Use of Voriconazole in Lung Transplant Recipients Increases Risk of Skin Cancer, Death

Voriconazole significantly increases the risk for skin cancer and even death in lung transplant recipients, according to a study published in the American Journal of Transplantation.

"It is important for physicians to be aware of the impact of voriconazole on these outcomes," said senior author Sarah Arron, MD, University of California San Francisco High Risk Skin Cancer Clinic, San Francisco, California. "We recommend that all providers counsel lung transplant recipients on skin cancer risk and photo-protection in addition to scheduling routine skin cancer screening with a trained dermatologist after transplantation. Lung transplant programs should also consider patient-specific risk factors when deciding on the type, dose and duration of antifungal prophylaxis regimens."

Lung transplant recipients are particularly susceptible to cutaneous squamous cell carcinoma (SCC) due to older age at transplant and more intensive immunosuppression. They also have high rates of fungal infections after transplant, which can result in significant morbidity and mortality. SCC is a serious side effect of voriconazole, which has no clear guidelines for prophylaxis regimens despite its widespread use.

For the current study, Dr. Arron and colleagues evaluated single-lung, double-lung or heart-lung transplant recipients receiving a transplant between October 1991 and December 2012. These 455 individuals were analysed for voriconazole exposure and its impact on SCC, Aspergillus colonisation, invasive aspergillosis, and all-cause mortality.

The researchers found that voriconazole exposure resulted in a 73% greater risk for SCC, with each additional 30-day exposure increasing the risk by 3%.

Further, the drug significantly reduced the risk of Aspergillus colonisation, especially in the first year after transplant, but not aspergillosis. It also reduced all-cause mortality among those transplant recipients who developed Aspergillus colonisation but had no significant impact on those without colonisation.

"Among lung transplant recipients with risk factors for SCC, including those with older age, male sex, and white race or those in whom prolonged voriconazole administration may not have clear benefit, transplant physicians should consider limiting exposure to high doses of voriconazole or using alternative pharmacologic options that do not pose an increased risk for SCC," said lead author Matthew Mansh, MD, Stanford University, Stanford, California.