Ibuprofen (eg, Advil, Motrin) is one of the most commonly used oral analgesics in the emergency department (ED) for the treatment of mild to moderate pain as a single analgesic or in combination with acetaminophen, or severe pain in combination with opioid analgesics.1 It is a nonselective, nonsteroidal anti-inflammatory drug (NSAID) that primarily inhibits (reversibly) the activity of both cyclooxygenase-1 (constitutive) and cyclooxygenase-2 (inducible) enzymes and blocks the synthesis of prostaglandins and thromboxanes.2 Ibuprofen possesses analgesic, antipyretic, and anti-inflammatory properties and is available in oral, rectal, intravenous, and topical forms. It has been widely used in the ED for treatment of a variety of acute painful conditions such as musculoskeletal pain, dental pain, tension headache, and dysmenorrhea.1 Ibuprofen has a half-life of 2 to 2.5 hours and is extensively metabolized in the liver and eliminated through the kidneys.2 It has multiple drug-drug interactions, many of which arise from the reduction in glomerular filtration induced by blockade of cyclooxygenase or by competitive displacement of the second drug from protein-binding sites.3 Coadministration of ibuprofen with aspirin results in antagonism of the irreversible platelet inhibition induced by aspirin and loss of cardioprotective function; combination of ibuprofen with warfarin leads to worsening of gastrointestinal hemorrhage; with steroids, it leads to peptic ulcer disease; with diuretics and angiotensin-converting enzyme inhibitors, it elevates systolic blood pressure and worsens renal functions; and it increases toxicity of lithium.3, 4, 5Editor’s Capsule Summary
What is already known on this topic
Many advocate ibuprofen doses greater than 400 mg orally, assuming a greater effect.
What question this study addressed
Do ibuprofen doses of 600 or 800 mg improve analgesia relative to 400 mg in emergency department patients with a variety of pain syndromes?
What this study adds to our knowledge
In this adequately powered, randomized, double-blind trial of 225 adults, there were similar decreases in pain scores at 60 minutes with all 3 dosages.
How this is relevant to clinical practice
Ibuprofen doses greater than 400 mg orally do not appear to provide more effective analgesia.
NSAIDs are commonly prescribed at doses above their analgesic ceiling, which is a dosing threshold beyond which any further increase in a dose will not offer an incremental analgesic advantage and potentially increases the risk of harm.2, 6, 7 The data from dental and oral surgery literature support an analgesic ceiling dose of ibuprofen of 400 mg per dose with 1,200 mg/day.8, 9, 10, 11, 12, 13, 14, 15
The analgesic ceiling dose of ibuprofen based on these studies is lower than both the dosing regimen recommended in emergency medicine textbooks and the Food and Drug Administration–approved doses: 400 to 800 mg orally every 4 to 6 hours, with a maximum daily dose of 2,400 mg.15, 16 Furthermore, the rates of the adverse effects of ibuprofen as a single analgesic and NSAIDs as a class are dose and duration dependent.17, 18 A meta-analysis evaluating gastrointestinal complications of nonselective NSAIDs found that ibuprofen had the lowest odds ratio, 1.9, for development of gastrointestinal bleeding at doses of less than or equal to 1,200 mg/day. However, the odds ratios doubled to 3.9 when ibuprofen was given at doses of greater than or equal to 1,800 mg/day.18, 19 Similarly, the relative risk of cardiovascular adverse effects nearly doubles (from 1.05 to 1.78) when ibuprofen is used in doses greater than 1,200 mg/day.18 Last, according to the Oxford League Table, the number needed to treat to achieve at least 50% pain reduction from baseline to 6 hours in patients with a variety of painful conditions is similar between ibuprofen dosages of 400 and 600 mg.7
A single dose of ibuprofen of 400, 600, and even 800 mg lacks severe toxicity and does not result in serious adverse effects. Because of linear kinetic pattern, the higher dosing of ibuprofen results in a longer duration of analgesia.20, 21 The anti-inflammatory ceiling dose of ibuprofen is much higher than its analgesic ceiling dose, with a dosing range of 2,400 to 3,200 mg/day.22, 23