Pharmacokinetic drug–drug interactions between calcineurin inhibitors and proliferation signal inhibitors with anti-microbial agents: Implications for therapeutic drug monitoring

Page, Robert L.; Mueller, Scott W.; Levi, Marilyn E.; Lindenfeld, JoAnn

doi:10.1016/j.healun.2010.09.001

Cited by 17 publications

(10 citation statements)

References 69 publications

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“…11,13-20,23,40-42 By inhibiting intestinal and hepatic CYP3A4, clarithromycin and erythromycin alter CNI metabolism and increase serum concentrations of CNIs. 43 The CNI concentrations can increase 1.6- to 6-fold within 2 to 6 days of starting clarithromycin and 1.6- to 5-fold within 1 to 18 days of initiating erythromycin. 43 Acute CNI nephrotoxicity can result in acute arteriolopathy due to vasoconstriction of afferent arterioles, isometric vacuolization of the tubular cytoplasm, as well as de novo thrombotic microangiopathy seen on kidney biopsy.…”

Section: Discussionmentioning

confidence: 99%

“…43 The CNI concentrations can increase 1.6- to 6-fold within 2 to 6 days of starting clarithromycin and 1.6- to 5-fold within 1 to 18 days of initiating erythromycin. 43 Acute CNI nephrotoxicity can result in acute arteriolopathy due to vasoconstriction of afferent arterioles, isometric vacuolization of the tubular cytoplasm, as well as de novo thrombotic microangiopathy seen on kidney biopsy. 44 In contrast, azithromycin does not affect CYP3A4 or produce enzyme/metabolite complexes and is likely safer to prescribe than clarithromycin or erythromycin for patients on CNIs.…”

Section: Discussionmentioning

confidence: 99%

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Outcomes Following Macrolide Use in Kidney Transplant Recipients

Jeong

Quinn

Lentine

et al. 2019

Can J Kidney Health Dis

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Background: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. Objective: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. Design: Retrospective cohort study. Setting: We used linked health care databases in Alberta, Canada. Patients: We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. Measurements: The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. Methods: We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). Results: Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (−5.4 vs −1.9 mL/min/1.73 m 2 , P < .05). Limitations: We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. Conclusion: Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Outcomes Following Macrolide Use in Kidney Transplant Recipients

Jeong

Quinn

Lentine

et al. 2019

Can J Kidney Health Dis

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“…Heart failure programs offering heart transplantation and mechanical circulatory support (MCS) as options for care rely on a multidisciplinary team approach—including cardiologists, surgeons, nurses, social workers, and clinical pharmacists—to provide effective care across the transplant continuum. With the complex pharmacokinetics of current immunosuppressive drugs, the clinical pharmacist's expertise to identify potential drug–drug interactions and adverse events and to provide patient specific dosing, monitoring recommendations, and medication education also is needed on the transplant team . The American Society for Transplantation (AST) Transplant Pharmacy Community of Practice recently published a white paper on the fundamental and recommended roles of, and optimal training for, clinical pharmacists working within a transplant team …”

Section: Clinical Pharmacist On the Transplant/mechanical Circulatorymentioning

confidence: 99%

Clinical Pharmacy Services in Heart Failure: An Opinion Paper from the Heart Failure Society of America and American College of Clinical Pharmacy Cardiology Practice and Research Network

et al. 2013

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Heart failure (HF) care takes place in multiple settings, with a variety of providers, and generally involves patients who have multiple comorbidities. This situation is a "perfect storm" of factors that predispose patients to medication errors. The goals of this paper are to outline potential roles for clinical pharmacists in a multidisciplinary HF team, to document outcomes associated with interventions by clinical pharmacists, to recommend minimum training for clinical pharmacists engaged in HF care, and to suggest financial strategies to support clinical pharmacy services within a multidisciplinary team. As patients transition from inpatient to outpatient settings and between multiple caregivers, pharmacists can positively affect medication reconciliation and education, assure consistency in management that results in improvements in patient satisfaction and medication adherence, and reduce medication errors. For mechanical circulatory support and heart transplant teams, the Centers for Medicare and Medicaid Services considers the participation of a transplant pharmacology expert (e.g., clinical pharmacist) to be a requirement for accreditation, given the highly specialized and complex drug regimens used. Although reports of outcomes from pharmacist interventions have been mixed owing to differences in study design, benefits such as increased use of evidence-based therapies, decreases in HF hospitalizations and emergency department visits, and decreases in all-cause readmissions have been demonstrated. Clinical pharmacists participating in HF or heart transplant teams should have completed specialized postdoctoral training in the form of residencies and/or fellowships in cardiovascular and/or transplant pharmacotherapy, and board certification is recommended. Financial mechanisms to support pharmacist participation in the HF teams are variable. Positive outcomes associated with clinical pharmacist activities support the value of making this resource available to HF teams.

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“…The preceding findings could be attributed to cytochrome P450 3A5 (CYP3A5), the main enzyme involved in drug metabolism. Current clinical data reveal that Itsumi Kokosu (the main component of a five-ester capsule), grapefruit juice (grapefruit), diltiazem, and imidazoles combined with tacrolimus can increase the blood concentration of tacrolimus to different degrees; the inhibitory mechanism of CYP3A5 activity on tacrolimus involves CYP3A substrate (Chang et al, 2010;Press et al, 2010;Page et al, 2011;Pavan et al, 2011). If patients are taking medications or other substances that interact with CYP3A5, blood tacrolimus concentrations may be maintained within the normal range by appropriately reducing the tacrolimus dose and determining its concentration in the blood.…”

Section: Discussionmentioning

confidence: 99%

Analysis of tacrolimus blood concentrations in renal transplant patients

Wang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. This study aimed to 1) analyze the results of tacrolimus blood concentration monitored in patients after renal transplantation, 2) observe and establish an optimal therapeutic window for patients, and 3) provide evidence for the clinical and rational use of drugs. Tacrolimus blood concentration was determined by enzyme-linked immunosorbent assay. A total of 1824 cases were obtained from the monitoring of 74 patients after renal transplantation. These cases were then retrospectively analyzed. Over time, the mean whole blood tacrolimus trough concentration after transplantation gradually decreased. This result suggests that the optimal therapeutic windows for patients with renal transplants are as follows: 5 to 20 µg/L at 1 month after surgery; 5 to 15 µg/L at 1-3 months after surgery; 4 to 12 µg/L at 3-6 months after surgery; 4 to 10 µg/L at 6-12 months after surgery; and 3 to 8 µg/L at >12 months after surgery. The absorption of tacrolimus is highly variable. Therefore, tacrolimus concentration in the blood and the recommended clinical therapeutic window should be routinely monitored to adjust the treatment regimen and reduce adverse reactions. In this way, treatment can be optimized.

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Pharmacokinetic drug–drug interactions between calcineurin inhibitors and proliferation signal inhibitors with anti-microbial agents: Implications for therapeutic drug monitoring

Cited by 17 publications

References 69 publications

Outcomes Following Macrolide Use in Kidney Transplant Recipients

Outcomes Following Macrolide Use in Kidney Transplant Recipients

Clinical Pharmacy Services in Heart Failure: An Opinion Paper from the Heart Failure Society of America and American College of Clinical Pharmacy Cardiology Practice and Research Network

Analysis of tacrolimus blood concentrations in renal transplant patients

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