researching whether another known cyp3a4 inhibitor drug is already contraindicated with the active drug of the medication in question. examples of such known cyp3a4 inhibitors include cisapride (propulsid), erythromycin, itraconazole (sporanox), ketoconazole (nizoral), and mibefradil (posicor). by enzyme drugs that interact with grapefruit compounds at cyp3a4 include benzodiazepines: triazolam (halcion), orally administered midazolam (versed), orally administered nitrazepam (mogodon), diazepam (valium), clonazepam (klonopin), alprazolam (xanax) and quazepam (doral, dormalin) ritonavir (norvir): inhibition of cyp3a4 prevents the metabolism of protease inhibitors such as ritonavir. sertraline (zoloft and lustral) verapamil (covera-hs, calan, verelan, and isoptin) drugs that interact with grapefruit compounds at cyp1a2 include caffeine drugs that interact with grapefruit compounds at cyp2d6 include dextroamphetamine (dexedrine) dextroamphetamine (75%)/ levoamphetamine (25%) (adderall) dextromethamphetamine (desoxyn) research has been done on the interaction between amphetamines and cyp2d6 enzyme, and researchers concluded that some parts of substrate molecules contribute to the binding of the enzyme. other interactions additional drugs found to be affected by grapefruit juice include, but are not limited to some statins, including atorvastatin (lipitor), lovastatin (mevacor), and simvastatin (zocor, simlup, simcor, simvacor) in contrast, pravastatin (pravachol), fluvastatin (lescol), and rosuvastatin (crestor) are unaffected by grapefruit. anti-arrhythmics including amiodarone (cordarone), dronedarone (multaq), quinidine (quinidex, cardioquin, quinora), disopyramide (norpace), propafenone (rythmol) and carvedilol (coreg) amlodipine: grapefruit increases the available amount of the drug in the blood stream, leading to an unpredictable increase in antihypertensive effects. anti-migraine drugs ergotamine (cafergot, ergomar), amitriptyline (elavil, endep, vanatrip) and nimodipine (nimotop) erectile dysfunction drugs sildenafil (viagra), tadalafil (cialis) and vardenafil (levitra) acetaminophen/paracetamol (tylenol) concentrations were found to be increased in murine blood by white and pink grapefruit juice, with the white juice acting faster. "the bioavailability of paracetamol was significantly reduced following multiple gfj administration" in mice and rats. this suggests that repeated intake of grapefruit juice reduces the efficacy and bioavailability of acetaminophen/paracetamol in comparison with a single dose of grapefruit juice, which conversely increases the efficacy and bioavailability of acetaminophen/paracetamol. anthelmintics: used for treating certain parasitic infections; includes praziquantel buprenorphine: metabolized into norbuprenorphine by cyp3a4 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. codeine is a prodrug that produces its analgesic properties following metabolism to morphine entirely by cyp2d6. ciclosporin (cyclosporine, neoral): blood levels of ciclosporin are increased if taken with grapefruit juice, orange juice, or apple juice. a plausible mechanism involves the combined inhibition of enteric cyp3a4 and mdr1, 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 ciclosporin, as both drugs are calcineurin inhibitors. dihydropyridines including felodipine (plendil), nicardipine (cardene), nifedipine, nisoldipine (sular) and nitrendipine (bayotensin) erlotinib (tarceva) exemestane, aromasin, and by extension all estrogen-like compounds and aromatase inhibitors that mimic estrogen in function will be increased in effect, causing increased estrogen retention and increased drug retention. etoposide interferes with grapefruit, orange, and apple juices. fexofenadine (allegra) concentrations are decreased rather than increased as is the case with most grapefruit–drug interactions. fluvoxamine (luvox, faverin, fevarin and dumyrox) 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 mdr1 when taken concomitantly with ciclosporin. ketamine: after drinking 200 ml of grapefruit juice daily for five days, the overall absorption of orally ingested ketamine was three-fold compared to a control group of a clinical trial. the peak blood ketamine concentration was over two-fold. levothyroxine (eltroxin, levoxyl, synthroid): "grapefruit juice may slightly delay the absorption of levothyroxine, but it seems to have only a minor effect on its bioavailability." losartan (cozaar) methadone: inhibits the metabolism of methadone and raises serum levels. omeprazole (losec, prilosec) oxycodone: grapefruit juice enhances the exposure to oral oxycodone. and a randomized, controlled trial 12 healthy volunteers ingested 200 ml of either grapefruit juice or water three times daily for five days. on the fourth day 10 mg of oxycodone hydrochloride were administered orally. analgesic and behavioral effects were reported for 12 hours and plasma samples were analyzed for oxycodone metabolites for 48 hours. grapefruit juice and increased the mean area under the oxycodone concentration-time curve (auc(0-∞)) by 1.7 fold, the peak plasma concentration by 1.5-fold and the half-life of oxycodone by 1.2-fold as compared to water. the metabolite-to-parent ratios of noroxycodone and noroxymorphone decreased by 44% and 45% respectively. oxymorphone auc(0-∞) increased by 1.6-fold but the metabolite-to-parent ratio remained unchanged. quetiapine (seroquel) repaglinide (prandin) tamoxifen (nolvadex): tamoxifen is metabolized by cyp2d6 into its active metabolite 4-hydroxytamoxifen. grapefruit juice may potentially reduce the effectiveness of tamoxifen. trazodone (desyrel): little or no interaction with grapefruit juice. verapamil (calan sr, covera hs, isoptin sr, verelan): atrioventricular conduction disorders. warfarin (coumadin) zolpidem (ambien): little or no interaction with grapefruit juice drugs affected by grapefruit juice drug classmajor interactionsminor interactions antiarrhythmic agentsamiodarone (cordarone)dronedarone (multaq)dofetilide (tikosyn) antihistaminesterfenadine (seldane) (off the market)diphenhydramine (benadryl) (partially)astemizole (hismanal) (off the market) calcium channel antagonistsfelodipine (plendil)nicardipine (cardene) nifedipine (procardia)nimodipine (nimotop)nisoldipine (sular) isradipine (dynacirc) statins (hmg-coa reductase inhibitors)simvastatin (zocor) lovastatin (mevacor)atorvastatin (lipitor)cerivastatin (baycol) (off the market) cough suppressant/nmda antagonistdextromethorphan erectile dysfunction drugssildenafil (viagra)tadalafil (cialis) vardenafil (levitra) hiv protease inhibitorssaquinavir (invirase)ritonavir (norvir)nelfinavir (viracept)amprenavir (agenerase) hormonesethinylestradiol (ortho-cept, many others) methylprednisolone (medrol) immunosuppressantsciclosporin (sandimmune neoral) tacrolimus (prograf)sirolimus (rapamune)mercaptopurine sedatives, hypnotics, and anxiolyticsbuspirone (buspar)triazolam (halcion)midazolam (versed)diazepam (valium)zaleplon (sonata) alprazolam (xanax) clonazepam (klonopin) ketamine other psychotropicscarbamazepine (tegretol) trazodone (desyrel)quetiapine (seroquel)fluvoxamine (luvox) nefazodone (serzone) other miscellaneous drugscisapride (prepulsid, propulsid) ivabradine (corlanor)