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Master Thesis

Interactions médicamenteuses entre aprépitant et chimiothérapies anticancéreuses substrats du cytochrome p3A4 : analyse de signaux de disproportionnalité extraits de la base mondiale de pharmacovigilance

Abstract : Introduction: Aprepitant, widely used for the prevention of chemotherapy-induced nausea and vomiting, exerts modest inhibitory and inductive effect on CYP3A4. Since several cytotoxic chemotherapies are CYP3A4 substrates, the question of the potential consequences of the drug-drug interactions (DDI) between aprepitant and these CYP3A4 substrates is a concern for health care professionals. We aimed to study real-life data on the consequences of this association, using a pharmacovigilance database. Methods: The WHO pharmacovigilance database was used to compare the proportion of adverse drug reactions (ADR) with twelve chemotherapeutic agents that are CYP3A4 substrates, alone and in combination with aprepitant, using the reporting odds ratio (ROR) with relevant 95% confident interval (95% CI). For each chemotherapy, a representative dose-dependent ADR was selected according to the preferred terms (PT) or the standardized MedDRA Queries (SMQ) of the Medical Dictionary for Regulatory Activities (MedDRA). The additive model was applied to detect drug-drug interactions. Results: We extracted 82,167 cases of ADR from Vigibase®. Concomitant exposure to ifosfamide and aprepitant was associated with a higher reporting of encephalopathy (no. of cases = 110; ROR = 300.3; 95% CI = 233.7-385.8). Concomitant exposure to trabectedin and aprepitant was associated with a higher reporting of rhabdomyolysis (no. of cases = 7; ROR = 121.9; 95% CI = 53.7-276.9). No DDI disproportionality signal was observed when aprepitant was associated with cyclophosphamide, doxorubicin, etoposide, irinotecan, taxanes and vinca-alcaloids, according to the additive model. Conclusion: This study highlights the need for further investigation, especially pharmacokinetic studies, of the aprepitant-ifosfamide interaction; and to investigate the aprepitant-trabectedine interaction to confirm or not the detected signal.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03631389
Contributor : Jean-Hugues Morneau Connect in order to contact the contributor
Submitted on : Thursday, April 21, 2022 - 9:10:11 AM
Last modification on : Friday, April 22, 2022 - 3:36:30 AM

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Marianne Cumin. Interactions médicamenteuses entre aprépitant et chimiothérapies anticancéreuses substrats du cytochrome p3A4 : analyse de signaux de disproportionnalité extraits de la base mondiale de pharmacovigilance. Sciences pharmaceutiques. 2021. ⟨dumas-03631389⟩

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