Interaction between cyclosporin and erythromycin in a kidney transplant patient

Kessler, Michèle; Louis, J.; Renoult, E.; Vigneron, B.; Netter, Patrick

doi:10.1007/bf00542427

Cited by 27 publications

(7 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Erythromycin (Gupta et al 1988), is thought to increase absorption; phenytoin (Rowland & Gupta 1987) to decrease cyclosporin absorption. Another explanation is inhibition of cyclosporin metabolism by erythromycin (Kessler et al 1986) or the induction of metabolism by phenytoin (Freeman et al 1984).…”

Section: Other Effectsmentioning

confidence: 99%

Cyclosporin Clinical Pharmacokinetics

Fahr

1993

Clinical Pharmacokinetics

315

161

View full text Add to dashboard Cite

Cyclosporin is a powerful immunosuppressive drug used in transplantation medicine and to treat autoimmune diseases. It is a lipophilic molecule, with its bioavailability dependent on food, bile and other interacting factors. Cyclosporin is extensively metabolised in the liver by the cytochrome P450 3A system, which is subject to considerable interindividual variation. Distribution of cyclosporin depends not only on physicochemical characteristics, but also on biological carriers such as lipoproteins and erythrocytes in blood. Cyclophilin, a binding protein for cyclosporin, influences distribution of cyclosporin in the body. Despite its lipophilicity, cyclosporin does not appear in the brain. The distribution of metabolites in the body can differ from that of cyclosporin itself. Elimination of the drug is mainly via the bile as metabolites, other routes not being very important. Pharmacokinetic parameters of cyclosporin are highly variable and depend on factors such as age, the physical condition of the patient, type of organ transplant or comedication. Renal side effects of cyclosporin are dose-related, but the influence of the dosage regimen has not been thoroughly investigated. An important factor in the reported variability is the different analytical methods used. Following the recommendations of recent consensus documents to monitor blood concentrations, this source of variability may diminish in the future. Several metabolites are reported as having less immunosuppressive activity than the parent drug. Metabolites with renal side effects have been reported. These and other effects of metabolites have not been clearly defined in the literature, presumably because of the highly variable activity of cyclosporin-metabolising liver enzymes and the paucity of data available on metabolite pharmacokinetics. The therapeutic range and dosage of cyclosporin are therefore highly dependent on many individual parameters in patients. Dosages of less than 5 mg/kg/day, however, rarely cause renal side effects. Further studies to correlate the clinical pharmacokinetics of metabolites with their activity and adverse effects are needed.

show abstract

Section: Other Effectsmentioning

confidence: 99%

Cyclosporin Clinical Pharmacokinetics

Fahr

1993

Clinical Pharmacokinetics

315

161

View full text Add to dashboard Cite

show abstract

“…9 Clarithromycin and erythromycin can inhibit the metabolism of CNIs by binding to CYP3A4. 10 Case reports describe a rise in CNI blood, serum, and plasma levels in the setting of a clarithromycin 11-15 or erythromycin 16-23 co-prescription. In contrast, azithromycin is a macrolide that is prescribed for similar indications as clarithromycin or erythromycin, but differs in that it does not inhibit CYP3A4 and is not associated with changes in CNI metabolism.…”

Section: Introductionmentioning

confidence: 99%

Outcomes Following Macrolide Use in Kidney Transplant Recipients

Jeong

Quinn

Lentine

et al. 2019

Can J Kidney Health Dis

View full text Add to dashboard Cite

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.

show abstract

“…Another important point related to erythromycin in liver transplant patients is the interaction with drugs commonly used in these patients. Erythromycin-CyA interaction has been described in renal transplant patients [5,7]. The mechanism proposed for this interaction is not clear, but the inhibiting effect of cytochrome P-450 by erythro-mycin could be the main factor increasing CyA levels during concomitant administration of erythromycin and CyA [6,11,16] as occurred in our patients.…”

Section: Discussionmentioning

confidence: 70%

Erythromycin ototoxicity in liver transplant patients

Moral

Navasa²,

Rimola

et al. 1994

Transplant Int

View full text Add to dashboard Cite

We report on three liver transplant patients who developed erythromycin-related ototoxicity. This complication has been described in renal transplant patients and in patients with liver dysfunction, but to our knowledge it has not yet been reported in liver transplant patients. The influence of hepatic dysfunction, common renal failure, and the interaction between cyclosporin and erythromycin in the development of erythromycin ototoxicity are discussed.

show abstract

Interaction between cyclosporin and erythromycin in a kidney transplant patient

Cited by 27 publications

References 5 publications

Cyclosporin Clinical Pharmacokinetics

Cyclosporin Clinical Pharmacokinetics

Outcomes Following Macrolide Use in Kidney Transplant Recipients

Erythromycin ototoxicity in liver transplant patients

Contact Info

Product

Resources

About