Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate.

These results may explain the increased potency of the MTX-HCQ combination over MTX as a single agent and also the sustained effects of MTX when administered with HCQ. In addition, the reduced Cmax of MTX observed during the coadministration may explain diminution of acute liver adverse effects. Extra vigilance for MTX adverse effects during combination therapy with HCQ is recommended, especially if renal function is known to be decreased.