Real clinical impact of drug–drug interactions of immunosuppressants in transplant patients

GAGO, ANA ISABEL; Font, Pilar; Cárdenas, M.; Aumente, M.D.; Prado, José Ramón Del; Calleja, Miguel Ángel

doi:10.1002/prp2.892

Cited by 10 publications

(14 citation statements)

References 49 publications

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“…6 The use of many drugs increases the risk of adverse reactions and drug interactions, which can lead to treatment withdrawal, further contributing to the non-compliance of the transplant recipient with drug therapy. 38,39 Adherence to treatment is an important factor for successful transplantation to avoid acute rejection and graft loss, so transplant patients need specific care with adequate instructions. 40 When comparing our results with those of Melchiors, Correr and Fernandez-Llimos, who employed MRCI in diabetic patients, we found that the relation between score and number of medications was divergent.…”

Section: Discussionmentioning

confidence: 99%

Medication Regimen Complexity Index After Kidney Transplant in Fortaleza, Brazil

et al. 2023

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Background: The Medication Regimen Complexity Index (MRCI) is a reliable tool to evaluate the complexity of pharmacotherapy and can predict the treatment adherence of post-transplant patients. The MRCI was evaluated in the post-kidney transplant period. Materials and Methods: In a descriptive, observational, and cross-sectional study, we evaluated the pharmacotherapy and the MRCI of kidney transplant patients for a year in a kidney transplant outpatient clinic at a university hospital in Fortaleza, Brazil. A convenience sample was obtained and analyzed the records of kidney transplant recipients who had at least two visits with pharmacists. The main outcome measures are characterization of immunosuppressive regimen, MRCI score, correlations between MRCI score and a period post-transplant. Results: 109 patients were included in the study. The predominant class was antineoplastic and immunomodulating agents (27.7%), and the most frequent immunosuppressive regimen was tacrolimus, mycophenolate sodium and prednisone (63.30%). The mean points in MRCI were 46; minimum of 19 points associated with 3 drugs and maximum of 83.5 points with 16. About sections A, B and C of the MRCI, the means found were 2.60, 13.2 and 30.6 points, respectively. Correlations between MRCI score and number of medications were checked, and a period less than 180 days after transplantation had score >40 points. Conclusion: MRCI in the kidney transplant patient is linked to the number of medications, dose and additional instructions. To improve adherence to the treatment, patient orientation is necessary especially in the first year after transplant.

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Section: Discussionmentioning

confidence: 99%

Medication Regimen Complexity Index After Kidney Transplant in Fortaleza, Brazil

et al. 2023

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“…Transplant recipients are at considerable risk of adverse effects from drug interactions due to polypharmacy, the narrow therapeutic index of immunosuppressants, and the vulnerability of CNI to CYP3A4‐ and p‐glycoprotein‐mediated drug interactions. Up to 1 in 5 transplant recipients have a clinically significant drug interaction, which can contribute to adverse drug effects 58 . Transplant recipients starting azole antifungal agents should be evaluated for the need to adjust immunosuppression (e.g., CNI and mTORi) and non‐immunosuppressant therapies (e.g., statins, proton pump inhibitors, calcium channel blockers) as the result of drug interactions 26,59,60 .…”

Section: Navigating Drug Interactionsmentioning

confidence: 99%

“…Up to 1 in 5 transplant recipients have a clinically significant drug interaction, which can contribute to adverse drug effects. 58 Transplant recipients starting azole antifungal agents should be evaluated for the need to adjust immunosuppression (e.g., CNI and mTORi) and nonimmunosuppressant therapies (e.g., statins, proton pump inhibitors, calcium channel blockers) as the result of drug interactions. 26,59,60 Importantly, the extent of a drug interaction and its clinical significance differs between agents within this medication class.…”

Section: Navig Ating Drug Inter Ac Tionsmentioning

confidence: 99%

Pharmacogenomics and beyond! Customized pharmacotherapy for solid organ transplant recipients

2023

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“…Due to polypharmacotherapy, ICU lung transplant recipients are at a greater risk for pDDIs. Especially pDDIs involving immunosuppressive drugs with a limited therapeutic index are particularly susceptible to adverse drug events (ADEs) ( Gago-Sánchez et al, 2021 ; Dewey et al, 2023 ). The tendency is complicated by illness severity and organ failure, which can alter medication pharmacologic response.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and clinical significance of potential drug-drug interactions among lung transplant patients

Zhang,

Ma,

Chen

et al. 2024

Front. Pharmacol.

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Background: Drug-drug interactions (DDIs) are a major but preventable cause of adverse drug reactions. There is insufficient information regarding DDIs in lung transplant recipients.Objective: This study aimed to determine the prevalence of potential DDIs (pDDIs) in intensive care unit (ICU) lung transplant recipients, identify the real DDIs and the most frequently implicated medications in this vulnerable population, and determine the risk factors associated with pDDIs.Methods: This retrospective cross-sectional study included lung transplant recipients from January 2018 to December 2021. Pertinent information was retrieved from medical records. All prescribed medications were screened for pDDIs using the Lexicomp® drug interaction software. According to this interaction software, pDDIs were classified as C, D, or X (C = monitor therapy, D = consider therapy modification, X = avoid combination). The Drug Interaction Probability Scale was used to determine the causation of DDIs. All statistical analysis was performed in SPSS version 26.0.Results: 114 patients were qualified for pDDI analysis, and total pDDIs were 4051. The most common type of pDDIs was category C (3323; 82.0%), followed by D (653; 16.1%) and X (75; 1.9%). Voriconazole and posaconazole were the antifungal medicine with the most genuine DDIs. Mean tacrolimus concentration/dose (Tac C/D) before or after co-therapy was considerably lower than the Tac C/D during voriconazole or posaconazole co-therapy (p < 0.001, p = 0.027). Real DDIs caused adverse drug events (ADEs) in 20 patients. Multivariable logistic regression analyses found the number of drugs per patient (OR, 1.095; 95% CI, 1.048–1.145; p < 0.001) and the Acute Physiology and Chronic Health Evaluation II (APACHE Ⅱ) score (OR, 1.097; 95% CI, 1.021–1.179; p = 0.012) as independent risk factors predicting category X pDDIs.Conclusion: This study revealed a high incidence of both potential and real DDIs in ICU lung transplant recipients. Immunosuppressive drugs administered with azole had a high risk of causing clinically significant interactions. The number of co-administered drugs and APACHE Ⅱ score were associated with an increased risk of category × drug interactions. Close monitoring of clinical and laboratory parameters is essential for ensuring successful lung transplantation and preventing adverse drug events associated with DDIs.

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Real clinical impact of drug–drug interactions of immunosuppressants in transplant patients

Cited by 10 publications

References 49 publications

Medication Regimen Complexity Index After Kidney Transplant in Fortaleza, Brazil

Medication Regimen Complexity Index After Kidney Transplant in Fortaleza, Brazil

Pharmacogenomics and beyond! Customized pharmacotherapy for solid organ transplant recipients

Prevalence and clinical significance of potential drug-drug interactions among lung transplant patients

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