What medications cannot be taken with grapefruit?

Medications That Cannot Be Taken with Grapefruit

Patients taking verapamil, amiodarone, ivabradine, lomitapide, simvastatin, lovastatin, atorvastatin (in large quantities), or ciclosporin must avoid grapefruit juice entirely due to dangerous drug interactions that can cause toxicity. 1, 2, 3, 4, 3

Cardiovascular Medications with Absolute Grapefruit Contraindications

Calcium Channel Blockers

• Verapamil is contraindicated with grapefruit juice due to CYP3A4 inhibition and P-glycoprotein effects, which can cause excessive drug levels leading to dangerous hypotension, bradycardia, and atrioventricular conduction disorders 1, 2, 5
• Diltiazem, as a CYP3A4 substrate, should also avoid grapefruit juice to prevent similar cardiovascular complications 1

Antiarrhythmic Agents

• Amiodarone must not be combined with grapefruit juice because grapefruit increases amiodarone AUC by 50% and peak concentration by 84%, risking severe toxicity including QT prolongation, torsades de pointes, and hepatotoxicity 1, 2, 3, 5
• The FDA drug label explicitly states "grapefruit juice should not be taken during treatment with oral amiodarone" 3
• Ivabradine is absolutely contraindicated with grapefruit juice per American Heart Association guidelines 1, 2

Lipid-Lowering Agents

• Simvastatin and lovastatin have the highest risk: grapefruit juice increases blood levels by approximately 260% when taken simultaneously (90% even when taken 12 hours apart), dramatically increasing rhabdomyolysis risk 4, 6, 5, 7
• Atorvastatin levels increase by 80% with grapefruit juice, and the FDA label warns against consuming large quantities (>1.2 liters daily) 4, 6, 5, 7
• Lomitapide must avoid grapefruit juice as it is a CYP3A4 substrate 1, 2
• Pravastatin, fluvastatin, and rosuvastatin are safe alternatives that do not interact with grapefruit 5

Immunosuppressive Medications

Ciclosporin (Cyclosporine)

• Patients must completely avoid grapefruit and grapefruit juice while taking ciclosporin, not just avoid concurrent ingestion, because the effect is long-lasting 1
• Grapefruit juice inhibits cytochrome P450 3A4 in both gut and liver, causing variable but potentially marked increases in ciclosporin blood levels 1
• This interaction can produce large changes in blood levels, and since ciclosporin has a narrow therapeutic index, small changes markedly influence both efficacy and toxicity 1

Cardiac Glycosides

• Digoxin interactions with grapefruit are less direct but warrant caution, as verapamil (which interacts with grapefruit) can increase digoxin levels and cause toxicity 1

Other Cardiovascular Agents

• Erectile dysfunction medications (sildenafil, tadalafil, vardenafil) may cause serious systemic vasodilatation when combined with grapefruit juice, especially dangerous when used with nitrates 5
• Clopidogrel's antiplatelet activity may be attenuated by grapefruit juice, reducing therapeutic effectiveness 5
• Quinidine, disopyramide, propafenone, and carvedilol have potential for enhanced toxicity with grapefruit juice 5

Mechanism and Clinical Implications

Why Grapefruit Causes These Interactions

• Grapefruit irreversibly inactivates intestinal CYP3A4 through furanocoumarins, reducing presystemic metabolism and increasing oral drug bioavailability 5, 8
• Enhanced bioavailability can occur up to 24 hours after juice consumption 5
• Grapefruit also inhibits P-glycoprotein and organic anion transporting polypeptides, further affecting drug absorption 5, 8

Critical Pitfalls to Avoid

• Do not assume timing separation solves the problem: the CYP3A4 inhibition is irreversible and long-lasting, so avoiding concurrent ingestion is insufficient 1, 5
• Even a single normal serving (200-300 mL) can cause significant interactions 5
• Elderly patients are at particular risk as they are often prescribed multiple interacting medications and frequently consume grapefruit juice 5
• Other citrus fruits are generally safe alternatives and do not share grapefruit's interaction profile 6

Safe Alternatives

• For statins: switch to pravastatin, fluvastatin, or rosuvastatin 5
• For calcium channel blockers: amlodipine does not significantly interact with grapefruit 5
• For antiarrhythmics: consider alternative agents without CYP3A4 metabolism 6

Monitoring Recommendations

• If grapefruit-interacting drugs cannot be avoided, exclude grapefruit entirely from the diet rather than attempting dose adjustments 6, 5
• For drugs with low inherent bioavailability from CYP3A4 metabolism and potential for serious toxicity, complete avoidance of grapefruit is mandatory 5