Retinoids, death and pharmacovigilance
Tretinoin is a retinoid drug (vitamin A analogue) that has been used to treat many dermatologic conditions (“label” and “off label”) as acne, wrinkles, photoaged skin, melasma, stretch marks, and to prevent non melanoma skin cancers.
The recent study published in the January 2009 by Weinstock in the Archives of Dermatology was very perturbing for all dermatologists and consumers. The study showed that elderly men patients treated in a VA hospital with 0.1% tretinoin topically to prevent skin cancer had a higher risk of death than those not using tretinoin. The veterans in this study were predominately elderly men.
Various factors in the study to try to determine the explanation for the increased number of deaths among tretinoin users. It is difficult to know for sure because the study was not designed to look for risk of death, but it seems that it is smokers who are at greater risk.
There were many limitations to the study since the information was obtained from VA databases which might have been incompletely filled, and also commorbidities and smoking incidence were not matched equally for both groups thus failing the comparison between the groups.
Smoking causes lung disease, heart disease and cause deep folds and wrinkles. We are not really sure that retinoid topic products in addition to smoking may increase the risk of death, but I totally agree with Dr. Baumann to inform all the patients that are using retinoids as tretinion, retinol, adapalene, tazarotene or taking vitamin A or beta carotene supplements to not smoke.
Adverse drug effects, side effects, drug interactions are manifold and heterogenous.The detection of unknown and unexpected connections between drugs exposure, commorbidities and adverse events is one of the major targets of pharmacovigilance. Pharmacovigilance serves to detect previously unrecognized adverse events associated with the use of the drugs but this is only possible if the drug is rigid controlled. In Brazil we have a very important problem; patients do not go to the dermatologist to ask for a retinoid topical cosmeceutical or drug as they proceed to use a systemic one. If we control the topic retinoid use, it will be possible to understand the connections (or not) and mechanisms involved in the detection of adverse drug effects or increased risk of death in using topical retinoid. There are papers describing risks in using beta carotene and develop lung malign disease, but I do not remember papers linking systemic retinoid intake and lung cancer. Better than limited phase IV clinical trials, rigid retinoids´ pharmacovigilance may elucidate retinoids and death connections.
Best wishes from Brazil!
Dr. Érica Monteiro - Cosmetic Dermatology
www.dermatologia.com.br
Tags: pharmacovigilance, retinoic acid, retinoid, tretinoin
