Section 14. Pain Management

Nonselective NSAIDs (COX-1 and 2 inhibitors)

Aspirin

325–1,000 mg PO Q 4–6 h

• Though data are limited, it appears other NSAIDs may interfere with the antiplatelet effects of aspirin (J Clin Pharm. 2008;48:117; J Am Coll Cardiol. 2004;43:985.); administer NSAIDs 2 h after aspirin
• IV ketorolac should be limited to 5 days of therapy due to risk of AKI (Ann Int Med. 1997;126:193)
• NSAIDs are one of the most commonly implicated drugs leading to hospitalization due to an adverse effect (Br J Clin Pharmacol. 2007;63:136), see Table 14.1.2
• In patients requiring an NSAID: consider naproxen if high CV risk, consider a COX-2 inhibitor if high GI risk; consider adding a PPI to naproxen if high CV and GI risk (Aliment Pharmacol Ther. 2009;29:481)

Diclofenac

50 mg PO Q 8 h

Etodolac

200–400 mg PO Q 6–8 h

Fenoprofen

200 mg PO Q 4–6 h

Ibuprofen

200–400 mg PO Q 4–6 h

Ketoprofen

25–50 mg PO Q 6–8 h

Ketorolac

15–30 mg IV Q 6 h

Naproxen

250 mg PO Q 6–8 h, or

500 mg PO Q 12 h

Selective NSAIDs (COX-2 inhibitors)

Celecoxib

200 mg PO Q 12 h

• Meloxicam and nabumetone lose COX-2 selectivity at higher doses; more GI bleeds observed with 15 mg vs. 7.5 mg meloxicam (Am J Med. 2004;117:100)
• Cross-sensitivity to celecoxib in sulfonamide allergic patients appears low (Drug Safety. 2003;26:187)

Meloxicam

7.5–15 mg PO QD

Nabumetone

1,000–2,000 mg PO QD

Other

Acetaminophen

325–1,000 mg PO Q 4–6 h

• Historically, the maximum daily dose of acetaminophen has been 4 g/day (2 g in liver disease); in 2011 the FDA suggested lowering this limit to 2.6 g/day and to avoid acetaminophen in patients with liver disease over concerns for increasing incidence of overdose

Cardiovascular

• Heart failure exacerbation
• Increased risk of MI in patients with CAD
• Hypertension

• ACC/AHA recommends avoiding NSAIDs when possible in patients with heart failure (Circulation. 2009;119(14):e391) or post-MI (J Am Coll Cardiol. 2007;50:e1)
• Naproxen appears to have lower risk of MI (Aliment Pharmacol Ther. 2009;29:481)
• Increased hospitalizations for heart failure associated with NSAIDs (Arch Intern Med. 2009;169:141) likely secondary to fluid retention and systemic vasoconstriction
• Short- and long-term NSAIDs are associated with slight increased risk of MI and death in patients with a history of MI (Circulation. ...