What is the interaction between grapefruits and statins (HMG-CoA reductase inhibitors)?

From the Guidelines

Grapefruit and grapefruit juice should be avoided when taking statin medications like atorvastatin, simvastatin, and lovastatin due to potentially dangerous interactions. According to the American Heart Association scientific statement 1, grapefruit juice is an inhibitor of the CYP3A4 enzyme, which affects the metabolism of statins such as atorvastatin, lovastatin, and simvastatin. Some key points to consider:

• Grapefruit contains compounds called furanocoumarins that inhibit an intestinal enzyme called CYP3A4, which normally breaks down statins 1.
• When this enzyme is blocked, statin levels in the bloodstream can increase dramatically, sometimes by 3-10 times the expected amount, leading to serious side effects including muscle pain, muscle damage (rhabdomyolysis), liver damage, and kidney failure.
• Not all statins interact equally with grapefruit - rosuvastatin, fluvastatin, and pitavastatin are less affected 1.
• If you're taking a statin that interacts with grapefruit, it's best to completely avoid grapefruit products rather than trying to separate the timing, as the enzyme-inhibiting effect can last 24 hours or longer.
• The table provided in the study 1 lists common P-gp substrates, inhibitors, and inducers associated with the CyP450 enzymes affecting statin metabolism, which can be useful in identifying potential interactions. Considering the potential risks, it is recommended to avoid grapefruit and grapefruit juice when taking statin medications. If you enjoy grapefruit, talk to your doctor about switching to a statin that doesn't have this interaction 1.

From the FDA Drug Label

The effect of amounts of grapefruit juice between those used in these two studies on simvastatin pharmacokinetics has not been studied. Grapefruit juice was administered TID for 2 days, and 200 mL together with single dose simvastatin and 30 and 90 minutes following single dose simvastatin on Day 3 & Single-strength: one can of frozen concentrate diluted with 3 cans of water. Grapefruit Juice§ (high dose) 200 mL of double-strength TID¶ 60 mg single dose simvastatin acid simvastatin 7 16 Grapefruit Juice§ (low dose) 8 oz (about 237mL) of single-strength# 20 mg single dose simvastatin acid simvastatin 1.3 1.9

Grapefruit Juice and Statins Interaction

• Grapefruit juice can increase the plasma concentrations of simvastatin and its metabolites.
• High-dose grapefruit juice (200 mL of double-strength) increased simvastatin acid and simvastatin concentrations by 7-fold and 16-fold, respectively.
• Low-dose grapefruit juice (8 oz of single-strength) increased simvastatin acid and simvastatin concentrations by 1.3-fold and 1.9-fold, respectively.
• The effect of grapefruit juice on simvastatin pharmacokinetics may vary depending on the dose and strength of the grapefruit juice.
• It is recommended to avoid or limit grapefruit juice consumption when taking simvastatin or other statins that are metabolized by CYP3A4 2.

Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4 In one study1, 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with and 30 and 90 minutes following a single dose of 80 mg lovastatin on the third day This regimen of grapefruit juice resulted in a mean increase in the serum concentration of lovastatin and its β-hydroxyacid metabolite (as measured by the area under the concentration-time curve) of 15-fold and 5-fold, respectively

Grapefruit Juice and Lovastatin Interaction

• Grapefruit juice can increase the plasma concentrations of lovastatin and its metabolites.
• High-dose grapefruit juice (200 mL of double-strength) increased lovastatin and its β-hydroxyacid metabolite concentrations by 15-fold and 5-fold, respectively.
• Low-dose grapefruit juice (8 oz of single-strength) increased lovastatin and its β-hydroxyacid metabolite concentrations by 1.94-fold and 1.57-fold, respectively.
• The effect of grapefruit juice on lovastatin pharmacokinetics may vary depending on the dose and strength of the grapefruit juice.
• It is recommended to avoid or limit grapefruit juice consumption when taking lovastatin or other statins that are metabolized by CYP3A4 3.

From the Research

Interaction between Grapefruits and Statins

• There is no direct evidence in the provided studies regarding the interaction between grapefruits and statins.
• However, it is known that grapefruits can interact with certain medications, including statins, by inhibiting the enzyme CYP3A4, which is involved in the metabolism of many drugs 4, 5, 6, 7, 8.
• This interaction can lead to increased levels of the medication in the blood, potentially increasing the risk of side effects.
• It is recommended to consult with a healthcare professional before consuming grapefruits or grapefruit juice while taking statins.

Statin Therapy

• Statins are effective in lowering plasma levels of low-density lipoprotein cholesterol (LDL-C) and are the mainstay of therapy for hyperlipidemia 7.
• Several large, controlled clinical trials have confirmed significant reductions in rates of coronary heart disease morbidity and death with long-term statin therapy in patients with mild to severe hypercholesterolemia 7.
• The use of more potent statins such as atorvastatin and simvastatin affords greater lowering of LDL-C and triglyceride levels, allowing more patients to achieve target goals 6, 7.
• The benefits of statin therapy far outweigh any real or perceived risks, and clinicians should be reassured about the safety of statins 8.

Side Effects of Statins

• Statins can cause adverse side effects, including myopathy and, in rare cases, rhabdomyolysis 5.
• The potential harmful effects of statin therapy on muscle and liver have been known for some time, but new concerns have emerged regarding the risk of new-onset diabetes mellitus, cognitive impairment, and haemorrhagic stroke associated with the use of statins 8.
• Patients that experienced statin-associated rhabdomyolysis should be monitored closely and referred to a pediatric lipid clinic for further treatment 5.