Intranasal or oral ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), is FDA-approved for short-term (no more than 5 days) management of acute moderate to severe pain, usually in the postoperative setting, that requires pain management at the opioid level.

Oral ketorolac is only approved for use after therapy initiation with intravenous or intramuscular ketorolac. Therefore, a prescription for a parenteral form of ketorolac should precede treatment with oral ketorolac to satisfy manufacturer and FDA recommendations.

The maximum recommended dosage for oral ketorolac is 40 mg/24 hours given in divided doses every 4 to 6 hours. Dosages exceeding this recommendation will be reviewed.

Intranasal ketorolac is dosed as one spray (15.75 mg) in each nostril every 6 to 8 hours for a maximum total of 8 sprays (126 mg) in a 24-hour period for patients less than 65 years of age. In patients with renal impairment, age greater than or equal to 65 years, or those weighing less than 50 kg, intranasal ketorolac should be dosed as one spray (15.75 mg) in one nostril every 6 to 8 hours for a total of 4 doses (63 mg) per 24-hour period.   Discard the intranasal ketorolac bottle after 24 hours, even if liquid is still present in the bottle, as the delivery system is not designed to deliver the intended dose after 24 hours.

Ketorolac is not FDA-approved for pediatric patients younger than 17 years of age as safety and efficacy in this age group have not been established. In adolescents 17 years of age and older, the maximum oral daily ketorolac dose is 40 mg in divided doses as continuation from parenteral ketorolac therapy. The maximum intranasal dose in pediatric patients 17 years of age and older is 126 mg per 24 hours in divided doses [one spray (15.75 mg) in each nostril (31.5 mg total) every 6 to 8 hours]. Discard the intranasal ketorolac bottle after 24 hours, even if liquid is still present in the bottle, as the delivery system is not designed to deliver the intended dose after 24 hours.

The maximum treatment duration for oral and parenteral ketorolac, combined, is 5 days due to increased frequency and severity of adverse effects associated with extended use. The maximum treatment period for nasal ketorolac when used as monotherapy or sequentially with other ketorolac dosage forms is also 5 days.  Treatment regimens exceeding these requirements will be reviewed.

Elderly patients frequently utilize prescription and nonprescription NSAIDs to manage acute and chronic pain. Several issues surface with NSAID use in elderly patients, including potential adverse effects and drug interactions. NSAID-induced gastrointestinal and renal toxicity as well as adverse central nervous system effects are more prevalent in elderly patients due to changes in metabolism, underlying disease states, and concurrent drug therapy. The majority of fatal gastrointestinal events associated with ketorolac use have been seen in elderly or debilitated patients. The potential for increased cardiovascular risk with NSAID use is also a factor when evaluating NSAID therapy in elderly patients. Elderly patients prescribed NSAIDs, especially those at higher risk, should be evaluated for appropriateness of therapy as well as potential for drug-drug interactions. Appropriate ketorolac therapy duration as well as appropriate dosages should also be evaluated.

Some clinical trials have shown that patients prescribed selective and nonselective NSAIDs may be at increased risk for serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, all of which can be fatal. Patients at greater risk are those with known CV disease or risk factors for CV disease. Due to the lack of long-term clinical trial data, CV risks associated with NSAID use remains controversial, especially in high-risk patients. Risk also varies between nonselective NSAIDs and cyclooxygenase-2 (COX-2) inhibitors, as well as between individual NSAIDs. The Center for Drug Evaluation and Research has determined that the increased risk of CV events associated with NSAID use should be considered a class effect for both selective and nonselective NSAIDs until more results are available. Patients should be prescribed the lowest effective NSAID dose for the shortest possible treatment duration to minimize the potential for cardiovascular adverse events.

NSAIDs may induce new onset hypertension or worsen pre-existing hypertension in some patients, which may contribute to the development of cardiovascular adverse events. Blood pressure should be routinely monitored in patients prescribed NSAIDs.

NSAIDs may cause fluid retention or edema in some patients, and should be used cautiously in patients with a history of fluid retention or heart failure.

All NSAIDs may be associated with an increased risk of serious gastrointestinal (GI) adverse events, including potentially fatal GI bleeding, ulceration, or gastric/intestinal perforation. The risk of NSAID-associated severe GI adverse events increases in patients with a history of peptic ulcer disease, GI bleeding, smoking, alcohol use, concurrent use of anticoagulants or oral corticosteroids, advanced age, poor health and prolonged NSAID use. Ketorolac has a greater incidence of gastritis, gastric ulceration with or without perforation and gastric bleeding compared to other NSAIDs and is contraindicated for use in patients with a history of or active peptic ulcer disease, GI bleeding, or perforation, and should be used cautiously in patients with other types of GI disease (e.g., inflammatory bowel disease). Additionally, total systemic use for ketorolac is limited to 5 days due to increased incidence of severe adverse events, including GI events, with prolonged use.