Sildenafil Contraindications and Medicines You Should Not Mix It With

Most pages on this subject give you one long list of medicines and let you assume they are all equally dangerous. They are not, and treating them as if they were causes two opposite problems. People take real risks because a genuine danger is buried in a list of minor cautions, and people stop treatment they could safely have because a medicine with no documented interaction looks alarming next to one that can kill.

This page sorts the same information into three tiers instead of one list. There are medicines that are an absolute exclusion, where no timing, spacing or strength makes the combination acceptable. There are medicines that raise sildenafil levels in the blood and need a prescriber who knows about it. And there is a substantial group with no documented effect on sildenafil at all, including several that worry people unnecessarily.

Key things to know

• Nitrates and nitric oxide donors are the absolute exclusion. The combination can cause a dangerous fall in blood pressure. There is no safe gap or dose
• Riociguat is the other absolute exclusion
• Antidepressants have no documented effect. SSRIs and tricyclic antidepressants showed no effect on sildenafil pharmacokinetics
• Warfarin showed no significant interaction with sildenafil, and sildenafil did not increase the bleeding time caused by aspirin
• Beta blockers, ACE inhibitors, calcium channel blockers and diuretics showed no effect on sildenafil pharmacokinetics
• Erythromycin raised sildenafil exposure by 182%. Antifungals such as ketoconazole and itraconazole are expected to have greater effects
• Alpha blockers need you to be stable on them first before sildenafil is started
• Treatment suitability depends on an individual clinical assessment

Who Cannot Take Sildenafil

The Contraindications in Full

A contraindication is a situation where a medicine should not be used at all, as opposed to a caution where it can be used with care. These are the documented contraindications.

Sildenafil should not be taken by anyone who:

• Takes any medicine called a nitrate or a nitric oxide donor
• Takes riociguat, used to treat pulmonary arterial hypertension
• Takes ritonavir, which can cause a very large increase in sildenafil exposure
• Is allergic to sildenafil or any of the other ingredients
• Has been advised to avoid activity that strains the heart because of a heart or blood vessel problem, such as a heart attack or stroke within the last 6 months, unstable angina or severe cardiac failure
• Has previously lost vision in one eye because of non-arteritic anterior ischaemic optic neuropathy
• Has low blood pressure, or high blood pressure that is not controlled
• Has a severe liver problem
• Has a disease or deformity affecting the penis, such as Peyronie's disease

Sildenafil is licensed for adult men aged 18 and over, and is not indicated for women.

The Contraindications That Are About Medicines

Three of those are medicines rather than health conditions: nitrates and nitric oxide donors, riociguat, and ritonavir. These are why a complete medicines list is essential before sildenafil is prescribed or supplied.

The rest of this page deals with medicines, because that is where most of the confusion sits and where the documented figures are most useful.

How the Interactions Actually Work

Many clinically important sildenafil interactions involve CYP3A4, the main enzyme responsible for its metabolism.

Sildenafil is broken down in the liver, mainly by CYP3A4, with a smaller contribution from CYP2C9. Medicines that block CYP3A4 slow that breakdown, so more sildenafil stays in the blood for longer. Medicines that speed up CYP3A4 do the opposite and reduce sildenafil levels.

That gives you a rule covering most of the list. If a medicine is a CYP3A4 inhibitor, it raises sildenafil levels and may increase side effects. If it is a CYP3A4 inducer, it lowers them and the medicine may work less well.

Nitrates are the exception to that pattern, and that is exactly why they are the dangerous one. Nitrates do not change how sildenafil is processed. They act on the same blood pressure pathway at the same time, and the effects add together.

Does Sildenafil Affect Other Medicines?

Mostly no, and this is a question people rarely think to ask.

Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. Because that inhibition is weak, it is unlikely that sildenafil will alter the clearance of medicines processed by those enzymes.

In plain terms, the traffic is mostly one way. Other medicines change sildenafil levels far more than sildenafil changes theirs.

The Interaction List in One Table

Start Your Free Assessment

The Medicines That Are an Absolute No

Nitrate Medicines

This is the interaction that matters more than everything else on this page combined, and it is an absolute exclusion rather than a caution.

Nitrates and nitric oxide donors widen blood vessels and lower blood pressure. Sildenafil must not be taken with them, because of the risk of a potentially dangerous fall in blood pressure.

The practical problem is that people do not always recognise their medicine as a nitrate. These are the common forms:

• Glyceryl trinitrate, often called GTN, as a spray under the tongue, tablets or a skin patch
• Isosorbide mononitrate and isosorbide dinitrate, usually daily tablets
• Nicorandil, which is a hybrid of a potassium channel activator and a nitrate. Because of the nitrate component it has the potential to result in a serious interaction
• Amyl nitrite, sometimes sold as poppers

Nicorandil is the one most often missed, because the name gives no clue and people do not think of it as a nitrate at all. Amyl nitrite is the second, because people do not think of it as a medicine.

If you have ever been given something to put under your tongue for chest pain, treat it as a nitrate until a prescriber tells you otherwise. Say so even if you use it once a year.

Angina Medication

Angina medication is where the nitrate problem usually lives, so it deserves its own answer.

Nitrates are a mainstay of angina treatment, which means a large proportion of people with angina are taking a medicine that absolutely excludes sildenafil. If you have angina, the question is not whether sildenafil is safe for angina in general. It is which specific medicines you take.

Not all angina medication is a nitrate. Beta blockers and calcium channel blockers are also commonly prescribed for angina, and both showed no effect on sildenafil pharmacokinetics. So two people with the same diagnosis can get two different answers, and the deciding factor is the prescription rather than the condition.

Unstable angina is a separate matter and is a documented contraindication in its own right.

The Medicines That Need Care

Antibiotics

Not all antibiotics are expected to affect sildenafil, but some require specific consideration. The macrolide group is the exception, and the figure is substantial.

When a single dose of sildenafil was given with erythromycin at steady state, taken as 500mg twice daily for 5 days, there was a 182% increase in sildenafil systemic exposure. That is close to tripling how much sildenafil the body is exposed to from the same tablet.

Clarithromycin is also a CYP3A4 inhibitor and can increase sildenafil exposure. Neither is a reason to refuse treatment outright, but both are a reason for a prescriber to know before anything is supplied.

Antibiotics outside that group are not documented as affecting sildenafil. If you are prescribed a course while already taking sildenafil, that is worth mentioning rather than assuming either way.

Antifungal Medicines

Antifungals are the strongest inhibitors on this list, and the product information is explicit that they exceed the antibiotic figures.

Stronger CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have greater effects than erythromycin. Since erythromycin produced a 182% increase in exposure, that expectation is meaningful.

Note the wording carefully, because honesty matters here. The product information says these are expected to have greater effects. It does not publish a measured figure for them in the material reviewed, so the direction is documented and the exact size is not. This page will not invent a number to fill that gap.

Other Strong Enzyme Inhibitors

Two more medicines have measured figures worth knowing.

Saquinavir, a strong CYP3A4 inhibitor, produced a 140% increase in sildenafil peak concentration and a 210% increase in exposure when taken at steady state alongside a single sildenafil dose. That is the largest measured increase in the reviewed material.

Cimetidine, at 800mg, caused a 56% increase in plasma sildenafil concentrations. It is worth singling out because it is used for stomach acid problems, and people often do not think of stomach medicines as interacting with anything.

Not all stomach medicines behave this way. Single doses of antacid, specifically magnesium hydroxide and aluminium hydroxide, did not affect the bioavailability of sildenafil.

Alpha Blockers

Alpha blockers are the one blood pressure class that needs specific attention, and there is documented practical advice attached rather than just a warning.

Giving sildenafil to patients already taking alpha blocker therapy may lead to symptomatic low blood pressure in a few susceptible individuals. Where doxazosin and sildenafil were taken at the same moment by people already settled on doxazosin, the recorded extra falls in supine blood pressure came out at 7/7 mmHg, 9/5 mmHg and 8/4 mmHg across the measurements taken.

The documented advice is specific and often left out of other pages. Patients should be stabilised on alpha blocker therapy before starting sildenafil, and the reason given is to minimise the potential for postural hypotension, meaning dizziness on standing up.

Common alpha blockers include doxazosin, tamsulosin and alfuzosin. They are prescribed for prostate symptoms as well as blood pressure, so plenty of people take one without thinking of themselves as being on blood pressure medication.

Medicines That Lower Sildenafil Levels

The interaction can run the other way, and this is the explanation people rarely get when a tablet stops working.

Strong CYP3A4 inducers, such as rifampicin, are expected to cause greater decreases in plasma concentrations of sildenafil. An inducer speeds up the enzyme that clears sildenafil, so less of it stays in the blood.

The practical consequence may be reduced exposure and a weaker treatment response. Do not compensate by increasing the dose yourself. Discuss the combination with your prescriber.

Start Your Free Assessment

The Medicines With No Documented Interaction

This group includes medicines for which the reviewed pharmacokinetic evidence did not identify an interaction with sildenafil.

Although specific interaction studies were not conducted for every medicine, pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when medicines were grouped by class.

Antidepressants

No documented effect. The analysis grouped CYP2D6 inhibitors, including selective serotonin reuptake inhibitors and tricyclic antidepressants, and found no effect on sildenafil pharmacokinetics.

This matters for a specific and common reason. Antidepressants can themselves contribute to difficulty with erections, so a large number of people asking this question are taking both. The documented answer is that the antidepressant does not change how sildenafil is processed.

That is a statement about pharmacokinetics rather than a general clearance to combine anything. It remains something to disclose at a consultation, and your prescriber will determine the appropriate treatment.

Heart Medication

Heart medication is not one thing, and the answer splits cleanly down the middle.

Beta blockers such as bisoprolol, atenolol and propranolol are among the most commonly prescribed heart medicines in the UK, so this covers a large number of people who assume any heart medicine is a problem.

One of the most important questions is whether a nitrate or nitric oxide donor is on the medicine list, but the person's cardiovascular condition and other medicines also need to be assessed.

Separately from the medicines, the condition itself can be an exclusion. Severe cardiovascular disorders, including a recent heart attack or stroke within 6 months, unstable angina and severe cardiac failure, are contraindications regardless of what is prescribed.

Blood Thinners

No documented interaction, and there are two separate findings here rather than one.

For warfarin, no significant interactions were shown when it was given alongside sildenafil. Tolbutamide, processed by the same enzyme, was tested alongside it with the same result.

For aspirin, sildenafil did not increase the bleeding time caused by acetylsalicylic acid at 150mg. That addresses the specific worry that sildenafil might add to the bleeding tendency, and the answer in that study was that it did not.

Newer anticoagulants are not individually named in the reviewed material, so no documented statement covers them either way. Their use should be disclosed to the prescriber rather than assumed to be equivalent to warfarin.

Statins

No documented interaction appears in the reviewed material for statins with sildenafil.

Some statins are processed by CYP3A4, the same enzyme that clears sildenafil, so the question is a sensible one to ask. The relevant documented fact is that sildenafil is only a weak inhibitor of CYP3A4, and it is unlikely to alter the clearance of medicines processed by that enzyme.

Statins are not listed as a contraindication, and the reviewed information does not identify a clinically significant interaction.

Herbal Supplements

Herbal supplements are the biggest genuine blind spot in this whole topic, and the honest answer has two halves.

The reviewed product information does not list individual herbal products or publish figures for them, so there is no documented interaction to quote in either direction.

That absence is not reassurance. Some herbal products, such as St John's wort, are known to affect the same liver enzymes that clear sildenafil, and the documented principle about strong inducers lowering sildenafil levels applies to anything that acts as one, whether or not it came from a pharmacy shelf. The difference is that a prescribed medicine has measured figures behind it and a supplement usually does not.

The practical position is straightforward. The instruction in the product information is to tell your pharmacist or prescriber if you are taking, have recently taken, or might take any other medicines. Supplements count, so do vitamins, and so does anything bought without a prescription.

Can You Take Sildenafil With Other Medicines?

Sildenafil can be used with many medicines, but the specific medicine, dose and the person's medical history need to be considered.

The exceptions are specific and short. Nitrates, nicorandil, riociguat and ritonavir are absolute exclusions. Strong enzyme inhibitors including erythromycin, clarithromycin, ketoconazole, itraconazole, saquinavir and cimetidine raise sildenafil levels and need a prescriber's judgement. Alpha blockers need you to be stable on them first. Strong inducers such as rifampicin lower sildenafil levels.

Everything else in the reviewed material either showed no effect or is not documented, and undocumented is not the same as dangerous. It means disclose it and let a prescriber judge.

Start Your Free Assessment

Checking Interactions Before Taking Sildenafil

A Checklist

Work through this before a consultation. It takes a few minutes and it covers everything in the absolute tier.

1. Anything for chest pain or angina. Sprays, tablets under the tongue, patches, or a daily tablet. This is the tier one check
2. Nicorandil specifically, by name, because it is a nitrate that does not sound like one
3. Riociguat, for pulmonary arterial hypertension
4. Ritonavir
5. Antibiotics, particularly erythromycin or clarithromycin, including a course you are about to start
6. Antifungal tablets, particularly ketoconazole or itraconazole
7. Alpha blockers such as doxazosin, tamsulosin or alfuzosin, including those taken for prostate symptoms
8. Cimetidine or other stomach medicines
9. Rifampicin
10. Every supplement, vitamin and herbal product, and anything bought without a prescription
11. Recreational substances, particularly amyl nitrite

What Good Disclosure Looks Like

Three things get left off medicine lists again and again, and each one has caused a preventable problem.

Medicines taken occasionally. A GTN spray used twice a year is still an absolute exclusion. People list daily tablets and forget the emergency one in a drawer.

Medicines prescribed by someone else. A short antibiotic course from a different appointment often does not make it onto the list given at a consultation.

Things not thought of as medicines. Supplements, herbal products and anything bought without a prescription. Our guide to what to avoid when taking sildenafil covers the non-medicine cautions alongside these.

Circumstances change, and a list that was complete a year ago may not be complete now. If your medicines change while you are being supplied sildenafil tablets, that is a reason to raise it before the next supply rather than at the one after. This medicine should only be used under the supervision of an appropriately qualified prescriber.

When to Seek Help Urgently

Stop and seek medical attention immediately for any of the following:

• Chest pain during or after use
• Fainting, collapse or severe dizziness, which can indicate a large fall in blood pressure
• An erection lasting longer than 4 hours
• A sudden decrease or loss of vision, or of hearing
• An allergic reaction

If sildenafil has been taken with a nitrate, whether by mistake or without knowing the medicine was a nitrate, that needs urgent medical attention rather than waiting to see what happens.

Start Your Free Assessment