| Optional initial loading dose | | | Selected characteristics and role in therapy |
Para-aminophenol derivative |
Acetaminophen* (paracetamol, APAP) | | 325 to 650 mg every 4 to 6 hours 1000 mg every 6 hours up to three times per day | | Effective for noninflammatory pain; may be opioid-sparing. Doses <2000 mg per day do not increase risk of serious GI complications. Does not alter platelet functioning. Can cause hepatotoxicity in chronic or acute overdose. Avoid or use a lower total daily dose (maximum 2000 mg per day) in older adults, patients at risk for hepatotoxicity (eg, regular alcohol use, malnourished) or with organ dysfunction. For short-term or one-time use, may use a total dose of up to 4000 mg per day in selected medically supervised patients. Interacts with warfarin (prolongs INR), isoniazid, and CYP450-inducing drugs¶ (transaminitis). Warn patients about acetaminophen content in combination prescription (eg, oxycodone-acetaminophen) and OTC preparations. |
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Applies to all nonselective NSAIDs: Effective for treatment of acute and chronic painful and inflammatory conditions. May decrease opioid requirements. Short-to-moderate-acting NSAIDs (eg, naproxen, ibuprofen) are preferred for most patients. Dose- and age-related risk of gastropathy. May cause or worsen renal impairment. Nonselective NSAIDs reversibly inhibit platelet functioning and can alter cardioprotective effects of aspirin. Avoid NSAIDs in patients with renal insufficiency (CrCl <60 mL/minute), GI bleeding, platelet dysfunction, reduced cardiac output, difficult-to-control hypertension, hypovolemia, hyponatremia, aspirin-sensitive asthma, or cirrhosis. Safety concerns of NSAID use in patients with, or at elevated risk for, cardiovascular disease or thrombotic events are addressed in a separate topic in UpToDate. Use with caution or avoid in patients receiving comedication with anticoagulants, systemic glucocorticoids, lithium, loop diuretics, and other interacting drugs.Δ Though some older adults may benefit from a brief course of NSAIDs at the lowest effective dose, use in most older adults should be avoided. Refer to the UpToDate topics on treatment of pain in older adults and older adults with organ dysfunction. |
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| | 325 to 650 mg every 4 to 6 hours | | Standard for comparison, but now used infrequently for treatment of chronic pain and inflammation. Unlike other NSAIDs, irreversibly inhibits platelet functioning for life of the platelet (7 to 10 days). |
Salicylates (nonacetylated) |
| | 500 mg every 8 to 12 hours | | Applies to all nonacetylated salicylates: No significant effect on platelet function at usual analgesic doses. Less frequently associated with GI bleeding than nonselective NSAIDs at usual analgesic doses. Generally tolerated by adults with asthma at lower daily doses: Diflunisal ≤1000 mg, choline magnesium trisalicylate and salsalate ≤2000 mg. 500 mg dose of diflunisal has a comparable analgesic effect with 650 mg acetaminophen or aspirin. |
Choline magnesium trisalicylate | | 750 mg every 8 to 12 hours | |
| | 750 to 1000 mg every 8 to 12 hours | |
Propionic acids (phenyl-propionic acid) |
| | 250 to 500 mg every 12 hours (naproxen base) 275 to 550 mg every 12 hours (naproxen sodium) | 1250 mg acute, 1000 mg chronic (naproxen base) 1375 mg acute, 1100 mg chronic (naproxen sodium) | A good choice for treatment of acute or chronic pain and inflammation in most patients if NSAID therapy is indicated. High doses (eg, 500 mg twice daily) may have less cardiovascular toxicity than comparable doses of other NSAIDs.◊ For the treatment of rheumatologic disorders, total daily dose may be increased to a maximum of 1500 mg base (1650 mg naproxen sodium), when needed. Naproxen sodium has more rapid absorption and onset of effect than naproxen base. |
| | 400 mg every 4 to 6 hours | 3200 mg (acute), 2400 mg (chronic) | 200 to 400 mg dose has a comparable analgesic effect with 650 mg acetaminophen or aspirin. Short duration of effect. Useful alternative to naproxen in patients without cardiovascular risks. |
| | 50 mg every 6 hours or 75 mg every 8 hours | | 25 mg dose has a comparable analgesic effect to 400 mg ibuprofen. Short duration of effect. |
| | 50 to 100 mg every 6 to 12 hours | | Lozenge preparation available in some countries. |
| | | 26 mg/kg up to 1800 mg (whichever is lower) | |
Acetic acids (pyrano-indoleacetic acid) |
| 75 or 100 mg (conventional tablets) | | Approved maximum daily dose in Canada is 100 mg | Diclofenac is also available as a topical patch, solution, and gel for treatment of musculoskeletal pain and osteoarthritis of superficial joints, which may be useful in combination with or as an alternative to systemic NSAIDs. Refer to the UpToDate topic on initial treatment of osteoarthritis and separate table. Interacts with drugs that are strong inhibitors or inducers of CYP2C9 drug metabolism; use Lexi-Interact to determine specific interactions. |
| | Immediate release: 200 to 400 mg every 6 to 8 hours Extended release: 400 to 1000 mg once daily | Immediate release: 1000 mg Extended release: 1200 mg | Relatively COX-2 selective at lower total daily dose of 600 to 800 mg. 200 mg dose has a comparable analgesic effect with 400 mg of ibuprofen. |
| | Immediate release: 25 to 50 mg every 8 to 12 hours Controlled release: 75 mg once or twice daily | | Useful for treatment of acute gout and specific types of headache. Potent inhibitory effects on renal prostaglandin synthesis. More frequently associated with CNS side effects (eg, headache) compared with other NSAIDs. Carefully select and monitor patients to reduce risk of renal and cardiovascular toxicities. |
| | 400 to 600 mg every 8 hours | | |
| | 150 to 200 mg every 12 hours | | More frequently associated with hepatic inflammation (idiosyncratic or with features of hypersensitivity) compared with other NSAIDs. Sulindac metabolites implicated in the formation of renal calculi; refer to the UpToDate topic on nonselective NSAID adverse effects. Prescribing should be limited to specialists with experience in treatment of chronic pain and inflammation. |
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| 7.5 mg (conventional tablets) | | | Long duration of effect; slow onset. Relatively COX-2 selective and minimal effect on platelet function at lower total daily dose of 7.5 mg. Rarely associated with serious cutaneous allergic reactions, including Stevens-Johnson syndrome. |
| | | | A long-acting option for treatment of chronic pain and inflammation poorly responsive to other NSAIDs. Daily doses ≥20 mg increase risk of serious GI complications. Concurrent pharmacologic gastroprotection is suggested. Rarely associated with serious cutaneous allergic reactions, including Stevens-Johnson syndrome. Prescribing should be limited to specialists with experience in treatment of chronic pain and inflammation. |
Fenamates (anthranilic acids) |
Meclofenamate (meclofenamic acid) | | | | Alternate NSAID choice for treatment of acute or chronic pain, inflammation, and dysmenorrhea. Appears to be associated with higher incidence of GI disturbance (including diarrhea) compared with other nonselective NSAIDs. |
| | | | Alternate NSAID choice for treatment of acute pain and dysmenorrhea. Duration of use not to exceed seven days (acute pain) or three days (dysmenorrhea). Anti-inflammatory efficacy is comparatively low. Not indicated for treatment of chronic pain or inflammation. |
Nonacidic (naphthylalkanone) |
| | 500 to 750 mg every 8 to 12 hours or 1000 to 1500 mg once daily | | Moderate duration of effect; slow onset. Relatively COX-2 selective at lower total daily dose of 1000 mg or less. Minimal effect on platelet function at total daily dose of 1000 mg or less. |
Selective COX-2 inhibitors§ |
| | 200 mg daily or 100 mg every 12 hours | | Relative reduction in GI toxicity compared with nonselective NSAIDs. No effect on platelet function. Cardiovascular and renal risks are dose-related and appear similar to those of nonselective NSAIDs. Patients with indications for cardioprotection require aspirin supplement; individuals may require concurrent gastroprotection. |
Etoricoxib (not available in the United States) | | | 60 mg (chronic pain and inflammation) 120 mg (acute pain for up to eight days) | May be associated with more frequent and severe dose-related cardiovascular effects (eg, hypertension) compared with nonselective and other COX-2 selective NSAIDs. Otherwise, risks and benefits as with celecoxib (see above). |
