NSAIDs, celecoxib, ketorolac and acetaminophen

NSAIDs and acetaminophen are the backbone of multimodal analgesia. Exam questions turn on safety: renal "triple whammy," aspirin interference, ketorolac dose limits, pregnancy cutoffs, Beers listings and total acetaminophen dose.

1. Nonopioids first for many acute pains. After dental extraction, ADA 2024 suggests (conditional recommendation) nonopioid analgesics as first-line: an NSAID alone or combined with acetaminophen, with acetaminophen alone when NSAIDs are contraindicated and opioids reserved for rare inadequate responses ¹.
2. NSAIDs can precipitate acute kidney injury. Blocking prostaglandin-mediated afferent dilation, combined with an ACE inhibitor or ARB and a diuretic, raised acute kidney injury risk, most in the first 30 days (rate ratio 1.82) ².
3. Ketorolac has strict labeled limits. Reduce the dose for age 65 or over, weight under 50 kg, or renal impairment (15 mg every 6 hours, maximum 60 mg/day), and limit total use to 5 days ³. Beers lists ketorolac and indomethacin to avoid in older adults ⁴.
4. Celecoxib contraindications are classic. Prior asthma, urticaria or allergic-type reactions to aspirin or NSAIDs, sulfonamide hypersensitivity, and the CABG setting contraindicate it; CYP2C9 poor metabolizers get a 50% dose reduction, not avoidance ⁵.
5. Ibuprofen can blunt aspirin cardioprotection. Ibuprofen interferes with low-dose aspirin's antiplatelet effect; spacing helps only immediate-release aspirin, not the enteric-coated form ⁶.
6. Acetaminophen: count every source. Most liver injury occurs above 4,000 mg/day and often involves several products, so the prescription tablet, cold remedies and sleep aids all count. The dose-limiting toxicity is hepatic, not renal ⁷.

From 20 weeks of pregnancy, the FDA advises avoiding NSAIDs because of fetal kidney dysfunction and oligohydramnios; low-dose aspirin for obstetric indications is the exception ⁸.

• Triple whammy: NSAID plus RAS inhibitor plus diuretic, especially early in combined use ².
• Ketorolac reduced regimen: 15 mg every 6 hours, 60 mg/day maximum, 5 days total ³.
• Beers: avoid ketorolac and indomethacin; avoid chronic use of other nonselective NSAIDs unless alternatives fail and a gastroprotective agent is used ⁴.
• Aspirin-exacerbated reactions contraindicate celecoxib as well as nonselective NSAIDs ⁵.
• After extraction, NSAIDs alone or with acetaminophen relieved pain better than opioids, which add dizziness, drowsiness, nausea and misuse risk ¹.
• If an NSAID is unavoidable between 20 and 30 weeks, use the lowest dose for the shortest time and consider amniotic fluid monitoring beyond 48 hours ⁸.

• Treating CYP2C9 poor-metabolizer status as a celecoxib contraindication; the label reduces the dose ⁵.
• Counting only the prescription tablet toward the acetaminophen limit ⁷.
• Spacing ibuprofen and enteric-coated aspirin and assuming the interaction is solved ⁶.