What medications can't you eat grapefruit with?

Medications That Interact with Grapefruit

Avoid grapefruit juice when taking medications metabolized by CYP3A4 or transported by P-glycoprotein, particularly those with narrow therapeutic indices or high first-pass metabolism.

Cardiovascular Medications

Calcium Channel Blockers

• Verapamil should not be taken with grapefruit juice due to CYP3A4 inhibition and P-glycoprotein effects 1
• Ivabradine must avoid grapefruit juice; the combination is contraindicated 1
• Diltiazem interactions with grapefruit juice can increase drug levels, though specific avoidance is less emphasized than with verapamil 2, 3
• Felodipine, nitrendipine, and nisoldipine show the most pronounced interactions with median AUC increases exceeding 70% 3

Antiarrhythmic Agents

• Amiodarone should not be combined with grapefruit juice due to its CYP3A4 substrate properties 1, 4
• The interaction can increase amiodarone plasma levels, potentially worsening QT prolongation and other adverse effects 4

Statins

• Atorvastatin: Large quantities of grapefruit juice (>1.2 liters daily) are not recommended 5
  • Grapefruit juice increases atorvastatin levels by approximately 80% regardless of timing 6
  • Despite increased levels, some evidence suggests the cardiovascular benefit may outweigh minimal rhabdomyolysis risk 6
• Simvastatin and lovastatin: Show the most dramatic interactions with ~260% increase when taken simultaneously, ~90% increase when taken 12 hours apart 6, 2
• Pravastatin, fluvastatin, and rosuvastatin: Do not interact with grapefruit juice and are safe alternatives 2

Lipid-Lowering Agents

• Lomitapide must avoid grapefruit juice as it is a CYP3A4 substrate; strong and moderate CYP3A4 inhibitors are contraindicated 1

Immunosuppressants

• Cyclosporine has clinically significant interactions with grapefruit juice 3, 7
• This interaction can lead to increased immunosuppressant levels and toxicity 7

Psychotropic Medications

• Benzodiazepines (midazolam, triazolam) show concentration increases with grapefruit juice 3, 7
• Carbamazepine has documented serious clinical consequences from grapefruit interactions 7

Antiretroviral Agents

• Indinavir and saquinavir interact with grapefruit juice 3, 7
• Saquinavir shows marked increases in drug levels with grapefruit consumption 3

Antihistamines

• Terfenadine demonstrates concentration increases with grapefruit juice, though this drug is rarely used currently 3

Mechanism and Clinical Implications

Primary Mechanism

• Grapefruit juice inhibits intestinal CYP3A4, reducing first-pass metabolism and increasing bioavailability 2, 3, 7
• P-glycoprotein and organic anion transporter proteins are also inhibited 7, 8
• The effect is most pronounced in drugs with high first-pass degradation 3

Key Characteristics of Interacting Drugs

• Extensive metabolism through intestinal CYP3A4 2
• Low bioavailability 2
• Narrow therapeutic index 2

Variability Considerations

• Grapefruit juice composition varies by variety, maturity, origin, climate, and manufacturing process 7
• Large inter-individual differences in enzyme efficiency make predicting interaction magnitude difficult 7
• The interaction does not generally decrease pharmacokinetic variability 3

Duration of Effect

• The inhibitory effect persists even when grapefruit juice is consumed hours before medication 6, 3

Clinical Management

Patient Counseling

• Advise patients to completely avoid grapefruit products (juice, fresh fruit, preserves, extracts, zest) when taking interacting medications 7
• Other citrus fruits can be safely substituted 2

Alternative Medications

• When grapefruit-drug interactions are problematic, switch to equally effective alternatives that don't interact with grapefruit 2
• Examples: pravastatin instead of simvastatin, or alternative calcium channel blockers 2

Common Pitfall

• Do not assume small amounts of grapefruit are safe—even a single glass can cause significant interactions with susceptible drugs 3, 7
• The interaction risk applies to all grapefruit products, not just juice 7