Interactions between anti‐infective agents and immunosuppressants—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

Abstract

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation provide an update on potential drug‐drug interactions between anti‐infectives and immunosuppressants, which are most notable with calcineurin and mTOR inhibitors. Drug‐drug interactions may occur through pharmacokinetic mechanisms leading to altered drug concentrations of either the anti‐infective or immunosuppressive drug, or by pharmacodynamic interactions increasing or decreasing the efficacy or toxicity of the medications. Many of the significant pharmacokinetic interactions occur through inhibition or induction of the cytochrome 3A4 system by anti‐infective agents leading to increased or decreased immunosuppressive agent levels, respectively. The membrane transporter P‐glycoprotein is also often involved in drug interactions. Since the last iteration of these guidelines, multiple new hepatitis C virus direct‐acting antivirals have become available for use in SOT recipients. Of these agents, some are substrates of cytochrome and drug transporter systems, while others inhibit these systems and may affect immunosuppressive agents. Due to the high risk for drug‐drug interactions in the solid organ transplant population, practitioners must be aware of potential interactions and be vigilant in monitoring and adjusting drug dosing when appropriate.

Risk factors and clinical outcomes of tuberculosis among kidney transplant recipients in high endemic country

“…Rifampicin significantly decreases level of CNI and mTORi which might result in allograft rejection. 20,21 Among three patients who had rejection after diagnosis of TB, only one developed allograft rejection at 19 days with evidence of sub therapeutic cyclosporine level. This represented 4% incidence of potential rifampicin associated allograft rejection.…”

“…3 Management of TB in transplant recipients is challenging as anti-tuberculosis agents have significant interaction with immunosuppressants and the disease contains high mortality up to 40%. 3,4 Incidence of post-transplant TB varies among countries and types of transplanted organ. Overall incidence in kidney transplant (KT) recipients was 1.69%, however, the number was reported as high as 15% in high endemic country.…”

Repurposing of auranofin and honokiol as antifungals against Scedosporium species and the related fungus Lomentospora prolificans

“…This triazole drug may induce visual disturbances, as well as hepatotoxicity and phototoxicity events in CF patients [52,53]. In addition, its concomitant use with immunosuppressants in solid organ transplant recipients needs careful evaluation of serum level of the immunosuppressant [54]. Importantly, the demonstrated MIC values for ARF mirror the achievable blood levels following an oral or parenteral dose of ARF (maximum plasma concentration: 0.68 ± 0.45 μg/ ml).…”

The Current State of Antifungal Stewardship in Immunocompromised Populations

“…In one study, contraindicated DDIs were reported in nearly 25% of inpatients prescribed mold-active triazoles [ 56 ]. Many of the novel therapeutics in hematology-oncology and drugs used for maintenance of immunosuppression in SOT patients also have clinically actionable DDIs with triazoles [ 57 , 58 ]. These interactions may require the monitoring of serum levels and/or dose adjustments.…”