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Tadalafil Interactions Guide

Kelly Brown MD, MBA

Reviewed by Kelly Brown MD, MBA

Written by Geoffrey C. Whittaker

Published 02/10/2021

Updated 05/25/2024

The erectile dysfunction (ED) medication tadalafil (generic Cialis®) is safe and effective for millions of men who use it all over the world — but it’s not perfect. There are potentially dangerous tadalafil interactions to consider.

Other prescription drugs or over-the-counter (OTC) supplements can amplify the side effects of tadalafil. In severe cases of misuse, the effects could potentially be fatal.

So, what can you not take with tadalafil? We’ll give you a thorough list for informational purposes, but the most critical drug information is how, why, and when these interactions happen.

Below, we’ll cover the medications tadalafil can interact with and outline a few health conditions that might interact with tadalafil.

Tadalafil is one of the most commonly prescribed PDE5 inhibitors (short for phosphodiesterase-5 inhibitors). To understand why and how interactions happen, you need to first understand what it actually does.

This ED medication blocks the action of PDE5, an enzyme that plays a role in regulating blood vessel size.

PDE5 inhibitors like tadalafil are prescribed for the treatment of erectile dysfunction. But there are other tadalafil uses, including treating pulmonary arterial hypertension (PAH) and benign prostatic hyperplasia (BPH).

Regardless of why you’re taking tadalafil, interactions are possible, especially since this prescription drug can stay in the body longer than other ED medications — up to two days. And as with any prescription medication, adverse effects can happen, particularly when it interacts with another drug.

A drug interaction happens when two different substances react. A major interaction means mixing the 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 effects.

Learn more about how Cialis works in our guide.

The main risks of tadalafil drug interactions are increased and more severe side effects.

The most common side effects of tadalafil include:

  • Headache

  • Nasal congestion

  • Indigestion

  • Back pain

Another major potential adverse effect of PDE5 inhibitors is priapism, when an erection lasts longer than four hours. If your erection isn’t going away, seek medical attention immediately 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

Signs of a potential allergic reaction from tadalafil include:

  • Hives or 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.

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

While some interactions may not necessarily be life-threatening, they can be serious enough to require hospitalization. So it’s vital to never mix medications without professional guidance.

The major Cialis drug interaction warnings you should know about include:

  • Other erectile dysfunction drugs

  • Pulmonary arterial hypertension drugs

  • Benign prostatic hyperplasia drugs

  • Nitrates

  • Some antifungal drugs

  • HIV protease inhibitors

  • Other CYP3A4-inhibiting meds

  • Some antibiotics

  • Other blood pressure medications

  • ACE inhibitors

Get more details below.

1. Other Erectile Dysfunction Drugs

PDE5 inhibitors like tadalafil are probably best known for their ability to improve blood flow to the penis. But more of something isn’t always better.

Taking too much tadalafil or mixing tadalafil with other PDE5 inhibitors can worsen serious side effects.

2. Pulmonary Arterial Hypertension Drugs

PAH is 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.

3. Benign Prostatic Hyperplasia Drugs

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.

However, other drugs for BPH can give similar side effects when combined, including tamsulosin (Flomax®) and alfuzosin (Uroxatral®). Alpha-blockers can treat BPH, too, and should be avoided when taking tadalafil.

4. Nitrates

Healthcare professionals prescribe nitrates to treat angina (chest pain resulting from limited blood flow to the heart). These include isosorbide dinitrate, isosorbide mononitrate, and nitroglycerin.

FYI: 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 your medical provider about safe treatment options.

5. Some Antifungal Drugs

Certain antifungals, like ketoconazole and itraconazole, can interact with tadalafil. These oral and topical medications should be avoided when taking Cialis.

6. HIV Protease Inhibitors

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

7. Other CYP3A4-Inhibiting Meds

Cialis interactions can happen with other meds that inhibit the enzyme CYP3A4. These include carbamazepine, phenobarbital, and phenytoin.

8. Some Antibiotics

Antibiotics like clarithromycin (generic for Biaxin®), telithromycin (Ketek®), rifampin, and erythromycin can interact with tadalafil.

9. Other Blood Pressure Medications

Taking tadalafil with blood pressure medications can cause hypotension, a severe dip in blood pressure.

Blood pressure medications include alpha-blockers like doxazosin, prazosin, and terazosin hydrochloride. Beta-blockers, such as propranolol, nadolol, and penbutolol, should also be avoided.

10. ACE Inhibitors

What about Cialis and lisinopril — can you take Cialis with lisinopril? ACE inhibitors (ACE stands for angiotensin-converting-enzyme) like lisinopril should be avoided with tadalafil.

They also include diuretics, angiotensin II receptor blockers, calcium channel blockers, and central alpha-2 receptor agonists.

There are actually over 300 tadalafil/Cialis drug interactions. So if you take something we haven’t mentioned, still definitely check with your healthcare provider to see if it’s safe to take with your ED meds.

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Substances with moderate tadalafil warnings include:

  • Alcohol. PDE5 inhibitors and alcohol don’t play well together. Alcohol can exacerbate the blood pressure-lowering effects of these medications. Mixing them 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. 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.

  • Poppers. 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.

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

So a thick steak or burger before sex might be fine with Cialis but not other ED medications. 

Choose your chew

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 could increase heart attack risk if you have a pre-existing heart condition. Only take tadalafil if your healthcare provider says it’s safe.

  • Vision problems. You should avoid tadalafil if you have the rare genetic eye disease retinitis pigmentosa. Additionally, taking tadalafil could put you at risk for 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 choose not to prescribe it at all.

Make sure your provider knows about all medical conditions you have — even ones we didn’t list above. 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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Tadalafil’s longer half-life means it’s a great option for people who’d prefer not to actively think about timing their medication with sexual activity. But because of how long Cialis lasts, it’s important to be mindful of potential tadalafil interactions.

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

  • Medication interactions are serious. Erectile dysfunction treatments, like PDE5 inhibitors, can interact with several medications and can cause hypotension (low blood pressure) — among many other dangerous effects.

  • Medical conditions can make an otherwise safe medication dangerous. ED medications might not be safe to take if you have certain medical conditions because it can increase your risk of adverse side effects.

  • Dosage. It’s crucial 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.

17 Sources

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  2. ADIRCA-tadalafil tablet. (2023). http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ff61b237-be8e-461b-8114-78c52a8ad0ae.
  3. American Heart Association. (2021). Angina (chest pain). https://www.heart.org/en/health-topics/heart-attack/angina-chest-pain
  4. American Heart Association (2023). Types of blood pressure medications. https://www.heart.org/en/health-topics/high-blood-pressure/changes-you-can-make-to-manage-high-blood-pressure/types-of-blood-pressure-medications
  5. Cascorbi I. (2012). Drug interactions—principles, examples and clinical consequences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444856/
  6. CIALIS (tadalafil) tablets, for oral use. (2003). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021368s030lbl.pdf.
  7. Coward RM, et al. (2008). Tadalafil in the treatment of erectile dysfunction. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643112/
  8. Huang SA, et al. (2013). Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776492/
  9. Dhaliwal A, et al. (2021). PDE5 Inhibitors. https://www.ncbi.nlm.nih.gov/books/NBK549843/
  10. Frajese GV, et al. (2006). Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699638/
  11. Gong B, et al. (2017). Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: A systematic review and meta-analysis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603624/
  12. National Heart, Lung, and Blood Institute (NHLBI). (2023). What is pulmonary hypertension?. https://www.nhlbi.nih.gov/health/pulmonary-hypertension
  13. National Heart, Lung, and Blood Institute (NHLBI). (2022). Symptoms. https://www.nhlbi.nih.gov/health/pulmonary-hypertension/symptoms
  14. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (2014). Prostate enlargement (Benign prostatic hyperplasia). https://www.niddk.nih.gov/health-information/urologic-diseases/prostate-problems/prostate-enlargement-benign-prostatic-hyperplasia
  15. Lee PM, et al. (2023). Nitrates. https://www.ncbi.nlm.nih.gov/books/NBK545149/
  16. Statpearls. (2020, July 20). Tadalafil. https://www.ncbi.nlm.nih.gov/books/NBK559659/
  17. U.S. Food and Drug Administration (FDA). (2015). Questions and answers for Cialis (tadalafil). https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-cialis-tadalafil
Editorial Standards

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references. See a mistake? Let us know at [email protected]!

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. Learn more about our editorial standards here.

Kelly Brown MD, MBA
Kelly Brown MD, MBA

Dr. Kelly Brown is a board certified Urologist and fellowship trained in Andrology. She is an accomplished men’s health expert with a robust background in healthcare innovation, clinical medicine, and academic research. Dr. Brown is a founding member of Posterity Health where she is Medical Director and leads strategy and design of their Digital Health Platform, an innovative education and telehealth model for delivering expert male fertility care.

She completed her undergraduate studies at University of North Carolina at Chapel Hill (go Heels!) with a Bachelor of Science in Radiologic Science and a Minor in Chemistry. She took a position at University of California Los Angeles as a radiologic technologist in the department of Interventional Cardiology, further solidifying her passion for medicine. She also pursued the unique opportunity to lead departmental design and operational development at the Ronald Reagan UCLA Medical Center, sparking her passion for the business of healthcare.

Dr. Brown then went on to obtain her doctorate in medicine from the prestigious Northwestern University - Feinberg School of Medicine and Masters in Business Administration from Northwestern University - Kellogg School of Management, with a concentration in Healthcare Management. During her surgical residency in Urology at University of California San Francisco, she utilized her research year to focus on innovations in telemedicine and then served as chief resident with significant contributions to clinical quality improvement. Dr. Brown then completed her Andrology Fellowship at Medical College of Wisconsin, furthering her expertise in male fertility, microsurgery, and sexual function.

Her dedication to caring for patients with compassion, understanding, as well as a unique ability to make guys instantly comfortable discussing anything from sex to sperm makes her a renowned clinician. In addition, her passion for innovation in healthcare combined with her business acumen makes her a formidable leader in the field of men’s health.

Dr. Brown is an avid adventurer; summiting Mount Kilimanjaro in Tanzania (twice!) and hiking the incredible Torres del Paine Trek in Patagonia, Chile. She deeply appreciates new challenges and diverse cultures on her travels. She lives in Denver with her husband, two children, and beloved Bernese Mountain Dog. You can find Dr. Brown on LinkedIn for more information.

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