Recommend: ACETAMINOPHEN + NSAID
KEY POINTS:
- Use acetaminophen AND non-steroidal medications TOGETHER around the clock for the first 3-5 days, unless contraindicated
- Use either medication or the combination as needed for pain for the days to follow
ACETAMINOPHEN SAFETY AND SIDE EFFECTS:
| Drug | Usual Dose | Max Daily Dose | Relative COX selectivity |
| Acetaminophen | 1000 mg three to four times a day | 4000 | COX-1 COX-2
– –
|
- Caution should be observed in patients with liver disease, active alcohol use, and G6PD deficiency
- Consider all sources of acetaminophen including combination products and OTC cough/cold products when recommending acetaminophen
- Acetaminophen overdose may occur with 5-6 grams daily for prolonged use (6-8+ weeks) or acute ingestion of at least 7.5 grams
NON-STEROIDAL ANTI-INFLAMMATORY SAFETY AND SIDE EFFECTS
| Drug | Usual Dose | Max Daily Dose (mg) | Relative COX Selectivity | |
|---|---|---|---|---|
| COX-1 | COX-2 | |||
| Ibuprofen | 400-800 mg three to four times per day | 3200 | ++ | |
| Naproxen | 200-400 mg two or three times per day | 1375-1500 | ++ | |
| Ketorolac | 10 mg four times per day | 40 | +++ | |
| Diclofenac | 35-50 mg two to three times per day | 200 | ++ | |
| Meloxicam | 15 mg daily | 15 | +++ | |
| Celecoxib | 100-200mg two times per day | 400 | +++ | |
- Caution should be observed in patients with a history of cardiovascular, gastrointestinal, and kidney disease.
- Cardiovascular: avoid use in patients with heart failure. Coronary, vascular, and death are risks associated with long term use. Out of hospital cardiac arrest is associated with short term use.
- Gastrointestinal: Risk is low (<2%) but present in long term use and those at risk. Risk may be mitigated with the use of concomitant proton pump inhibitor (PPI, e.g. over the counter omeprazole) during treatment course
- Increased risk of gastrointestinal complications (all NSAIDs), which remains constant over time
- Caution in those over 60 years of age, history of peptic ulcers, gastrointestinal bleeds, and Helicobacter pylori infections
- Increased risk of gastrointestinal complications (all NSAIDs), which remains constant over time
- Kidney: acute kidney injury is mostly present in those with other risk factors, including older age. Use with caution in those with chronic kidney disease
- Bleeding: anti-platelet effect is due to COX-1 inhibition, but NSAIDs block COX in a reversible fashion. Normal platelet function returns within 1-3 days depending on the drug (e.g. 1 day for ibuprofen, 2 days for naproxen, diclofenac, and 3 days for piroxicam)
SURGICAL SPECIFIC HIGHLIGHTS
- Pre-operative interruption of chronic NSAIDs may be warranted, but should be patient, procedure, and drug specific
- There appears to be no increased risk of post-operative bleeding with celecoxib or ibuprofen
- Post-operative bleeding may occur with ketorolac, although studies provide conflicting data
- Enhanced Recovery After Surgery (ERAS) protocols commonly include peri-operative use of NSAIDs including just prior to surgery, day 0 and for the several post-operative days without an increased risk of complications
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