Mechanism of Action of Hydroxychloroquine as an Antirheumatic Drug

Mechanism of Action of Hydroxychloroquine as an Antirheumatic Drug

Abstract

The antimalarial agents chloroquine and hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus. These compounds lead to improvement of clinical and laboratory parameters, but their slow onset of action distinguishes them from glucocorticoids and nonsteroidal antiinflammatory agents. Chloroquine and hydroxychloroquine increase pH within intracellular vacuoles and alter processes such as protein degradation by acidic hydrolases in the lysosome, assembly of macromolecules in the endosomes, and posttranslation modification of proteins in the Golgi apparatus. It is proposed that the antirheumatic properties of these compounds results from their interference with "antigen processing" in macrophages and other antigen-presenting cells. Acidic cytoplasmic compartments are required for the antigenic protein to be digested and for the peptides to assemble with the alpha and beta chains of MHC class II proteins. As a result, antimalarials diminish the formation of peptide-MHC protein complexes required to stimulate CD4+ T cells and result in down-regulation of the immune response against autoantigenic peptides. Because this mechanism differs from other antirheumatic drugs, antimalarials are well suited to complement these other compounds in combination drug therapy.

How to act on malaria

Dosage Forms & Strengths

tablet

• 200mg

Malaria

Prophylaxis

• Indicated for prophylaxis of malaria in geographic areas where chloroquine resistance is not reported
• 400 mg (310 mg base) PO weekly, starting 2 weeks before exposure and continued for 4 weeks after departure from endemic area OR
• Weight-based dosing: 6.5 mg/kg (5 mg/kg base) PO once weekly, not to exceed 400 mg (310 mg base), starting 2 weeks before exposure and continued for 4 weeks after leaving the endemic area  

Acute treatment

• Indicated for treatment of uncomplicated malaria due to P falciparum, P malariae, P ovale, and P vivax
• 800 mg (620 mg base) PO, then 400 mg (310 mg base) PO at 6 hr, 24 hr, and 48 hr after initial dose
• Weight-based dosing: 13 mg/kg (10 mg/kg base), not to exceed 800 mg (620 mg base) followed by 6.5 mg/kg (5 mg/kg base), not to exceed 400 mg (310 mg base), PO at 6 hr, 24 hr, and 48 hr after initial dose  

Rheumatoid Arthritis

Indicated for treatment of acute and chronic rheumatoid arthritis

400-600 mg/day (310-465 mg base/day) PO as a qDay or in BID

When a good response is obtained, reduce dosage by 50% and continue maintenance dose of 200-400 mg/day (155-310 mg base/day) PO as a qDay or in BID; not exceed 600 mg or 6.5 mg/kg (5 mg/kg base) per day, whichever is lower, as the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded

Use corticosteroids and salicylates in conjunction with hydroxychloroquine; gradually decrease dosage or eliminate after a maintenance dose has been achieved

Systemic Lupus Erythematosus

Indicated for treatment of chronic discoid lupus erythematosus and systemic lupus erythematosus

200-400 mg/day (155-310 mg base/day) PO as a single daily dose or in two divided doses

Doses >400 mg/day are not recommended

Incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded

Coronavirus Disease 2019 (COVID-19) (Off-label)

Data available as of March 24, 2020

Note: Limited data available; no drug is FDA approved to treat COVID-19

Hydroxychloroquine may be considered for use as part of an investigational protocol for patients with COVID-19
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