title: Drug interactions with aprepitant or fosaprepitant: Review of literature and implications for clinical practice.
abstract: Purpose Aprepitant and its parenteral formulation fosaprepitant are widely used for the prevention of chemotherapy-induced nausea and vomiting. Aprepitant exerts modest inhibitory effect on CYP3A4 and modest inductive effect on CYP2C9 substrates such as some antineoplastics and multiple other medications. This article is aimed to provide pharmacists and other healthcare professionals with an updated summary of drug-drug interactions of aprepitant/fosaprepitant and implications for clinical practice. Method We reviewed publications reporting drug-drug interactions between aprepitant/fosaprepitant and other medications. Results Coadministration of aprepitant with antineoplastics or opiods may result in significant elevations in the serum levels of the agents metabolized via CYP3A4, with the best documentation for cyclophosphamide, ifosfamide, erlotinib and oxycodone. These alterations did not translate into adverse outcomes and/or necessitate dosing adjustments. The levels of warfarin were significantly decreased by aprepitant requiring prolonged monitoring after discontinuation of aprepitant. Among direct oral anticoagulants, a theoretical interaction between aprepitant and rivaroxaban or apixaban exists. Interactions between aprepitant and quetiapine or diltiazem or sirolimus required dose reductions to avoid adverse outcomes. The intravenous route had a weaker inhibitory effect on CYP3A4 than the oral pathway. Conclusion The evidence on drug interactions of aprepitant with other medications is limited, and the impact on therapeutic outcomes remains to be determined. The intravenous regimen may be a preferred option. As utilization of aprepitant is expanding, practitioners and patients need to be educated about the potential for drug interactions and a need for careful monitoring of patients concurrently receiving aprepitant and CYP2C9 or CYP3A4 substrates, especially those with a narrow therapeutic window.
authors.affiliation: School of Pharmacy, Fairleigh Dickinson University, NJ, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Dushenkov
authors.affiliation: School of Pharmacy, Fairleigh Dickinson University, NJ, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Kalabalik
authors.affiliation: School of Pharmacy, Fairleigh Dickinson University, NJ, USA.
authors.forename: Antonia
authors.initials: A
authors.lastname: Carbone
authors.affiliation: School of Pharmacy, Fairleigh Dickinson University, NJ, USA.
authors.forename: Paiboon
authors.initials: P
authors.lastname: Jungsuwadee
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077608:Aprepitant; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000925:Anticoagulants; D000932:Antiemetics; D000970:Antineoplastic Agents; D009025:Morpholines; D000077608:Aprepitant; C579707:fosaprepitant; D051544:Cytochrome P-450 CYP3A
keywords: Aprepitant; cytochrome P450 enzyme system; drug interactions; fosaprepitant