Grapefruit Drug Interactions - Affected Drugs

Affected Drugs

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The following drugs are affected by CYP3A4 inhibition with grapefruit compounds:

• The benzodiazepines triazolam (Halcion), orally administered midazolam (Versed), orally administered triazepam (Mogodon), diazepam (Valium), alprazolam (Xanax) and quazepam
• ritonavir (Norvir) inhibits CYP3A4 preventing the metabolism of protease inhibitors
• sertraline (Zoloft and Lustral)

Additional drugs found to be affected by grapefruit juice include, but are not limited to:

• Some statins such as atorvastatin (Lipitor), lovastatin (Mevacor), and simvastatin (Zocor, Simlup, Simcor, Simvacor) but not Pravastatin (Pravachol), fluvastatin (Lescol) or rosuvastatin (Crestor) which are unaffected by grapefruit.
• Dihydropyridines including felodipine (Plendil), nicardipine (Cardene), nifedipine, nisoldipine (Sular), nitrendipine (Bayotensin)
• losartan (Cozaar)
• The cough suppressant dextromethorphan
• modafinil (Provigil, Alertec, Modavigil, Modalert, Modiodal, Modafinilo, Carim, Vigia)
• repaglinide (Prandin)
• verapamil (Calan SR, Covera HS, Isoptin SR, Verelan)
• buspirone (Buspar) Grapefruit juice increased peak and AUC plasma concentrations of buspirone 4.3- and 9.2-fold, respectively, in a randomized, 2-phase, ten-subject crossover study.
• levothyroxine (Eltroxin, Levoxyl, Synthroid) Effects of grapefruit juice on the absorption of levothyroxine.
• Antiarrhythmics including amiodarone (Cordarone), dronedarone (Multaq), quinidine (Quinidex, Cardioquin, Quinora), disopyramide (Norpace), propafenone (Rhythmol), and carvedilol (Coreg)
• Antihistamines astemizole (Hismanal) and terfenadine (Seldane) - now removed from the US and Canadian markets
• cisapride (Prepuslid, Propulsid) (which treats GERD) - now removed from the US and Canadian markets
• Erectile dysfunction drugs sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra)
• The anti-migraine drugs ergotamine (Cafergot, Ergomar), amitryptiline (Elavil, Endep, Vanatrip) and nimodipine (Nimotop)
• Fluvoxamine (Luvox, Faverin, Fevarin and Dumyrox)
• Codeine and Tramadol. It reduces the amount of codeine converted by CYP3A4 into norcodeine thus increasing the amount metabolized into morphine. Morphine itself, however, is not affected by grapefruit juice, as it is not metabolized by the cytochrome P450 system.
• Cyclosporine (Neoral). Blood levels of cyclosporine are increased if taken with grapefruit juice. A plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein, which potentially leads to serious adverse events (e.g., nephrotoxicity).Blood levels of tacrolimus (Prograf) can also be equally affected for the same reason as with cyclosporine.
• omeprazole (Losec, Prilosec)
• zolpidem (Ambien) Little or no interaction with grapefruit juice.
• oxycodone (Oxycodone is metabolized by the cytochrome P450 system, specifically CYP3A4, of which the bergamottin flavonoid is a strong inhibitor)
• hydrocodone (The hepatic cytochrome P450 enzyme CYP2D6 converts it into hydromorphone, a more potent opioid.)
• dihydrocodeine
• quetiapine (Seroquel)
• methadone Inhibits the metabolism of methadone and raises serum levels.
• buprenorphine Metabolized into norbuprenorphine by cytochrome-P450 isoenzyme 3A4
• Tyrosine kinase inhibitors, including imatinib (Gleevec) and nilotinib (Tasigna), used to treat chronic myelogenous leukemia and gastrointestinal stromal tumors.
• trazodone (Desyrel) Little or no interaction with grapefruit juice.
• Anthelmintics (Used for treating certain parasitic infections, includes praziquantel albendazole and mebendazole)
• carbamazepine (Tegretol) Grapefruit or grapefruit juice slows the breakdown of this drug, increasing the level of it in blood
• imatinib (Gleevec) Although no formal studies with imatinib and grapefruit juice have been conducted, the fact that grapefruit juice is a known inhibitor of the CYP 3A4, suggests that co-administration may lead to increased imatinib plasma concentrations. Likewise, although no formal studies were conducted, co-administration of imatinib with another specific type of citrus juice called Seville orange juice (SOJ) may lead to increased imatinib plasma concentrations via inhibition of the CYP3A isoenzymes. Seville orange juice is not usually consumed as a juice because of its sour taste, but it is found in marmalade and other jams. Seville orange juice has been reported to be a possible inhibitor of CYP3A enzymes without affecting P-glycoprotein when taken concomitantly with cyclosporine.
• Loperamide (Imodium)
• colchicine (Colcrys)
• erlotinib (Tarceva)
• In a mouse study, blood concentrations of acetaminophen/paracetamol (Tylenol) were found to be increased by white and pink grapefruit juice, with the white juice acting faster.