Efficacy and safety of tenofovir disoproxil fumarate in patients with chronic hepatitis B

Abstract

Chronic hepatitis B (CHB) is prevalent worldwide. It may cause cirrhosis and hepatocellular carcinoma. Treatment for this condition may need to be lifelong, thus the drugs used must be both efficacious and safe. Clinical trials of tenofovir have demonstrated a good safety profile for this drug and it has potent antiviral properties. However, to better characterize the safety of this drug, the postmarketing surveillance must be taken into account. Clinicians need to be vigilant, as infrequent adverse events may be revealed during this phase. The current review presents a detailed exposé of preclinical and clinical data on tenofovir to increase awareness of possible adverse events and drug-drug interactions, based on the large experience of this drug in human immunodeficiency virus (HIV) treatment (and to date in patients with CHB). Several recommendations that may help the clinician to prevent the development of adverse events associated with tenofovir disoproxil fumarate (TDF) treatment are outlined, along with a suggested surveillance protocol for the timely and proper identification of possible renal and bone toxicity.

Keywords: adverse drug event; drug interactions; hepatitis B virus; hypophosphatemia; mitochondrial toxicity; osteomalacia; tenofovir; treatment outcome.

Figure 1.

Proposed algorithm for the assessment and follow-up of renal and bone abnormalities potentially associated with tenofovir disoproxil fumarate treatment. BUN, blood urea nitrogen; Cr, serum creatinine, P, phosphate; ULN, upper limit of normal; CrCl, creatinine clearance; FE, fractional excretion; TDF, tenofovir disoproxil fumarate. ¹HVB-related glomerulonephritis, infection, undernourishment, alcoholism, refeeding syndrome, volume depletion, diarrhea/malabsorption, diuretics, antacids. ²If suspicion of acute kidney injury, laboratory tests must be performed within 48 hours. ³Poor intake alone is rarely responsible for phosphate depletion, but it is recommended to assess this possibility with a nutriologist. Evident signs may develop if grade 3 or 4 hypophosphatemia occurs, and may include: myopathy, ileus, hemolysis, metabolic encephalopathy, respiratory and congestive heart failure; consider hospitalization. ⁴According to the Acute Kidney Injury Network. ⁵CrCl: creatinine clearance (urinary creatinine × urine volume / serum creatinine × time). The usefulness of CrCl is remarkably reduced in the presence of decompensated cirrhosis and its evaluation is not warranted. ⁶Specially if not assessed previously or when considering postrenal causes. ⁷FE of phosphate: fractional excretion of phosphate (urinary phosphate × plasma creatinine / plasma phosphate × urinary creatinine). [Bagnis et al. 2009; Garcia-Tsao et al. 2008].