Drug Interactions of Fruit Juices

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Fruit juices like Grapefruit Juice (GFJ), Seville orange (Bitter Orange) Juice, Pomelo Juice, Lime Juice, Orange Juice (OJ) and Apple Juice (AJ) can interact with certain medicines and alter their pharmacokinetic behaviours.

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Interactions of Fruit Juices with Certain Drugs:

Interactions of Fruit Juices with Certain Drugs Dr. P.Naina Mohamed PhD Pharmacologist

introduction:

introduction The pharmacokinetics of some drugs significantly altered by the consumption of Fruit juices. Oral availability of many drugs may increase or decrease depending on the type of juice consumed and whether the drug is a substrate for specific enzymes or transporters in the intestinal wall. The pharmacokinetic behaviors of the drugs could be altered by the consumption of Fruit juices like Grapefruit Juice (GFJ), Seville orange ( Bitter Orange ) Juice, Pomelo Juice, Lime Juice, Orange Juice (OJ ) and Apple Juice (AJ).

Grapefruit Juice Interactions:

Grapefruit Juice Interactions Increased bioavailability of felodipine associated with grapefruit juice (GFJ) ingestion, was the first Fruit Juice -Drug interaction to be identified. http:// www.ncbi.nlm.nih.gov/pubmed/2612087?dopt=Abstract The bioavailability of certain drugs was found to be increased by the inhibition of intestinal CYP3A4 by the furanocoumarins of GFJ. http :// ajcn.nutrition.org/content/83/5/1097.abstract?ijkey=161f00005d9f48d23f689ada722918d4cf842a4d&keytype2=tf_ipsecsha Bergamottin and 6’,7’-dihydroxybergamottin were identified as major furanocoumarins of GFJ. http://dmd.aspetjournals.org/content/25/11/1228.abstract?ijkey=d99648824c085a75c35d81f62afbbff5a4b26511&keytype2=tf_ipsecsha

Drugs with gfj interaction potential:

Drugs with gfj interaction potential Name of the Drug Predicted Interaction Risk Dose related Adverse event Simvastatin, Lovastatin Very High Rhabdomyolysis Atorvastatin High Rhabdomyolysis Domperidone , Dronedarone , Lurasidone Very High Torsade de pointes Amiodarone , Quinine,, Quinidine, Erythromycin, Crizotinib , Dasatinib , Lapatinib , Nilotinib , Pazopanib , Sunitinib , Vandetanib , Venurafenib , Rilpivirine , Pimozide , Ziprasidone High Torsade de pointes Cyclosporine, Tacrolimus , Sirolimus , Everolimus High Nephrotoxicity Ketamine (oral) Very High Respiratory depression Fentanyl (oral), Alfentanil (oral), Oxycodone High Respiratory depression Apixaban , Rivaroxaban , Ticagrelor High GI Bleeding Felodipine, Nifedipine , Intermediate Hypotension Dextromethorphan High Hallucinations, somnolence

Seville orange (Bitter Orange) Juice Interactions:

Seville orange (Bitter Orange) Juice Interactions Seville orange, which is commonly found in marmalades, contained two of the major furanocoumarins bergamottin and 6’,7’-dihydroxybergamottin. Seville orange juice can also inhibit intestinal CYP3A4 and could interact with the same range of drugs as grapefruit, theoritically . Increased oral availability of Felodipine has been demonstrated using undiluted Seville orange juice. http://www.ncbi.nlm.nih.gov/pubmed/11180034 Seville orange juice also found to increase the oral availability of Dextromethorphan . http :// www.ncbi.nlm.nih.gov/pubmed/12095536

Pomelo Or Pummelo Juice Interactions :

Pomelo Or Pummelo Juice Interactions Pummelo or pomelo (Citrus grandis (L.)) is a citrus fruit closely related to grapefruit (Citrus paradise Macf ). Fruit juice of the pummelo was found to have substantial furanocoumarin content and to cause inhibition of CYP3A4-mediated testosterone 6b-hydroxylation by human liver microsomes . Pummelo juice 250 mL augmented the AUC and Cmax of F elodipine . http :// www.ncbi.nlm.nih.gov/pubmed/10859150 Clinically , pummelo juice 240 mL increased the AUC and Cmax of C yclosporine . In a case report involving a renal transplant patient, pummelo juice induced an increase in the blood concentrations of Tacrolimus . http:// dmd.aspetjournals.org/content/32/8/828.long

Lime Juice Interactions:

Lime Juice Interactions Lime juice was found to contain high bergamottin (Furanocoumarin) content. In a study of eight healthy volunteers assessing the potential for a clinical drug interaction, lime and grapefruit juices had measured concentrations of bergamottin of 100 and 25 mmol /L, respectively. http://www.ncbi.nlm.nih.gov/pubmed/12811362 250 mL of Lime juice has been found to increase one-third oral bioavailability of F elodipine compared to grapefruit juice. Consumption of as little as 62 mL of lime juice may produce a relevant drug interaction in grapefruit juice-sensitive individuals . http://www.ncbi.nlm.nih.gov/pubmed/12811362

Pomegranate Juice Interactions:

Pomegranate Juice Interactions The component(s ) of pomegranate juice was found to inhibit the CYP3A-mediated metabolism of Carbamazepine . http:// dmd.aspetjournals.org/content/33/5/644.full Pomegranate may inhibit CYP2D6 enzyme. Pomegranate juice may interact with CYP2D6 substrates such as Amitriptyline, Codeine , Desipramine , Flecainide , Fluoxetine, Ondansetron and Tramadol which increase the effects and side effects of medicines. Pomegranate juice may also interact with Captopril , Enalapril , Lisinopril, Ramipril, and Rosuvastatin to increase their side effects.

Mechanism of CYP3A4 Inhibition:

Mechanism of CYP3A4 Inhibition

Apple Juice (AJ) & Orange Juice (OJ) Interactions:

Apple Juice (AJ) & Orange Juice (OJ ) Interactions Apple Juice (AJ) and Orange Juice (OJ) can interact with Fexofenadine through inhibition of O rganic A nion T ransporting P olypeptide 2B1 (OATP2B1) mediated absorption. http:// journals.lww.com/jpharmacogenetics/Abstract/2011/02000/The_effects_of_the_SLCO2B1_c_1457C_T_polymorphism.4.aspx Significant fruit juice–drug interactions have been identified for several β-blockers, including Atenolol , C eliprolol , and T alinolol , all of which are substrates of OATP1A2. Celiprolol and talinolol are also OATP2B1 substrates . Orange juice has been shown to reduce Ciprofloxacin exposure by ~20 %, probably due to inhibition of OATP1A2-mediated uptake. A modest decrease in Montelukast (OATP2B1 substrate) exposure was observed with orange juice. Aliskiren exposure was found to be decreased by the coadministration of Grapefruit, Orange, and A pple juice. http ://www.ncbi.nlm.nih.gov/pubmed/23033114

Drugs with OJ & AJ interaction potential:

Drugs with OJ & AJ interaction potential Orange Juice (OJ) Apple Juice (AJ) Interaction Result Atenolol Fexofenadine Decreased efficacy Celiprolol Cyclosporine Decreased efficacy Ciprofloxacin Aliskiren Decreased efficacy Clofazimine Decreased efficacy Fexofenadine Decreased efficacy Itraconazole Decreased efficacy Levofloxacin Decreased efficacy Montelukast Decreased efficacy Aliskiren Decreased efficacy

Mechanism of OATPs Inhibition:

Mechanism of OATPs Inhibition

FDA’s Tips for patients:

FDA’s Tips for patients Patients should ask a pharmacist or other health care provider if they can drink grapefruit and other juices with prescribed medications. Patients must read the leaflet that comes with medications to identify any fruit juice interactions. Patients should check the labels of flavored drinks to ensure that they do not contain juices to be avoided. Patients should be educated on other fruits that should be avoided, such as Seville oranges and tangelos, with medications known to interact with grapefruit. The adverse drug interactions of GFJ could be minimized by Pharmacists and other health professionals who properly screen and educate patients about potential fruit juice interactions. www.fda.gov/ForConsumers/ConsumerUpdates/ucm292276.htm

Conclusion:

Conclusion Among all fruit juices, grape fruit juice (GFJ) possesses high interaction with almost all types of drugs. Any problems can be solved by avoiding Fruit juices (FJ). A scientific report suggests that health professionals and patients are often unaware that fruit juices can cause significant drug interactions. Patients must ask their doctor or pharmacist if their medicines have the potential to interact with fruit juices. Pharmacists must educate patients about FJ-Drug interactions to decrease the likelihood of adverse events.

References:

References Handbook of Drug – Nutrient Interactions 2 nd Edition Joseph I.Boullata , Vincent T.Armenti Stockley’s Drug Interactions 9 th Edition Karen Baxter http :// www.nature.com/clpt/journal/v92/n5/full/clpt2012159a.html http:// www.pharmaceutical-journal.com/learning/learning-article/drug-interactions-and-fruit-juices/10032123.article http:// dmd.aspetjournals.org/content/early/2012/12/20/dmd.112.049635.full.pdf+html http :// www.nature.com/clpt/journal/v69/n1/full/clpt20013a.html

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