title: Serum Sirolimus Level Elevation Induced by Acitretin: Report of a Novel Drug-Drug Interaction.
abstract: Long-term immunosuppression in the organ transplant recipient (OTR) population places these individuals at higher risk of developing skin malignancies. Oral retinoids have become a useful tool for pharmacologic prophylaxis in the OTR population. Immunosuppressants that inhibit mTOR, such as sirolimus, may be used in combination with a systemic retinoid for chemoprophylaxis of cutaneous malignancies. We present the case of a male patient status post second renal transplant who developed an abrupt and unexpected rise in sirolimus levels to supra-therapeutic levels after initiation of prophylactic acitretin for innumerable squamous cell carcinomas (SCC). The sirolimus levels returned to baseline after cessation of acitretin. Systemic drug-drug interactions are an important phenomenon, especially in the solid OTR population. It is postulated that this interaction was mediated by acitretin inhibition of CYP3A4, the primary enzyme responsible for sirolimus metabolism. The Drug Interaction Probability Scale (DIPS) indicates this was a "probable" drug-drug interaction. To date, this interaction has not been reported in the literature. This case accentuates the importance of close monitoring of solid OTRs for adverse medication interactions when multiple medications are taken.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Rossi
authors.forename: Brian P
authors.initials: BP
authors.lastname: Hibler
authors.forename: Hillary
authors.initials: H
authors.lastname: Johnson-Jahangir
mesh_terms: D017255:Acitretin / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use; D007641:Keratolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000097:blood* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000517:prevention & control
chemical_list: D007166:Immunosuppressive Agents; D007641:Keratolytic Agents; D017255:Acitretin; D020123:Sirolimus