Interactions between Tacrolimus and Metronidazole in a renal transplant patient

AbstractWe present a case which reports the occurrence of a potential elevation of Tacrolimus (Tac) plasma levels to toxic values in a renal transplant recipient after adding Metronidazole (Met) to the medication regimen. A 30-year old female, status post living-related renal transplant, who was stabilized on Tac 4.5 mg, twice daily, for 4 months, presented to the clinic with diarrhea. We used Microparticle Enzyme Immunoassay (MEIA) to determine Tac trough concentration (trough concentrations 5–10 ng/ml). After 6 days of Met therapy on 1.5 g/d, Tac trough concentration and serum creatinine (sCr) increased to 20.2 ng/ml and 7.8 mg/dl respectively. Met therapy was discontinued, also one dose of Tac was withheld, while daily dose was decreased to 2 mg/d. Four days after Met discontinuation, Tac concentration dropped to 8.7 ng/ml, sCr to 2.1 mg/dl, warranting Tac dose increase to 3 mg/d. Co-administration of Tac with Met may result in elevated Tac concentrations, possibly leading to tacrolimus nephrotoxicity. Clinicians should be aware of this potential interaction and closely monitor Tac concentration and renal function.

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Potential Elevation of Tacrolimus Trough Concentrations with Concomitant Metronidazole Therapy

Annals of Pharmacotherapy ◽

10.1345/aph.1e399 ◽

2005 ◽

Vol 39 (6) ◽

pp. 1109-1113 ◽

Cited By ~ 29

Author(s):

Robert Lee Page ◽

Patrick M Klem ◽

Christin Rogers

Keyword(s):

Renal Transplant ◽

Serum Creatinine ◽

Potential Interaction ◽

Medication Regimen ◽

Severe Diarrhea ◽

Tacrolimus Trough Concentration ◽

Trough Concentrations ◽

Living Related ◽

Stool Cultures ◽

Tacrolimus Dose

OBJECTIVE: To report the occurrence of a potential tacrolimus elevation in a renal transplant recipient after adding metronidazole to the medication regimen. CASE SUMMARY: A 24-year-old white man status post living-related renal transplant who had been stabilized on tacrolimus 4 mg twice daily (trough concentrations 7–10 ng/mL) for 2 months and prednisone 20 mg daily presented to the clinic with severe diarrhea. Stool cultures were positive for Clostridium difficile, and therapy with metronidazole 500 mg 4 times daily was initiated. Between days 4 and 14 of metronidazole therapy, the patient's tacrolimus trough concentration and serum creatinine level increased to maximum levels of 26.3 ng/mL and 3.3 mg/dL (baseline 1.6–1.8 mg/dL), respectively. Tacrolimus was withheld for one dose and then decreased to 1 mg twice daily. Two days after metronidazole discontinuation, tacrolimus trough concentrations dropped to 9.4 ng/mL and serum creatinine to 2.3 mg/dL, warranting a tacrolimus dose increase to 3 mg daily. DISCUSSION: As of April 15, 2005, one other case has been reported documenting an elevation in tacrolimus concentrations with the addition of metronidazole. The possible mechanism may be related to metronidazole's weak inhibition of CYP3A4 and, possibly, P-glycoprotein. According to the Naranjo probability scale, metronidazole was the probable cause of this adverse reaction. CONCLUSIONS: Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function.

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Predictors of Voriconazole Trough Concentrations in Patients with Child–Pugh Class C Cirrhosis: A Prospective Study

Antibiotics ◽

10.3390/antibiotics10091130 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1130

Author(s):

Yichang Zhao ◽

Jingjing Hou ◽

Yiwen Xiao ◽

Feng Wang ◽

Bikui Zhang ◽

...

Keyword(s):

Trough Concentration ◽

Multiple Linear Regression Model ◽

Therapeutic Drug ◽

Time Activity ◽

Bivariate Correlation ◽

Significant Difference ◽

Daily Dose ◽

Pugh Class ◽

Trough Concentrations ◽

Class C

This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

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The Genetic Polymorphism of CYP3A4 rs2242480 is Associated with Sirolimus Trough Concentrations Among Adult Renal Transplant Recipients

Current Drug Metabolism ◽

10.2174/1389200221999201027203401 ◽

2020 ◽

Vol 21 (13) ◽

pp. 1052-1059

Author(s):

Lolita Lolita ◽

Ming Zheng ◽

Xiang Zhang ◽

Zhijian Han ◽

Jun Tao ◽

...

Keyword(s):

Trough Concentration ◽

Graft Function ◽

Renal Transplant Recipients ◽

Sequencing Analysis ◽

Nucleotide Polymorphisms ◽

Target Sequencing ◽

Immunosuppressant Regimen ◽

Microparticle Enzyme Immunoassay ◽

Trough Concentrations ◽

The Impact

Background:: The large interindividual variability in the genetic polymorphisms of sirolimus (SIR)- metabolizing enzymes, transporters, and receptors can lead to qualitatively and quantitatively distinct therapeutic responses. Objective:: We examined the impact of numerous candidate single-nucleotide polymorphisms (SNPs) involved in the trough concentration of SIR-based immunosuppressant regimen. Method:: This is a retrospective, long-term cohort study involving 69 renal allograft recipients. Total DNA was isolated from recipient blood samples and trough SIR concentrations were measured by microparticle enzyme immunoassay. Genome sequence reading was targeted based on next-generation sequencing. The association of tagger SNPs to SIR trough concentrations with non-genetic covariate adjusting was analyzed using logistic regression. Results:: A total of 300 SNPs were genotyped in the recipient DNA samples using target sequencing analysis. Only the SNP of CYP3A4 (Ch7: 99361466 C>T, rs2242480) had a significantly higher association with SIR trough concentration as compared to the other 36 tagger SNPs. The mean trough SIR concentration of patients in the CYP3A4 rs2242480-CC group was more significant compared to that of the CYP3A4 rs2242480-TC and TT group, respectively 533.3; 157.4 and 142.5 (ng/ml)/mg/kg, P<0.0001. After adjusting the SNPs, there was no significant association between clinical factors such as age, follow-up period, the incidence of delayed graft function, immunosuppression protocol, and sex with SIR trough concentration. Conclusion:: These findings indicated a significant association of polymorphism in the CYP3A4 (Ch7: 99361466 C>T, rs2242480) with SIR trough concentration after 1-year administration in patients who have undergone kidney transplantation.

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Evaluation of the tacrolimus II microparticle enzyme immunoassay (MEIA II) in liver and renal transplant recipients

Clinical Chemistry ◽

10.1093/clinchem/44.9.1942 ◽

1998 ◽

Vol 44 (9) ◽

pp. 1942-1946 ◽

Cited By ~ 47

Author(s):

Jan L Cogill ◽

Paul J Taylor ◽

Ian S Westley ◽

Raymond G Morris ◽

Stephen V Lynch ◽

...

Keyword(s):

Renal Transplant ◽

Renal Transplant Patient ◽

Transplant Patient ◽

Therapeutic Drug ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Significant Difference ◽

Microparticle Enzyme Immunoassay ◽

Clinically Significant ◽

Comparison Data

Abstract We evaluated the MEIA II with blood samples with added tacrolimus (3.0, 5.0, 11.0, and 22.0 μg/L). The assay had acceptable recoveries (99–103%) and intraday imprecision (<16.0%) across the range of concentrations studied, except for the recoveries at 3.0 μg/L (86.3%) and 5.0 μg/L (80.7%). Comparison of liver (n = 116) and renal (n = 113) patient samples measured by MEIA II against HPLC-tandem mass spectrometry (HPLC-MS/MS) found a mean overestimation of 15.6%. From these comparison data it can be calculated that at values of 5 and 20 μg/L in liver or renal transplant patient samples, measured by HPLC-MS/MS, MEIA II will have the corresponding range estimates of 3.6–7.9 μg/L and 20.9–25.4 μg/L, respectively. No clinically significant difference in results, in terms of overestimation or correlation, was observed between the two transplant groups studied. The MEIA II is an improvement on the previous MEIA I and is suitable for the therapeutic drug monitoring of tacrolimus where HPLC-MS/MS is unavailable.

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Fatal cytomegalic inclusion disease. Associated skin manifestations in a renal transplant patient

Archives of Dermatology ◽

10.1001/archderm.113.11.1569 ◽

1977 ◽

Vol 113 (11) ◽

pp. 1569-1571 ◽

Cited By ~ 12

Author(s):

N. Minars

Keyword(s):

Renal Transplant ◽

Renal Transplant Patient ◽

Transplant Patient ◽

Skin Manifestations ◽

Cytomegalic Inclusion Disease

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Bk Polyoma Virus Nephropathy In An Immunocompromised Host.

New Emirates Medical Journal ◽

10.2174/0250688201999200520125625 ◽

2020 ◽

Vol 01 ◽

Author(s):

Faraz Khan ◽

Maroun El Khoury ◽

Fahad Kouli ◽

Aaron Han

Keyword(s):

Renal Transplant ◽

Graft Failure ◽

Renal Transplant Patient ◽

Relevant Literature ◽

Late Complication ◽

Solid Organ Transplantation ◽

Immunocompromised Host ◽

Polyoma Virus ◽

Solid Organ ◽

Early Graft

Background: Post-transplant Lymphopoliferative disorders(PTLD) are a well known late complication after solid organ transplantation including renal transplant. Among others, graft failure due to reactivation of BK polyoma virus in the grafted kidney is also a well recognized complication but tends to present early in the first several months after transplant. Case: Here we present the case of PTLD Burkitt's lymphoma(BL-PTLD) in a renal transplant patient who was successfully treated with multiagent chemo-immunotherapy but later developed BK polyoma virus nephropathy(BKVN) with graft failure only after completion of her systemic therapy for lymphoma and 7 years after transplant. Relevant literature is reviewed. Conclusion: In this case, reactivation and progression of BKVN was most likely associated with immunosuppression from chemoimmunotherapy for her BL–PTLD unlike early graft failures associated with BKVN.

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