In light of the recent pandemic,
favipiravir (Avigan®), a
purine nucleic acid analog and
antiviral agent approved for use in
influenza in Japan, is being studied for the treatment of
coronavirus disease 2019 (COVID-19). Increase in blood
uric acid level is a frequent side effect of
favipiravir. Here, we discussed the mechanism of blood
uric acid elevation during
favipiravir treatment.
Favipiravir is metabolized to an inactive metabolite M1 by
aldehyde oxidase and
xanthine oxidase, and excreted into urine. In the kidney,
uric acid handling is regulated by the balance of reabsorption and tubular secretion in the proximal tubules.
Favipiravir and M1 act as moderate inhibitors of
organic anion transporter 1 and 3 (OAT1 and OAT3), which are involved in
uric acid excretion in the kidney. In addition, M1 enhances
uric acid reuptake via
urate transporter 1 (URAT1) in the renal proximal tubules. Thus,
favipiravir is thought to decrease
uric acid excretion into urine, resulting in elevation of
uric acid levels in blood. Elevated
uric acid levels were returned to normal after discontinuation of
favipiravir, and
favipiravir is not used for long periods of time for the treatment of
viral infection. Thus, the effect on blood
uric acid levels was subclinical in most studies. Nevertheless, the adverse effect of
favipiravir might be clinically important in patients with a history of
gout,
hyperuricemia, kidney function impairment (in which blood concentration of M1 increases), and where there is concomitant use of other drugs affecting blood
uric acid elevation.