Common antibiotics may risk liver injury in elderly

By Sarah Guy, MedWire Reporter

Regulatory warnings should be considered for the antibiotics moxifloxacin and levofloxacin because of a potential risk for liver injuries in the elderly, Canadian researchers suggest.

Compared with clarithromycin use, treatment with these drugs was associated with a twofold increased risk for liver injuries, which included toxic liver disease, hepatitis, hepatic necrosis, or unspecified acute hepatic failure, reports the team.

"Fluroquinolones are among the most widely prescribed antibiotic agents in North America, and the use of broad-spectrum fluoroquinolones such as levofloxacin and moxifloxacin is increasing," say David Juurlink (Institute for Clinical Evaluative Sciences, Toronto, Ontario) and co-investigators.

However, safety concerns have led to the withdrawal of several members of this class of drugs because of an association with adverse reactions including hemolysis, renal failure, and hepatotoxicity, they add.

The team matched 144 individuals aged 65 years or older who were admitted to hospital for acute liver injury after using one of five broad-spectrum antibiotics, with up to 10 control patients (total=1409) who received these antibiotics without adverse effects.

The median time between dispensing of the antibiotic and admission to hospital was 9 days, the researchers observed.

Compared with patients who received clarithromycin, those treated with moxifloxacin were 2.20 times more likely to be admitted to hospital for acute liver injury, and those treated with levofloxacin were 1.85 times more likely. Both associations were statistically significant.

The risk associated with ciprofloxacin and cefuroxime axetil ‑ the other drugs studied ‑ did not differ significantly from that with clarithromycin.

Clarithromycin was chosen as the comparator drug because while it has similar clinical indications to fluoroquinolones, "it is not generally implicated as a cause of idiosyncratic liver injury," say the researchers in the Canadian Medical Association Journal.

The crude incidences of hospital admission for liver injury supported these results, with rates of 7.98 per 100,000 exposures to moxifloxacin and 8.62 per 100,000 exposures to levofloxacin that were double those seen for clarithromycin, at 3.95 per 100,000 exposures.

"Our findings make an important contribution to an evidence base that is currently limited to case reports and registries of drug-induced liver injury," remark Juurlink et al.

And while their findings do not point to a precise mechanism of injury, they note that the latency period they observed is consistent with many hypersensitivity reactions to drugs.

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