- Medicines and Healthcare products Regulatory Agency
- Therapeutic area:
- Pain management and palliation and Rheumatology
Prescribing advice should be followed carefully, particularly recommended upper dose limits due to associated higher gastrointestinal risk than most other NSAIDs in the class.
Article date: October 2007
Although epidemiological studies have suggested that piroxicam is associated with a higher gastrointestinal risk than most non-steroidal anti-inflammatory drugs (NSAIDs), these studies have also raised concern about the relative gastrointestinal safety of ketorolac 1 2 3 4 5 6 7 8 and ketoprofen. 9 10 Prescribers are reminded of the following restrictions:
- Ketorolac: treatment should be initiated only in hospital. Maximum duration of treatment should not exceed 7 days for tablets, or 2 days for continuous daily dosing with intravenous or intramuscular formulations
- Ketoprofen: recommended maximum daily dose range is 100–200 mg in divided doses. The balance of risks and benefits should be considered carefully before commencing treatment with 200 mg daily
Ketoprofen and ketorolac are contraindicated in patients with active peptic ulcer, or with any history of gastrointestinal bleeding, ulceration, or perforation.
General advice on gastrointestinal safety for all NSAIDs
- Use the lowest dose and shortest duration of treatment necessary to control symptoms
- Avoid use with other concomitant NSAIDs (including COX-2 selective inhibitors)
- Consider combination therapy with protective agents (eg, misoprostol or a proton pump inhibitor) for high-risk patients (eg, elderly people and patients who need concomitant low-dose aspirin)
- Patients with a history of any gastrointestinal toxicity, particularly those who are elderly, should report any unusual abdominal symptoms, particularly in the initial stages of treatment. If gastrointestinal bleeding or ulceration occurs, withdraw treatment immediately
- Give NSAIDs with care to patients who have a history of gastrointestinal disease (eg, ulcerative colitis, Crohn’s disease) because these conditions may be exacerbated
Interactions and gastrointestinal risk
Corticosteroids, antiplatelet agents, and selective serotonin reuptake inhibitors (SSRIs) may increase the risk of gastrointestinal ulceration or bleeding. NSAIDs may enhance the effects of anticoagulants, such as warfarin.
See also Information about dosing of ketorolac in The electronic Medicines Compendium (eMC)
Article citation: Drug Safety Update October 2007; Vol 1, Issue 3: 3.
Traversa G, et al. Epidemiology 1995; 6: 49–54 ↩
Strom B, et al. JAMA 1996; 275: 376–82 ↩
Garcia-Rodriguez LA, et al. Arch Intern Med 1998: 158: 33–39 ↩
Menniti-Ippolito F, et al. Eur J Clin Pharmacol 1998; 54: 393–97 ↩
Laporte JR, et al. Drug Saf 2004; 27: 411–20 ↩
Lanas A, et al. Eur J Gastroenterol Hepatol 2003; 15: 173–78 ↩
Gallerani M, et al. J Clin Epidemiol 2004; 57: 103–10 ↩
Llorente-Melero MJ, et al. Rev Esp Enferm Dig 2002; 94: 7–12 ↩
Henry D, et al. Int J Clin Pract 2003; 135 (Suppl): 43–49 ↩
Lanas A, et al. Gut 2006; 55: 1731–38 ↩