Hydroxychloroquine Drug Classification
Hydroxychloroquine is an antimalarial agent and disease-modifying antirheumatic drug (DMARD), specifically classified as a conventional synthetic DMARD (csDMARD) when used for rheumatologic conditions. 1
Primary Drug Classes
Antimalarial agent: Hydroxychloroquine is a 4-aminoquinoline compound originally developed and FDA-approved for malaria prophylaxis and treatment, having been used for nearly 80 years in this capacity 1, 2
Disease-modifying antirheumatic drug (DMARD): When used in rheumatology, hydroxychloroquine functions as a conventional synthetic DMARD (csDMARD), distinct from biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) 3, 4
Immunomodulatory/immunosuppressive agent: The drug possesses immunosuppressive activity that reduces T-cell and B-cell hyperactivity and pro-inflammatory cytokine gene expression 5, 6
Mechanism of Action
Hydroxychloroquine accumulates in intracellular vesicles (endosomes and lysosomes) where it becomes protonated, leading to increased vesicular pH 1
This pH elevation inhibits pH-dependent proteases involved in processing secretory proteins, including tumor necrosis factor-α and interleukin-6, thereby modulating immune cell behavior and attenuating inflammatory processes 1, 4
The drug acts as an alkalizing agent, ionized amphiphilic molecule, and binds to numerous cellular targets, providing pleiotropic effects on multiple physiological functions 7
FDA-Approved Indications
Malaria: Treatment and prophylaxis of malaria caused by chloroquine-sensitive Plasmodium species 2
Rheumatoid arthritis: Treatment as a conventional synthetic DMARD 3, 2
Systemic lupus erythematosus: Disease modification and symptom control 2, 5
Chronic discoid lupus erythematosus: Skin manifestation management 2
Clinical Context and Positioning
In rheumatology, hydroxychloroquine is classified alongside other csDMARDs such as methotrexate, sulfasalazine, leflunomide, and azathioprine, but has weaker clinical efficacy and no structural efficacy in preventing joint damage compared to methotrexate 3, 4
Current guidelines position hydroxychloroquine as having limited place in rheumatoid arthritis treatment, mainly reserved for patients with mild disease activity or as part of combination therapy (particularly triple therapy with methotrexate and sulfasalazine) 3, 4
The drug is not recommended as first-line monotherapy for moderate-to-high disease activity rheumatoid arthritis, where methotrexate is strongly preferred 3, 4