Drug Interactions with Grapefruit Juice

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What You Should Know
It is important to recognize that most prescription drugs are not affected by grapefruit juice at all. In addition, no interactions have been observed with non-prescription medications and grapefruit juice. For those medications that are affected, the interaction can result in higher levels of such drugs in the blood, which may lead to adverse reactions. If your medication interacts and you do not wish to comply with a grapefruit juice restriction, your doctor or pharmacist can generally suggest a non-interacting, alternative medication to treat your condition with no need to avoid grapefruit juice. This option is on a case-by-case basis.
 
Talk to Your Physician and Pharmacist
It is wise to ask your physician or pharmacist about the potential for any medicine to interact with food, other prescriptions, or common nonprescription remedies. Have him or her explain any potential interactions and side effects as well as the expected benefits of the medicine.  Most pharmacists will make sure you understand such potential interactions and exactly how to take your medication to maximize the benefit and minimize side effects.
 
Mechanism of the Drug—Grapefruit Interaction
Grapefruit segments or an extract of unprocessed grapefruit cause drug interactions to a similar extent. Seville oranges (used in some marmalades, but not in commercial orange juice), purnmelos and tangelos may also cause similar interactions. Based on metabolic pathways of drugs that interact with grapefruit, we can predict other drugs that may have significant interactions with grapefruit. Grapefruit inhibits metabolism of oral medications by cytochrome P450 3A4 isoenzymes in the intestinal wall, decreasing the metabolism of affected drugs and increasing the amount of drug entering the bloodstream. Increased drug levels can cause more side effects and/or toxicity.

The effect of grapefruit on intestinal enzymes is irreversible and persists for up to 72 hours after grapefruit consumption, until more of the drug metabolizing enzymes are produced. Grapefruit is also an inhibitor of p-glycoprotein, an efflux pump in intestinal cell wall enterocytes that actively secretes absorbed drug back into the gut lumen. Organic anion transporting polypeptide (OATP) is another transporter system affected by grapefruit. Drugs that are significantly handled by p-glycoprotein or OATP may have decreased absorption when taken with grapefruit, possibly leading to loss of efficacy.
 
Reasonable Guideline
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The most reasonable guideline for pharmacists and other health care professionals to follow is to counsel patients that if they are not currently taking their medications with GJ regularly, don’t start.  If they are already taking their medications with GJ regularly, don’t stop.
 
The exceptions to this guideline are for:
terfenadine (Seldane®) 
astemizole (Hismanal®) 
cisapride (Prepulsid®, Propulsid®)
 pimozide (Orap®)
ziprasidone (Geodon®) 

statin type cholesterol-lowering drugs known to interact with GJ:
lovastatin (Mevacor®) 
simvastatin (Zocor®) 
atorvastatin (Lipitor®). 

Always contact your physician to get specific instructions. Your physician may want you to use other medications with similar therapeutic action that do not have the concern with grapefruit juice.

  1. Fatalities have occurred.
  2. Use with grapefruit only on advice of a physician.
  3. Serum plasma level monitoring required/recommended.
  4. Minor interaction, not clinically significant.
  5. Interaction suspected, but no formal studies.
  6. No specific study, but lacks a cardiac metabolite.
  7. Not metabolized by CYP 3A4, no interaction suspected.
  8. No interaction when administered parenterally (IV).
  9. Withdrawn from market.
  10. Blood levels/bioavailability decreased.

Medications that should be avoided with grapefruit
amiodarone (Cordarone)8
astemizole (Hismanal)5,9
atorvastatin (Lipitor)
budesonide (Entocort)8
buspirone (BuSpar)
cerivastatin (Baycol)5,9
cilostazol (Pletal)5
cisapride (Propulsid, Prepulsid)9
colchicine 5
eletriptan (Relpax)5
etoposide (Vepesid)8,10
halofantrine (Halfan)
indinavir (Crixivan)10
lovastatin (Mevacor)
mifepristone (Mifeprex)5
pimozide (Orap)5
sildenafil (Viagra)
simvastatin (Zocor)
sirolimus (Rapamune)5
terfenadine (Seldane)1,9
ziprasidone (Geodon)5

Use with grapefruit with caution 
albendazole (Albenza)
carbamazepine (Tegretol)3
clomipramine (Anafranil)8
cyclosporine (Neoral)2,3,8
dextromethorphan
diazepam (Valium)8
dofetilide (Tikosyn)5
erythromycin (E-mycin)
felodipine (Renedil, Plendil)
fexofenadine (Allegra)10
gefitinib (Iressa)
imatinib mesylate (Gleevec/Glivec)
itraconazole (Sporanox)10
losartan (Cozaar)
methadone5
methylprednisolone (Medrol)8,9
midazolam (Versed)9
montelukast (Singulair)5
nicardipine (Cardene)8
nifedipine (Procardia)
nimodipine (Nimotop)
nisoldipine (Sular)
pranidipine
quetiapine (Seroquel)5
quinidine (Ouinaglute, Quinidex)8
quinine
saquinavir (Invirase)2
sertraline (Zoloft)
tacrolimus (FK-506, Prograf)2,3,8
tamoxifen (Nolvadex)5
tamsulosin (Flomax)5
tolterodine (Detrol)5
triazolam (Halcion)

Medications with no significant interaction with grapefruit

Drugs in this section have all been studied with GJ, and found to have minimal/negligible interaction
alprazolam (Xanax)4
amlodipine (Norvasc)4
amprenavir (Agenerase)4,10
caffeine4
carvedilol (Coreg)4
clarithromycin (Biaxin)
clozapine (Clozaril)4
digoxin (Lanoxin)
diltiazem (Cardizem)4 17-B
estradiol4
ethinyl estradiol 4,8
haloperidol (Haldol)
omeprazole (Losec, Prilosec)4
phenytoin (Dilantin)
prednisone (Deltasone)
scopolamine (Hyoscine)4
theophylline (Theo-Dur, Uniphyl)
verapamil (Calan, Isoptin, Verelan)

Medications considered safe for use with grapefruit
cetirizine (Zyrtec, Reactine)6
desloratadine (Aerius, Clarinex)7
fluvastatin (Lescol)7
loratadine (Claritin)6
pravastatin (Pravachol)7
rosuvastatin (Crestor)7

Table compiled by Dean Elbe BSc (Pharm), BCPP, Clinical Pharmacist, Richmond, BC, Canada
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 From Food-Medication Interactions 13th Edition for PDA.

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