Tadalafil interactions: nitrates, blood pressure medicines, alcohol and grapefruit

Status: FDA-approved prescription medicine for ED. Source: Cialis prescribing information (Eli Lilly), DailyMed, checked 2026-10-17.

In short: tadalafil, sold as Cialis and as generics, has a short list of combinations that are never allowed and a longer list that only need a prescriber’s attention. The never list is nitrate heart medicines, nitrite “poppers” and the lung-pressure drug riociguat (Cialis prescribing information, DailyMed). The careful list covers alpha blockers, other blood pressure medicines, heavy drinking, and medicines that change how the liver clears tadalafil. One thing sets tadalafil apart from sildenafil: it stays in the body much longer, so its interaction window is longer too. Everything here comes from the current FDA label (revised March 2026), the National Library of Medicine’s drug guide, the American Urological Association guideline and the published interaction studies. Evidence level: approved drug, with most interaction data from small controlled studies that measured blood pressure and blood levels, not from large real-world outcome studies.

What should not be taken with tadalafil?

Nitrates, nitrite “poppers” and riociguat should never be taken with tadalafil, and the label lists all three as contraindications. Other ED medicines and other PDE5 inhibitors, including Adcirca (tadalafil sold for lung blood pressure) and Revatio (sildenafil), should not be combined with it either. The rest of the list below calls for caution and a prescriber’s review rather than an outright ban (Cialis prescribing information, DailyMed).

Source for every row: Cialis prescribing information, DailyMed, sections 4, 5, 7, 12 and 17. This page does not give doses. Where the label changes a dose because of an interaction, that is the prescriber’s call.

Why can’t tadalafil be taken with nitrates like nitroglycerin?

Tadalafil and nitrates act on the same blood-vessel relaxing pathway, so together they can cause a sudden, severe drop in blood pressure. The label states that tadalafil “was shown to potentiate the hypotensive effect of nitrates” and makes use with “any form of organic nitrate, either regularly and/or intermittently” a contraindication (Cialis prescribing information, DailyMed). The American Urological Association guideline describes the same combination as able to cause “a precipitous drop in blood pressure” and says men taking nitrates regularly should not use these medicines (AUA erectile dysfunction guideline).

Nitrates come in more forms than most men expect. The patient information lists nitroglycerin tablets, sprays, ointments, pastes and patches, isosorbide dinitrate and mononitrate, and recreational “poppers” such as amyl nitrite and butyl nitrite. MedlinePlus, the National Library of Medicine’s drug guide, adds that nitrates also come as tablets placed under the tongue (MedlinePlus: Tadalafil). If you are not sure whether a medicine is a nitrate, the label says to ask a prescriber or pharmacist.

How long after tadalafil can nitrates be given?

The label says at least 48 hours should pass after the last tadalafil dose before a nitrate is even considered in a life-threatening emergency, and then only under close medical supervision with blood pressure monitoring (Cialis prescribing information, DailyMed). That is a rule for emergency teams, not a waiting period that makes routine nitrate use safe. The contraindication still stands.

The 48-hour figure comes from a controlled crossover study of 150 men, which the label describes as aged 40 and over and including some with diabetes or controlled high blood pressure, who took tadalafil or placebo daily for a week and were then given nitroglycerin under the tongue at set times. More men on tadalafil had standing systolic blood pressure fall below 85 mmHg at 4, 8 and 24 hours, but there was no difference at 48, 72 or 96 hours (Kloner et al., J Am Coll Cardiol 2003). The label adds that at 48 hours a few more men on tadalafil still had a larger drop than on placebo. The reason the window is so much longer than sildenafil’s is tadalafil’s half-life of about 17.5 hours, which the same study and the label both report. The AUA guideline makes the same point: men who carry nitroglycerin for angina should leave at least 24 hours after an ED pill, “and possibly longer” for tadalafil (AUA erectile dysfunction guideline).

If chest pain starts after taking tadalafil, the label says to seek immediate medical attention, and MedlinePlus says to tell the treating team when you last took it (MedlinePlus: Tadalafil).

Does Cialis lower blood pressure?

Only slightly when taken alone. In healthy men, the label reports no significant difference from placebo in blood pressure: the extra maximum drop was 1.6/0.8 mmHg lying down and 0.2/4.6 mmHg standing, with no significant effect on heart rate (Cialis prescribing information, DailyMed). A cardiology review describes the whole drug class as mild vasodilators with “small (and in general, clinically insignificant) decreases in blood pressure” (Kloner, Am J Cardiol 2005).

The effect matters in combination, with nitrates, alpha blockers, other blood pressure medicines or heavy drinking, and in certain heart conditions. The label notes that men with a narrowed outflow from the heart, such as aortic stenosis, can be sensitive to vasodilators, and that tadalafil was not studied in men with low blood pressure (below 90/50) or uncontrolled high blood pressure. Cialis is not a treatment for high blood pressure. The same drug is sold as Adcirca for pulmonary arterial hypertension, which is high pressure in the lung’s blood vessels, a different condition (MedlinePlus: Tadalafil).

Can tadalafil be taken with blood pressure medicines like lisinopril?

Often yes, with the prescriber’s knowledge. The label’s studies tested tadalafil with several common blood pressure medicines and found small extra drops in blood pressure compared with placebo (Cialis prescribing information, DailyMed):

Lisinopril itself was not one of the medicines tested. It belongs to the same class as enalapril, the ACE inhibitors (MedlinePlus: Lisinopril), so the enalapril row is the closest evidence the label offers. A review of these combinations concluded they are usually well tolerated when baseline blood pressure is at least 90/60, with nitrates and alpha blockers as the two exceptions (Reffelmann and Kloner, Vasc Health Risk Manag 2006). The same review stresses that effective blood pressure treatment should not be stopped. If you think a blood pressure medicine is affecting erections, raise it with the prescriber rather than stopping it yourself; our page on medicines that can affect erections covers that side.

Can tadalafil be taken with alpha blockers like tamsulosin?

For ED, yes, with caution and in a set order, but the label does not recommend the combination for treating an enlarged prostate. Alpha blockers are often prescribed for prostate symptoms or high blood pressure, and the patient information names terazosin, tamsulosin, doxazosin, prazosin, alfuzosin, silodosin and the dutasteride-tamsulosin combination (Cialis prescribing information, DailyMed). Both drug types widen blood vessels, so blood pressure can drop enough to cause dizziness or fainting.

Not every alpha blocker behaved the same in testing. In two controlled studies in healthy men, tadalafil added a mean 9.8 mmHg to the standing systolic drop with doxazosin, and 28% of men on the combination fell below 85 mmHg against 6% on doxazosin alone; with tamsulosin the extra drop was about 2 mmHg and no one fell below 85 mmHg (Kloner et al., J Urol 2004). The label’s guidance is about sequence: be stable on the alpha blocker before starting tadalafil, and start whichever medicine comes second at its lowest dose. Tadalafil is also approved on its own for enlarged prostate symptoms (MedlinePlus: Tadalafil).

Can you drink alcohol with tadalafil?

In the label’s studies, a large amount of alcohol drunk quickly lowered blood pressure further with tadalafil, while a somewhat smaller amount did not. Two studies gave men alcohol equal to about 6 ounces of 80-proof vodka for an 80 kg man within 10 minutes, and more men on tadalafil plus alcohol had significant blood pressure drops than on alcohol alone, with some dizziness on standing. With a lower amount, about 4 ounces, no blood pressure drop on standing was seen and dizziness was no more common than with alcohol alone (Cialis prescribing information, DailyMed).

The label warns that substantial drinking, 5 units or more, together with tadalafil can raise the chance of a faster heartbeat, a drop in standing blood pressure, dizziness and headache. The patient information gives 5 glasses of wine or 5 shots of whiskey as examples of too much. Alcohol and tadalafil did not change each other’s blood levels; the risk comes from both widening blood vessels. Our tadalafil side effects page covers the headache and dizziness picture in full.

Can you have grapefruit with tadalafil?

Probably best to ask first. The label says grapefruit juice has not been specifically studied with tadalafil but “would likely increase tadalafil exposure,” because grapefruit slows CYP3A4, the liver enzyme that clears it (Cialis prescribing information, DailyMed). MedlinePlus says to talk to your doctor about eating grapefruit and drinking grapefruit juice while taking tadalafil (MedlinePlus: Tadalafil). There are no tadalafil-specific numbers on how large the effect is, so this page does not guess at one.

Can you take ibuprofen with tadalafil?

Neither the Cialis label nor MedlinePlus lists ibuprofen or other anti-inflammatory pain relievers among the medicines that interact with tadalafil. In the label’s trials, when the back pain tadalafil can cause needed treatment, acetaminophen or non-steroidal anti-inflammatory drugs (the group that includes ibuprofen) “were generally effective” (Cialis prescribing information, DailyMed).

Two related points from the label: tadalafil did not add to the bleeding-time effect of aspirin, and it has not been given to men with bleeding disorders or active stomach ulcers, where its use needs a careful risk-benefit judgment. Anti-inflammatory pain relievers carry their own cautions for some people, so a pharmacist is the right person to check the whole list with.

Which drugs raise or lower tadalafil levels?

Medicines that block the liver enzyme CYP3A4 raise tadalafil levels, and medicines that speed it up lower them. In the label’s studies, ketoconazole increased tadalafil exposure by up to 312% and ritonavir by up to 124%, while rifampin cut it by 88% (Cialis prescribing information, DailyMed). Because of the raised levels, the label caps the dose, and for as-needed use how often it is taken, with strong blockers such as ritonavir, ketoconazole and itraconazole.

Sources: Cialis prescribing information, DailyMed, section 7; MedlinePlus: Tadalafil. The MedlinePlus list is longer than this table and also names amiodarone, diltiazem, verapamil, sertraline and others, and asks you to mention herbal products, especially St. John’s wort. The label notes one small effect the other way: with theophylline, tadalafil added about 3 beats per minute to the heart-rate rise.

Does daily tadalafil change the interaction picture?

Yes, in one important way: with once-daily use, tadalafil is in the body all the time, so there is no “off” period between doses for an interaction to wait out. The label asks prescribers to discuss “the clinical implications of continuous exposure” with men on daily tadalafil, especially with nitrates, alpha blockers, other blood pressure medicines, strong CYP3A4 blockers and heavy drinking (Cialis prescribing information, DailyMed). Our comparison of daily vs on-demand tadalafil covers the other differences between the two approaches.

Can a “natural” product contain hidden tadalafil?

Yes. The FDA has found tadalafil hidden in products sold for sexual enhancement. In one notice, first posted in 2022 and updated in September 2026, FDA lab testing confirmed tadalafil in a honey product and later in additional versions of it, and the agency warned that the undeclared ingredient “may interact with nitrates” and may lower blood pressure to dangerous levels (FDA, Vital Honey notification). A man taking nitrates could face the full interaction risk without any label to warn him. Our guide to whether generic ED medications are safe covers how to tell a legitimate product from a risky one.

When should you talk to a clinician about interactions?

Before starting tadalafil, and again whenever another medicine is added or changed. The patient information asks men to tell their prescriber about all prescription and non-prescription medicines, vitamins and herbal supplements, and to check before starting or stopping any medicine (Cialis prescribing information, DailyMed). Heart history matters as much as the medicine list: the label says ED treatment should not be used when sexual activity is inadvisable because of heart status, and it was not studied in men with a heart attack in the last 90 days, unstable angina, recent heart failure or uncontrolled heart rhythm or blood pressure.

Our guide to heart disease and ED explains how clinicians assess cardiac risk before prescribing, and sildenafil interactions compares the same rules for the shorter-acting drug.

Sources

1. Cialis (tadalafil) prescribing information, Eli Lilly and Company, revised March 2026, DailyMed
2. MedlinePlus: Tadalafil. U.S. National Library of Medicine
3. MedlinePlus: Lisinopril. U.S. National Library of Medicine
4. Kloner RA, et al. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol. 2003
5. Kloner RA, et al. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. J Urol. 2004
6. Kloner RA. Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions. Am J Cardiol. 2005
7. Reffelmann T, Kloner RA. Sexual function in hypertensive patients receiving treatment. Vasc Health Risk Manag. 2006
8. American Urological Association. Erectile Dysfunction: AUA Guideline
9. U.S. Food and Drug Administration. Public Notification: Vital Honey contains hidden drug ingredient