Aprepitant and fosaprepitant drug interactions: a systematic review

Br J Clin Pharmacol. 2017 Oct;83(10):2148-2162. doi: 10.1111/bcp.13322. Epub 2017 Jun 10.

Abstract

Aims: Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant.

Methods: We systematically reviewed the literature to September 11, 2016, to identify articles evaluating drug interactions involving aprepitant/fosaprepitant. The clinical significance of each reported pharmacokinetic drug interaction was evaluated based on the United States Food and Drug Administration guidance document on conducting drug interaction studies. The probability of an adverse event reported in case reports being due to a drug interaction with aprepitant/fosaprepitant was determined using the Drug Interaction Probability Scale.

Results: A total of 4377 publications were identified. Of these, 64 met inclusion eligibility criteria: 34 described pharmacokinetic drug interactions and 30 described adverse events ascribed to a drug interaction. Clinically significant pharmacokinetic interactions between aprepitant/fosaprepitant and bosutinib PO, cabazitaxel IV, cyclophosphamide IV, dexamethasone PO, methylprednisolone IV, midazolam PO/IV, oxycodone PO and tolbutamide PO were identified, as were adverse events resulting from an interaction between aprepitant/fosaprepitant and alcohol, anthracyclines, ifosfamide, oxycodone, quetiapine, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and warfarin.

Conclusions: The potential for a drug interaction with aprepitant and fosaprepitant should be considered when selecting antiemetic therapy.

Keywords: aprepitant; drug-drug interactions; fosaprepitant.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antiemetics / pharmacology*
  • Antiemetics / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Aprepitant
  • Cytochrome P-450 CYP2C9 Inducers / pharmacology
  • Cytochrome P-450 CYP2C9 Inducers / therapeutic use
  • Cytochrome P-450 CYP3A Inhibitors / pharmacology*
  • Cytochrome P-450 CYP3A Inhibitors / therapeutic use
  • Drug Interactions
  • Ethanol / pharmacology
  • Humans
  • Injection Site Reaction / etiology
  • Morpholines / pharmacology*
  • Morpholines / therapeutic use
  • Nausea / chemically induced
  • Nausea / prevention & control
  • Oxycodone / pharmacology
  • Oxycodone / therapeutic use
  • Quetiapine Fumarate / pharmacology
  • Quetiapine Fumarate / therapeutic use
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin and Noradrenaline Reuptake Inhibitors / pharmacology
  • Serotonin and Noradrenaline Reuptake Inhibitors / therapeutic use
  • Vomiting / chemically induced
  • Vomiting / prevention & control

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Cytochrome P-450 CYP2C9 Inducers
  • Cytochrome P-450 CYP3A Inhibitors
  • Morpholines
  • Serotonin Uptake Inhibitors
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Aprepitant
  • Quetiapine Fumarate
  • Ethanol
  • fosaprepitant
  • Oxycodone