Evidence map›Paper›PMID 32712713›Full record

ArticleEuropean journal of clinical pharmacology2020

Flucloxacillin decreases tacrolimus blood trough levels: a single-center retrospective cohort study.

Herman Veenhof, Hugo M Schouw, Martine T P Besouw, Daan J Touw, Valentina Gracchi

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In one paragraph

Article in European journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Trial
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Herman VeenhofDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands. h.veenhof@umcg.nl.ORCID http://orcid.org/0000-0002-4929-4834
Hugo M SchouwDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.ORCID https://orcid.org/0000-0002-8996-4353
Martine T P BesouwDepartment of Pediatric Nephrology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0002-3452-0683
Daan J TouwDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.ORCID https://orcid.org/0000-0002-1429-4789
Valentina GracchiDepartment of Pediatric Nephrology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0002-0330-4283
University Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTacrolimus and everolimus are widely used to prevent allograft rejection. Both are metabolized by the hepatic cytochrome P450 (CYP) enzyme CYP3A4 and are substrate for P-glycoprotein (P-gp). Drugs influencing the activity or expression of CYP enzymes and P-gp can cause clinically relevant changes in the metabolism of immunosuppressants. Several case reports have reported that flucloxacillin appeared to decrease levels of drugs metabolized by CYP3A4 and P-gp. The magnitude of this decrease has not been reported yet.

methodsIn this single-center retrospective cohort study, we compared the tacrolimus and everolimus blood trough levels (corrected for the dose) before, during, and after flucloxacillin treatment in eleven transplant patients (tacrolimus n = 11 patients, everolimus n = 1 patient, flucloxacillin n = 11 patients).

resultsThe median tacrolimus blood trough level decreased by 37.5% (interquartile range, IQR 26.4-49.7%) during flucloxacillin treatment. After discontinuation of flucloxacillin, the tacrolimus blood trough levels increased by a median of 33.7% (IQR 22.5-51.4%). A Wilcoxon signed-rank test showed statistically significantly lower tacrolimus trough levels during treatment with flucloxacillin compared with before (p = 0.009) and after flucloxacillin treatment (p = 0.010). In the only available case with concomitant everolimus and flucloxacillin treatment, the same pattern was observed.

conclusionsFlucloxacillin decreases tacrolimus trough levels, possibly through a CYP3A4 and/or P-gp-inducing effect. It is strongly recommended to closely monitor tacrolimus and everolimus trough levels during flucloxacillin treatment and up to 2 weeks after discontinuation of flucloxacillin.

Indexed as

AdultAgedATP Binding Cassette Transporter, Subfamily BChildChild, PreschoolCytochrome P-450 CYP3ADrug InteractionsEverolimusFemaleFloxacillinGraft RejectionHumansImmunosuppressive AgentsMaleMiddle AgedOrgan TransplantationABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BCYP3A4 protein, humanCytochrome P-450 CYP3AEverolimusFloxacillinImmunosuppressive AgentsTacrolimusBlood trough levelsCYP3A4Drug-drug interactionEverolimusFlucloxacillinTacrolimusTherapeutic drug monitoring

Identifiers

PMID32712713
PMCPMC7661399
OpenAlexW3044056976

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.