Grapefruit Dosing and Safety

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 (GRAS) status in the United States. Adverse effects from grapefruit juice have been reported only rarely and have been limited to those in combination with drug therapy. 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.
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 who drink red wine. Red wine in combination with grapefruit juice appears to have an additive inhibitory effect on the way liver breaks down some agents, theoretically increasing the risk for interactions with other drugs.
Use cautiously in patients who drink tonic water or smoke.
Use cautiously in patients with liver cirrhosis, at risk for kidney stones, or who have undergone gastric bypass surgery.

Pregnancy and 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. For metabolic syndrome, grapefruit capsules, fresh grapefruit, or 8 oz. of grapefruit juice three times daily before each meal has been studied for 12 weeks.

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.

interactions

Interactions with Drugs

Grapefruit juice may interfere with the way the body breaks down certain drugs in the liver. As a result, the levels of some drugs may be increased in the blood, and may cause increased effects or potentially serious adverse reactions. Patients using medications such as amitriptyline, clomipramine, clozapine, cyclobenzaprine, haloperidol, naproxen, ondansetron, propranolol, theophylline, and verapamil should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
Grapefruit juice may also interact with nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., diclofenac, ibuprofen, meloxicam, piroxicam), oral antidiabetic agents (tolbutamide, glipizide), and angiotensin II blockers (e.g., losartan).
Caution is advised when mixing grapefruit juice with proton pump inhibitors (e.g., lansoprazole, omeprazole, pantoprazole), anti-epileptics (e.g., diazepam, phenytoin), carisoprodol, citalopram, and nelfinavir.
Grapefruit juice may increase drug levels and the risk of adverse effects when taken with 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, numerous 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, and zolpidem. 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 interactions when coadministered with caffeine.
Grapefruit may 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 the absorption of vinblastine or alter the permeation of vincristine across the blood-brain barrier.

Interactions with Herbs and Dietary Supplements

Theoretically, grapefruit may increase the adverse effects associated with antiarrhythmic, anticonvulsant, antihistamine, immunosuppressant, anti-cancer, beta-blocking, 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.
In theory, grapefruit juice may increase concentrations of digitalis (foxglove) and vitamin C levels, although clinical significance is unknown.
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.
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.
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 has a weak interaction with theophylline-containing drugs. In theory, grapefruit may interact with xanthine-containing herbs and caution is advised.