Important Safety Information |Prescribing Information
SPRIX® (ketorolac tromethamine) Nasal Spray is also contraindicated:
  • in patients with known hypersensitivity or history of asthma, urticaria, or other allergic-type reactions to aspirin, ketorolac, other NSAIDs or EDTA
  • in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates
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Ketorolac: An Extensive History of Pain Relief

Ketorolac is a hospital-strength nonsteroidal antiinflammatory drug (NSAID) that has been available for over 20 years.1 A nonselective NSAID, ketorolac inhibits prostaglandin production by inhibiting COX-1 and COX-2.2,3 It has potent analgesic activity,4 and has been extensively studied in postoperative patients.5

Popular parenteral analgesic

Ketorolac was the first NSAID approved in the United States for parenteral use as an analgesic.5 Premarketing clinical trials involving more than 5,000 patients demonstrated that ketorolac’s analgesic efficacy was similar to that of parenteral opiates in patients undergoing general and oral surgery.5

Ketorolac is widely used intramuscularly and intravenously for moderately severe acute pain: there have been more than 500 million injections in the United States since its introduction, and nearly 40 million injections in 2010 alone.6

An NSAID alternative to opioids

Ketorolac has similar efficacy to morphine and meperidine.7 A 30-mg dose of ketorolac IM delivers pain relief equivalent to that of morphine 6 mg to 12 mg.8

In two double-blind studies of postoperative patients with moderate to severe pain, IM ketorolac injection was compared with meperidine or morphine IM, and IV ketorolac was compared with morphine administered intravenously or via patient-controlled analgesia. During the first hour, the onset of analgesic action was similar for ketorolac tromethamine and the opioids, but analgesia lasted longer with ketorolac tromethamine.7

Clinical studies have also demonstrated that combining ketorolac and opioids significantly reduces the need for morphine.9,10

Ketorolac is non-narcotic

As an NSAID, ketorolac does not bind to opiate receptors.8 A study to evaluate the sedative and addictive potential of ketorolac showed no withdrawal symptoms upon cessation of dosing with ketorolac 30 mg IM four times daily for 5 days.8 Ketorolac IM also has no significant adverse effects on psychomotor measurements, including reaction time, computerized driving skills, ataxia, and sedation.8

Ketorolac: 20+ years of experience
  • Ketorolac was approved in 1989 as the first injectable NSAID1
  • In 1990, it was introduced as Toradol® Injection by Roche Laboratories11
  • More than 500 million injections administered in the United States since its introduction6
  • Toradol® Tablets were approved in 1991
  • Injection and tablet forms are currently available in generic formulation
  • Ketorolac is marketed as Acular® for the topical treatment of ocular itching due to seasonal allergies12

SPRIX® (ketorolac tromethamine) Nasal Spray is the first and only intranasal NSAID. It is indicated for the short-term (up to 5 days) management of moderate to moderately severe pain that requires analgesia at the opioid level.

Acular® is a registered trademark of Roche L.L.C.
RETHINKING OPIOIDS Often a good choice; alternatives may be appropriate
Prescribing SPRIX® How to dose, prescribe, and dispense SPRIX®

REFERENCES:

  • Boyer KC, McDonald P, Zoetis T. A novel formulation of ketorolac tromethamine for intranasal administration: Preclinical safety evaluation. Int J Toxicol. 2010;29(5):467-478.
  • Block BM, Hurley RW, Raja SN. Mechanism-based therapies for pain. Drug News Perspect. 2004;17(3):172-186.
  • Krenzischek DA, Dunwoody CJ, Polomano RC, Rathmell JP. Pharmacotherapy for acute pain: implications for practice. Pain Manag Nurs.
    2008;9(1 Suppl):S22-S32.
  • Moodie JE, Brown CR, Bisley EJ, Weber HU, Bynum L. The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. Anesth Analg. 2008;107(6):2025-2031.
  • Strom BL, Berlin JA, Kinman JL, Spitz PW, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study. JAMA. 1996;275(5):376-382.
  • Data on file. Shirley, NY: Luitpold Pharmaceuticals.
  • Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs. 1997;53(1):139-188.
  • SPRIX® [package insert]. Shirley, NY: American Regent, Inc; 2011.
  • Singla N, Singla S, Minkowitz HS, Moodie J, Brown C. Intranasal ketorolac for acute postoperative pain. Curr Med Res Opin. 2010;26(8):1915-1923.
  • Brown C, Moodie J, Bisley E, Bynum L. Intranasal ketorolac for postoperative pain: A phase 3, double-blind, randomized study. Pain Med. 2009;10(6):1106-1114.
  • Luitpold Pharmaceuticals, Inc. and Daiichi Sankyo, Inc. Press release. May 17, 2011.
  • Acular® [package insert]. Irvine, CA: Allergan, Inc; 2009.
Important Safety Information

WARNING: LIMITATIONS OF USE, GASTROINTESTINAL, BLEEDING, CARDIOVASCULAR, and RENAL RISK

Limitations of Use
SPRIX® (ketorolac tromethamine) Nasal Spray, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for short-term (up to 5 days in adults) management of moderate to moderately severe pain that requires analgesia at the opioid level. Do not exceed a total combined duration of use of SPRIX® and other ketorolac formulations (IM/IV or oral) of 5 days.

SPRIX® is not indicated for use in pediatric patients and it is not indicated for minor or chronic painful conditions.

Gastrointestinal Risk
Ketorolac tromethamine, including SPRIX®, can cause peptic ulcers, gastrointestinal bleeding and/or perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Therefore, SPRIX® is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Elderly patients are at greater risk for serious gastrointestinal events.

Bleeding Risk
Ketorolac tromethamine inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding.

Cardiovascular Risk
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.

SPRIX® is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Renal Risk
SPRIX® is contraindicated in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion.

SPRIX® (ketorolac tromethamine) Nasal Spray is also contraindicated:

  • in patients with known hypersensitivity or history of asthma, urticaria, or other allergic-type reactions to aspirin, ketorolac, other NSAIDs or EDTA
  • as a prophylactic analgesic prior to major surgery
  • in labor and delivery

Additional Warnings and Precautions:

  • SPRIX® should not be used concomitantly with IM/IV or oral ketorolac, aspirin, or other NSAIDs, or with probenecid or pentoxifylline.

  • Risk of GI Ulceration, Bleeding, and Perforation: Ketorolac can cause serious adverse events including bleeding, ulceration, and perforation which can be fatal. Elderly patients are at increased risk for serious GI events. Treat patients for the shortest duration possible, and do not exceed 5 days of therapy with SPRIX® alone or sequentially with other forms of ketorolac.
  • Hematological Effects: NSAIDs affect platelet aggregation and may cause bleeding complications. SPRIX® should be used with caution in patients who have coagulation disorders or are on therapy that affects hemostasis. Do not use SPRIX® in patients for whom hemostasis is critical.

  • Renal Effects: Ketorolac can cause renal injury. SPRIX® should not be used in patients with advanced renal disease or patients at risk for renal failure due to volume depletion, and should be used with caution in patients taking diuretics or ACE inhibitors. Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury such as interstitial nephritis and nephrotic syndrome.

  • Anaphylactoid Reactions: Anaphylactoid reactions may occur in patients with or without a history of allergic reactions to aspirin or NSAIDs.

  • CV Effects: CV Thrombotic Events, Hypertension, Congestive Heart Failure (CHF) and Edema: NSAIDs can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response when taking NSAIDs. Fluid retention, edema, retention of NaCl, oliguria, and elevations of serum urea nitrogen and creatinine have been reported in clinical trials of ketorolac. SPRIX® should be used with caution in patients with cardiac decompensation or similar conditions.

  • Skin Reactions: NSAIDs, including ketorolac, can cause serious dermatologic adverse reactions such as exfoliative dermatitis, Stevens- Johnson syndrome, and toxic epidermal necrolysis, which can be fatal. These serious events may occur without warning. SPRIX® should be discontinued immediately with skin reactions or other signs of hypersensitivity.

  • Pregnancy: During pregnancy, use of SPRIX® beyond 30 weeks gestation can cause premature closure of the ductus arteriosus, resulting in fetal harm (Pregnancy Category D). Prior to 30 weeks gestation, SPRIX® should be used during pregnancy only if potential benefit justifies the potential risk to the fetus (Pregnancy Category C).

  • Hepatic Effects: Use SPRIX® with caution in patients with impaired hepatic function or history of liver disease.

  • Inflammation and Fever: The pharmacologic activity of SPRIX® in reducing inflammation and fever may diminish the utility of these diagnostic signs in detecting infections.

  • Preexisting Asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal.

  • Eye Exposure: Avoid contact of SPRIX® with the eyes. If eye contact occurs, wash out the eye with water or saline, and consult a physician if irritation persists for more than an hour.

Additional Drug Interactions:

  • Aspirin: Protein binding is reduced when ketorolac is administered with aspirin although the clearance of free ketorolac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of SPRIX® and aspirin is not generally recommended because of the potential of increased adverse effects.

  • Diuretics: Ketorolac can reduce the natriuretic effect of furosemide and thiazides in some patients.

  • ACE Inhibitors/Angiotensin II Receptor Antagonists: Concomitant use of ACE inhibitors and/or angiotensin II receptor antagonists may increase the risk of renal impairment, particularly in volume-depleted patients. NSAIDs may diminish the antihypertensive effect of ACE inhibitors and/or angiotensin II receptor antagonists. Consider this interaction in patients taking SPRIX® concomitantly with ACE inhibitors and/or angiotensin II receptor antagonists.

Most Common Adverse Reactions:
The most common adverse reactions (incidence ≥ 2%) in patients treated with SPRIX® and occurring at a rate at least twice that of placebo are nasal discomfort, rhinalgia, increased lacrimation, throat irritation, oliguria, rash, bradycardia, decreased urine output, increased ALT and/or AST, hypertension, and rhinitis.

Administration:
SPRIX® is not an inhaled product. Patients should be instructed not to inhale when using the product.

Please see Important Safety Information and complete Prescribing Information, including Boxed Warning at www.sprix.com.