Propofol Injection

04 February 2010

Products Affected - Description

Reason for the Shortage

• Hospira recalled several lots of their propofol injection in mid-October, 2009 due to the presence of particulate matter in the vials.¹
• Teva recalled several lots of their propofol injection at the end of October, 2009 due to possible microbial contamination.²
• APP cannot keep up with increased demand for product.³

Estimated Resupply Dates

• All Diprivan and Diprivan Novaplus presentations are being released weekly. APP has received approval for generic propofol, however all presentations are on backorder. The company expects the 20 mL vials, 50 mL vials, and 100 mL vials will be available by mid-February, 2010.
• In cooperation with FDA, APP was providing Propoven 10 mg/mL injection to the US market to help alleviate the shortage. All supplies are now depleted and this product will no longer be available.  Propoven is manufactured in FDA-approved facilities by Fresenius Kabi AG, the parent company of APP.^4,5 Propoven is different from Diprivan in that it is preservative-free and contains medium-chain triglycerides as well as long-chain triglycerides. (Diprivan contains only long-chain triglycerides and also contains EDTA).^4,5 APP has 2 Dear Healthcare professional letters available that include detailed information and the product labeling for Propoven.^4,5 Report any offers to sell Propoven by an entity other than APP Pharmaceuticals to drugshortages@fda.hhs.gov.  For additional information, please visit the FDA's Propofol Injection Shortage notice.
• Teva has all presentations of propofol 10 mg/mL injection on intermittent back order and is shipping product as it becomes available.²
• Hospira has all presentations of propofol 10 mg/mL injection on intermittent back order and is shipping product as it becomes available.¹
  

Implications for Patient Care

• Propofol is a sedative hypnotic agent labeled for the induction of anesthesia in patients 3 years and older as part of an overall anesthesia regimen in patients undergoing surgery.  Propofol is labeled for maintenance of anesthesia in patients 2 months of age and older, as part of an overall anesthesia regimen in patients undergoing surgery.  Propofol is labeled for monitored anesthesia care in patients undergoing diagnostic or surgical procedures. Propofol is labeled for continuous sedation in adult patients who are mechanically ventilated in the intensive care unit.^6,7
• Unlabeled uses of propofol include management of refractory status epilepticus or complex-partial seizures, treatment of postoperative nausea and vomiting or prevention of chemotherapy induced nausea and vomiting, conscious sedation, and treatment of itching secondary to cholestasis or opioid use.⁷
• Strict aseptic technique is recommended for all propofol products, but is essential for Propoven which is preservative-free. Propoven products are single-dose vials and each vial may only be used for a single patient. Propoven also differs from Diprivan in lipid composition. Clinicians must take this difference into account for patients receiving total parenteral nutrition (TPN), patients with fat metabolism disorders, or patients in which lipid emulsions must be used cautiously.^4,5
• Propoven and US-labeled propofol products both contain soybean oil.^4,5 The product labeling for Propoven includes a contraindication for use in patients with peanut or soy allergy due to a theoretical concern for cross-reactivity.

Alternative Agents & Management

• Alternative intravenous hypnotic agents for the induction and maintenance of anesthesia vary in time of onset and duration of action, as shown in Table 1. 
• Intravenous sedative medications used in the ICU include propofol, benzodiazepines (eg, midazolam, lorazepam), opioids, haloperidol, and dexmedetomidine.^8,9  Table 2 compares select intravenous medications used for sedation in the intensive care unit.
• Intravenous medications used for procedural sedation include propofol, methohexital, dexmedetomidine, and benzodiazepines (eg, midazolam, lorazepam) in combination with opioids (eg, fentanyl, morphine). Table 3 summarizes alternatives for specific clinical situations.
• Minimize any potential drug waste. Propofol must be used within 12 hours if administered from original container and used within 6 hours if transferred to alternate container (eg, syringe).⁶
• Fospropofol (Lusedra) was approved by the FDA in December, 2008 and became available mid-November, 2009.¹⁰ Orders for fospropofol, NDC 62856-0350-01, must be placed through the wholesaler; the product may not be ordered directly from Eisai Pharmaceuticals. Fospropofol is a water-soluble prodrug of propofol and is FDA approved for monitored anesthesia care in adult patients who are undergoing diagnostic or therapeutic procedures.¹¹

Related Shortages

• Thiopental Injection

1. Hospira (personal communications). October 19 and 28, November 11, December 1 and 6, 2009; and January 25, 2010.
2. Teva (personal communications). October 28, November 11, and November 30, and December 16, 2009; and January 11 and 25, 2010.
3. APP (personal communications). October 28, November 4, 11, and 16, and November 30, and December 16 and 21, 2009; and January 11 and 25, and February 4, 2010.
4. APP. Dear Healthcare Professional Letters (Fresenius Propoven, customer letter). November 16, 2009.
5. APP. Dear Healthcare Professional Letters (Fresenius Propoven, shipment letter). November 16, 2009.
6. Diprivan (propofol injection) product information. Wilmington, DE: AstraZeneca, 2005.
7. McEvoy GK, Snow EK, Kester L, Litvak K, Miller J, Welsh OH, eds. AHFS 2009 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2009.
8. Rhoney DH, Murry KR. National survey of the use of sedating drugs, neuromuscular blocking agents, and reversal agents in the intensive care unit. J Intensive Care Med 2003; 18: 139-45.
9. Precedex (dexmedetomidine injection) product information. Lake Forest, IL: Hospira; 2008.
10. Eisai (personal communications). November 3, 11, and 24, 2009.
11. Lusedra (fospropofol disodium) injection product information. Woodcliff Lake, NJ: Eisai; 2009.
12. Donnelly AJ, Baughman VL, Gonzales JP, Golembiewski J, Tomsik EA, eds. Anesthesiology and Critical Care Drug Handbook. 8th ed. Hudson, OH: Lexi-Comp; 2008.
13. Hutchison TA, Shahan DR, Anderson ML, eds. Drugdex System [internet database]. Greenwood Village, CO: Thomson Healthcare; 2009. Updated periodically.
14. Bahn EL, Holt, KR. Procedural sedation and analgesia: a review and new concepts. Emerg Med Clin N Am 2005; 23:503-15.
15. Miner JR, Burton JH. Clinical practice advisory: emergency department procedural sedation with propofol. Ann Emerg Med 2007; 50:182-7.
16. Miner JR, Danahy M, Moch A, Biros M. Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department. Ann Emerg Med 2007; 49:15-22.
17. Falk J, Zed PJ. Etomidate for procedural sedation in the emergency department. Ann Pharmacother 2004; 38:1272-7.

Updated

Updated February 4, 2010 by Jane Chandramouli, Pharm.D., Drug Information Specialist and Erin R. Fox, Pharm.D., Manager, Drug Information Service. Created October 28, 2009 by Jane Chandramouli, Pharm.D., Drug Information Specialist. Copyright 2010, Drug Information Service, University of Utah, Salt Lake City, UT.

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