KETOROLAC NASAL FORMULATION APPROVED BY FDA FOR MANAGEMENT OF SHORT-TERM PAIN

May 17, 2010 — Roxro Pharma (Menlo Park, California) today announced that the US Food and Drug Administration has approved an intranasal formulation of ketorolac tromethamine (Sprix Nasal Spray) for the short-term management of moderate to moderately severe pain requiring analgesia at the opioid level.
The formulation can be used for up to 5 days in patients outside the hospital setting. Ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), is most often given in the hospital setting as an intramuscular (IM) injection for short-term treatment of moderately severe pain, a statement from the company notes. The new formulation, given intranasally and absorbed through nasal mucosa, achieves peak blood levels as fast as an IM injection, the statement adds.
The new product "fills the need for a new non-opioid, non-injectable option for ambulatory pain control, because it minimizes the potential for abuse as well as the negative side effects associated with narcotic pain relievers while providing potent control of moderate to moderately severe pain at the opioid level," said Askomur Buvanendran, director of orthopedic anesthesia at Rush University Medical Centers in Chicago, Illinois, in the company release. "The convenient nasal spray formulation will also provide pain relief outside of the hospital setting."
The new formulation has been studied in patients with moderate to moderately severe pain, alone and in combination with morphine, the statement notes. The new drug application package included data from 14 clinical trials with more than 1000 subjects, the release notes, as well as 4 controlled efficacy studies of adults in all of which primary endpoints were met.
Two phase 3 trials, each including more than 300 patients undergoing elective abdominal or orthopedic surgery, showed a statistically significantly greater reduction in the summed pain intensity difference, an accepted measure of pain, vs placebo over 48 hours, the company statement adds. Use of the intranasal formulation was also shown to reduce morphine use by 26% to 36% over 48 hours vs placebo.
Again, the total duration of use of this intranasal formulation, as with other ketorolac formulations, should be for the shortest duration possible and not exceed 5 days, the statement notes.
Other risks and contraindications include the following:
• Ketorolac can cause peptic ulcers, gastrointestinal (GI) bleeding, and/or perforation of the stomach or intestines, which can be fatal. Intranasal ketorolac is contraindicated in patients with peptic ulcer disease or a history of GI bleeding;
• Intranasal ketorolac inhibits platelet function and is contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or a high risk of bleeding;
• NSAIDs may cause an increased risk for serious cardiovascular events, myocardial infarction, and stroke, which can be fatal, the release notes. Risk may increase with duration of use and be higher in patients with cardiovascular disease or cardiovascular risk factors. This intranasal formulation of ketorolac is contraindicated for treatment of perioperative pain from coronary artery bypass grafting surgery;
• Intranasal ketorolac is contraindicated in patients with advanced renal impairment and in those at risk for renal failure due to volume depletion; and
• In addition, the product is contraindicated in patients with known hypersensitivity or a history of allergic reactions to aspirin, ketorolac, other NSAIDs, or EDTA, in those with prior major surgery, and during labor and delivery. It also should not be used concurrently with probenecid or pentoxifylline.
Mild, transient nasal discomfort was the most frequently reported adverse effect of the intranasal formulation.
"Currently approved injectable forms of ketorolac are already well accepted by the physician community for in-hospital use, so we believe uptake of this more convenient form will be rapid," said Roberto Rosenkranz, chief executive officer of Roxro Pharma in the company statement.
The full prescribing information for the intranasal ketorolac formulation is available on the Roxro Pharma Website.