Does Grapefruit Interact With Amlodipine?

In our latest question and answer, the pharmacist discusses whether or not grapefruit interacts with Norvasc (amlodipine).

Jul 15, 2018

TX Chick asked

Does grapefruit juice negate the effects of Norvasc (amlodipine)?


There is a potential drug interaction with grapefruit juice and amlodipine. Due to the amlodipine metabolism mechanism, grapefruit juice can impact the breakdown of amlodipine and therefore have an increased effect on blood pressure. However, studies have shown this may not have a clinical effect. Read below for more information about amlodipine.

Amlodipine (Norvasc) is a calcium channel blocker that is primarily used for treatment of hypertension (high blood pressure). In fact, it is commonly used as a first line agent for many patients.

Amlodipine is metabolized extensively by the liver via CYP3A4.  Because of this, the most significant drug interactions with amlodipine come with medications that reduce or increase the activity of CYP3A4. CYP3A4 is the most common enzyme responsible for breaking down medications. Many drug interactions are due to inhibition or induction of CYP3A4 and other CYP enzymes.

Inhibiting the enzyme allows for drugs that require CYP metabolism to stay in the body longer at a higher concentration. Inhibitors can increase the effect of amlodipine, which may lead to an enhanced effect on blood pressure and an increased risk of side effects such as edema (swelling). Examples of CYP3A4 inhibitors include grapefruit, diltiazem, digoxin, and many HIV medications.

Inducing the enzyme would cause rapid metabolism of the drug and would therefore diminish its effect. CYP3A4 inducers reduce the activity of Lipitor. Examples of CYP3A4 inducers include some antiepileptics and rifampin.

While there is a theoretical drug interaction, the Norvasc package insert states that there was no significant effect of drinking one glass (240 mL) of grapefruit juice with a single dose of amlodipine. This does not rule out long-term use of grapefruit juice nor excessive amounts of grapefruit juice.

To conclude, grapefruit juice could inhibit CYP3A4 which metabolizes amlodipine. While at least one study showed no clinical effect of this interaction, avoiding use of grapefruit juice with amlodipine could help avoid low blood pressure or other amlodipine side effects such as swelling of the feet.

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