What medications are affected by grapefruit consumption?

From the Guidelines

Grapefruit can interact with numerous medications, including statins, calcium channel blockers, immunosuppressants, anti-anxiety medications, and certain antihistamines, by inhibiting an enzyme called CYP3A4 in the intestines, and patients taking these medications should avoid grapefruit, grapefruit juice, and similar citrus fruits like Seville oranges and pomelos. The medications affected by grapefruit include:

• Statins like atorvastatin (Lipitor), simvastatin (Zocor), and lovastatin (Mevacor) 1
• Calcium channel blockers such as felodipine (Plendil), nifedipine (Procardia), and amlodipine (Norvasc) 1
• Immunosuppressants like cyclosporine (Neoral) and tacrolimus (Prograf) 1
• Anti-anxiety medications including buspirone (BuSpar) and diazepam (Valium)
• Certain antihistamines such as fexofenadine (Allegra)
• Some antibiotics (erythromycin, clarithromycin), antiarrhythmics (amiodarone, dronedarone), and erectile dysfunction drugs (sildenafil, tadalafil)
• Lomitapide, which is used to treat homozygous familial hypercholesterolemia, and its use with grapefruit juice is contraindicated due to increased exposure to lomitapide 1 The interaction can last up to 72 hours after consuming grapefruit, so even occasional consumption can be problematic. Always consult your healthcare provider or pharmacist about potential grapefruit interactions with your specific medications.

From the FDA Drug Label

The maximum LDL-C reduction of simvastatin is usually achieved by 4 weeks and is maintained after that 12. Simvastatin is metabolized by CYP3A4. Table 4 displays the effect of coadministered drugs or grapefruit juice on simvastatin systemic exposure Grapefruit Juice§ (high dose) 200 mL of double-strength TID¶ 60 mg single dose simvastatin acid simvastatin 7 16 Grapefruit Juice§ (low dose) 8 oz (about 237mL) of single-strength# 20 mg single dose simvastatin acid simvastatin 1.3 1.9

Lovastatin is a substrate for cytochrome P450 isoform 3A4 (CYP3A4) Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4 In one study1, 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with and 30 and 90 minutes following a single dose of 80 mg lovastatin on the third day This regimen of grapefruit juice resulted in a mean increase in the serum concentration of lovastatin and its β-hydroxyacid metabolite (as measured by the area under the concentration-time curve) of 15-fold and 5-fold, respectively Grapefruit Juice¶ (high dose) 10 200 mL of double-strength TID# 80 mg single dose 15.3 5.0 Grapefruit Juice¶ (low dose) 16 8 oz (about 250 mL) of single-strengthÞ for 4 days 40 mg single dose 1.94 1. 57

The meds affected by grapefruit are:

• Simvastatin: Grapefruit juice can increase the systemic exposure of simvastatin, with a high dose of grapefruit juice increasing the AUC of simvastatin acid by 7-fold and simvastatin by 16-fold, and a low dose increasing the AUC of simvastatin acid by 1.3-fold and simvastatin by 1.9-fold 2.
• Lovastatin: Grapefruit juice can increase the plasma concentrations of lovastatin, with a high dose of grapefruit juice increasing the AUC of lovastatin by 15.3-fold and lovastatin acid by 5-fold, and a low dose increasing the AUC of lovastatin by 1.94-fold and lovastatin acid by 1.57-fold 3.

From the Research

Medications Affected by Grapefruit

• Statins: Grapefruit consumption can increase the risk of toxicity and adverse effects of statins, which are commonly used to lower cholesterol levels 4, 5, 6.
• Antiarrhythmic agents: These medications, used to treat irregular heartbeats, can interact with grapefruit and increase the risk of adverse effects 4.
• Immunosuppressive agents: Grapefruit can affect the metabolism of immunosuppressive agents, such as cyclosporin, and increase the risk of toxicity 4, 7, 6.
• Calcium channel blockers: These medications, used to treat high blood pressure and other heart conditions, can interact with grapefruit and increase the risk of adverse effects 4, 7.
• Antihistamines: Grapefruit consumption can increase the bioavailability of antihistamines, which can lead to increased risk of adverse effects 7.
• Neuropsychiatric medications: Grapefruit can affect the metabolism of certain neuropsychiatric medications, increasing the risk of adverse effects 5.

Mechanism of Interaction

• Grapefruit inhibits the activity of cytochrome P450 3A4 isoenzyme in the intestinal wall, preventing the presystemic first-pass metabolism of certain medications 8, 7, 5.
• Furanocoumarins, compounds found in grapefruit, are responsible for the inhibition of cytochrome P450 3A4 8, 7.
• Polyphenolic compounds, such as flavonoids, can also interact with P-glycoprotein and uptake transporters, affecting the bioavailability of certain medications 7.