From the FDA Drug Label
The most serious risks associated with ketorolac tromethamine are: Gastrointestinal Effects – Risk of Ulceration, Bleeding and Perforation: Ketorolac tromethamine is contraindicated in patients with previously documented peptic ulcers and/or gastrointestinal (GI) bleeding Ketorolac tromethamine can cause serious GI adverse events including bleeding, ulceration and perforation, of the stomach, small intestine, or large intestine, which can be fatal. NSAIDs, including diclofenac, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal.
The relationship between intravenous (IV) or intramuscular (IM) Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and gastrointestinal (gastric) issues is that NSAIDs can cause serious GI adverse events, including:
- Bleeding
- Ulceration
- Perforation of the stomach, small intestine, or large intestine, which can be fatal 1, 2. Risk factors for GI bleeding, ulceration, and perforation include:
- Prior history of peptic ulcer disease and/or GI bleeding
- Longer duration of NSAID therapy
- Concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs)
- Smoking
- Use of alcohol
- Older age
- Poor general health status To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration 1, 2.
From the Research
Intravenous (IV) and intramuscular (IM) NSAIDs pose a significant risk of systemic gastric complications, despite bypassing direct gastric irritation, and therefore require careful consideration of prophylactic gastric protection, especially in high-risk patients. When administering parenteral NSAIDs like ketorolac (typical dose 15-30mg IV/IM every 6 hours, maximum 5 days), consider prophylactic gastric protection with a proton pump inhibitor such as pantoprazole 40mg daily or omeprazole 20mg daily, especially for high-risk patients (elderly, history of peptic ulcer disease, concurrent steroid or anticoagulant use) 3. The risk of upper GI complications can occur even with short-term NSAID use, and the rate of events is linear over time with continued use 3.
Key Considerations
- The systemic effect of NSAIDs explains why parenteral NSAIDs can still cause gastric ulceration, bleeding, and perforation despite avoiding direct gastric contact 3.
- For patients requiring longer NSAID therapy, transition to oral COX-2 selective agents like celecoxib (100-200mg twice daily) may offer better gastric safety profiles while maintaining analgesic efficacy 4.
- Always use the lowest effective dose for the shortest duration possible to minimize gastrointestinal risks 4.
- Risk factors for NSAID-related peptic ulcer include a previous history of peptic ulcer, advanced age, high dose, concomitant use of corticosteroids, anticoagulants, other NSAIDs including low-dose aspirin 5.
Prevention and Treatment
- Preventive measures, such as COX-2 inhibitor, proton pump inhibitor or misoprostol, should be done for patients requiring NSAID therapy who have high-risk factors for peptic ulcer 5.
- The eradication of Helicobacter pylori is recommended for high-risk NSAID-users 5.
- Treatment strategies for peptic ulcers in NSAID users are mostly the same for peptic ulcers in NSAID non-users 5.