Interactions of grapefruit juice and cardiovascular medications: A potential risk of toxicity

Recently, drug interactions with grapefruit juice (GFJ) have received considerable attention from basic scientists, physicians, industry and drug regulatory agencies. GFJ has been shown to inhibit cytochrome P-450 3A4 isoenzyme and P-glycoprotein transporters in the intestine and liver. The GFJ-induced inhibitory effects are considered to be responsible for alterations in drug bioavailability, and pharmacokinetic and pharmacodynamic changes when drugs are ingested concurrently with GFJ. However, little or no interaction is observed when GFJ is taken concomitantly with parentally administered drugs. It is well known that risk factors for cardiovascular disease increase with advancing age, while hepatic metabolic activity decreases in elderly individuals. It is, therefore, possible that the combination of GFJ and cardiovascular medications may pose a health risk, especially in elderly patients. A number of studies have shown interactions of GFJ with cardiovascular drugs such as calcium-channel blockers, angiotensin II receptor antagonists, beta-blockers, and statins. Such interactions are likely to change the pharmacokinetics and pharmacodynamics of these drugs, consequently causing undesirable health effects. Therefore, health care professionals and the public need to be advised of the potential risks associated with the concomitant use of GFJ and interacting medications, especially cardiovascular drugs and agents with a narrow therapeutic index. This review focuses on the adverse interactions of GFJ and cardiovascular medications, and the proposed underlying mechanisms of such interactions.