free 1 mL Luer-lock syringes are on back order and the company estimates a release date of July 2013. Midazolam 1 mg/mL 2 mL and 5 mL Novaplus preservative-free vials are on allocation.³
• Bedford has midazolam 5 mg/mL 5 mL vials available with short expiration dating. All other midazolam presentations are on back order and the company cannot estimate a release date. Other presentations of midazolam will not be produced until capacity permits.²
• Sagent has midazolam 1 mg/mL10 mL multidose vials, and 5 mg/mL 5 mL and 10 mL multidose vials on allocation. The company estimates additional product will be available in June 2013.⁶  
  

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.⁸ Midazolam administered by continuous infusion is labeled for sedation in patients requiring mechanical ventilation.⁸

Midazolam is also available as 2 mg/mL oral syrup.⁹  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.⁹

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.⁹
• Ravitskiy et al¹⁰ 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.¹⁰ 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.¹¹
• 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.^12-16

Table. Pharmacokinetics of Injectable Benzodiazepines^17-21

Related Shortages

• Amobarbital Injection— Resolved
• Chloral Hydrate Oral Solution and Capsules— No Longer Available
• Droperidol Injection
• Hydroxyzine Injection
• Lorazepam injectable presentations

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, and May 1 and 31, 2013.
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, and May 1 and 29, 2013.
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, and June 4, 2013.
4. APP (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, and June 4, 2013.
5. Akorn (personal communications). July 6, August 10 and 16, September 5, and October 5 and 30, 2012; March 18, April 18, May 1, and June 4, 2013.
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, and May 1 and 28, 2013.
7. Caraco (personal communications). September 14, October 2, and December 19, 2012; January 23, March 6 and 25, and June 7, 2013.
8. Midazolam injection prescribing information. Lake Forest, IL: Hospira, Inc., September 2009.
9. Midazolam syrup prescribing information. Princeton, NJ: Ranbaxy Pharmaceuticals Inc., October 2009.
10. Ravitskiy L, Phillips PK, Roenigk RK and Weaver AL et al. The use of oral midazolam for perioperative anxiolysis of healthy patients undergoin Mohs surgery: Conclusions from randomized controlled and prospective studies. Journal of the American Academy of Dermatology. February 2011;64(2):310-22.
11. American Society of Health-System Pharmacists. Drug Shortage Resource Center available online. Accessed on December 14, 2011.
12. Aminoff MJ, Greenberg DA, Simon RP, eds. Clinical Neurology. 6^th ed. New York, NY: Lange Medical BooksMcGraw-Hill; 2005.
13. 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.
14. 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.
15. Rabinstein AA. Management of status epilepticus in adults. Neurol Clin. Nov 2010;28(4):853-862.
16. Rowland LP, ed. Merritt's Neurology. 6^th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005. 
17. McEvoy, G. K., E. K. Snow, et al., Eds. (2011). AHFS DI (Lexi-Comp Online). Bethesda, MD, American Society of Health-System Pharmacists.
18. Wickersham, R. M., K. K. Novak, et al., Eds. (2010). Drug Facts and Comparisons (eFacts). St. Louis, MO, Wolters Kluwer Health, Inc.
19. Baughman, V. L., J. Golembiewski, et al., Eds. (2010). Anesthesiology and Critical Care Drug Handbook. Hudson, OH, Lexi-Comp.
20. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill. Am J Health-Syst Pharm. 2002;59:150-178.
21. Mosby’s Drug Consult 2006. St Louis, MO: Elsevier-Mosby; 2006.

Updated

Updated: June 7, 2013, by Ginny Jones, RPh, Drug Information Specialist; April 23, 2013, by Jane Chandramouli, PharmD, Drug Information Specialist. Created December 14, 2011, by Kristen Jefferies, PharmD, Drug Information Specialist. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.