Diacerein (DB11994): A Comprehensive Pharmacological and Clinical Monograph

1.0 Executive Summary

Diacerein is a small molecule drug of the anthraquinone class, developed as a symptomatic slow-acting drug for osteoarthritis (SYSADOA).[1] Its therapeutic activity is mediated by its active metabolite, rhein, which exerts a unique mechanism of action centered on the inhibition of the pro-inflammatory interleukin-1β (IL-1β) pathway. This mode of action distinguishes it from traditional non-steroidal anti-inflammatory drugs (NSAIDs), as it does not involve the inhibition of prostaglandin synthesis.[3] In its approved indication for osteoarthritis of the hip and knee, clinical evidence demonstrates a modest but statistically significant effect on pain reduction, characterized by a slow onset of action and a notable "carryover effect" where benefits persist after treatment cessation.[1]

However, the clinical utility of oral Diacerein is significantly limited by a challenging safety and tolerability profile. The most prominent adverse event is frequent, often severe, diarrhea, a direct consequence of its anthraquinone structure and pharmacokinetic properties.[1] Furthermore, post-marketing surveillance has revealed a risk of rare but serious hepatotoxicity.[6] These safety concerns have led to significant regulatory restrictions, including recommendations from the European Medicines Agency (EMA) against its use in patients over 65 and in those with liver disease.[3] The drug is not approved by the U.S. Food and Drug Administration (FDA) for osteoarthritis.[7]