Products Affected - Description

• • Ketorolac injection, Almaject, 30 mg/mL, 1 mL vial, 25 count, NDC 72611-0722-25 - discontinued
  • Ketorolac injection, Baxter, 15 mg/mL, 1 mL vial, 10 count, NDC 00338-0069-10
  • Ketorolac injection, Fresenius Kabi, 30 mg/mL, 1 mL RFID Smart Label prefilled syringe, 24 count, NDC 76045-0209-10
  • Ketorolac injection, Pfizer, 15 mg/mL, 1 mL vial, 25 count, NDC 00409-3793-01

Reason for the Shortage

• • Almaject discontinued ketorolac injection.[1]
  • Amphastar has discontinued ketorolac injection.[2]
  • Athenex closed down in 2023.[3]
  • Baxter has ketorolac on shortage due to increased demand.[4]
  • BD RX is now part of Fresenius Kabi.[5]
  • Fresenius Kabi did not provide a reason for the shortage.[7]
  • Fosun Pharma has ketorolac available.[6]
  • Pfizer has ketorolac injection on back order due to manufacturing delays.[8]
  • Sola has ketorolac injection available.[9]
  • Sagent has ketorolac injection available.[10]
  • Hikma is not actively manufacturing ketorolac at this time.[11]
  • Ben Venue closed its plant in Bedford, Ohio in July 2014.[12]
  • Virtus discontinued ketorolac in March 2019.[13]
  • FDA imposed an import ban in mid-2013 on several Wockhardt products including ketorolac.[14]
  • Sprix Nasal Spray is not affected by this shortage.[15]

Available Products

• • Ketorolac injection, Baxter, 30 mg/mL, 1 mL vial, 25 count, NDC 00338-0072-25
  • Ketorolac injection, Fosun Pharma, 15 mg/mL, 1 mL vial, 25 count, NDC 72266-0234-25
  • Ketorolac injection, Fosun Pharma, 30 mg/mL, 1 mL vial, 25 count, NDC 72266-0118-25
  • Ketorolac injection, Fosun Pharma, 30 mg/mL, 2 mL vial, 25 count, NDC 72266-0119-25
  • Ketorolac injection, Fresenius Kabi, 15 mg/mL, 1 mL prefilled syringe, 24 count, NDC 76045-0107-10
  • Ketorolac injection, Fresenius Kabi, 15 mg/mL, 1 mL vial, 25 count, NDC 63323-0161-01
  • Ketorolac injection, Fresenius Kabi, 30 mg/mL, 1 mL vial, 25 count, NDC 63323-0162-01
  • Ketorolac injection, Fresenius Kabi, 30 mg/mL, 2 mL for intramuscular use prefilled syringe, 24 count, NDC 76045-0105-20
  • Ketorolac injection, Fresenius Kabi, 30 mg/mL, 2 mL for intramuscular use vial, 25 count, NDC 63323-0162-02
  • Ketorolac injection, Pfizer, 30 mg/mL, 1 mL vial, 25 count, NDC 00409-3795-01
  • Ketorolac injection, Pfizer, 30 mg/mL, 2 mL for intramuscular use vial, 10 count, NDC 00409-3796-01
  • Ketorolac injection, Sola, 15 mg/mL, 1 mL vial, 25 count, NDC 70512-0842-25
  • Ketorolac injection, Sola, 30 mg/mL, 1 mL vial, 25 count, NDC 70512-0843-25

• • Baxter has ketorolac 15 mg/mL 1 mL vials available in limited supply.[4]
  • Fresenius Kabi has ketorolac 30 mg RFID 1 mL prefilled syringes on back order and the company estimates a release date of early-April 2024.[7]
  • Pfizer has ketorolac 15 mg/mL 1 mL vials available in limited supply.[8]

• • Ketorolac is a nonsteroidal anti-inflammatory drug labeled for use in adults with moderate to severe acute pain who require short-term analgesia at the opioid level, typically following surgery.[16] Ketorolac can be used alone, or in combination with opioid analgesics. Ketorolac is useful in situations where opioids are contraindicated or to reduce opioid dosage requirements when used in combination with opioids. Total duration of ketorolac given intravenous, intramuscular, or orally should not exceed 5 days due to the increased frequency and severity of adverse reactions. Ketorolac, given intramuscularly, is used off-label for the management of migraine.[17-18]

• • Dosage recommendations and administration times vary significantly between alternative agents. Patient harm can occur if these agents are used erroneously. Use extra caution when switching to alternative agents.[16,19-21]

• • No single agent can be substituted for ketorolac injection. The choice of alternative agent must be patient-specific, procedure-specific, and based on the clinical situation and other comorbid conditions. Utilize stakeholder clinicians to help make specific plans for individual patient populations.
  • Tables 1 and 2 summarize the differences between some potential alternatives to ketorolac for acute pain. Injectable diclofenac was recently approved by the FDA (December 2014) but the product is not currently available and not included in the tables.[8,16-23]
  • During this shortage, ensure appropriate pain control and explore all therapeutic modalities. Utilize oral and rectal medications whenever possible.

  Table 1. Comparison of Select Non-Opioid Injectable Agents Used for Acute Pain16-19,21-23

  Medication	Description	Labeled Indication for Adults	How Supplied	Storage and Handling	Dose Preparation
  Ketorolac	Nonsteroidal anti-inflammatory (NSAID)	Moderate to severe pain that requires analgesia at opioid level; for short-term use only (< 5 days).	Injection: 15 mg in1 mL single-dose vial or syringe 30 mg in 1 mL single-dose vial or syringe 60 mg in 2 mL single-dose vial (30 mg/mL) Intranasal: 15.75 mg/spray Oral: 10 mg tablet	Store at room temperature (20-25 degrees C). Protect from light.	Withdraw the correct dose from vial into appropriate sterile syringe. Discard unused portion of single-dose vials. To avoid precipitation, do not mix ketorolac with morphine, meperidine, promethazine, or hydroxyzine in a syringe or other small volume. An intravenous bolus is given over 15 seconds.
  Ibuprofen (Caldolor) Cumberland Pharmaceuticals	Nonsteroidal anti-inflammatory	Mild to moderate pain. Moderate to severe pain with adjunctive opioids. Fever reduction.	Injection: 100 mg/mL 8 mL single-dose vial Oral: multiple presentations	Diluted solutions stable for <24 hours at room temperature. Store unopened vials at room temperature (20-25 degrees C).	Prior to administration, dilute to < 4mg/mL concentration, in 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection. Infusion time must be no less than 30 minutes.
  Acetaminophen (Ofirmev) Cadence Pharmaceuticals	Non-salicylate, non-opioid agent with antipyretic and analgesic effects	Mild to moderate pain. Moderate to severe pain with adjunctive opioids. Fever reduction.	Injection: 10 mg/mL 100 mL single use vial Oral: multiple presentations Rectal: multiple presentations	Store at room temperature (20-25 degrees C). Do not refrigerate or freeze. Use within 6 hours of opening the vial.	Do not mix or administer with other medications. Doses of 1000 mg may be given undiluted from original vial using vented IV set. Doses of <1000 mg must be withdrawn from original vial and placed in a separate empty container (glass bottle, plastic IV container, or syringe) prior to administration. Discard unused portion of vial. Infusion time is 15 minutes.
  Meloxicam (Anjeso) Baudax Bio	Nonsteroidal anti-inflammatory	Moderate to severe pain.	Injection: 30 mg/mL 2 mL single use vial Oral: multiple presentations	Store at room temperature (15-25 degrees C). Do not freeze. Protect from light.	Withdraw the correct dose from vial into appropriate sterile syringe. An intravenous bolus is given over 15 seconds.

  
  

  Table 2. Comparison of Non-Opioid Injectable Agents Used for Acute Pain: Pharmacokinetic Parameters, Warnings and Contraindications 16-23

  Medication	Mean Volume of Distribution	Mean Half-life	Protein binding	Black Box Warnings	Contraindications
  Ketorolac	Intravenous: 0.21 L/kg Intramuscular: 0.18 L/kg	Racemate: 5.6 hours (intravenous) 5.3 hours (oral, intramuscular) 4.8 hours (intranasal)	99%	Not for minor or chronic pain Not for pediatric patients Risk of potentially fatal GI bleeding or perforation; elderly patients at increased risk Increased risk of potentially fatal cardiovascular thrombotic events, myocardial infarction, and stroke Peri-operative pain in CABG surgery Renal toxicity risk Bleeding risk due to platelet function inhibition Not for use prior to major surgery Risk of hypersensitivity reactions; must have measures available to treat at first-dose administration Contains alcohol, do not administer via intrathecal or epidural routes Risk of fetal harm if used during labor and delivery Risk to nursing neonate if used by mother Risk of additive adverse events if used with other NSAIDs Reduce dose in patients >65 years old, patients weighing <50 kg, or patients with elevated serum creatinine. Do not exceed total daily dose of 60 mg injectable ketorolac Do not exceed 5 days (combined duration, any route)	History of allergic reaction to ketorolac, aspirin, or any other NSAID Active peptic ulcer disease Recent GI bleeding or perforation History of GI bleeding or peptic ulcer disease Peri-operative pain in CABG surgery Advanced renal impairment Patients at risk of renal failure resulting from volume depletion Cerebrovascular bleeding (suspected or confirmed) Hemorrhagic diathesis Incomplete hemostasis Patients with high risk of bleeding Prior to any major surgery Intrathecal or epidural administration During labor and delivery Nursing mothers Concomitant use with aspirin or other NSAIDs Concomitant use with probenecid or pentoxifylline
  Ibuprofen (Caldolor)	Not available	2.4 hours	>99%	Increased risk of potentially fatal cardiovascular thrombotic events, myocardial infarction, and stroke; do not use for CABG surgery peri-operative pain Risk of potentially fatal GI bleeding, ulceration, or perforation; elderly patients at increased risk	Known hypersensitivity to ibuprofen History of allergic reactions, asthma, or urticaria with aspirin or any other NSAID Peri-operative pain in CABG surgery
  Acetaminophen(Ofirmev)	Intravenous: 0.8 L/kg	2.4 hours	10 to 25%	Risk of medication errors and hepatotoxicity. Dosing errors could lead to accidental death and overdose. Risk of acute liver failure, liver transplant, or death	Known hypersensitivity to acetaminophen or excipients Severe hepatic impairment or active liver disease
  Meloxicam (Anjeso)	Intravenous: 9.63 L	23.6 hours	99.4%	Risk of potentially fatal GI bleeding or perforation; elderly patients at increased risk Increased risk of potentially fatal cardiovascular thrombotic events, myocardial infarction, and stroke Peri-operative pain in CABG surgery	Known hypersensitivity to meloxicam or components History of allergic reactions, asthma, or urticaria with aspirin or any other NSAID Peri-operative pain in CABG surgery Patients at risk of renal failure resulting from volume depletion

  
  

• 1. Almaject (personal communication). April 7, May 17, October 11, December 20, 2018; February 7, May 2 and 21, June 5, July 2 and 22, December 16, 2019; January 20 and 30, March 6 and 13, May 4, July 14, September 11, October 14, 2020; January 8, April 14, 2021; May 11, October 30, 2022; January 26, and June 21, 2023.
  2. Amphastar (personal communications). October 4, 2016; January 9, August 29, and September 11, 2017; May 14, July 9, and August 1, 2018; April 30, 2019; January 29, 2020; and May 12, 2021.
  3. Athenex (personal communications). February 20, March 8 and 12, April 4, May 14, July 3, August 1, September 12, December 27, 2018; February 7, April 30, June 26, August 27, November 5, 2019; February 19, March 5, April 20, May 28, October 12, December 10, 2020; April 13, June 7, October 19, November 30, 2021; March 1, April 13, June 1, August 9, October 29, December 1, 2022; January 23, and April 27, 2023.
  4. Baxter (personal communication). July 14 and 21, October 6, December 8, 2020; January 5, February 2 and 16, March 9, April 6, May 13, June 1, October 19, November 22, 2021; March 15, May 3, June 1, August 9, November 1 and 22, December 13, 2022; February 28, April 18 and 25, May 23, June 13, July 25, August 8 and 22, October 17, November 14, 2023; January 16 and 30, February 27, and March 12, 2024.
  5. BD Rx (personal communications). November 11, 2015; and February 4, 2016.
  6. Fosun Pharma (personal communications). June 10, 2019; July 31, 2020; January 8, September 14, 2021; June 3, August 9, November 22, 2022; March 7, June 8, October 18, 2023; and January 15, 2024.
  7. Fresenius Kabi (personal communications). February 2, 11, 18, and 24, March 11, 18, and 31, May 6 and 20, June 30, July 6, August 6, September 10, October 8, November 4, December 11, 2015; January 20, February 5 and 18, March 7, May 13 and 23, June 8 and 30, July 29, September 6, October 4 and 27, 2016; January 28, February 20, March 21, June 2 and 20, July 7 and 28, August 24, September 21, November 10, 17, and 30, December 15, 2017; January 12, February 5 and 15, March 2, 9, 20, and 23, April 6 and 27, May 3, 10, and 25, July 5 and 27, August 29, September 6 and 28, October 5, November 2, December 14, 2018; January 3 and 11, February 1, March 21 and 29, April 5 and 26, May 3, 11, 17, and 30, June 7 and 24, July 5, 12, and 16, August 2, 16, and 30, September 16 and 27, October 18, November 1, 8, and 22, December 13 and 20, 2019; January 17, 21, and 24, March 6, 13, and 20, April 17, May 1, July 17 and 24, October 9 and 23, December 4 and 23, 2020; January 8 and 29, February 12, March 5 and 12, April 9, May 14 and 28, June 25, October 15, December 3, 2021; March 11, April 29, June 3, August 9, October 28, November 18, December 9, 2022; March 3, April 21 and 28, May 19, June 16, July 27, August 17 and 24, September 22, October 5 and 12, November 9, 2023; January 11 and 25, February 29, and March 14, 2024.
  8. Pfizer (personal communications and website). February 10 and 24, March 2, 13, and 20, April 1 and 7, May 11 and 22, July 2 and 27, September 15, October 12, November 12, December 11, 2015; January 26, February 5, 22, and 25, March 7, April 28, May 20, June 16 and 23, July 7, August 2, September 6, October 4, November 6, 2016; January 30, February 23, March 24, June 2, 5, and 23, July 7, 14, and 28, August 28, September 29, October 11, November 15, 20, and 28, December 1 and 18, 2017; January 12, February 2, 16 and 23, March 5, 9, and 23, April 2, May 1, 11, and 25, June 22, July 10 and 25, August 30, October 4, November 6, December 18, 2018; January 17, February 7, March 25, April 1 and 30, May 5, 21, and 31, June 24, July 9, 12, and 23, August 2, 20, and 30, September 17 and 27, October 21, November 4 and 25, December 13 and 20, 2019; January 22, March 6 and 13, April 17, 1, July 20 and 31, October 9 and 23, December 4, 2020; January 5, February 3 and 16, March 10, April 12, May 14, June 2 and 25, October 19, December 3, 2021; March 11, May 3, June 3, August 9, October 28, November 22, December 16, 2022; March 3, April 23 and 30, May 22, June 16, July 28, August 19 and 25, October 6 and 17, November 15, 2023; January 17 and 29, and March 1 and 17, 2024.
  9. Sola (personal communication). October 18, 2023; February 28, and March 18, 2024.
  10. Sagent (personal communications). February 9, 19, and 26, March 12, 20, and 27, April 2, May 7 and 21, July 2 and 30, September 10, October 8, November 5, December 10, 2015; January 21, February 4 and 18, March 7, April 28, May 19 and 26, June 16, July 7 and 29, September 6, October 4, November 3, 2016; January 27, February 23, March 23, June 1 and 22, July 7 and 28, August 24, September 28, November 9, 16, 22, and 30, December 14, 2017; January 11, February 1 and 22, March 1, 22, and 29, May 3, 10, and 24, June 21, July 5 and 26, August 30, October 4, November 1, December 13, 2018; January 3 and 17, February 7, March 21 and 28, April 4 and 25, May 16 and 30, July 5 and 12, August 1 and 30, September 12 and 27, October 17, November 6 and 21, December 12, 2019; January 16, March 6 and 13, April 16 and 30, July 16 and 30, October 8 and 22, December 3 and 31, 2020; February 4 and 11, March 11, April 8, May 13 and 27, June 24, October 14, November 18, 2021; March 10, April 28, June 3, August 9, November 3 and 17, December 9, 2022; March 7, November 10, 2023; January 17 and 24, February 28, and March 14, 2024.
  11. Hikma (personal communications). January 29, February 18, March 11, April 2, and May 6, June 24, July 29, September 1, 2015; January 27, March 29, 2016; May 2, 10, and 23, June 20, July 3 and 25, August 29, September 5, October 3 and 31, 2018; January 16 and 30, March 20 and 27, April 3 and 24, May 2, 16, and 29, June 19, July 3, 10, 24, and 31, August 21, September 18 and 25, October 16, November 6 and 20, December 11 and 18, 2019; January 22, March 4 and 12, April 15 and 29, July 15 and 29, October 7 and 21, December 30, 2020; and February 3 and 17, 2021.
  12. Ben Venue (personal communications). August 5, 2014.
  13. Virtus. (personal communications). February 20, April 4, May 15, July 10, October 4, 2018, February 7, and May 1, 2019.
  14. Wockhardt (personal communications). December 9, 2013.
  15. Egalet Corporation (personal communications). April 1, 2015.
  16. Hospira. Ketorolac tromethamine injection solution [product information]. Lake Forest, IL: Hospira 2014.
  17. Anon, editor. Drugdex System. Micromedex 2.0 [internet database]. Greenwood Village, CO: Truven Health Analytics; 2015.
  18. Wickersham RM, Novak KK, managing eds., editors. Drug Facts and Comparisons (Facts & Comparisons eAnswers). St. Louis, MO: Wolters Kluwer Health, Inc.; 2015.
  19. Cumberland Pharmaceuticals Inc. Caldolor (ibuprofen) Injection, for intravenous use [product information]. Nashville, TN: Cumberland Pharmaceuticals Inc.; 2014.
  20. Hospira. Dyloject (diclofenac sodium) Injection [product information]. Lake Forest, IL: Hospira 2014.
  21. Cadence Pharmaceuticals. Ofirmev (acetaminophen) Injection [product information]. San Diego, CA: Cadence Pharmaceuticals, Inc.; 2010.
  22. Regency Therapeutics. Sprix (ketorolac tromethamine) nasal spray [product information]. Shirley, NY: American Regent 2014.
  23. Baudax Bio. Anjeso (meloxicam) Injection, for intravenous use [product information]. Malvern, PA: Baudax Bio, Inc.; 2020.