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Ketorolac Tromethamine Injection

[23 June 2016]

Products Affected - Description

Ketorolac injection, Fresenius Kabi
30 mg/mL, 2 mL for intramuscular use vial, 25 count (NDC 63323-0162-02)
 
Ketorolac Injection, Hospira
15 mg/mL 1 mL Carpuject syringe, 10 count (NDC 00409-2288-31) - discontinued
30 mg/mL, 1 mL iSecure syringe, 10 count (NDC 00409-2287-23)
 
Ketorolac injection, Sagent
30 mg/mL, 1 mL vial, 25 count (NDC 25021-0701-01)
30 mg/mL, 2 mL for intramuscular use vial, 25 count (NDC 25021-0701-02)

Reason for the Shortage

  • BD Rx has ketorolac injection available. BD RX is now part of Fresenius Kabi.1
  • Fresenius Kabi has ketorolac injection available.2
  • Hospira has ketorolac on shortage due to manufacturing delays for quality improvement activities and increased demand for the product.3
  • Sagent states the reason for the shortage is manufacturing delay.4
  • West-Ward is not actively marketing ketorolac injection.5
  • Ben Venue closed its plant in Bedford, Ohio in July 2014.6
  • FDA imposed an import ban in mid-2013 on several Wockhardt products including ketorolac.7
  • Sprix Nasal Spray is not affected by this shortage.8

Available Products

Ketorolac injection, BD Rx
30 mg/mL, 1 mL prefilled syringe, 24 count (NDC 76045-0104-10)
30 mg/mL, 2 mL for intramuscular use prefilled syringe, 24 count (NDC 76045-0105-20)
 
Ketorolac Injection, Fresenius Kabi
15 mg/mL 1 mL vial, 25 count (NDC 63323-0161-01)
30 mg/mL 1 mL vial, 25 count (NDC 63323-0162-01)
 
Ketorolac Injection, Hospira
15 mg/mL 1 mL vial, 25 count (NDC 00409-3793-01)
30 mg/mL 1 mL Carpuject syringe, 10 count (NDC 00409-2287-31)
30 mg/mL 1 mL vials, 25 count (NDC 00409-3795-01)
30 mg/mL, 2 mL for intramuscular use Carpuject syringe, 10 count (NDC 00409-2287-61)
30 mg/mL 2 mL vials for intramuscular use, 10 count (NDC 00409-3796-01)
 
Ketorolac injection, Sagent
15 mg/mL, 1 mL vial, 25 count (NDC 25021-0700-01)

Estimated Resupply Dates

  • Hospira has ketorolac 30 mg/mL 1 mL iSecure syringes on back order and the company estimates a release date of late-July 2016.3
  • Sagent has ketorolac 30 mg/mL 2 mL vials for intramuscular injection on back order and the company estimates a release date of July 2016. The 30 mg/mL 1 mL vials are on allocation.4
  • Fresenius Kabi has ketorolac 30 mg/mL 2 mL vials for intramuscular injection on back order and the company estimates a release date of late-June 2016.2

Implications for Patient Care

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.9 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.10,11

Safety

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.9,12,13,14

Alternative Agents & Management

  • 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.3,9,10,11,12,13,14
  • 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 Pain9,10,11,12,14,15 
 

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.





Table 2. Comparison of Non-Opioid Injectable Agents Used for Acute Pain: Pharmacokinetic Parameters, Warnings and Contraindications 9,10,11,12,13,14,15
  

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

 

Related Shortages

References

  1. BD Rx (personal communications). November 11, 2015; and February 4, 2016.
  2. 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, and June 8, 2016.
  3. Hospira (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, and June 16 and 23, 2016.
  4. 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, and June 16, 2016.
  5. West-Ward (personal communications). January 29, February 18, March 11, April 2, and May 6, June 24, July 29, and September 1, 2015; January 27 and March 29, 2016.
  6. Ben Venue (personal communications). August 5, 2014.
  7. Wockhardt (personal communications). December 9, 2013.
  8. Egalet Corporation (personal communications). April 1, 2015.
  9. Hospira. Ketorolac tromethamine injection solution [product information]. Lake Forest, IL: Hospira 2014.
  10. Anon, editor. Drugdex System. Micromedex 2.0 [internet database]. Greenwood Village, CO: Truven Health Analytics; 2015.
  11. Wickersham RM, Novak KK, managing eds., editors. Drug Facts and Comparisons (Facts & Comparisons eAnswers). St. Louis, MO: Wolters Kluwer Health, Inc.; 2015.
  12. Cumberland Pharmaceuticals Inc. Caldolor (ibuprofen) Injection, for intravenous use [product information]. Nashville, TN: Cumberland Pharmaceuticals Inc.; 2014.
  13. Hospira. Dyloject (diclofenac sodium) Injection [product information]. Lake Forest, IL: Hospira 2014.
  14. Cadence Pharmaceuticals. Ofirmev (acetaminophen) Injection [product information]. San Diego, CA: Cadence Pharmaceuticals, Inc.; 2010.
  15. Regency Therapeutics. Sprix (ketorolac tromethamine) nasal spray [product information]. Shirley, NY: American Regent 2014.

Updated

Updated June 23, 2016 by Leslie Jensen, PharmD, Drug Information Specialist. Created August 6, 2015 by Jane Chandramouli, PharmD, Drug Information Specialist. Copyright 2016, 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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