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Nitroglycerin Injection

[14 August 2014]

Products Affected - Description

Nitroglycerin injection, American Regent
5 mg/mL, 10 mL vials, packages of 25 (NDC 00517-4810-25)

Nitroglycerin in Dextrose 5%, Hospira
10 mg/100 mL, 250 mL glass bottles (NDC 00409-1483-02)
10 mg/100 mL, 500 mL glass bottles (NDC 00409-1483-03)
20 mg/100 mL, 250 mL glass bottles (NDC 00409-1482-02)
40 mg/100 mL, 250 mL glass bottles (NDC 00409-1484-02)
 
Imported Product
Nitronal (Glyceryl Trinitrate) Injection, Arbor Pharmaceuticals (Pohl Boskamp label)
1 mg/mL, 25 mL ampule, 120 count (NDC 62627-0100-25)
1 mg/mL, 50 mL vial, 80 count (NDC 62627-0100-50)

Reason for the Shortage

  • American Regent has recently upgraded their manufacturing plant. Product will become available in stages as production resumes.1
  • Hospira states the shortage is due to manufacturing delays.2
  • Hospira discontinued nitroglycerin in Dextrose 5%, 40 mg/100 mL, 500 mL glass bottles (NDC 00409-1484-03) in 2010.2
  • Baxter had nitroglycerin premixes on shortage due to a raw material supply issue.3
  • In cooperation with FDA, Arbor Pharmaceuticals is importing glyceryl trinitrate (Nitronal) injection to the US market to help alleviate the national shortage. This glyceryl trinitrate is manufactured in an FDA-approved facility in Germany by Pohl Boskamp. Glyceryl trinitrate is another name for nitroglycerin.4

Available Products

Nitroglycerin in Dextrose 5%, Baxter
10 mg/100 mL, 250 mL glass bottles (NDC 00338-1047-02)
20 mg/100 mL, 250 mL glass bottles (NDC 00338-1049-02)
40 mg/100 mL, 250 mL glass bottles (NDC 00338-1051-02)

Estimated Resupply Dates

  • American Regent has nitroglycerin 5 mg/mL 10 mL vials on back order and the company cannot estimate a release date.1
  • Arbor Pharmaceuticals has imported Nitronal 1 mg/mL 25 mL ampules and 50 mL vials available. Orders for this product must be placed with your wholesaler and product will be supplied by Cardinal SPD, ASD Specialty, or McKesson Specialty.5
  • Hospira has all nitroglycerin injection products on back order and the company estimates a release date in late 4th quarter 2014.2

Implications for Patient Care

Nitroglycerin is a vasodilating agent. Intravenous nitroglycerin is used for a variety of therapeutic indications including angina, hypertension, acute myocardial infarction, heart failure, low cardiac output states, short term management of pulmonary hypertension, induced intraoperative hypotension, and uterine relaxation.4,5

Safety

  • Dosing differs between the imported and FDA approved product. Use caution when switching between products.4
  • The nitroglycerin concentration is 2.5 to 10 fold higher in the imported Nitronal product as compared to the FDA-approved nitroglycerin premixed solutions, but a lower concentration than the vials supplied by American Regent.4
  • Nitronal can be diluted with 5% dextrose to obtain concentrations of 100 mcg/mL, 200 mcg/mL and 400 mcg/mL. Directions for preparing these solutions are available in the Dear Healthcare Professional letter.4
  • Bar coding systems should not be used on Nitronal ampules and vials as incorrect information may be provided if the item is scanned.
  • Report any offers to sell Nitronal by an entity other than Arbor Pharmaceuticals to drugshortages@fda.hhs.gov. Arbor Pharmaceuticals will only be releasing product to the following distributors: Amerisource Bergen, McKesson, and Cardinal.

Alternative Agents & Management

  • Glyceryl trinitrate is another name for nitroglycerin. Both the FDA-approved products and the imported product contain the same active ingredient. Nitronal is supplied in a 1 mg/mL concentration in 25 mL ampules or 50 mL vials and for single use only. Pohl Boskamp has a Dear Healthcare Professional letter that summarizes the key differences between the imported product and FDA-approved products.4
  • No single agent can be substituted for intravenous nitroglycerin. Alternatives will depend on the specific therapeutic indication and patient characteristics. The Table outlines potential alternatives for selected clinical situations.
  • Consider using nitroglycerin ointment or sublingual formulations of nitroglycerin whenever possible.
  • Consider reserving nitroglycerin injection for situations where no therapeutic alternatives exist.
  • Some centers may consider drawing up doses of nitroglycerin injection used in procedure areas to preserve supplies. Nitroglycerin (unspecified concentration) in 3 mL plastic syringes lost 5% to 7% potency when stored at 4 degrees C for 7 days and lost less than 2% potency when stored at – 20 degrees C for 30 days.8 Nitroglycerin (unspecified concentration diluted in dextrose 5% or sodium chloride 0.9%) is stable for 7 days in glass containers when refrigerated.7

Table. Alternatives to Nitroglycerin Injection for Selected Clinical Situations 

Clinical Situation

Treatment Options

Comments

Perioperative use to relax vascular grafts

No alternatives available, consider drawing up doses to conserve supply

Papaverine, or solutions of nitroglycerin or nitroglycerin plus verapamil may be used, however papaverine and nitroglycerin are in short supply.9-18

Unstable angina / NSTEMI

Topical nitroglycerin options such as sublingual tablets, spray, or ointment in patients who do not have refractory ischemic symptoms.19

Limit intravenous nitroglycerin use to 24 hours when possible and convert to topical options as soon as possible.19 http://www.cardiosource.com/guidelines/UA-NSTEMI.FullText.pdf


Related Shortages

References

  1. American Regent (personal communications and website). June 26, July 25, August 20, October 5 and 25, November 13, 2012; January 11, February 13, March 20, April 29, June 24, August 30, October 21, November 26, 2013; January 20, February 25, March 5 and 18, April 4 and 22, June 23, July 9, and August 11, 2014.
  2. Hospira (personal communications and website). June 25, July 25, August 20, October 5 and 24, November 13, 2012; January 11, February 13, March 21, April 29, June 24, August 30, October 21, November 26, 2013; January 21, February 25, March 7 and 19, April 7 and 23, June 23, July 9, and August 11, 2014.
  3. Baxter (personal communications. June 27, July 25, August 20, October 5, 25, and 31, November 14, 2012; January 11, February 13, March 2, May 10, June 24, September 30, October 21, November 26, 2013; January 20, February 25 and 28, March 7 and 19, April 7 and 23, June 23, and August 11, 2014. 
  4. Pohl Boskamp. Dear Healthcare Professional Letter. Accessed May 5, 2014.
  5. Arbor Pharmaceuticals (personal communications). May 5, June 23,  and August 11, 2014.
  6. McEvoy GK, Snow EK, Kester L, Litvak K, Miller J, Welsh OH, eds. AHFS DI (Lexi-Comp Online). Bethesda, MD: American Society of Health-System Pharmacists; 2014.
  7. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc.; 2014.
  8. Trissel LA. Handbook of Injectable Drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013.
  9. Anon. Drug Evaluation: Nitroglycerin. In: Hutchison TA, Shahan DR, Anderson ML, eds. Drugdex System [internet database]. Greenwood Village, CO: Thomson Healthcare; 2014. Updated periodically.
  10. Rosenfeldt FL, He GW, Buxton BF, Angus JA. Pharmacology of coronary artery bypass grafts. Ann Thorac Surg. Mar 1999;67(3):878-888.
  11. Attaran S, John L, El-Gamel A. Clinical and potential use of pharmacological agents to reduce radial artery spasm in coronary artery surgery. Ann Thorac Surg. Apr 2008;85(4):1483-1489.
  12. Owens CD. Adaptive changes in autogenous vein grafts for arterial reconstruction: clinical implications. J Vasc Surg. 2010; Mar;51(3):736-746.
  13. Roubos N, Rosenfeldt FL, Richards SM, Conyers RA, Davis BB. Improved preservation of saphenous vein grafts by the use of glyceryl trinitrate-verapamil solution during harvesting. Circulation. Nov 1 1995;92(9 Suppl):II31-36.
  14. Adcock OT, Jr., Adcock GL, Wheeler JR, Gregory RT, Snyder SO, Jr., Gayle RG. Optimal techniques for harvesting and preparation of reversed autogenous vein grafts for use as arterial substitutes: a review. Surgery. Nov 1984;96(5):886-894.
  15. Chanda J, Canver C. Reversal of preexisting vasospasm in coronary artery conduits. Ann Thorac Surg 2001; 72:476-80.
  16. Mussa S, Guzik T, Black E et al. Comparative efficacies and durations of action of phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for radial artery coronary bypass grafting. J Thorac Cardiovasc Surg 2003; 126:1798-805.
  17. He GW. Arterial grafts: clinical classification and pharmacological management. Ann Cardiothorac Surg 2013; 2(4):507-18.
  18. Rehman SM, Yi G, Taggart DP. The radial artery: current concepts on its use in coronary artery revascularization. Ann Thorac Surg 2013; 96:1900-9.
  19. Anderson JL, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction); American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association of Cardiovascular and Pulmonary Rehabilitation; Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007 Aug 14;50(7):e1-e157. Erratum in: J Am Coll Cardiol. 2008 Mar 4;51(9):974. PubMed PMID: 17692738.

Updated

Updated August 14, 2014 by Elyse A. MacDonald, PharmD, Drug Information Specialist. Created February 28, 2014, by Erin R. Fox, PharmD, FASHP, Director, Drug Information Service and Michelle Wheeler, 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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