Drug–Drug Interactions Involving Dexamethasone in Clinical Practice: Myth or Reality?

Bourdin, Venceslas; Bigot, William; Vanjak, Anthony; Burlacu, Ruxandra; Lopes, Amanda; Champion, Karine; Depond, Audrey; Amador-Borrero, Blanca; Sene, Damien; Comarmond, Chloe; Mouly, Stéphane

doi:10.3390/jcm12227120

Cited by 6 publications

(3 citation statements)

References 141 publications

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“…DEX is moderate inducer to CYP3A4 so the metabolism of TAM can be increased when combined with DEX [ 88 ]. Endoxifen, an active metabolite of TAM, is produced through N-demethylation mediated by CYP3A4 and hydroxylation mediated by CYP2D6.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone–tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells

Gaballah,

Elsherbiny,

Sharaky

et al. 2024

Bioscience Reports

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Tamoxifen (TAM) is a key player in estrogen receptor-positive (ER+) breast cancer (BC); however, ∼30% of patients experience relapse and a lower survival rate due to TAM resistance. TAM resistance was related to the over expression of SOX-2 gene, which is regulated by the E2F3 transcription factor in the Wnt signaling pathway. It was suggested that SOX-2 overexpression was suppressed by dexamethasone (DEX), a glucocorticoid commonly prescribed to BC patients. The aim of the present study is to explore the effect of combining DEX and TAM on the inhibition of TAM-resistant LCC-2 cells (TAMR-1) through modulating the E2F3/SOX-2-mediated Wnt signaling pathway. The effect of the combination therapy on MCF-7 and TAMR-1 cell viability was assessed. Drug interactions were analyzed using CompuSyn and SynergyFinder softwares. Cell cycle distribution, apoptotic protein expression, gene expression levels of SOX-2 and E2F3, and cell migration were also assessed. Combining DEX with TAM led to synergistic inhibition of TAMR-1 cell proliferation and migration, induced apoptosis, reduced SOX-2 and E2F3 expression and was also associated with S and G2-M phase arrest. Therefore, combining DEX with TAM may present an effective therapeutic option to overcome TAM resistance, by targeting the E2F3/SOX-2/Wnt signaling pathway, in addition to its anti-inflammatory effect.

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Section: Discussionmentioning

confidence: 99%

Dexamethasone–tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells

Gaballah,

Elsherbiny,

Sharaky

et al. 2024

Bioscience Reports

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“…The extent of voriconazole–dexamethasone interaction seems to depend on the dexamethasone dose. The induction of CYP450 enzymes, particularly CYP3A4, by dexamethasone is dose-dependent ( Bourdin et al, 2023 ). Co-administration of dexamethasone with high and moderate doses (20 and 12.5 mg) seemed to impact voriconazole C min.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, voriconazole has a long-lasting and potent inhibitory effect on CYP3A activity ( Huang et al, 2021 ). Dexamethasone and methylprednisolone are primarily metabolized by CYP3A4 ( Blanco-Dorado et al, 2020 ; Bourdin et al, 2023 ). The maximum plasma concentration (C max ) and the AUC from 0 h to infinity (AUC 0→inf ) of dexamethasone could be increased by 2.44-fold and 2.60-fold, respectively, when combined with voriconazole.…”

Section: Discussionmentioning

confidence: 99%

Case report: dose-dependent interaction between dexamethasone and voriconazole in severely ill patients with non-Hodgkin’s lymphoma being treated for invasive pulmonary aspergillosis

Huang,

Chen,

Zhong

et al. 2024

Front. Pharmacol.

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BackgroundVoriconazole is primarily metabolized by CYP2C19 and CYP3A4. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted voriconazole concentrations.Case summaryIn this case report, we describe the case of a 64-year-old man who was treated for non-Hodgkin’s lymphoma with continuous glucocorticoids co-administrated with voriconazole against invasive pulmonary aspergillosis. A decrease in trough concentration (Cmin) of voriconazole was observed and related with co-administration of dexamethasone in the patient carrying the CYP2C19 *1*2 genotype: voriconazole Cmin/dose ratios of 0.018 (0.1 mg L−1/5.7 mg kg−1 day−1), 0.18 (1 mg L−1/5.7 mg kg−1 day−1), and 0.23 (2 mg L−1/8.6 mg kg−1 day−1) at dexamethasone doses of 20, 12.5, and 2.5 mg, respectively. Sub-therapeutic voriconazole Cmin was associated with high- and moderate-dose dexamethasone (20 and 12.5 mg), leading to failure of antifungal treatment.ConclusionThe extent of voriconazole–dexamethasone interaction was determined by the dose of dexamethasone and associated with the CYP2C19 *1*2 genotype. Therapeutic drug monitoring of voriconazole is necessary to avoid clinically relevant interactions for optimal antifungal therapy.

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The Impact of Dexamethasone and Prednisone on Apixaban and Rivaroxaban Exposure in COVID‐19 Patients: A Physiologically Based Pharmacokinetic Modeling Study

Terrier,

Abouir,

Gaspar

et al. 2024

Clin Pharma and Therapeutics

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Dexamethasone (DEX) is currently the treatment of choice for patients with oxygen‐dependent COVID‐19. It has been observed, primarily in vitro, that dexamethasone induces the expression of CYP3A and the ABCB1 gene, which encodes P‐glycoprotein (P‐gp). This has raised concerns about potential interactions between DEX and substrates of CYP3A and P‐gp, such as direct oral anticoagulants (DOAC). Currently, there is limited robust evidence to support a clinically significant interaction between DEX and DOAC. Using physiologically based pharmacokinetic modeling (PBPK), we investigated the impact of DEX administered in the context of SARS‐CoV‐2 infection on the pharmacokinetics of apixaban (APX) and rivaroxaban (RVX). After validating the induction effect of the DEX compound on two CYP3A4 substrates using the limited available studies, we optimized the compound in a COVID‐19 patient population, where significantly higher DEX plasma concentrations were observed compared to healthy volunteers. Our PBPK‐based PK simulations showed a 20% decrease in the AUC of APX and RVX in a worst‐case scenario and when DEX was administered at 6 mg PO for 10 days. This finding confirms the limited clinical data currently available and supports the use of APX and RVX with DEX in COVID‐19 patients at low‐risk for thrombo‐embolism. In addition, our results suggest that prednisone (PRED), when used at an equipotent dose, could serve as a viable alternative to DEX, given its less pronounced induction effect on APX and RVX. Further research is needed to validate these findings and to explore the clinical implications of using PRED in place of DEX in such scenarios.

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Drug–Drug Interactions Involving Dexamethasone in Clinical Practice: Myth or Reality?

Cited by 6 publications

References 141 publications

Dexamethasone–tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells

Dexamethasone–tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells

Case report: dose-dependent interaction between dexamethasone and voriconazole in severely ill patients with non-Hodgkin’s lymphoma being treated for invasive pulmonary aspergillosis

The Impact of Dexamethasone and Prednisone on Apixaban and Rivaroxaban Exposure in COVID‐19 Patients: A Physiologically Based Pharmacokinetic Modeling Study

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