Hydroxychloroquine + Metoprolol = Precautionary

Effect on Concentration

Hydroxychloroquine
Unknown
Applies within class?
No
Metoprolol
Increase
Applies within class?
No

Pharmacologic Effects

Hydroxychloroquine
Effect
N/A
Applies within class?
No
Metoprolol
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 19-May-2020

Summary

Marked increases in metoprolol concentrations (via CYP2D6 inhibition). Some variability noted as well. Clinical significance is indeterminate however the magnitude of exposure indicates very high caution and close monitoring for metoprolol therapy management.

Sources

Influence of hydroxychloroquine on the bioavailability of oral metoprolol. ^

Study Design

Metoprolol and dextromethorphan (DM) were selected as probe drugs because they are well-studied and widely used test substrates of CYP2D6. In this randomized, double-blind crossover study, seven healthy volunteers with extensive metabolizer phenotype for CYP2D6 ingested either 400 mg hydroxychloroquine or placebo daily for 8 days after which single oral dose pharmacokinetics of metoprolol were investigated. Dextromethorphan metabolic ratio (DM-MR) was also determined at baseline and after the ingestion of HCQ or placebo.

Study Results

Concomitant administration of HCQ increased the bioavailability of metoprolol, as indicated by significant increases in the area under the plasma concentration-time curve (65 /- 4.6) and maximal plasma concentrations (72 /- 6.9) of metoprolol. While the DM-MR values were not significantly changed, the phenotypic classification of one individual, who was heterozygous for a mutant CYP2D6 allele, was converted to a poor metabolizer by HCQ administration.

Study Conclusions

HCQ inhibits metoprolol metabolism most probably by inhibiting its biotransformation by CYP2D6. The inhibitory effect of HCQ on dextromethorphan metabolism was not apparent when DM-MR was used as an indicator, except in an individual with limited CYP2D6 capacity.

References

Somer M. Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br J Clin Pharmacol. 2000; 6: 549-54.