What happens if you mix Cialis and grapefruit?

Whether you’re taking Cialis for erectile dysfunction (ED) and/or an enlarged prostate, you likely want it to work as safely and effectively as possible. That means knowing not only how to take it but also what foods to avoid — if any. One combo to steer clear of? Cialis and grapefruit. 

Mixing tadalafil — the active ingredient in Cialis — and grapefruit (or grapefruit juice) can result in higher levels of the drug in your bloodstream and more severe side effects. 

Keep reading to learn more. 

Combining Cialis and grapefruit can raise the level of tadalafil in your bloodstream, which may intensify, strengthen, or extend side effects. This happens because grapefruit disrupts how your body processes tadalafil (and other medications).

Grapefruit contains natural compounds called flavonoids (like naringin) and furanocoumarins. These block or slow the activity of CYP3A4, an enzyme that helps break down many medications before they enter the bloodstream. 

As such, grapefruit is a known CYP3A4 inhibitor and notorious for causing drug interactions.   

When grapefruit interferes with CYP3A4, here’s what happens:

• Less tadalafil is broken down by this enzyme in the intestine.

• More tadalafil enters the bloodstream and circulates throughout your body.

• Higher blood levels of tadalafil mean stronger effects and a higher chance of Cialis side effects.

• The process of clearing tadalafil from your body slows down. (This is because tadalafil is mainly eliminated from your body via the liver, where CYP3A4 is also present.)

Studies haven’t directly tested the effect of grapefruit on tadalafil levels. But it’s likely a substantial increase. 

• In animal studies, grapefruit juice increased the highest blood concentrations of tadalafil by 75%. 

• In studies of other CYP3A4 inhibitors, for example, the antifungal drug ketoconazole increased tadalafil levels by about 100%--300% depending on the dose and study design. In fact, healthcare providers usually reduce the dosage of tadalafil when prescribing ketoconazole or other CYP3A4 inhibitors.

Grapefruit interactions vary depending on individual health factors and how much  furanocoumarin the fruit or juice contains. The juice usually has more because these compounds are most concentrated in the peel, and the whole fruit gets squeezed to make juice. 

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Eating grapefruit or drinking grapefruit juice can make Cialis side effects more likely or more intense.  

PDE5 inhibitors, including Cialis, work by relaxing blood vessels to increase blood flow. If Cialis is taken with grapefruit juice, blood vessels can widen too much, leading to a drop in blood pressure (hypotension). 

The risk of hypotension may increase with higher doses of Cialis or larger amounts of grapefruit juice. The combo is especially risky for people who are also taking other medications that lower blood pressure or widen blood vessels (vasodilators). 

Side effects that may be amplified by combining Cialis and grapefruit include:

• Dizziness, lightheadedness, or fainting (signs of low blood pressure)

• Headache

• Flushing

• Stuffy nose

• Indigestion

• Back or muscle aches

Serious side effects are uncommon but may be more likely if there’s too much Cialis in your body. Seek immediate medical attention if you develop:

• Sudden vision loss

• Sudden  hearing problems

• Prolonged erection that may be painful and lasts more than four hours (priapism)

Because of these risks, the manufacturer of Cialis advises lower maximum doses or less frequent dosing when taking both Cialis and a CYP3A4 inhibitor. Always check with your prescriber before changing your dosage.

In general, healthcare providers recommend that people stop consuming grapefruit for 72 hours before starting a medication that may interact with it. 

As mentioned, grapefruit blocks CYP3A4, an enzyme that breaks down Cialis. It can take several days to a week for your body to replace the blocked enzymes, which is why the grapefruit effect can linger.

Okay, so how long does grapefruit stay in your system? 

Here’s what research tells us about the timeline after consuming grapefruit or its juice:

• Within four hours, the activity of CYP3A4 enzymes may be reduced by nearly half. 

• Within 1 to 3 days, the body starts to replace those enzymes. But the timeline varies from person to person. An 8-ounce serving of grapefruit juice may affect intestinal CYP3A4 enzymes for 24–72 hours.

• Within 3–7 days of drinking large amounts of grapefruit juice, the effect goes away.

This means you can’t avoid the Cialis-grapefruit interaction by separating them at different times of day. For example, even if you drink grapefruit juice in the morning, it can still interact with a dose of Cialis taken later that day in the evening.

• For daily Cialis, this means completely avoiding grapefruit and grapefruit juice. If you refuse to give up your morning grapefruit, a dosage reduction may be an option, but talk with your prescriber before making changes. 

• For as-needed Cialis, you’ll want to hold off on taking a dose until 3 days after you consume grapefruit or its juice. But the safest option is to avoid grapefruit and grapefruit juice entirely while taking tadalafil.

Check in with your healthcare provider for personalized medical advice on managing Cialis interactions.

Besides grapefruit, pomelo and Seville orange could interact with Cialis and raise the risk of side effects. 

No fruits or juices have been directly studied with Cialis to confirm these effects in humans. But interactions are theoretically possible because some fruits contain furanocoumarins. These are the same compounds in grapefruit that block CYP3A4, the enzyme that breaks down tadalafil. 

In addition to grapefruit juice, other juices that have been shown to block CYP3A4 (and thus should generally be avoided with Cialis) include:

• Pomelo (aka pummelo) juice

• Seville orange juice (aka bitter orange or sour orange), which is often found in orange marmalade

It’s a good idea to check food labels and ask about ingredients. For example, Seville oranges may be found in orange marmalade, and grapefruit juice is added to some cocktails. 

Note that orange juice is made from sweet oranges (not Seville). In general, commercially made apple juice and orange juice do not block CYP enzymes and are typically safe to enjoy while taking Cialis.

Yes, other ED medications can also interact with grapefruit and grapefruit juice. This is particularly true of other PDE5 inhibitors, including: 

• Sildenafil (Viagra)

• Vardenafil (formerly available as brand-name Levitra)

• Avanafil (Stendra) 

These medications are broken down in similar ways by your body. So, grapefruit can have the same effect on them as it does on Cialis: raising drug levels and increasing the chance of side effects.

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Some foods and medications don’t get along. Cialis and grapefruit interact in a way that increases the risk of side effects. Here’s a recap of how grapefruit affects Cialis and how to avoid unsafe interactions:

• Grapefruit interferes with enzymes that break down Cialis. An enzyme called CYP3A4 is responsible for metabolizing many medications, including Cialis and other pills for erectile dysfunction. 

• Grapefruit can raise tadalafil levels in your bloodstream, which can make side effects stronger or more dangerous, including headaches, flushing, dizziness, or low blood pressure.

• It’s best to avoid grapefruit for at least 72 hours before starting medications that interact with it, including Cialis. If you take daily Cialis, skip grapefruit entirely. For as-needed doses, the general consensus is to wait three days after eating or drinking grapefruit before taking your medication.

• Grapefruit is a common cause of drug interactions. Before taking an ED medication, always read the drug guide or check with a healthcare professional to learn about any foods or drinks to avoid.