Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients

• Published in: Transplant infectious disease 2018-12, Vol.20 (6), p.e12979-n/a
• Main Authors: Laub, Melissa R., Crow, Stacy A., Personett, Heather A., Dierkhising, Ross, Boilson, Barry, Razonable, Raymund
• Format: Article
• Language: English
• Subjects: Administration, Oral; Antifungal agents; Antifungal Agents - pharmacology; Candidiasis; Candidiasis, Oral - immunology; Candidiasis, Oral - prevention & control; Clotrimazole; Clotrimazole - pharmacology; Dosage; Drug Interactions; Enzymatic activity; Enzyme activity; Female; Fungicides; Graft rejection; Graft Rejection - epidemiology; Graft Rejection - immunology; Graft Rejection - prevention & control; heart transplant; Heart transplantation; Heart Transplantation - adverse effects; Humans; Immunosuppression; Immunosuppression - adverse effects; Immunosuppression - methods; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacology; Intestine; Male; Middle Aged; Prophylaxis; Retrospective Studies; Tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - blood; Tacrolimus - pharmacology; thrush; Transplantation; Transplants & implants; Treatment Outcome
• ISSN: 1398-2273; 1399-3062
• DOI: 10.1111/tid.12979

Background Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described. Methods To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole. Results The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was −42.5% (IQR −52.3%, −30.9%). Five cases of allograft rejection were observed. Conclusion In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single‐center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.