An In-Depth Pharmacological and Clinical Review of Alitretinoin (9-cis-Retinoic Acid)

Executive Summary

Alitretinoin, also known as 9-cis-retinoic acid, is an endogenous, first-generation retinoid and a structural derivative of vitamin A.[1] Classified as a small molecule antineoplastic and dermatological agent, it possesses a unique pharmacological profile that distinguishes it from other retinoids.[2] The core of its activity lies in its function as a pan-agonist, capable of binding to and activating all known intracellular retinoic acid receptor (RAR) and retinoid X receptor (RXR) subtypes.[1] This broad receptor engagement underpins its efficacy in two distinct, formulation-dependent therapeutic areas. As a 0.1% topical gel, marketed under the brand name Panretin®, it is indicated for the treatment of localized, cutaneous lesions associated with AIDS-related Kaposi's sarcoma (KS).[5] In its oral capsule form, primarily known as Toctino®, it is approved for the management of severe chronic hand eczema (CHE) that is refractory to potent topical corticosteroids.[8]

The clinical application of alitretinoin, particularly its systemic formulation, is governed by its most significant safety concern: high teratogenicity. This risk necessitates the implementation of stringent risk management protocols, most notably the comprehensive Pregnancy Prevention Programme (PPP), which is a mandatory condition for its prescription to women of childbearing potential.[8] Alitretinoin thus represents a valuable therapeutic option for specific and often debilitating dermatological conditions, but its use demands a careful and systematic assessment of its benefits against its considerable risk profile.

Chemical Identity and Physicochemical Properties