Medications That Cannot Be Taken with Grapefruit

Cardiovascular Medications with Absolute Grapefruit Contraindications

The American College of Cardiology recommends that patients taking verapamil, amiodarone, ivabradine, lomitapide, simvastatin, lovastatin, atorvastatin, or ciclosporin must avoid grapefruit juice entirely due to dangerous drug interactions that can cause toxicity 1, 2, 3
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, 3
Diltiazem, as a CYP3A4 substrate, should also avoid grapefruit juice to prevent similar cardiovascular complications 1
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, 3
Ivabradine is absolutely contraindicated with grapefruit juice per American Heart Association guidelines 1, 3
Lomitapide must avoid grapefruit juice as it is a CYP3A4 substrate 1, 3

Patients must completely avoid grapefruit and grapefruit juice while taking ciclosporin, not just avoid concurrent ingestion, because the effect is long-lasting 2
Grapefruit juice inhibits cytochrome P450 3A4 in both gut and liver, causing variable but potentially marked increases in ciclosporin blood levels 2
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 2

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

Do not assume timing separation solves the problem: the CYP3A4 inhibition is irreversible and long-lasting, so avoiding concurrent ingestion is insufficient 2

Class I and III antiarrhythmics, such as flecainide, propafenone, and quinidine, are high-risk due to their low therapeutic index and potential for torsades de pointes when combined with grapefruit, according to the Liver International guidelines 4
Protease inhibitors, including boceprevir, telaprevir, simeprevir, tipranavir, saquinavir, darunavir, fosamprenavir, and nelfinavir, should be avoided with grapefruit due to increased drug levels and risk of overdose, as reported in Liver International 4
Oral midazolam is contraindicated with grapefruit juice due to significant increases in drug levels and sedation risk, as noted in Liver International 4
Ergot derivatives, such as dihydroergotamine and ergotamine, can lead to serious risks when combined with grapefruit, according to Liver International 4
Sildenafil requires caution due to CYP3A4 metabolism and potential increased drug levels when consumed with grapefruit, as reported in Liver International 4
Cisapride is contraindicated with grapefruit due to the risk of increased drug levels and toxicity, as noted in Liver International 4
Disopyramide and quinidine (Class IA antiarrhythmics) should avoid grapefruit due to CYP3A4 metabolism and QT prolongation risk, as reported in Circulation 5

Buprenorphine, methadone, tenofovir, and esomeprazole show no significant interactions with grapefruit, according to Liver International 4