Article Figures & Tables
Figures
- 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
- Table 1:
Selected drugs that interact with grapefruit, associated oral bioavailability, adverse event(s), predicted risk and possible alternative agents
Interacting drugs Innate oral bioavailability* Dose-related adverse event(s) Predicted interaction risk† Potential alternative agent(s)‡ Anticancer agents Crizotinib Intermediate Torsade de pointes, myelotoxicity High Dasatinib Not known Torsade de pointes, myelotoxicity High Imatinib Erlotinib Intermediate Myelotoxicity High Everolimus Low Myelotoxicity, nephrotoxicity High Lapatinib Incomplete Torsade de pointes, myelotoxicity High Nilotinib Intermediate Torsade de pointes, myelotoxicity High Imatinib Pazopanib Incomplete Torsade de pointes, myelotoxicity High Sorafenib Sunitinib Not known Torsade de pointes, myelotoxicity High Sorafenib Vandetanib Not known Torsade de pointes, myelotoxicity High Venurafenib Not known Torsade de pointes, myelotoxicity High Anti-infective agents Erythromycin Intermediate Torsade de pointes High Clarithromycin Halofantrine Low Torsade de pointes Very high Doxycycline Maraviroc Low Postural hypotension, syncope Very high Enfuvirtide Primaquine Intermediate Myelotoxicity High Doxycycline Quinine Intermediate Torsade de pointes High Doxycycline Rilpivirine Not known Torsade de pointes High Nevirapine Antilipemic agents Atorvastatin Low Rhabdomyolysis High Pravastatin, rosuvastatin, fluvastatin Lovastatin Very low Rhabdomyolysis Very high Pravastatin, rosuvastatin, fluvastatin Simvastatin Very low Rhabdomyolysis Very high Pravastatin, rosuvastatin, fluvastatin Cardiovascular agents Amiodarone Intermediate Torsade de pointes High Sotalol Apixaban Intermediate GI bleeding High Warfarin Clopidogrel Very low Loss of efficacy High Acetylsalicylic acid Dronedarone Low Torsade de pointes Very high Sotalol Eplerenone Intermediate Hyperkalemia, serious arrhythmias High Spironolactone Felodipine Low Hypotension, peripheral edema Intermediate Amlodipine Nifedipine Intermediate Hypotension, peripheral edema Intermediate Amlodipine Quinidine High Torsade de pointes Intermediate Rivaroxaban High GI bleeding Intermediate Warfarin Ticagrelor Intermediate GI or kidney bleeding High Acetylsalicyclic acid CNS agents Alfentanil (oral) Intermediate Respiratory depression High Hydromorphone, morphine Buspirone Very low Dizziness, sedation High Oxazepam, tamazepam Dextromethorphan Very low Hallucinations, somnolence High Fentanyl (oral) Intermediate Respiratory depression High Hydromorphone, morphine Ketamine (oral) Low Respiratory depression Very high Hydromorphone, morphine Lurasidone Low Torsade de pointes, orthostatic hypotension, syncope Very high Haloperidol, risperidone olanzapine Oxycodone Intermediate Respiratory depression High Hydromorphone, morphine Pimozide Intermediate Torsade de pointes High Haloperidol, risperidone, olanzapine Quetiapine Very low Dizziness, somnolence High Haloperidol, risperidone, olanzapine Triazolam Intermediate Sedation Intermediate Alprazolam, lorazepam Ziprasidone Intermediate Torsade de pointes High Haloperidol, risperidone olanzapine Gastrointestinal agents Domperidone Low Torsade de pointes Very high Metoclopramide Immunosuppressants Cyclosporine Low Nephrotoxicity High Everolimus Low Myelotoxicity, nephrotoxicity High Sirolimus Low Myelotoxicity, nephrotoxicity High Tacrolimus Low Nephrotoxicity High Urinary tract agents Darifenacin Low Urinary retention, constipation Intermediate Fesoterodine Intermediate Urinary retention, constipation Intermediate Solifenacin High Torsade de pointes Intermediate Silodosin Intermediate Postural hypotension, dizziness Intermediate Tamsulosin Intermediate Postural hypotension, dizziness Intermediate 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.
- Table 2:
Case reports of serious adverse events related to grapefruit–drug interaction18–26
Serious adverse event Drug Amount of grapefruit consumed Torsade de pointes Amiodarone18 Juice, 1–1.5 L/d on a regular basis Quinine in tonic water19 Juice, high volume during preceding days Complete heart block Verapamil20 Juice, high volume during preceding days Rhabdomyolysis Atorvastatin21,22 Juice, 1–2 glasses/d for 5 d; juice from fresh grapefruit daily for 2 mo Simvastatin23 Whole fruit, 1 fruit/d for 2 wk Nephrotoxicity Tacrolimus24 Marmalade, 1.5 kg eaten during preceding 1 wk Myelotoxicity Colchicine25 Juice, 1 L/d for preceding 2 mo Venous thrombosis Ethinylestradiol26 Whole fruit, 1 fruit/d for breakfast for preceding 3 d
In this issue
Article tools
Respond to this article
Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?
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
Related Articles
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
More in this TOC Section
Similar Articles
Collections
