What blood pressure meds Cannot be taken with grapefruit?

Grapefruit and grapefruit juice can interact with several medications, including some blood pressure medications. This interaction can cause higher levels of the drug in your blood, increasing your risk for dangerous side effects. Not all blood pressure medications interact with grapefruit, but it’s important to know which ones to avoid if you regularly consume grapefruit products. In this comprehensive article, we’ll provide a full overview of grapefruit medication interactions, discuss how and why they occur, and detail which specific blood pressure drugs have been shown to have negative interactions with grapefruit. We’ll also provide tips for identifying blood pressure medications that may interact and advice for staying safe if you have grapefruit as part of your diet.

Overview of Grapefruit Medication Interactions

Grapefruit contains compounds known as furanocoumarins, including bergapten and bergamottin. These chemicals interfere with enzymes in your gut and liver that normally break down many medications and drugs. By inhibiting these digestive enzymes, grapefruit causes more of the drug to enter your bloodstream and remain there for a longer period of time. With some medications, this “grapefruit effect” can cause drug levels to reach toxic concentrations, resulting in an increased risk of dangerous side effects.

The degree of the interaction can vary based on the individual, the particular drug, and the amount of grapefruit consumed. In general, the higher the grapefruit dose, the greater the potential effect. Consuming grapefruit occasionally or in small amounts may not cause clinically significant interactions. But regular intake or consumption of larger servings can result in substantial interactions with susceptible medications.

Medications Most Affected by Grapefruit

According to research, medications most likely to interact with grapefruit include:

  • Some calcium channel blockers (used for high blood pressure, angina, and abnormal heart rhythms)
  • Some statins (used for high cholesterol)
  • Antiarrhythmics (used for irregular heart rhythms)
  • Benzodiazepines (used for anxiety, insomnia)
  • Immunosuppressants (used after organ transplant)
  • Some corticosteroids (anti-inflammatory drugs)
  • Opioid pain medications
  • Some antidepressants
  • Some antipsychotics

Of these drug classes, calcium channel blockers and statins seem to be among those most sensitive to grapefruit interactions. But there are significant differences between individual medications within each drug class.

Mechanism of Grapefruit-Drug Interactions

Most documented grapefruit medication interactions are related to furanocoumarins impairing cytochrome P450 enzymes and P-glycoprotein transporters in the gut. These mechanisms normally help metabolize drugs and transport them out of GI cells, respectively. By inhibiting them, grapefruit can cause more of an orally-administered drug to enter the blood and last longer within the body:

  • Inhibition of CYP3A4 enzyme – This cytochrome P450 enzyme metabolizes roughly 50% of clinical drugs. Furanocoumarins can almost completely inhibit intestinal CYP3A4, markedly increasing bioavailability of medications.
  • Inhibition of P-glycoprotein transporter – P-gp transports drugs out of intestinal epithelial cells. By blocking P-gp, grapefruit leads to increased intestinal absorption of medications.

The highest concentration of furanocoumarins is found in grapefruit juice. But they are also present in lower amounts in the fruit pulp and seeds. The juices of some other citrus fruits, such as limes, Seville oranges, and pomelos also contain furanocoumarins and may potentially interact with medications. But grapefruit juice appears to provide the highest and most significant levels of these enzyme-inhibiting compounds.

Blood Pressure Medications with Grapefruit Interactions

Among the drug classes most likely to interact with grapefruit, some specific blood pressure medications are known to have significant interactions. If you regularly consume grapefruit, these antihypertensive drugs should be avoided or used with caution under medical supervision:

Calcium Channel Blockers

Calcium channel blockers (CCBs) are among the blood pressure drug classes with the greatest potential for grapefruit interactions. The following CCBs have shown clinically significant interactions:

  • Amlodipine (Norvasc)
  • Felodipine (Plendil)
  • Nifedipine (Adalat, Procardia)
  • Nisoldipine (Sular)
  • Nitrendipine

These interactions occur because grapefruit furanocoumarins inhibit CYP3A4, the enzyme responsible for metabolizing most dihydropyridine CCBs. This inhibition causes increased drug bioavailability and plasma concentrations.

Studies show that grapefruit can increase the area under the plasma concentration-time curve (AUC) for felodipine by 230-400%. Significant elevations are also seen with nifedipine, nisoldipine, and other CCBs affected by grapefruit. These higher plasma levels are associated with enhanced pharmacologic effects, including excessive blood pressure reduction, which could result in complications like hypotension, syncope, and falls.

Other CCBs, including diltiazem (Cardizem) and verapamil (Calan, Isoptin), are not significantly impacted by grapefruit. These drugs undergo metabolism by CYP enzymes other than CYP3A4, making them less susceptible to grapefruit interactions.


Like CCBs, some statins are subject to grapefruit interactions that can increase the risk of adverse effects. The most problematic include:

  • Atorvastatin (Lipitor)
  • Lovastatin (Mevacor)
  • Simvastatin (Zocor)

These statins are all metabolized by CYP3A4, allowing grapefruit furanocoumarins to inhibit their breakdown. Documented effects include increased drug AUC by up to three-fold along with enhanced lipid-lowering response.

While enhanced efficacy may seem beneficial, significantly increased blood concentrations of statins raise the risk of dose-related adverse effects. These include muscle toxicity (myopathy or rhabdomyolysis), liver damage, and kidney injury.

Other statins like pravastatin (Pravachol), rosuvastatin (Crestor), and fluvastatin (Lescol) appear less susceptible to grapefruit interactions. But combining any statin with grapefruit juice could potentially lead to elevated plasma drug levels.

Other Hypertensive Medications

A few other blood pressure drugs have shown possible grapefruit interactions, although the effects are generally weaker and less established. These may include:

  • Eplerenone (Inspra) – CYP3A4 metabolized potassium-sparing diuretic
  • Losartan (Cozaar) – Angiotensin II receptor blocker (ARB)
  • Aliskiren (Tekturna) – Direct renin inhibitor

However, large-scale studies have not consistently demonstrated significant grapefruit effects on plasma levels of eplerenone, losartan or aliskiren. Any interactions that might exist are likely to be modest compared to those seen with CCBs and statins.

Most other blood pressure medications, including ACE inhibitors, beta-blockers, thiazide diuretics, and others, are not significantly affected by grapefruit. But it’s always wise to consult your doctor or pharmacist when taking any hypertensive drug with grapefruit products on a regular basis.

Tips for Medication Safety with Grapefruit Consumption

If you take medications that may interact with grapefruit, these tips can help you consume both more safely:

  • Check your medications for grapefruit warnings – Prescription bottles or packages may be labeled if an interaction is known.
  • Ask your pharmacist about potential interactions – Pharmacists have the most comprehensive information on which drugs may be affected.
  • Separate doses from grapefruit intake – Take medications at least 4 hours before or after consuming grapefruit products.
  • Inform your doctor about grapefruit intake – Your physician may monitor you more closely for adverse effects.
  • Limit grapefruit portion sizes – Small amounts may have less significant interactions than large servings.
  • Switch to lower risk citrus fruits – Oranges, tangerines, lemons and limes contain lower levels of furanocoumarins.

With appropriate precautions, you may be able to have occasional grapefruit servings without affecting medication safety. But avoid taking grapefruit close to administration of drugs with known interactions. Speak with your healthcare professional for personalized advice regarding your medications, medical conditions, and preferred diet.

Are Grapefruit Interactions a Concern with All Blood Pressure Drugs?

No, grapefruit interactions are not a universal concern with all blood pressure medications. But there are specific antihypertensive drug classes and individual agents that are more likely to have clinically relevant interactions:

  • Calcium channel blockers – Amlodipine, felodipine, nifedipine and other CCBs are most prone to grapefruit effects.
  • Statins – Atorvastatin, lovastatin and simvastatin have shown significant interactions.
  • Potassium-sparing diuretics – The diuretic eplerenone may potentially have modest interactions.

In contrast, most common blood pressure drugs are not significantly affected by grapefruit. This includes ACE inhibitors (lisinopril, enalapril, etc.), angiotensin receptor blockers (losartan, valsartan), beta blockers (metoprolol, atenolol), thiazide diuretics (HCTZ) and more. But when in doubt, consult a doctor or pharmacist about your specific medications.

Should I Avoid Grapefruit Completely if Taking Blood Pressure Medications?

You do not necessarily need to avoid grapefruit altogether if taking antihypertensives. But these tips can help reduce interaction risks:

  • Consume grapefruit in moderation – Larger amounts are more likely to cause interactions.
  • Separate grapefruit and medications – Take drugs at least 4 hours before or after eating grapefruit.
  • Ask your doctor about lower-risk citrus fruits – Oranges, tangerines, lemons may be safer alternatives.
  • Check labels and talk to your pharmacist – Look for grapefruit warnings or interactions with your specific medications.
  • Monitor your blood pressure – With your doctor, watch for blood pressure reductions that are too low.

With precautions, limited grapefruit intake may be possible for many people on blood pressure medications. But a grapefruit-free diet is recommended if you take drugs with known significant interactions, like amlodipine, felodipine and atorvastatin.


While grapefruit can interact with some blood pressure drugs, not all antihypertensives are affected. The highest-risk medications include calcium channel blockers like amlodipine, felodipine, nifedipine and statins like atorvastatin, lovastatin, simvastatin. Grapefruit furanocoumarins inhibit enzymes that metabolize these drugs, causing increased plasma levels and enhanced effects. To prevent excessive blood pressure reduction or statin side effects, either avoid grapefruit or take precautions if consuming it regularly. Speak to your doctor and pharmacist to ensure the safety of any hypertensive medications you take with grapefruit products.

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