Voriconazole therapy and flouride toxicity

Submitted by Aspergillus Administrator on 23 February 2011

Patients who are in receipt of a transplant are known to be vulnerable to infection by Aspergillus as part of their post operative regimen includes immune-suppressive drugs to combat rejection of the transplanted organ. Suppression of the immune system to prevent rejection also leaves the patients more vulnerable to infections of all kinds, some of the most difficult to treat infections are fungal infections such as aspergillosis. For this reason transplant patients are often started off on an immune-suppressive regimen that is quite powerful but that regimen is tapered down to the point at which there is still no rejection of the transplanted organ, but the patients’ immune system can recover enough to fight infection.

The authors of this paper describe a patient on long term treatment with voriconazole, required after aspergillosis complicated her heart transplant.  That treatment seems to have been successful but 4 years later she was still taking voriconazole, presumably to prevent the fungus reappearing.
Unfortunately the patient was suffering from bony outgrowths in several parts of her body (see picture).

Tests revealed very high levels of flouride in her bones, but there was no evidence that there was any excessive intake of flouride in her diet e.g. flouride containing medications, excessive black tea consumpton, swallowing toothpaste.

The voriconazole molecule contains 3 flouride atoms so it was discontinued and replaced with itraconazole. Within 3 months the patient’s symptoms and clinical signs had improved dramatically.

This is the first suggestion that voriconazole may cause flouride toxicity, so the authors of the paper decided to test the theory that voriconazole was causing this problem. 20 post transplant patients were recruited and consented to having their voriconazole and flouride levels tested. 5 patients receiving voriconazole started to develop bony outgrowths (periostitis) and all recovered within 3 months of stopping voriconazole therapy.

We can conclude that there is reason to suspect that voriconazole is causing flouride toxicity in some patients. This study was small so we cannot positively conclude that this is the case but there is enough to decide that awareness and vigilance of this possibility amongst transplant patients taking long term voriconazole therapy is desirable and necessary.