Grapefruit

safety

Allergies

Avoid in individuals with a known allergy or hypersensitivity to grapefruit.

Side Effects and Warnings

Grapefruit appears to be well-tolerated. Grapefruit is likely safe when used in amounts commonly found in foods by individuals not on concurrent drug therapy. Grapefruit has generally recognized as safe status (GRAS) in the United States. Adverse effects from grapefruit juice have been reported only rarely in clinical trials and limited to those in combination with drug therapy. Effects on drug pharmacokinetics may be desired or undesired dependent upon opinion and individual circumstances. Inter-individual grapefruit juice/drug bioavailability variation has been observed. The severity of the interaction may depend on how much and how often the grapefruit juice is consumed, the timing of the grapefruit juice, the specific brand of juice, and the medication dose.
When grapefruit juice is taken with nifedipine and terazosin, blood pressure may decrease.
Experts report that topically applied grapefruit seed extract can be irritating to the skin.
High doses may cause pseudohyperaldosteronism (Liddle's syndrome), increases in potassium clearance, mineralocorticoid excess, lowered elevated hematocrits, the development of kidney stones, or increases in enamel loss and tooth surface loss.
Use cautiously in patients taking cytochrome P450 3A4 substrates such as anticoagulant/antiplatelets, antiarrhythmics, anticonvulsants, antidepressants, antihistamines, antihypertensives, benzodiazepines, calcium channel blockers, caffeine, corticosteroids, erectile dysfunction medications, estrogens, immune modulators, HMG-CoA reductase inhibitors, macrolide antibiotics, and protease inhibitors.
Use cautiously in patients that drink red wine. Red wine in combination with grapefruit juice appears to have an additive inhibitory effect on CYP3A4, theoretically increasing the risk for interactions with other drugs.
Use cautiously in patients that drink tonic water or smoke.
Use cautiously in patients with liver cirrhosis, at risk for kidney stones, or that have undergone gastric bypass surgery.

Pregnancy & Breastfeeding

Grapefruit is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.

dosing

Adults (over 18 years old)

There is no proven effective dose for grapefruit. Grapefruit is typically taken as a fruit, seed extract or pectin by mouth. It has also been applied on the skin as a disinfectant for skin wounds. For atopic eczema, 150 milligrams of grapefruit seed extract has been taken by mouth three times daily for one month. For heart disease, 15 grams of grapefruit pectin in divided doses with meals for 16 weeks has been used.
Grapefruit is likely safe when used in amounts commonly found in foods by individuals not on concurrent drug therapy. Grapefruit has generally recognized as safe status (GRAS) in the United States.

Children (under 18 years old)

There is no proven effective dose for grapefruit in children. Grapefruit is likely safe when used in amounts commonly found in foods by individuals not on concurrent drug therapy. Grapefruit has generally recognized as safe status (GRAS) in the United States.

interactions

Interactions with Drugs

Grapefruit juice may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be increased in the blood, and may cause increased effects or potentially serious adverse reactions. Patients using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
Preliminary evidence suggests that grapefruit juice may inhibit cytochrome P450 1A2. Currently, this interaction has not been reported in humans. Drugs metabolized by cytochrome P450 1A2 include amitriptyline, clomipramine, clozapine, cyclobenzaprine, haloperidol, naproxen, ondansetron, propranolol, theophylline, and verapamil.
Preliminary evidence suggests that grapefruit juice may inhibit cytochrome P450 2C9. Currently, this interaction has not been reported in humans. Drugs metabolized by CYP2C9 include nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., diclofenac, ibuprofen, meloxicam, piroxicam), oral hypoglycemics (tolbutamide, glipizide), and angiotensin II blockers (e.g., losartan).
Preliminary evidence suggests that grapefruit juice may inhibit cytochrome P450 2C19. Currently, this interaction has not been reported in humans. Drugs metabolized by CYP2C19 include proton pump inhibitors (e.g., lansoprazole, omeprazole, pantoprazole), anti-epileptics (e.g., diazepam, phenytoin), carisoprodol, citalopram, and nelfinavir.
Grapefruit juice can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. Some drugs metabolized by CYP3A4 that might be affected include macrolide antibiotics (e.g., erythromycin, clarithromycin), anti-arrhythmics (e.g., quinidine), benzodiazepines (e.g., alprazolam, midazolam, diazepam, triazolam), immune modulators (e.g., cyclosporine, tacrolimus), protease inhibitors (e.g., ritonavir, saquinavir), prokinetic agents (e.g., cisapride), antihistamines (e.g., terfenadine), calcium channel blockers (e.g., amlodipine, felodipine, diltiazem), HMG-CoA reductase inhibitors (e.g., atorvastatin, lovastatin), alfuzosin, etc.
Although not well studied in humans, other potential interactions with grapefruit juice may occur with acebutolol, alfentanil, alprazolam, amlodipine, amprenavir, anthelmintics (e.g., praziqauntel), antiarrhythmics (e.g., amiodarone, propafenone, quinidine), anticonvulsants (e.g. carbamazepine), antifungal agents (e.g., itraconazole), antimalarial agents (e.g., halofantrine, artemether, quinine), antineoplastic agents, aripiprazole, atorvastatin, beta-blocking agents, benzodiazepines, budesonide, celiprolol, digoxin, eplerenone, etoposide, felodipine, fentanyl, hormone replacement, imatinib, indinavir, lovastatin, levothyroxine, oral contraceptives (e.g., estradiol, progesterone), methylprednisolone, mifepristone, nifedipine, nimodipine, nitrendipine, opioids, pranidipine, ranolazine, scopolamine, selective serotonin reuptake inhibitors (e.g., sertraline), simvastatin, sufentanilbuspirone, sunitinib, talinolol, tolterodine, trazadone, triazolam, zolpidem. Grapefruit juice may either increase the bioavailability of these agents or increase the risk for side effects. Check with a qualified healthcare professional, including a pharmacist, for any interactions.
Grapefruit may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
Grapefruit has been shown to modestly increase the absorption of sildenafil, an erectile dysfunction agent. Theoretically, grapefruit may have similar effects if used with other erectile dysfunction agents, such as tadalafi or vardenafil.
Clinical studies show that the ingestion of grapefruit juice should not cause any pharmacokinetic or pharmacodynamic interaction when coadministered with caffeine.
Grapefruit may also reduce the effectiveness of antihistamines such as fexofenadine.
Theoretically, grapefruit juice may inhibit the hepatic metabolism of oxybutynin leading to increased drug levels and associated adverse events.
Grapefruit juice was found to have no significant effect on the metabolism of prednisone or prednisolone in one study of kidney transplant patients.
Based on laboratory study, grapefruit may inhibit absorption of vinblastine or alter the permeation of vincristine across the blood-brain barrier.

Interactions with Herbs & Dietary Supplements

Theoretically, grapefruit may increase the adverse effects associated with antiarrhythmic, anticonvulsant, immunosuppressant, or estrogen-containing herbs and supplements. Concomitant use of grapefruit and green tea may increase caffeine levels leading to an increased risk of cardiovascular and central nervous system stimulatory effects, along with other caffeine-related adverse effects due to caffeine in green tea. However, currently, this effect has not been reported in humans.
Theoretically, grapefruit may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
Grapefruit may increase the bioavailability and side effects associated with antihistaminic or estrogen-containing herbs and supplements. Theoretically, grapefruit may interfere with metabolism of opioids by the liver and small intestine cytochrome P450 3A4 enzyme. Grapefruit has been shown to increase the bioavailability of methadone.
Grapefruit may reduce the effectiveness of antineoplastic herbs/supplements.
Grapefruit juice has caused decreases in concentrations of beta-blocking herbs/supplements.
Preliminary evidence suggests that grapefruit juice may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may become too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
In theory, grapefruit juice may increase concentrations of digitalis (foxglove), although clinical significance is unknown.
Grapefruit may interfere with the body's conversion of cortisol to cortisone. If both licorice and grapefruit are taken together, the risk of high blood pressure and other side effects may be increased.
Grapefruit juice may increase serum concentrations of lovastatin, a constituent of red yeast. Grapefruit has also been shown to increase plasma vitamin C levels.
Grapefruit juice has a weak interaction with theophylline-containing drugs. In theory, grapefruit may interact with xanthine-containing herbs, and caution is advised.