Products Affected - Description

• • Midazolam injection, Akorn, 1 mg/mL, 10 mL vial, 10 count, NDC 17478-0523-10
  • Midazolam injection, Akorn, 1 mg/mL, 2 mL vial, 10 count, NDC 17478-0523-02
  • Midazolam injection, Akorn, 1 mg/mL, 5 mL vial, 25 count, NDC 17478-0523-55
  • Midazolam injection, Akorn, 5 mg/mL, 1 mL vial, 10 count, NDC 17478-0524-01
  • Midazolam injection, Akorn, 5 mg/mL, 10 mL vial, 10 count, NDC 17478-0524-10
  • Midazolam injection, Akorn, 5 mg/mL, 2 mL vial, 10 count, NDC 17478-0524-02
  • Midazolam injection, Akorn, 5 mg/mL, 5 mL vial, 10 count, NDC 17478-0524-05
  • Midazolam injection, Caraco, 5 mg/mL, 5 mL vial, 10 count, NDC 57664-0634-44
  • Midazolam injection, Fresenius Kabi, 1 mg/mL, 5 mL vial, 25 count, NDC 63323-0411-25
  • Midazolam injection, Fresenius Kabi, 5 mg/mL, 10 mL vial, 10 count, NDC 63323-0412-10
  • Midazolam injection, Pfizer, 5 mg/mL, 2 mL preservative-free vial, 10 count, NDC 00409-2308-02
  • Midazolam injection, Sagent, 1 mg/mL, 10 mL vial, 10 count, NDC 25021-0660-10
  • Midazolam injection, Sagent, 1 mg/mL, 2 mL preservative-free vial, 10 count, NDC 25021-0655-02
  • Midazolam injection, Sagent, 1 mg/mL, 5 mL preservative-free vial, 10 count, NDC 25021-0655-05
  • Midazolam injection, Sagent, 5 mg/mL, 10 mL vial, 10 count, NDC 25021-0661-10
  • Midazolam injection, Sagent, 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
  • Midazolam injection, The Medicines Company, 1 mg/mL, 2 mL vial, 25 count, NDC 65293-0411-25
  • Midazolam injection, The Medicines Company, 1 mg/mL, 5 mL vial, 25 count, NDC 65293-0416-25
  • Midazolam injection, The Medicines Company, 5 mg/mL, 1 mL vial, 25 count, NDC 65293-0417-25
  • Midazolam injection, The Medicines Company, 5 mg/mL, 10 mL vial, 10 count, NDC 65293-0415-10
  • Midazolam injection, The Medicines Company, 5 mg/mL, 2 mL vial, 10 count, NDC 65293-0413-10
  • Midazolam injection, The Medicines Company, 5 mg/mL, 5 mL vial, 10 count, NDC 65293-0414-10
  • Midazolam injection, Wockhardt USA, 1 mg/mL, 5 mL vial, 10 count, NDC 64679-0762-02
  • Midazolam injection, Wockhardt USA, 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 on shortage due to manufacturing delays and demand exceeding supply due to current market conditions.[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]
  • 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, BD Rx, 1 mg/mL, 2 mL prefilled syringe, 24 count, NDC 76045-0001-20
  • Midazolam injection, BD Rx, 5 mg/mL, 1 mL prefilled syringe, 24 count, NDC 76045-0002-10
  • Midazolam injection, BD Rx, 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
  • Midazolam injection, Fresenius Kabi, 1 mg/mL, 2 mL vial, 25 count, NDC 63323-0411-12
  • Midazolam injection, Fresenius Kabi, 5 mg/mL, 1 mL fill in 2 mL vial, 25 count, NDC 63323-0412-25
  • Midazolam injection, Fresenius Kabi, 5 mg/mL, 2 mL vial, 25 count, NDC 63323-0412-02
  • Midazolam injection, Fresenius Kabi, 5 mg/mL, 5 mL vial, 10 count, NDC 63323-0412-05
  • Midazolam injection, Pfizer, 1 mg/mL, 10 mL vial, 10 count, NDC 00409-2587-05
  • Midazolam injection, Pfizer, 1 mg/mL, 2 mL preservative-free Luer Lock syringe, 10 count, NDC 00409-2306-62
  • Midazolam injection, Pfizer, 1 mg/mL, 2 mL preservative-free iSecure syringe, 10 count, NDC 00409-2306-12
  • Midazolam injection, Pfizer, 1 mg/mL, 2 mL preservative-free vial, 25 count, NDC 00409-2305-17
  • Midazolam injection, Pfizer, 1 mg/mL, 5 mL preservative-free vial, 10 count, NDC 00409-2305-05
  • Midazolam injection, Pfizer, 5 mg/mL, 1 mL preservative-free Luer Lock syringe, 10 count, NDC 00409-2307-60
  • Midazolam injection, Pfizer, 5 mg/mL, 1 mL preservative-free vial, 10 count, NDC 00409-2308-01
  • Midazolam injection, Pfizer, 5 mg/mL, 10 mL vial, 10 count, NDC 00409-2596-05
  • Midazolam injection, Pfizer, 5 mg/mL, 5 mL vial, 10 count, NDC 00409-2596-03
  • Midazolam injection, Sagent, 5 mg/mL, 1 mL preservative-free vial, 10 count, NDC 25021-0656-01
  • Midazolam injection, Sagent, 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
  • Midazolam injection, West-Ward, 1 mg/mL, 2 mL latex-free vial, 10 count, NDC 00641-6057-10
  • Midazolam injection, West-Ward, 1 mg/mL, 2 mL vial, 25 count, NDC 00641-6057-25
  • Midazolam injection, West-Ward, 1 mg/mL, 5 mL vial, 10 count, NDC 00641-6059-10
  • Midazolam injection, West-Ward, 5 mg/mL, 1 mL vial, 10 count, NDC 00641-6061-10
  • Midazolam injection, West-Ward, 5 mg/mL, 1 mL vial, 25 count, NDC 00641-6061-25
  • Midazolam injection, West-Ward, 5 mg/mL, 10 mL vial, 10 count, NDC 00641-6060-10
  • Midazolam injection, West-Ward, 5 mg/mL, 2 mL vial, 10 count, NDC 00641-6063-10
  • Midazolam injection, West-Ward, 5 mg/mL, 2 mL vial, 25 count, NDC 00641-6063-25

• • Akorn has all midazolam presentations on back order. The company estimates a release date of late July 2015 for the 5 mg/mL 10 mL vials and the company cannot estimate a release date for the other presentations.[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-July 2015.[4]
  • Hospira has midazolam 5 mg/mL 2 mL preservative-free vials available in limited supply.[3]
  • Sagent has several midazolam presentations 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]

• • 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]

• • 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.
  • 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.[15,16,17,18,19]

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

  
  

• 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, 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, and July 13, 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, and July 9, 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, and July 14, 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, 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, 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 23, 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.