Tadalafil Interactions Guide

So, you’ve started taking tadalafil (Cialis®)? Congrats! Or maybe you’re thinking about asking your healthcare provider about it. Either way, we commend you for taking steps to improve your sexual health.

You started this journey thinking you were well on your way to some of the best sex in recent memory. But the desired results of taking this medication aren’t the only thing to consider.

Can’t imagine the words “Cialis” and “heart attack” in the same sentence? Think again.

We know — bummer.

While the erectile dysfunction (ED) medication tadalafil (the generic version of Cialis®) is safe and effective for most people — i.e., millions of men who use it all over the world — it’s not perfect. And that goes for pretty much any medication, really. 

Potential tadalafil interactions can happen— especially if you’re already taking other prescription drugs or over-the-counter (OTC) supplements. 

Let’s dive into the specifics of Cialis interactions. Below, we’ll cover the medications tadalafil can interact with, grouping them into severe and moderate interactions. We’ll also outline a few health conditions that might interact with tadalafil.

Tadalafil Interactions and Adverse Effects

Tadalafil is one of the most commonly prescribed PDE5 inhibitors (short for phosphodiesterase type 5 inhibitors), alongside sildenafil.

How does Cialis work? It blocks the action of the — you guessed it — phosphodiesterase type 5 (PDE5) enzyme, which plays a role in regulating blood vessel size.

PDE5 inhibitors don’t just work on the penis. They can also affect other parts of the body with PDE5 enzymes (like the lower urinary tract).

Here’s a quick breakdown of tadalafil uses:

  • Erectile dysfunction. PDE5 inhibitors like tadalafil are probably best known for their ability to improve blood flow to the penis. Tadalafil dosage for ED starts at 2.5 milligrams (mg) before sexual activity, going up to a maximum of 20 milligrams, depending on how well it works and how you’re tolerating it.

  • Pulmonary arterial hypertension (PAH). PAH is a form of high blood pressure that specifically affects the arteries of the lungs. This impacts blood flow elsewhere in the body, causing symptoms like rapid heart rate, chest pain, fatigue and shortness of breath. PDE5 inhibitors like tadalafil help improve blood flow in the blood vessels supplying the lungs. Only two PDE5 inhibitors are approved for use with PAH: tadalafil (and brand-name Adcirca® or Cialis®) and sildenafil (generic for Revatio®). Healthcare professionals also prescribe riociguat (and brand-name Adempas®) for PAH.

  • Benign prostatic hyperplasia (BPH). BPH is a non-cancerous enlargement of the prostate that typically causes lower urinary tract symptoms. Cialis® (and generic tadalafil) is the only FDA-approved PDE5 inhibitor for the treatment of benign prostatic hyperplasia symptoms. Other drugs for BPH include tamsulosin (Flomax®) and alfuzosin (Uroxatral®).

As with any prescription medication, adverse effects can happen. The most common side effects of tadalafil include:

  • Headache

  • Nasal congestion

  • Indigestion

  • Back pain

  • Facial flushing

Facial flushing is the most common side effect of PDE5 inhibitors — including tadalafil! But a 2017 review found that tadalafil is less likely to cause facial flushing than some of its contemporaries — notably, sildenafil (the generic form of Viagra®).

Another major potential adverse effect of PDE5 inhibitors is priapism, when an erection lasts longer than four hours. Sounds great, but it’s really not.

If your woody isn’t going away, seek medical attention right away to avoid lasting damage to your penis. You’re at higher risk of experiencing this rare side effect if you have:

  • Multiple myeloma

  • Sickle cell anemia

  • Leukemia 

  • Penile anatomical deformations

Regardless of why you’re taking tadalafil, interactions can happen, especially since this prescription drug can stay in the body longer than other ED medications — up to two days.

Now that you know about potential side effects and why a healthcare professional might prescribe tadalafil, let’s go over some of the major and moderate tadalafil interactions. 

Major Tadalafil Drug Interactions

A drug interaction happens when two different substances react. A major interaction means mixing the two substances can produce serious, sometimes fatal effects.

You’re more likely to experience drug interactions if you have multiple prescriptions, which is more likely with older adults.

Always let a healthcare professional know about any medications, over-the-counter supplements or other substances you’re taking. Your provider should also be aware of any medical conditions you have to prevent potentially dangerous interactions. 

Here are the major Cialis drug interaction warnings you should know about.

PDE5 Inhibitors

What can you not take with tadalafil? This one is probably obvious.

More of something isn’t always better. Taking too much tadalafil or mixing tadalafil with other PDE5 inhibitors can worsen serious side effects.


Healthcare professionals prescribe nitrates for treating angina, chest pain resulting from limited blood flow to the heart. These include:

  • Isosorbide dinitrate

  • Isosorbide mononitrate

  • Nitroglycerin

FYI: Nitrates and Cialis aren’t friends. In fact, nitrates don’t play well with any PDE5 inhibitors. So if you’re taking nitrates and experiencing ED, it’s a good idea to talk with a healthcare professional about your treatment options.

Blood Pressure Medications

Same deal here. Taking tadalafil with blood pressure medications can cause a severe dip in blood pressure.

Blood pressure medications include:

  • Alpha-blockers like doxazosin, prazosin and terazosin hydrochloride

  • Beta-blockers like propranolol, nadolol and penbutolol

  • ACE inhibitors like lisinopril

  • Diuretics

  • Angiotensin II receptor blockers

  • Calcium channel blockers

  • Central alpha-2 receptor agonists

  • Vasodilators

Keep in mind healthcare professionals may prescribe blood pressure medications like alpha-blockers for conditions other than high blood pressure. Alpha-blockers can treat BPH, for example.

What’s more, ED is a potential side effect of some blood pressure meds (namely, beta-blockers). But it’s not a good idea to take erectile dysfunction meds to treat penis problems resulting from beta-blocker use. Whomp, whomp.


Imagine being allergic to your penis pill. We can’t think of anything more disappointing, honestly.

But it’s actually possible.

Signs of a potential allergic reaction from tadalafil include:

  • Hives

  • Rash

  • Swelling of the throat, lips or tongue

  • Problems breathing

  • Trouble swallowing

If you think you’re having an allergic reaction to tadalafil, seek emergency help right away.


Poppers are recreational drugs containing amyl nitrate or butyl nitrate. Since they contain nitrates, they can have the same blood pressure-lowering effects as prescription nitrates.

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Moderate Tadalafil Interactions

Moderate interactions may not necessarily be life-threatening, but they can be serious enough to require hospitalization.

Substances with moderate tadalafil warnings include:

  • Alcohol. PDE5 inhibitors and alcohol don’t play well together. Why not? Alcohol can exacerbate the blood pressure-lowering effects of these medications. Mixing the two can also increase your heart rate. Cialis and alcohol may not produce the same effects as they would when used separately since the interaction causes the body to absorb tadalafil more slowly.

  • Grapefruit. Who would’ve thunk this breakfast-y fruit would interact with medications? Not me (**cue gif of Paul Rudd from Hot Ones**). Tadalafil is primarily metabolized by CYP3A4 enzymes. Grapefruit juice is a CYP3A4 inhibitor. So combining tadalafil with grapefruit juice can increase the amount of the active drug in your system. It’s why Cialis and grapefruit aren’t friends.

  • Some antifungal drugs. Certain antifungals, like ketoconazole and itraconazole, can interact with tadalafil.

  • HIV protease inhibitors. Medications like ritonavir, which healthcare professionals use to treat HIV, inhibit certain enzymes, including CYP3A4 — which could increase the dose of tadalafil you’re exposed to.

  • Some antibiotics. Antibiotics like clarithromycin (Biaxin®), telithromycin (Ketek®), rifampin and erythromycin can interact with tadalafil.

  • Other medications that act on CYP3A4. These include carbamazepine, phenobarbital and phenytoin.

A note on tadalafil food interactions: While fatty meals can impact the absorption of the PDE5 inhibitors sildenafil and vardenafil, this isn’t the case with tadalafil, according to one 2008 review. 

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Health Condition Interactions With Tadalafil

Medication interactions can also happen if you have certain health conditions.

It may not be safe to take tadalafil if you have: 

  • Heart disease. Sex can be tough on the heart, and taking tadalafil can increase heart attack risk if you have a pre-existing heart condition. Only take tadalafil if your healthcare provider says it’s okay. And definitely avoid it if you’ve been told to skip sexual activity altogether.

  • Vision problems. You should avoid taking tadalafil if you have the rare genetic eye disease retinitis pigmentosa. Additionally, taking tadalafil can put you at risk of recurring non-arteritic anterior ischemic optic neuropathy (NAION), a condition that can cause severe vision loss.

  • Kidney disease. Since your kidneys are responsible for filtering blood, kidney problems can impact your body’s ability to flush tadalafil. This may cause the drug to stay in your body longer than it should, increasing the risk of side effects.

  • Liver problems. Your liver is another organ that helps clear your body of substances. Liver disease may cause tadalafil to stick around in your body, increasing your risk of side effects.

  • Bleeding disorders or peptic ulcers. Safety hasn’t yet been established for tadalafil’s use in people with bleeding disorders or peptic ulcers. It’s possible taking tadalafil with these conditions may worsen bleeding.

Let your healthcare provider know if you have any of these conditions. They may recommend a lower dosage, have you take the drug less frequently, monitor you closely or avoid prescribing it altogether.

Taking tadalafil may not be ideal for:

  • Older adults. People over 65 might metabolize drugs like tadalafil more slowly than younger folks, meaning the drug could build up in the body. A healthcare professional may recommend a lower starting dose to prevent this from happening.

  • Kids. Tadalafil isn’t intended for use in people under 18.

Make sure your healthcare provider knows about all medical conditions you have. They should also be aware of any medications, OTC products and herbs you’re taking before prescribing a PDE5 inhibitor like tadalafil. 

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Using Tadalafil Safely

Tadalafil’s longer half-life means it’s a great option for people who’d prefer not to actively think about popping a pill every time they want to get hot and heavy. But because of how long tadalafil lasts, it’s important to be mindful of potential interactions.

When taking any PDE5 inhibitor — tadalafil included — keep the following in mind:

  • Medication interactions. Erectile dysfunction treatments like PDE5 inhibitors can interact with several medications. 

  • Medical conditions. ED medications might not be safe to take if you have certain medical conditions.

  • Dosage. It’s important to follow medical advice and stick to the ED medication dosage instructions provided by your healthcare provider to avoid adverse effects. 

To learn more about tadalafil, check out our blog on getting the maximum effect from Cialis.

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment or medication.

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