KETOROLAC - A REAPPRAISAL OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND THERAPEUTIC USE IN PAIN MANAGEMENT

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with strong analgesic activity. The analgesic efficacy of ketorolac has been exte nsively evaluated in the postoperative setting, in both hospital inpat ients and outpatients, and in patients with various other acute pain s tates. After major abdominal, orthopaedic or gynaecological surgery or ambulatory laparoscopic or gynaecological procedures, ketorolac provi des relief from mild to severe pain in the majority of patients and ha s similar analgesic efficacy to that of standard dosages of morphine a nd pethidine (meperidine) as well as less frequently used opioids and other NSAIDs. The analgesic effect of ketorolac may be slightly delaye d but often persists for longer than that of opioids. Combined therapy with ketorolac and an opioid results in a 25 to 50% reduction in opio id requirements, and in some patients this is accompanied by a concomi tant decrease in opioid-induced adverse events, more rapid return to n ormal gastrointestinal function and shorter stay in hospital. In child ren undergoing myringotomy, hernia repair, tonsillectomy, or other sur gery associated with mild to moderate pain, ketorolac provides compara ble analgesia to morphine, pethidine or paracetamol (acetaminophen). I n the emergency department, ketorolac attenuates moderate to severe pa in in patients with renal colic, migraine headache, musculoskeletal pa in or sickle cell crisis and is usually as effective as frequently use d opioids, such as morphine and pethidine, and other NSAIDS and analge sics. Subcutaneous administration of ketorolac reduces pain in patient s with cancer and seems particularly beneficial to pain resulting from bone metastases. The acquisition cost of ketorolac is greater than th at of morphine or pethidine; however, in a small number of studies, th e higher cost of ketorolac was offset when treatment with ketorolac re sulted in a reduced hospital stay compared with alternative opioid the rapy. The tolerability profile of ketorolac parallels that of other NS AIDS; most clinically important adverse events affect the gastrointest inal tract and/or renal or haematological function. The incidence of s erious or fatal adverse events reported with ketorolac has decreased s ince revision of dosage guidelines. Results from a large retrospective postmarketing surveillance study in more than 20 000 patients demonst rated that the overall risk of gastrointestinal or operative site blee ding related to parenteral ketorolac therapy was only slightly higher than with opioids. However, the risk increased markedly when high dosa ges were used for more than 5 days, especially in the elderly. Acute r enal failure may occur after treatment with ketorolac but is usually r eversible on drug discontinuation. In common with other NSAIDs, ketoro lac has also been implicated in allergic or hypersensitivity reactions . In summary, ketorolac is a strong analgesic with a tolerability prof ile which resembles that of other NSAIDs. When used in accordance with current dosage guidelines, this drug provides a useful alternative, o r adjuvant, to opioids in patients with moderate to severe pain.