Arnouk Serena, Whitsett Maureen, Papadopoulos John, Stewart Lewis Zoe, Dagher Nabil N, Feldman David M, Park James S
Department of Pharmacy, NYU Langone Health, New York, NY, USA.
Department of Transplant Hepatology, Cleveland Clinic, Cleveland, OH, USA.
J Pharm Pract. 2023 Oct;36(5):1260-1263. doi: 10.1177/08971900221105042. Epub 2022 May 28.
Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.
