Hydroxychloroquine Increases Efficacy and Potential Toxicity of Methotrexate

November 29, 2002

NEW YORK (Reuters Health) Nov 28 - The addition of hydroxychloroquine (HCQ)

to methotrexate (MTX) therapy for rheumatoid arthritis increases a patient's

exposure to the methotrexate, which investigators in Australia believe may

explain the heightened efficacy of the drug combination compared with

methotrexate alone.

However, this increased potency may also heighten the risk for renal

toxicity, since methotrexate is almost entirely eliminated by the kidneys,

they note.

Dr. E. Tett, of the University of Queensland in Brisbane, and

associates administered to 10 healthy volunteers MTX alone, HCQ alone, and

MTX together with HCQ. They report in the October issue of the Journal of

Rheumatology that MTX co-administration had no effect on the

pharmacokinetics of HCQ.

However, the mean area under the concentration-time curve (AUC) for MTX was

approximately 65% higher when HCQ was given at the same time compared with

MTX on its own. Because the AUC was similar with oral and intravenous

administration, Dr. Tett's group believes the enhancement of MTX by HCQ is

not due to alteration in MTX bioavailability.

The maximum MTX concentration was reduced by coadministration of HCQ, which

the authors suggest may explain " the observation of reduced liver toxicity

with the combination therapy, as measured by elimination of elevations in

hepatic enzymes. "

However, the Australian researchers caution that extra vigilance is

warranted when prescribing the combination of MTX and HCQ in patients with

reduced renal function.

Dr. H. Giannini of the University of Cincinnati College of Medicine,

Ohio, adds in an accompanying editorial, " This well done study should serve

as yet another warning to rheumatologists of the potential for toxic

drug-drug interactions that may arise unexpectedly even when using drugs

that have been on the market for years. "

J Rheumatol 2002;29:2077-2083.

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