Which antihypertensive medications are contraindicated with grapefruit?

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Last updated: February 21, 2026 • View editorial policy

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Antihypertensive Medications Contraindicated with Grapefruit

Calcium channel blockers—specifically nifedipine, verapamil, diltiazem, and felodipine—are contraindicated with grapefruit juice due to CYP3A4 inhibition that causes dangerous increases in drug levels, leading to severe hypotension, bradycardia, and cardiovascular complications. 1, 2, 3

Calcium Channel Blockers with Absolute Grapefruit Contraindication

Verapamil

  • Verapamil is absolutely contraindicated with grapefruit juice because grapefruit inhibits both CYP3A4 and P-glycoprotein, causing excessive drug accumulation that leads to dangerous hypotension, severe bradycardia, and atrioventricular conduction disorders. 1
  • Patients must completely avoid all grapefruit products (juice, fresh fruit, preserves, extracts, zest)—not just avoid concurrent ingestion—because the CYP3A4 inhibition is irreversible and lasts several days. 1, 2

Nifedipine

  • Grapefruit juice should be avoided by patients on nifedipine, and intake should be stopped at least 3 days prior to initiating therapy. 3
  • A single dose of 250 mL double-strength grapefruit juice with 10 mg nifedipine increased AUC by 1.35-fold and Cmax by 1.13-fold. 3
  • Repeated doses of grapefruit juice (5 x 200 mL in 12 hours) after 20 mg nifedipine ER increased AUC and Cmax by 2-fold, doubling drug exposure. 3

Diltiazem

  • Diltiazem should avoid grapefruit juice as a CYP3A4 substrate to prevent similar cardiovascular complications seen with other calcium channel blockers. 1

Felodipine

  • Felodipine requires complete grapefruit avoidance due to risk of hypotension and cardiovascular effects when combined with grapefruit juice. 2

Other Cardiovascular Medications Contraindicated with Grapefruit

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
  • Class I and III antiarrhythmics (flecainide, propafenone, quinidine, disopyramide) are high-risk due to their low therapeutic index and potential for torsades de pointes when combined with grapefruit. 1
  • Ivabradine is absolutely contraindicated with grapefruit juice per American Heart Association guidelines. 1

Statins (Lipid-Lowering Agents)

  • Simvastatin, lovastatin, and atorvastatin require complete grapefruit avoidance due to risk of rhabdomyolysis with increased drug exposure. 1, 2
  • Patients on statins who consume grapefruit may develop muscle pain or weakness, indicating possible statin-related toxicity. 2

Other Cardiovascular Drugs

  • Lomitapide must avoid grapefruit juice as it is a CYP3A4 substrate. 1

Mechanism and Duration of Interaction

Why Timing Separation Doesn't Work

  • Grapefruit juice irreversibly inactivates intestinal CYP3A4 enzymes, reducing first-pass metabolism and increasing oral drug bioavailability; the effect lasts up to 24 hours after a single serving and cannot be mitigated by separating dosing times. 2
  • The interaction persists for several days after grapefruit exposure and affects both gut and liver CYP3A4, causing unpredictable and potentially marked increases in drug blood concentrations. 2

Complete Avoidance Required

  • Patients should eliminate all grapefruit products including juice, fresh fruit, preserves, extracts, and zest, as the interaction can last several days and is not eliminated by separating administration times. 2
  • The American Heart Association recommends complete avoidance of grapefruit and grapefruit juice for patients taking medications metabolized by CYP3A4 or transported by P-glycoprotein/OATP proteins. 2

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
  • Do not substitute other citrus fruits without verification: While oranges and lemons are safe alternatives, pomegranate, star fruit, and certain Asian citrus varieties can also inhibit CYP3A4. 2
  • Monitor for signs of increased drug effect: Watch for excessive hypotension, bradycardia, muscle pain/weakness (with statins), or other signs of drug toxicity. 2

References

1
Guideline

Medications That Cannot Be Taken with Grapefruit

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

2
Guideline

Grapefruit Interaction with Medications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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