A study on rats, published in the November early release, online edition of the Journal of Lipid Research (www.jlr.org), confirms findings of a previous study in the Archives of Internal Medicine (2001;161:2021-6) that a single 10 day course of erythromycin taken concurrently with the cholesterol lowering drug simvastatin can double or triple the risk of cataracts.
"The take-home message for ophthalmologists is that they should enquire whether their patients are taking statins, and also one of the several drugs that are known to inhibit statin metabolism," said Richard Cenedella, lead author of the rat study and professor of biochemistry at Kirksville College of Osteopathic Medicine, Kirksville, Missouri. Such drugs include itraconazole, ketoconazole, ramipril and ciclosporin, he said.
Statins, used by millions of people at some time in their life, lower cholesterol—and thus lower the risk of heart attack and stroke. Erythromycin slows the removal of most statins from the body and can greatly increase blood levels of these drugs.
The article last year in Archives of Internal Medicine by Christopher Meier of the University Hospital of Basle, Switzerland, and colleagues, was based on a case control analysis of UK patients aged 40 to 79 with first time diagnosis of cataract. It compared use of statins, fibrates and other lipid-lowering drugs with non-use of such drugs.
The conclusions stated: "Our analysis indicates that concomitant exposure to erythromycin with statins (which was almost exclusively exposure to simvastatin) may be associated with an approximately 2-fold to 3-fold increased risk of developing cataract in comparison with non-users of statins." But they warned their results should be interpreted cautiously.
Professor Cenedella and colleagues report that a specific strain of young rats called Chbb:Thom develop permanent cataracts within three to four weeks when treated with simvastatin.
Of three different rat strains tested, only the Chbb:Thom rats formed cataracts. These rats have a genetic defect controlling the concentration of a key enzyme needed to make cholesterol called hydroxymethyl glutaryl coenzyme A synthase (HMG CoA synthase). It is not known whether some humans have similar defects, but according to Professor Cenedella, people can develop cataracts independently of statin use because of genetic defects in other enzymes necessary to the formation of cholesterol. The combination of a defect and statin use could increase the risk.
Professor Cenedella says that, although large population studies show statins to be safe for the eye, safety should be assessed in individual ethnic and racial groups because of the great diversity among humans and the link between genetics and the rat cataract.
