A review of intranasal ketorolac tromethamine for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level

Abstract

Background:

An intranasal (IN) formulation of ketorolac was recently FDA approved in adult patients for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level.

Scope:

The aim of this paper is to provide an overview of the clinical pharmacology, pharmacokinetics, efficacy, and tolerability of IN ketorolac. Databases used for this literature search include PubMed, International Pharmaceutical Abstracts, Cochrane Library and ClinicalTrials.gov from January 1980 to January 2012. All primary papers on IN ketorolac were eligible, including pharmacologic, pharmacokinetic, clinical, outcomes, and meta-analyses. The approved product labeling was a source of information, as well as the bibliographies of published articles which were reviewed for additional pertinent literature.

Findings:

The search yielded six relevant studies all of which were selected for this review and included efficacy and safety trials, one pharmacokinetics study, and one preclinical study. IN ketorolac is a non-steroidal inflammatory drug that exhibits its effect mainly by inhibiting cyclo-oxygenase (COX) 1 and 2 with high affinity for COX-1. Absorption of IN ketorolac displays a median t_max of 0.50–0.75 hours and has a t_½ of approximately 5–6 hours. Primary analyses included evaluation of morphine use and summed pain intensity difference (SPID) which was assessed using a visual analog scale. In one of the two phase III studies, the mean SPID6 score was 83.3 in the IN ketorolac group versus 37.2 in the placebo group, p = 0.007. In another phase III study, the mean SPID6 score was 117.4 in the IN ketorolac group versus 89.9 in the placebo group, p = 0.032. IN ketorolac was well-tolerated with most adverse events associated with the route of administration.

Conclusion:

Based on the clinical trials reviewed, IN ketorolac was associated with significant pain reduction in patients with various post-operative procedures, with good tolerability.

Keywords::

• Acute pain
• Intranasal analgesic
• Intranasal ketorolac
• NSAIDs

Transparency

Declaration of funding

The creation of this manuscript was requested by Luitpold Pharmaceuticals. No funding was provided to the authors for the preparation of this manuscript.

Declaration of financial/other relationships

A.H. is an employee of St. John’s University and is currently in a fellowship at American Regent, Inc. E.H. is an employee of University of Pennsylvania and receives research funding from Luitpold Pharmaceuticals.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers of this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Employees of Luitpold Pharmaceuticals, Inc. reviewed the manuscript.