Drug & Device Development

For adefovir nephrotoxicity, just lower the dose

Last Updated: 2013-03-08 16:58:22 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Up to a third of patients taking adefovir for hepatitis B develop nephrotoxicity, but lowering the dose improves renal markers without compromising treatment efficacy, researchers report.

When nephrotoxicity develops, "either adefovir discontinuation or dose reduction can be implemented," Dr. Seng Gee Lim from National University Health System, Singapore told Reuters Health. "However, many patients taking adefovir already have viral resistant strains of hepatitis B, as adefovir is used mainly as rescue therapy for viral resistance. Hence the preference for dose reduction rather than discontinuation."

Rates of adefovir nephrotoxicity have ranged as high as 50% in clinical trials for chronic hepatitis B, but there are conflicting data with prolonged adefovir treatment in a real-life setting, Dr. Lim and colleagues said in a paper online February 21 in Alimentary Pharmacology and Therapeutics.

A search of their Computerized Patient Support System database identified 383 patients on adefovir treatment, 271 of whom satisfied their inclusion criteria. (Most of the exclusions were for cancer or a previous liver transplant.)

Thirty-three patients (12%) developed abnormal serum creatinine during 12 months of adefovir treatment. Twenty-five had changes in their adefovir treatment, and eight continued on the same dose.

The cumulative proportions of patients who developed renal dysfunction were 5.3% in year one and 33.8% at year six based on abnormal serum creatinine, 7.7% in year one and 38.3% at year six based on glomerular filtration rate (GFR) <60 mL/min, and 21.5% at five years based on a serum creatinine rise of at least 0.5 mg/dL.

"Importantly, all three methods of evaluating renal dysfunction show a similar pattern, with survival curves showing progressive renal impairment over time that did not appear to plateau," the authors wrote.

Baseline GFR of 76.1 mL/min or less was the only factor significantly associated with abnormal serum creatinine with adefovir.

Creatinine levels improved in three of the eight patients who continued with the same dose of adefovir despite elevated creatinine levels, but GFR levels were persistently abnormal in patients who remained on the same dose.

In contrast, creatinine levels normalized in the 17 patients whose adefovir dose was reduced from 10 mg daily to 10 mg every other day and in the eight patients who stopped taking it altogether.

Dose reduction of adefovir did not result in significant increases in HBV DNA, the researchers note.

Dr. Lim noted, "Currently tenofovir is the panacea for drug resistant HBV, but the safety data suggests that there is some nephrotoxicity as well. Consequently, a similar strategy for tenofovir may be effective but would need to be tested in a clinical study."

SOURCE: http://bit.ly/Wziiti

Aliment Pharmacol Ther 2013.