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Ketorolac Tromethamine Injection

[06 August 2015]

Products Affected - Description

Ketorolac Injection, Hospira
15 mg/mL 1 mL Carpuject syringe, 10 count (NDC 00409-2288-31)
30 mg/mL 2 mL Carpuject syringe for intramuscular use, 10 count (NDC 00409-2287-61)
 
Ketorolac Injection, Sagent
15 mg/mL 1 mL vial, 25 count (NDC 25021-0700-01)
30 mg/mL 1 mL vial, 25 count (NDC 25021-0701-01)
30 mg/mL 2 mL vial for intramuscular use, 25 count (NDC 25021-0701-02)
 
Ketorolac Injection, West-Ward  
15 mg/mL 1 mL vial, 25 count (NDC 00641-6041-25)
30 mg/mL 1 mL vial, 25 count (NDC 00641-6042-25)
30 mg/mL 2 mL vial for intramuscular use, 25 count (NDC 00641-6043-25)

Reason for the Shortage

  • Fresenius Kabi has ketorolac injection available.1
  • Hospira has ketorolac on shortage due to manufacturing delays for quality improvement activities and increased demand for the product.2
  • Hospira issued a voluntary recall of several presentations of ketorolac in January 2015 due to potential for particulate matter.
  • Sagent states the reason for the shortage is demand exceeding supply.3
  • West-Ward has ketorolac injection on shortage due to manufacturing delays.4
  • Ben Venue closed its plant in Bedford, Ohio in July 2014.5
  • FDA imposed an import ban in mid-2013 on several Wockhardt products including ketorolac.6 
  • Sprix Nasal Spray is not affected by this shortage.7

Available Products

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)
30 mg/mL 2 mL vial for intramuscular injection, 25 count (NDC 63323-0162-02)
 
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 1 mL iSecure Luer Lock syringe, 10 count (NDC 00409-2287-23)
30 mg/mL 2 mL vials for intramuscular use, 10 count (NDC 00409-3796-01)

Estimated Resupply Dates

  • Hospira has ketorolac 15 mg/mL 1 mL Carpuject syringes and 30 mg/mL intramuscular 2 mL Carpuject syringes on back order and the company cannot estimate a release date.2
  • Sagent has ketorolac 30 mg/mL intramuscular 2 mL vials and 30 mg/mL 1 mL vials on allocation. The ketorolac 15 mg/mL 1 mL vials are on back order and the company cannot estimate a release date.3
  • West-Ward has all ketorolac injection presentations on back order and the company cannot estimate a release date for these products.4

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.7 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.9,10

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.9,10

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.2,8-13
  • 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 Pain8-11,13,14
 
 

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 8-14
 

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 creatine. 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. Fresenius Kabi (personal communications). February 2, 11, 18, and 24, March 11, 18, and 31, May 6 and 20, and June 30, 2015.
  2. Hospira (personal communications and website). February 10 and 24, March 2, 13, and 20, April 1 and 7, May 11 and 22, and July 2, 2015.
  3. Sagent (personal communications). February 9, 19, and 26, March 12, 20, and 27, April 2, May 7 and 21, and July 2, 2015.
  4. West-Ward (personal communications). January 29, February 18, March 11, April 2, May 6, and June 24, 2015.
  5. Ben Venue (personal communications). August 5, 2014.
  6. Wockhardt (personal communications). December 9, 2013.
  7. Egalet Corporation (personal communications). April 1, 2015
  8. Hospira. Ketorolac tromethamine injection solution [product information]. Lake Forest, IL: Hospira 2014.
  9. Anon, editor. Drugdex System. Micromedex 2.0 [internet database]. Greenwood Village, CO: Truven Health Analytics; 2015.
  10. Wickersham RM, Novak KK, managing eds., editors. Drug Facts and Comparisons (Facts & Comparisons eAnswers). St. Louis, MO: Wolters Kluwer Health, Inc.; 2015.
  11. Cumberland Pharmaceuticals Inc. Caldolor (ibuprofen) Injection, for intravenous use [product information]. Nashville, TN: Cumberland Pharmaceuticals Inc.; 2014.
  12. Hospira. Dyloject (diclofenac sodium) Injection [product information]. Lake Forest, IL: Hospira 2014.
  13. Cadence Pharmaceuticals. Ofirmev (acetaminophen) Injection [product information]. San Diego, CA: Cadence Pharmaceuticals, Inc.; 2010.
  14. Regency Therapeutics. Sprix (ketorolac tromethamine) nasal spray [product information]. Shirley, NY: American Regent 2014.

Updated

Updated August 6, 2015 by Jane Chandramouli, PharmD, Drug Information Specialist. Created February 10, 2015 by Jane Chandramouli, PharmD, Drug Information Specialist and Erin R. Fox, Director, Drug Information Service. Copyright 2015, 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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