Drug Interactions between acitretin and conjugated estrogens / medroxyprogesterone

CONTRAINDICATED: Ethanol consumption with acitretin leads to the formation of etretinate, which has a much longer half-life than acitretin. Major human fetal abnormalities have been associated with the administration of acitretin, etretinate, and other retinoids. The longer elimination half-life of etretinate relative to acitretin increases the duration of teratogenic potential for female patients. In one case report of a patient with apparent sporadic ethanol intake, etretinate was present in plasma and fat for 52 months after acitretin was discontinued.

MANAGEMENT: Female patients should be warned that ethanol is contraindicated during active treatment with acitretin and for two months after cessation of therapy.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.