Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome

• Status: Completed
• Trial end date: 2019-05-22

Summary

The list of medications that prolong the QT interval and can provoke torsade de pointes keeps expanding. This list includes not only antiarrhythmic drugs, but also medications with no cardiac indications. All these medications prolong the QT interval because they block a specific potassium channel on the myocardial cell membrane: the channel for the rapid component of the delayed rectifier potassium current or "IKr". The risk for developing torsade de pointes for patients taking any of the medications with IKr blockade capabilities varies from >4% for antiarrhythmic drugs to <0.01% for non-cardiac medications. The risk depends on the strength of IKr blockade, but also on specific patient characteristics. The majority of patients who develop torsade de pointes from non-cardiac medications have identifiable risk factors. In this regard, patients with a congenital long QT syndrome are prone to develop torsade de pointes when treated with QT-prolonging medications. This is because, due to their genetically defective ion channels, patients with Long QT Syndrome (LQTS) have impaired ventricular repolarization and reduced "repolarization reserve." Therefore, it is common medical practice to strongly advise patients with congenital LQTS to avoid all medications that have IKr channel blocker capabilities. it was reported that some flavonoids contained in pink-grapefruit juice block the IKr channel. These investigators also reported that drinking 1 liter of pink-grapefruit juice causes QT prolongation in healthy volunteers. The magnitude of the QT prolongation provoked by grapefruit juice was small However, drugs causing minor QT prolongation in healthy volunteers may provoke major QT prolongation in rare or sick individuals who are then at risk for developing torsade de pointes. Consequently, one could argue that, until proven otherwise, pink-grapefruit should be added to the list of "drugs" that are forbidden for patients with LQTS

• Phase: N/A

Details

• Lead Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborator: Tel Aviv Medical Center
• Treatments: Moxifloxacin; Norgestimate, ethinyl estradiol drug combination