Grapefruit–drug interactions: Difference between revisions

Latest revision as of 17:49, 1 April 2025

Grapefruit–drug interactions refer to the phenomenon where consumption of grapefruit or grapefruit juice affects the metabolism of certain medications, leading to either diminished or enhanced drug effects. This interaction is a significant concern in pharmacology and clinical medicine due to its potential to alter therapeutic outcomes or cause adverse effects. The grapefruit, a common citrus fruit, is known for its unique taste and nutritional value, but it is also notable for its potential to interfere with the metabolism of numerous drugs. As of 2014, over 85 medications have been identified that may interact adversely with grapefruit. These interactions can lead to either subtherapeutic drug levels or dangerously high concentrations of active substances in the bloodstream.

Mechanism of Interaction[edit]

The interaction is primarily due to organic compounds in grapefruit known as furanocoumarins. These compounds inhibit the activity of cytochrome P450 3A4 (CYP3A4), an enzyme present in both the liver and the small intestine that plays a central role in the first-pass metabolism of many orally administered drugs.

When CYP3A4 is inhibited, drugs that are normally broken down by this enzyme may remain in the body at higher concentrations for longer periods, increasing the risk of side effects or toxicity. In contrast, some drugs may become less effective if their activation requires metabolic conversion by CYP3A4.

Commonly Affected Drugs[edit]

Grapefruit interactions can affect a wide variety of medications, including but not limited to:

Statins (e.g., simvastatin, atorvastatin) – increased risk of rhabdomyolysis
Calcium channel blockers (e.g., felodipine, nifedipine) – excessive hypotension
Immunosuppressants (e.g., cyclosporine, tacrolimus) – increased nephrotoxicity
Benzodiazepines (e.g., midazolam, triazolam) – enhanced sedative effects
Antihistamines (e.g., fexofenadine) – altered absorption
Psychotropic drugs (e.g., quetiapine, buspirone) – increased central nervous system effects

Clinical Implications[edit]

Healthcare providers should be vigilant when prescribing medications that are metabolized by CYP3A4 and advise patients to avoid grapefruit products if a potential interaction exists. Even a single serving of grapefruit juice can inhibit intestinal CYP3A4 for over 24 hours, meaning spacing the intake of grapefruit and the drug will not necessarily prevent the interaction.

Alternatives and Precautions[edit]

Patients who enjoy citrus fruits can often substitute oranges, lemons, or limes, which do not contain the same inhibitory compounds. However, Seville oranges (used in marmalade), pomelos, and tangelos may have similar effects as grapefruit and should also be avoided with susceptible medications.

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-[[File:Grapefruit Juice and Medicine May Not Mix (6921050581).jpg|thumb|upright=2.0|right|grapefruit interacts with the effects of some drugs]]
+[[File:Grapefruit Juice and Medicine May Not Mix (6921050581).jpg|thumb|upright=2.0|right|grapefruit interacts with the effects of some drugs]]'''Grapefruit–drug interactions''' refer to the phenomenon where consumption of [[grapefruit]] or [[grapefruit juice]] affects the metabolism of certain [[medications]], leading to either diminished or enhanced drug effects. This interaction is a significant concern in [[pharmacology]] and [[clinical medicine]] due to its potential to alter therapeutic outcomes or cause adverse effects. The [[grapefruit]], a common [[citrus fruit]], is known for its unique taste and nutritional value, but it is also notable for its potential to interfere with the metabolism of numerous drugs. As of 2014, over 85 medications have been identified that may interact adversely with grapefruit. These interactions can lead to either subtherapeutic drug levels or dangerously high concentrations of active substances in the bloodstream.
-The [[grapefruit]], a popular citrus fruit, and its juice, have long been noted for their potential to [[Drug interaction|interact]] with a wide array of [[drugs]], resulting in either diminished or enhanced effects of the medications. The count of drugs known to interact adversely with grapefruit has been steadily growing, with 85 identified interactions as of May 2014.<ref>{{cite doi|10.1503/cmaj.120951}}</ref> Understanding these interactions is vital to both the pharmaceutical industry and healthcare providers.
-=== Mechanism of Interaction ===
+== Mechanism of Interaction ==
+The interaction is primarily due to organic compounds in grapefruit known as '''[[furanocoumarins]]'''. These compounds inhibit the activity of '''[[cytochrome P450]] 3A4''' ('''CYP3A4'''), an enzyme present in both the liver and the [[small intestine]] that plays a central role in the first-pass metabolism of many orally administered drugs.
-The primary culprits behind grapefruit's ability to modulate drug effects are organic compounds known as [[furanocoumarin]] derivatives. These compounds inhibit the action of the [[cytochrome P450]] enzyme [[isoform]] [[CYP3A4]], which is found in the [[Liver|hepatic]] and [[Intestine|intestinal]] systems. This enzyme plays a pivotal role in drug metabolism, and its inhibition can significantly alter the bioavailability and clinical effect of various drugs.
+When CYP3A4 is inhibited, drugs that are normally broken down by this enzyme may remain in the body at higher concentrations for longer periods, increasing the risk of side effects or toxicity. In contrast, some drugs may become less effective if their activation requires metabolic conversion by CYP3A4.
-Furthermore, bioactive compounds present in grapefruit juice can interfere with other transport proteins like [[P-glycoprotein]] and [[organic anion transporting polypeptide]]s (OATPs). Such interference can either enhance or diminish the absorption and consequent effects of numerous drugs.
+== Commonly Affected Drugs ==
+Grapefruit interactions can affect a wide variety of medications, including but not limited to:
+* '''[[Statins]]''' (e.g., [[simvastatin]], [[atorvastatin]]) – increased risk of [[rhabdomyolysis]]
+* '''[[Calcium channel blockers]]''' (e.g., [[felodipine]], [[nifedipine]]) – excessive [[hypotension]]
+* '''[[Immunosuppressants]]''' (e.g., [[cyclosporine]], [[tacrolimus]]) – increased [[nephrotoxicity]]
+* '''[[Benzodiazepines]]''' (e.g., [[midazolam]], [[triazolam]]) – enhanced sedative effects
+* '''[[Antihistamines]]''' (e.g., [[fexofenadine]]) – altered [[absorption]]
+* '''[[Psychotropic drugs]]''' (e.g., [[quetiapine]], [[buspirone]]) – increased central nervous system effects
-Of interest is the [[pomelo]], the Asian fruit crossed with an orange to give rise to the grapefruit. It also contains substantial amounts of furanocoumarin derivatives. However, some hybrid varieties of [[grapefruit]]-[[pomelo]] have been developed with minimal to non-existent furanocoumarin content. There is even a commercially viable seedless type of this hybrid.<ref>{{cite web|url=http://www.futurity.org/health-medicine/hybrid-grapefruit-safe-for-prescription-meds/#more-42339 |title=– Hybrid grapefruit safe for prescription meds |publisher=Futurity.org |accessdate=2013-01-28}}</ref>
+== Clinical Implications ==
+Healthcare providers should be vigilant when prescribing medications that are metabolized by CYP3A4 and advise patients to avoid grapefruit products if a potential interaction exists. Even a single serving of grapefruit juice can inhibit intestinal CYP3A4 for over 24 hours, meaning spacing the intake of grapefruit and the drug will not necessarily prevent the interaction.
-=== Drugs Affected by Grapefruit ===
+== Alternatives and Precautions ==
+Patients who enjoy citrus fruits can often substitute [[oranges]], [[lemons]], or [[limes]], which do not contain the same inhibitory compounds. However, [[Seville oranges]] (used in marmalade), [[pomelos]], and [[tangelos]] may have similar effects as grapefruit and should also be avoided with susceptible medications.
-The following drugs have been identified to interact with grapefruit due to the inhibition of [[CYP3A4]]:
-Benzodiazepines: [[triazolam]] (Halcion), orally administered [[midazolam]] (Versed), orally administered [[nitrazepam]] (Mogodon), [[diazepam]] (Valium), [[alprazolam]] (Xanax) and [[quazepam]] (Doral, Dormalin).<ref>{{cite journal |author=Sugimoto K, Araki N, Ohmori M, et al. |title=Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam |journal=Eur. J. Clin. Pharmacol. |volume=62 |issue=3 |pages=209–15 |year=2006 |pmid=16416305 |doi=10.1007/s00228-005-0071-1}}</ref>
-Amphetamines: certain varieties such as dextroamphetamine and levoamphetamine have been noted to interact with grapefruit.<ref>{{cite pubmed.gov |author=Wu D1, Otton SV, Inaba T, Kalow W, Sellers EM |title=Interactions of amphetamine analogs with human liver CYP2D6.}}</ref>
-Antiretroviral drugs: [[ritonavir]] (Norvir) is particularly affected due to CYP3A4 inhibition which prevents its metabolism.<ref>{{cite web
-|url= http://hivinsite.ucsf.edu/InSite?page=ar-03-02
-|title= Ritonavir (Norvir)
-|work= HIV InSite
-|publisher= [[UCSF]]
-|date= 2006-10-18
-|accessdate= 2008-03-12
-}}</ref>
-Antidepressants: [[sertraline]] (Zoloft and Lustral) can have altered effects in the presence of grapefruit juice.<ref>{{cite journal
-|doi=10.1016/S0149-2918(00)86737-5
-|author=Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BC.
-|title=The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study.
-|journal=Clin Ther.
-|volume=21
-|issue=11
-|pages=1890–9
-|year=1999
-|pmid=10890261
-}}</ref>
-Further in-depth information is provided on Amphetamines:
-== Amphetamines and Grapefruit ==
-Amphetamines are a class of stimulants that can interact with the Cytochrome P450 CYP2D6 enzyme, which is affected by grapefruit. In particular, dextroamphetamine and levoamphetamine have interactions related to this enzyme.
-The primary mechanism involves the fact that grapefruit and its juice inhibit the action of CYP2D6, leading to a potential increase in the plasma concentrations of these amphetamines when they are consumed with grapefruit or grapefruit juice. An increase in plasma concentration may intensify the therapeutic effects of these amphetamines but can also increase the risk of side effects.<ref>{{cite pubmed.gov |author=Wu D1, Otton SV, Inaba T, Kalow W, Sellers EM |title=Interactions of amphetamine analogs with human liver CYP2D6.}}</ref>
-Patients who are on amphetamines or are considering starting them should consult with their healthcare provider regarding potential interactions and the consumption of grapefruit or grapefruit juice.
 == See Also ==
+* [[Drug metabolism]]
-* [[List of foods that may interact with medications]]
+* [[Cytochrome P450]]
-* [[Drug interaction]]
+* [[Enzyme inhibition]]
-== References ==
+* [[First-pass effect]]
+* [[Pharmacokinetics]]
-{{reflist|2}}
-== External Links ==
-* [https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm292276.htm FDA: Grapefruit Juice and Some Drugs Don't Mix]
-* [https://www.webmd.com/food-recipes/news/20130129/grapefruit-drug-interactions-avoided Grapefruit-Drug Interactions Can Be Deadly, Study Suggests]
-* [https://www.futurity.org/health-medicine/hybrid-grapefruit-safe-for-prescription-meds/#more-42339 Hybrid grapefruit safe for prescription meds]
-{{stub}}
-[[Category:Fruit]]
 [[Category:Pharmacology]]
 [[Category:Drug interactions]]
-[[Category:Medications]]
+[[Category:Food-drug interactions]]
-[[Category:Health]]
+[[Category:Hepatology]]
-{{DEFAULTSORT:Grapefruit-drug interactions}}
-[[Category:Pharmacology]]
-[[Category:Medical lists|Drugs affected by grapefruit]]
-[[Category:Grapefruit]]