RESEARCH IN PRACTICE
AT A GLANCE
- A single intranasal (IN) ketorolac 31.5-mg dose was well tolerated and provided effective pain relief in oral surgery patients for up to 8 hours1
- Median time to rescue medication for patients receiving SPRIX® (ketorolac tromethamine) Nasal Spray was significantly longer1
Grant GM, Mehlisch DR. Intranasal ketorolac for pain secondary to third molar impaction surgery: a randomized, double-blind, placebo-controlled trial. Oral Maxillofac Surg. 2010;68(5):1025-1031.
Nonopioid analgesics are sometimes prescribed in ambulatory settings to speed recovery time and decrease opioid-related side effects. Compared with other pain-relief treatments after oral impaction surgery, ketorolac has been associated with a reduced incidence of drowsiness and nausea. Intranasal ketorolac is self-administered and may be considered an option to injectable ketorolac and opioids that may support continuity of pain management immediately after surgery and on an outpatient basis.
Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of IN ketorolac in patients who had third molar extraction surgery with bony impactions.
- After surgery, patients were randomly assigned to receive IN ketorolac 31.5 mg (n=40) or IN placebo (n=40)
- Safety was assessed from spontaneously reported adverse events and measurement of vital signs
- Efficacy assessments included pain intensity, which was measured on a
100-mm visual analog scale, total pain relief, and global pain evaluation
up to 8 hours after dosing or until patients required rescue analgesia
- The primary efficacy variable was the summed pain intensity difference score over the first 8 hours after dosing
- Summed pain intensity difference (SPID) values ± SE were significantly higher (indicating better analgesia) in the ketorolac group compared with placebo (136.7 ± 33.0 vs -105.2 ± 29.1)1
- Total pain relief scores were significantly higher in the ketorolac group compared with placebo at all times1
- A larger proportion of subjects in the ketorolac group reported good, very good, or excellent pain control compared with the control group (60% vs 13%)1
- Median time to rescue medication in SPRIX® patients was significantly longer (360 minutes vs 96 minutes with placebo [P<0.001])1
- Eight patients in the placebo group and 3 in the ketorolac group had adverse events, none of which was serious1
IN ketorolac provides an alternative to injectable analgesics for ambulatory surgical patients, and may be especially valuable where oral medications are not practical. Because IN ketorolac can be self-administered, its use allows the same pain medication and dose to be used immediately after surgery and at home.
A single dose of IN ketorolac 31.5 mg was well tolerated and effectively managed postoperative pain in oral surgery patients for up to 8 hours.
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Patient Counseling Information
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REFERENCE:
- Grant GM, Mehlisch DR. Intranasal ketorolac for pain secondary to third molar impaction surgery: a randomized, double-blind, placebo-controlled trial. J Oral Maxillofac Surg. 2010;68(5):1025-1031.
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® is contraindicated in patients with known hypersensitivity or history of asthma, urticaria, or other allergic-type reactions to aspirin, ketorolac, other NSAIDs or EDTA. However, anaphylactoid reactions may occur in patients with or without a history of allergic reactions to aspirin or NSAIDs. SPRIX® is contraindicated in patients as a prophylactic analgesic prior to major surgery; or in labor, delivery, or nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.
SPRIX® should not be used concomitantly with IM/IV or oral ketorolac, aspirin, or other NSAIDs, or with probenecid or pentoxifylline. When ketorolac is administered with aspirin, its protein binding is reduced, 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.
Do not use SPRIX® in patients for whom hemostasis is critical.
Clinical studies, as well as postmarketing observations, have shown that ketorolac can reduce the natriuretic effect of furosemide and thiazides in some patients.
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.
Ketorolac can cause serious GI adverse events including bleeding, ulceration, and perforation. Elderly patients are at increased risk for serious GI events.
Use SPRIX® with caution in patients with impaired hepatic function or a history of liver disease.
The pharmacologic activity of SPRIX® in reducing inflammation and fever may diminish the utility of these diagnostic signs in detecting infections.
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.
Ketorolac can cause renal injury. SPRIX® Nasal Spray should be used with caution 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.
NSAIDs 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 in patients with skin reactions.
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).
NSAIDs can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cardiovascular events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. Fluid retention, edema, retention of NaCI, oliguria, and elevations of serum urea nitrogen and creatinine have been reported in clinical trials with ketorolac. Only use SPRIX® very cautiously in patients with cardiac decompensation or similar conditions.
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.
Treat patients for the shortest duration possible, and do not exceed 5 days of therapy with SPRIX®.
Please see accompanying complete Prescribing Information, including Boxed Warning.