Drug Interactions with Paracetamol

Abstract

Paracetamol (acetaminophen) is one of the most commonly used analgesic antipyretic drugs worldwide, and it is widely available by prescription and over the counter (OTC). Fortunately, few clinically significant drug interactions have been documented. There is probable potentiation of hepatotoxicity following an overdose from the paracetamol metabolite NAPQI by enzyme-inducing drugs. There is considerable controversy regarding the possible interaction with warfarin in its potential to increase its anticoagulant effects because of discrepancies between observational studies and those in healthy volunteers. Otherwise, no serious adverse drug interactions with therapeutic doses of paracetamol have been confirmed in humans. Because the absorption of paracetamol is so dependent on gastric emptying, other drugs that alter gastric emptying can change its pharmacokinetics; but this would not cause serious adverse effects. Although animal experiments have demonstrated that many compounds can modify paracetamol hepatotoxicity, these are unlikely to be important at therapeutic doses.

Postoperative Pain and Other Acute Pain Syndromes

“…[67][68][69] Acetaminophen has only limited potential for drug interactions that is independent of the route of administration. 70 In a qualitative systematic review of analgesic efficacy in relieving acute postoperative pain that assessed reductions in pain intensity scores and opioid consumption, 71 the combination of acetaminophen and NSAIDs was more effective than acetaminophen alone in 85% of relevant studies and more effective than NSAIDs alone in 64% of relevant studies. Several meta-analyses suggest that the use of NSAIDs, COX-2 inhibitors, or acetaminophen in combination with IV PCA does result in an opioid-sparing effect.…”

Polypharmacy and pain treatment

“…Durch eine Induktion der hepatischen Metabolisierung wird die Clearance für Paracetamol erhöht. Die gleichzeitige Anwendung beider Substanzen führte in Einzelfällen zu einer erhöhten Hepatotoxizität, insbesondere bei einer chronischen Einnahme [41,42].…”

Peri‐operative use of paracetamol

“…Very few clinically significant drug interactions with paracetamol have been documented [55]. Although case reports exist of hepatotoxicity following co-administration of paracetamol with drugs that induce the cytochrome P450 system (e.g.…”