Skip to main content

Main menu

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 Articles
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2022
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN

User menu

Search

  • Advanced search
CMAJ
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN
CMAJ

Advanced Search

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 Articles
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2022
  • Visit CMAJ on Facebook
  • Follow CMAJ on Twitter
  • Follow CMAJ on Pinterest
  • Follow CMAJ on Youtube
  • Follow CMAJ on Instagram
Review

Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?

David G. Bailey, George Dresser and J. Malcolm O. Arnold
CMAJ March 05, 2013 185 (4) 309-316; DOI: https://doi.org/10.1503/cmaj.120951
David G. Bailey
From the Lawson Health Research Institute (Bailey), London, Ont.; the Department of Medicine (Arnold, Dresser) and the Divisions of Cardiology (Arnold) and Clinical Pharmacology (Dresser), Western University, London, Ont.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: david.bailey@lhsc.on.ca
George Dresser
From the Lawson Health Research Institute (Bailey), London, Ont.; the Department of Medicine (Arnold, Dresser) and the Divisions of Cardiology (Arnold) and Clinical Pharmacology (Dresser), Western University, London, Ont.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Malcolm O. Arnold
From the Lawson Health Research Institute (Bailey), London, Ont.; the Department of Medicine (Arnold, Dresser) and the Divisions of Cardiology (Arnold) and Clinical Pharmacology (Dresser), Western University, London, Ont.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Tables
  • Related Content
  • Responses
  • Metrics
  • PDF
Loading

Article Figures & Tables

Figures

  • Tables
  • Figure 1:
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1:

    Sequential first-pass elimination of a drug, such as felodipine, through metabolism in enterocytes of the small intestine, then hepatocytes of the liver. The percentages of the initial dose that are available before and after passage through the gut wall and liver are shown. Although felodipine is 100% absorbed from the gastrointestinal tract, its bioavailability is only 15% after oral administration. CYP3A4 = cytochrome P450 enzyme 3A4.

    Image courtesy of Christine Kenny

Tables

  • Figures
    • View popup
    Table 1:

    Selected drugs that interact with grapefruit, associated oral bioavailability, adverse event(s), predicted risk and possible alternative agents

    Interacting drugsInnate oral bioavailability*Dose-related adverse event(s)Predicted interaction risk†Potential alternative agent(s)‡
    Anticancer agents
    CrizotinibIntermediateTorsade de pointes, myelotoxicityHigh
    DasatinibNot knownTorsade de pointes, myelotoxicityHighImatinib
    ErlotinibIntermediateMyelotoxicityHigh
    EverolimusLowMyelotoxicity, nephrotoxicityHigh
    LapatinibIncompleteTorsade de pointes, myelotoxicityHigh
    NilotinibIntermediateTorsade de pointes, myelotoxicityHighImatinib
    PazopanibIncompleteTorsade de pointes, myelotoxicityHighSorafenib
    SunitinibNot knownTorsade de pointes, myelotoxicityHighSorafenib
    VandetanibNot knownTorsade de pointes, myelotoxicityHigh
    VenurafenibNot knownTorsade de pointes, myelotoxicityHigh
    Anti-infective agents
    ErythromycinIntermediateTorsade de pointesHighClarithromycin
    HalofantrineLowTorsade de pointesVery highDoxycycline
    MaravirocLowPostural hypotension, syncopeVery highEnfuvirtide
    PrimaquineIntermediateMyelotoxicityHighDoxycycline
    QuinineIntermediateTorsade de pointesHighDoxycycline
    RilpivirineNot knownTorsade de pointesHighNevirapine
    Antilipemic agents
    AtorvastatinLowRhabdomyolysisHighPravastatin, rosuvastatin, fluvastatin
    LovastatinVery lowRhabdomyolysisVery highPravastatin, rosuvastatin, fluvastatin
    SimvastatinVery lowRhabdomyolysisVery highPravastatin, rosuvastatin, fluvastatin
    Cardiovascular agents
    AmiodaroneIntermediateTorsade de pointesHighSotalol
    ApixabanIntermediateGI bleedingHighWarfarin
    ClopidogrelVery lowLoss of efficacyHighAcetylsalicylic acid
    DronedaroneLowTorsade de pointesVery highSotalol
    EplerenoneIntermediateHyperkalemia, serious arrhythmiasHighSpironolactone
    FelodipineLowHypotension, peripheral edemaIntermediateAmlodipine
    NifedipineIntermediateHypotension, peripheral edemaIntermediateAmlodipine
    QuinidineHighTorsade de pointesIntermediate
    RivaroxabanHighGI bleedingIntermediateWarfarin
    TicagrelorIntermediateGI or kidney bleedingHighAcetylsalicyclic acid
    CNS agents
    Alfentanil (oral)IntermediateRespiratory depressionHighHydromorphone, morphine
    BuspironeVery lowDizziness, sedationHighOxazepam, tamazepam
    DextromethorphanVery lowHallucinations, somnolenceHigh
    Fentanyl (oral)IntermediateRespiratory depressionHighHydromorphone, morphine
    Ketamine (oral)LowRespiratory depressionVery highHydromorphone, morphine
    LurasidoneLowTorsade de pointes, orthostatic hypotension, syncopeVery highHaloperidol, risperidone olanzapine
    OxycodoneIntermediateRespiratory depressionHighHydromorphone, morphine
    PimozideIntermediateTorsade de pointesHighHaloperidol, risperidone, olanzapine
    QuetiapineVery lowDizziness, somnolenceHighHaloperidol, risperidone, olanzapine
    TriazolamIntermediateSedationIntermediateAlprazolam, lorazepam
    ZiprasidoneIntermediateTorsade de pointesHighHaloperidol, risperidone olanzapine
    Gastrointestinal agents
    DomperidoneLowTorsade de pointesVery highMetoclopramide
    Immunosuppressants
    CyclosporineLowNephrotoxicityHigh
    EverolimusLowMyelotoxicity, nephrotoxicityHigh
    SirolimusLowMyelotoxicity, nephrotoxicityHigh
    TacrolimusLowNephrotoxicityHigh
    Urinary tract agents
    DarifenacinLowUrinary retention, constipationIntermediate
    FesoterodineIntermediateUrinary retention, constipationIntermediate
    SolifenacinHighTorsade de pointesIntermediate
    SilodosinIntermediatePostural hypotension, dizzinessIntermediate
    TamsulosinIntermediatePostural hypotension, dizzinessIntermediate
    • Note: CNS = central nervous system, GI = gastrointestinal.

    • ↵* Population average: very low < 10%, low >10%–30%, intermediate >30%–70%, high > 70%.

    • ↵† Based on the seriousness of the adverse effect and adjusted for the innate oral bioavailability of the drug, which is used to determine the potential increase in systemic drug concentration. For older patients, particularly the elderly, it is recommended that grapefruit or other citrus fruits be contraindicated for drugs in the very high or high category, or that a suggested alternative noninteracting drug be employed when available.

    • ↵‡ Commonly prescribed drugs (Top 100 prescribed in 2011 in Canada) with the same therapeutic indication that have no or minor pharmacokinetic interaction with grapefruit or other citrus fruits.

    • View popup
    Table 2:

    Case reports of serious adverse events related to grapefruit–drug interaction18–26

    Serious adverse eventDrugAmount of grapefruit consumed
    Torsade de pointesAmiodarone18Juice, 1–1.5 L/d on a regular basis
    Quinine in tonic water19Juice, high volume during preceding days
    Complete heart blockVerapamil20Juice, high volume during preceding days
    RhabdomyolysisAtorvastatin21,22Juice, 1–2 glasses/d for 5 d; juice from fresh grapefruit daily for 2 mo
    Simvastatin23Whole fruit, 1 fruit/d for 2 wk
    NephrotoxicityTacrolimus24Marmalade, 1.5 kg eaten during preceding 1 wk
    MyelotoxicityColchicine25Juice, 1 L/d for preceding 2 mo
    Venous thrombosisEthinylestradiol26Whole fruit, 1 fruit/d for breakfast for preceding 3 d
PreviousNext
Back to top

In this issue

Canadian Medical Association Journal: 185 (4)
CMAJ
Vol. 185, Issue 4
5 Mar 2013
  • Table of Contents
  • Index by author

Article tools

Respond to this article
Print
Download PDF
Article Alerts
To sign up for email alerts or to access your current email alerts, enter your email address below:
Email Article

Thank you for your interest in spreading the word on CMAJ.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?
(Your Name) has sent you a message from CMAJ
(Your Name) thought you would like to see the CMAJ web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?
David G. Bailey, George Dresser, J. Malcolm O. Arnold
CMAJ Mar 2013, 185 (4) 309-316; DOI: 10.1503/cmaj.120951

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
‍ Request Permissions
Share
Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?
David G. Bailey, George Dresser, J. Malcolm O. Arnold
CMAJ Mar 2013, 185 (4) 309-316; DOI: 10.1503/cmaj.120951
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • What are the key scientific concepts of grapefruit–drug interactions?
    • What determines which drugs are affected?
    • What determines the clinical significance of the interaction?
    • Who is at higher risk of grapefruit–drug interactions?
    • What are examples of important grapefruit–drug interactions?
    • Gaps in knowledge
    • Conclusion
    • Footnotes
    • References
  • Figures & Tables
  • Related Content
  • Responses
  • Metrics
  • PDF

Related Articles

  • Highlights
  • PubMed
  • Google Scholar

Cited By...

  • Parallel evolution of UbiA superfamily proteins into aromatic O-prenyltransferases in plants
  • Natural Products as Modulators of CES1 Activity
  • Parallel evolution of UbiA superfamily proteins into aromatic O-prenyltransferases in plants
  • Regional Proteomic Quantification of Clinically Relevant Non-Cytochrome P450 Enzymes along the Human Small Intestine
  • Severity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study
  • Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction
  • Citrus Consumption and Risk of Cutaneous Malignant Melanoma
  • Assessment of a Candidate Marker Constituent Predictive of a Dietary Substance-Drug Interaction: Case Study with Grapefruit Juice and CYP3A4 Drug Substrates
  • Identification of Diet-Derived Constituents as Potent Inhibitors of Intestinal Glucuronidation
  • Grapefruit juice and clopidogrel
  • Grapefruit juice and clopidogrel
  • Comparing two types of macrolide antibiotics for the purpose of assessing population-based drug interactions
  • Grapefruit-medication interactions
  • Grapefruit-medication interactions
  • Google Scholar

More in this TOC Section

  • Diagnosis and management of postural orthostatic tachycardia syndrome
  • A practical approach to prescribing antiplatelet therapy in patients with acute coronary syndromes
  • Prevention and management of hyperkalemia in patients treated with renin–angiotensin–aldosterone system inhibitors
Show more Review

Similar Articles

Collections

  • Topics
    • Drugs: adverse reactions

 

View Latest Classified Ads

Content

  • Current issue
  • Past issues
  • Collections
  • Sections
  • Blog
  • Podcasts
  • Alerts
  • RSS
  • Early releases

Information for

  • Advertisers
  • Authors
  • Reviewers
  • CMA Members
  • CPD credits
  • Media
  • Reprint requests
  • Subscribers

About

  • General Information
  • Journal staff
  • Editorial Board
  • Advisory Panels
  • Governance Council
  • Journal Oversight
  • Careers
  • Contact
  • Copyright and Permissions
  • Accessibiity
  • CMA Civility Standards
CMAJ Group

Copyright 2022, CMA Impact Inc. or its licensors. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p)

All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association or its subsidiaries.

To receive any of these resources in an accessible format, please contact us at CMAJ Group, 500-1410 Blair Towers Place, Ottawa ON, K1J 9B9; p: 1-888-855-2555; e: cmajgroup@cmaj.ca

Powered by HighWire