Combination vs. single-drug nonprescription analgesics for acute pain management: A narrative review

Combining nonprescription analgesics with different mechanisms of action has been proposed as a rational strategy to optimize the management of acute pain. This review assessed the efficacy and safety of nonprescription analgesics, including paracetamol (acetaminophen), metamizole and nonsteroidal anti-inflammatory drugs (NSAIDs) used in combination vs. monotherapy in acute pain conditions. A literature search identified 25 studies that compared oral paracetamol combined with a nonprescription NSAID (oral or topical) vs. either or both components alone in an acute pain condition or in an acute episode or exacerbation of a chronic pain condition. Combination therapy provided superior pain relief vs. monotherapy in the dental impaction pain model; potential dose-sparing and opioid-sparing effects were also evident. After endodontic surgery, combination therapy provided greater pain relief vs. either component alone following a single dose, but a difference was not apparent with multiple dosing, indicating a faster onset of action with combination therapy. Studies in acute musculoskeletal pain yielded mixed results. Studies in patients with headache included caffeine in addition to paracetamol/NSAIDs and showed that this combination provided faster and more effective pain relief vs. paracetamol or an NSAID alone. Across all settings, oral combination therapy with paracetamol/NSAIDs was well tolerated, with adverse event rates similar to or even lower than those observed with monotherapy. Findings of this narrative review support the use of combination therapy with paracetamol and an NSAID in the postsurgical setting but not in acute non-low-back musculoskeletal pain. Fixed-dose oral combinations of caffeine/paracetamol/NSAIDs provide efficacy-related advantages over paracetamol or NSAID monotherapy.