Products Affected - Description

Reason for the Shortage

• APP cannot provide a reason for the shortage.
• American Regent had temporarily suspended manufacture of most drug products in April, 2011.
• American Regent resumed manufacturing in Shirley, New York in early-May, 2011, but some products are still affected.

Available Products

Estimated Resupply Dates

• APP has neostigmine 0.5 mg/mL 10 mL vials and 1 mg/mL 10 mL vials on back order and the company estimates a release date in early-June 2013.¹
• American Regent has neostigmine 0.5 mg/mL 10 mL vials and 1 mg/mL 10 mL vials on back order and the company cannot estimate a release date. There may be limited supply available for drop shipment or through wholesalers of the 1 mg/mL 10 mL vials.² 
  

Implications for Patient Care

Neostigmine is an acetylcholinesterase inhibitor and is an unapproved product.⁴ However, it is used to reverse the effects of nondepolarizing neuromuscular blocking agents after surgery, prevent and treat postoperative bladder distention and urinary retention, and for symptomatic treatment of myasthenia gravis.^5,6,7,8

Safety

• The acetylcholinesterase inhibitors differ in potency, onset of action, and duration of action. Use caution when switching between agents to prevent dosing errors.
• Neostigmine dose will depend on indication for use; a larger dose will be used for reversal of neuromuscular blockade compared to a dose used for diagnosis of myasthenia gravis.
  

Alternative Agents & Management

• Acetylcholinesterase inhibitors including edrophonium, neostigmine, and pyridostigmine are used to reverse non-depolarizing neuromuscular blocking agents. Depolarizing neuromuscular blocking agents (ie, succinylcholine) are not reversed by these agents and their toxicity may be worsened by concomitant administration.^5-8
• Acetylcholinesterase inhibitors are usually given in combination with anticholinergic agents like atropine or glycopyrrolate in order to minimize adverse effects such as bradycardia from the acetylcholinesterase inhibitors.^7-9 Edrophonium is available as a single agent (Enlon) and in combination with atropine (Enlon Plus).¹⁰
• The Table below compares the available acetylcholinesterase inhibitors when used to reverse non-depolarizing neuromuscular blocking agents.

Table. Comparison of acetylcholinesterase inhibitors used for the reversal of non-depolarizing neuromuscular blocking agents.^4-8

Related Shortages

• Pyridostigmine Bromide Injection

1. APP (personal communications). September 11, October 5 and 15, November 1, 5, 16, and 28, December 4 and 7, 2012; January 7 and 30, February 26, March 27, April 9, and May 9, 2013.
2. American Regent (personal communications and website). September 11, October 5 and 15, November 1, 5, 16, and 27, December 5 and 12, 2012; January 7 and 30, February 27, March 25, April 9, and May 13, 2013.
3. West-Ward (personal communications). September 11, October 5 and 15, November 1, 5, 16, 28, and 30, and December 7 and 28, 2012; January 25, February 22, March 22, April 5, and May 10, 2013.
   Center for Drug Evaluation and Research. Electronic Orange Book Query. Food and Drug Administration, Department of Health and Human Services. Updated January, 2011. Accessed March 1, 2011.
4. Neostigmine methylsulfate product information. Shirley, NY: American Regent, January 2009.
5. Baughman, V. L., J. Golembiewski, et al., Eds. (20010). Anesthesiology and Critical Care Drug Handbook. Hudson, OH, Lexi-Comp.
6. Wood, M. and A. J. J. Wood, Eds. (1990). Drugs and Anesthesia - Pharmacology for Anesthesiologists. Baltimore, MD, Williams & Wilkins.
7. Morgan, G. E., M. S. Mikhail, et al., Eds. (2006). Clinical Anesthesiology. New York, NY, Lange.
8. McEvoy, G. K., E. K. Snow, et al., Eds. (2011). AHFS DI (Lexi-Comp Online). Bethesda, MD, American Society of Health-System Pharmacists.

Updated

Updated May 13, 2013 by Jane Chandramouli, PharmD, Drug Information Specialist. Created March 2, 2011, by Jane Chandramouli, PharmD, Drug Information Specialist. Edited by Michelle Wheeler, PharmD, Drug Information Specialist. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.