RESEARCH IN PRACTICE
AT A GLANCE
- Over a 48-hour period, the use of morphine was reduced by 34% overall in the ketorolac group, compared with the placebo group1
- At every time point through 48 hours, pain intensity difference scores were higher for the ketorolac group compared with the placebo group2
Brown CR, Moodie JE, Bisley EJ, Bynum L. Intranasal ketorolac for postoperative pain: a phase 3, double-blind, randomized study. Pain Med. 2009;10(6):1106-1114.
The predose pain intensity score, as measured by the Visual Analog Scale (VAS), was 54.1 in the placebo group and 54.7 in the SPRIX® group. Pain intensity difference refers to the change with respect to the predose pain intensity value. Morphine use reduction was a secondary endpoint.3
The effectiveness of intravenous (IV) and intramuscular (IM) ketorolac is similar to that of morphine in patients who have undergone major surgery. In addition, ketorolac also decreases the need for opioid pain relief, and so decreases the frequency of opioid-related side effects, allowing for a faster return of normal gastrointestinal function. For these reasons, ketorolac may be considered as part of an analgesic regimen that promotes the return to normal activities while decreasing the expense related to opioid analgesia. As such, an option to parenteral injection of ketorolac for outpatients may eliminate the need for IV or IM administration while making ketorolac easier to use in ambulatory settings.
Randomized, double-blind, placebo-controlled study to evaluate analgesic efficacy and tolerability of IN ketorolac in postoperative patients.
- 300 patients (199 ketorolac, 101 placebo) were enrolled following primarily hysterectomies (135/300, 45%) and hip replacements (100/300, 33%)
- Patients received IN ketorolac (31.5 mg) or placebo 3 times daily for up to 5 days
- Patients had access to morphine by patient-controlled analgesia (PCA)
- 189 patients (115 ketorolac, 74 placebo) in a single-dose phase were removed from PCA 3 hours prior to the first study dose the day after surgery, and received a single IN ketorolac or placebo dose when visual analog scale scores were ≥40
Proven Efficacy in Postoperative Pain, Resulting in Less Morphine Use
Predose Visual Analog Scale (VAS) score was 54.1 in the placebo group and 54.7 in the SPRIX® (ketorolac tromethamine) Nasal Spray group.1
- At every time point, pain intensity difference scores were higher for the ketorolac group compared with the placebo group
- The primary efficacy endpoint, the single-dose summed pain intensity difference (SPID) score at 6 hours, was significantly higher in the ketorolac group compared with placebo (83.3 vs 37.2, P<0.007), indicating greater pain reduction with ketorolac1
- The duration of analgesia was significantly longer in the ketorolac group as represented by the time to restarting PCA or requesting rescue medication (median time 3 hours in the ketorolac group vs 1.3 hours in the placebo group)1
- Morphine use over 48 hours was reduced by 34% in the ketorolac group compared with the placebo group1
- A significantly greater proportion (P<0.05) of patients in the ketorolac group reported meaningful pain relief compared with placebo within 1 hour (84% vs 70%) and at 1.5 hours (84% vs 72%). The difference at 2 hours approached statistical significance, indicating a trend that was still in favor of the ketorolac group (84% vs 73%)1
- The incidence of adverse events was similar (~98%) in the 2 groups and were characteristic of events observed following major surgery; the most common AEs in both groups were nausea and vomiting1
- There was a trend in the ketorolac group for a lower incidence of opioid-related side effects such as constipation and pruritus1
- Nasal irritation, usually mild to moderate in severity and of short duration, occurred more frequently with ketorolac vs placebo (24% vs 2%)1
Parenteral ketorolac has been shown to be an effective component of postoperative pain management for office-based and ambulatory procedures. Earlier removal of IV catheters and avoidance of IM injections for ambulatory patients provide the rationale for an IN ketorolac option in this patient population.
IN ketorolac was effective and well tolerated in treating moderate to moderately severe postoperative pain and may be useful for ambulatory care.
Well Absorbed by the Nasal Mucosa
Peak plasma concentration in as little as 30 minutes
How to Use SPRIX®
See the procedure & review the patient guide
REFERENCES:
- 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.
- Levin RA. Clinical Review of NDA22.382. FDA Center for Drug Evaluation and Research. October 5, 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® 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.