How to Take Sildenafil Safely: Nitrates, Alpha Blockers, Alcohol and Dose Limits

Sildenafil has been on the market since 1998, and more than 3,700 men took it in clinical trials before approval. For most men it is a safe medicine. The problems are concentrated in a few predictable places: nitrates, alpha blockers for the prostate, drugs that stop the liver clearing it, heart conditions that make sex itself risky, and tablets that are not what the pack says.

This guide covers each of those in more depth than the usual list of dos and don'ts. Every number comes from the FDA prescribing information for Viagra, the EU product information, or a named study you can check.

The short answer

Do not take sildenafil if you use any nitrate (including nitroglycerin and poppers) or riociguat. Take it no more than once a day, about an hour before sex, at 50 mg unless you are in a group that should start at 25 mg. If you take an alpha blocker for your prostate, be stable on it first and start at 25 mg. Get help at once for an erection lasting over 4 hours, sudden vision or hearing loss, or chest pain during sex. Do not go above 100 mg: in the EU product information, 200 mg added side effects and no benefit.

Before the first dose: a checklist

The FDA and EU labels list the situations where sildenafil must not be used or needs a doctor's judgement first. If any of these apply to you, talk to a doctor before taking a tablet.

Situation	What the labels say
Any nitrate or nitric oxide donor, regular or occasional	Contraindicated (FDA and EU)
Riociguat or another guanylate cyclase stimulator	Contraindicated (FDA and EU)
Heart attack, stroke or life-threatening arrhythmia in the last 6 months	FDA: no controlled data, use with caution. EU: recent stroke or heart attack is a contraindication
Resting blood pressure below 90/50 mmHg	FDA: caution. EU: contraindicated
Blood pressure above 170/110 mmHg	FDA: no controlled data, use with caution
Unstable angina or heart failure	FDA: no controlled data, use with caution. EU: contraindicated in men for whom sex is inadvisable, such as severe heart failure or unstable angina
Aortic stenosis or other left ventricular outflow obstruction	FDA: particularly sensitive to vasodilators, use with caution
Previous NAION (sudden vision loss from the optic nerve)	FDA: higher risk of recurrence, caution. EU: contraindicated after NAION in one eye
Retinitis pigmentosa	FDA: caution. EU: contraindicated
Severe liver impairment	Not studied. EU: contraindicated
Bleeding disorder or active stomach ulcer	FDA: safety unknown
Penile deformity, Peyronie's disease, sickle cell anaemia, multiple myeloma, leukaemia	FDA: caution because of priapism risk

The EU product information also says a medical history and examination should come before treatment, to diagnose the erectile dysfunction and look for the cause. That matters because ED can be the first sign of heart disease or diabetes.

Nitrates and poppers: the one rule with no exceptions

Nitrates release nitric oxide, and sildenafil amplifies what nitric oxide does to blood vessels. Together they can drop blood pressure far enough to cause collapse. The FDA label contraindicates organic nitrates or nitrites "in any form either regularly and/or intermittently".

That covers:

• Nitroglycerin (glyceryl trinitrate, GTN) as a spray, tablet under the tongue, patch or ointment.
• Isosorbide mononitrate and isosorbide dinitrate, the daily tablets for angina.
• Poppers, the recreational inhalants sold as amyl or butyl nitrite or nitrate. The US patient information names them specifically.
• Nicorandil, an angina medicine in some countries. The EU product information warns it contains a nitrate component and can interact seriously.

There is no known safe gap. The FDA label notes that blood levels 24 hours after a dose are much lower than at the peak but says it is unknown whether nitrates can be given safely even then. If you develop chest pain after taking sildenafil, call emergency services and tell them what you took and when, so they do not give you a nitrate.

Riociguat, used for pulmonary hypertension, is contraindicated for the same reason: it acts on the same pathway.

Is your heart ready for sex?

The FDA label's first warning is not about the tablet. It is about sex. Sexual activity puts load on the heart, and the label says ED treatments should not generally be used by men for whom sex is inadvisable because of their heart condition.

The tablet itself has a modest effect on blood pressure. In healthy volunteers, 100 mg lowered sitting blood pressure by a mean maximum of 8.3/5.3 mmHg. The fall was greatest 1 to 2 hours after the dose and was no different from placebo by 8 hours. The size of the fall was similar at 25, 50 and 100 mg.

For most men that is of little consequence. For men with narrowing of the aortic valve, severely impaired control of blood pressure, or recent heart events, it can be. Serious heart and stroke events have been reported after sildenafil since it was approved. The label says most of those men had existing cardiovascular risk factors, many events happened during or shortly after sex, and it is not possible to say whether they were caused by the drug, by sex, or by the underlying disease.

Choosing the right first dose

The recommended starting dose for most men is 50 mg. The label says to consider 25 mg in the first four groups below, because each has higher blood levels of sildenafil, and to start at 25 mg with an alpha blocker.

Group	Why
Over 65	Total exposure about 84% higher than in younger men
Liver impairment, such as cirrhosis	Exposure 85% higher
Severe kidney impairment (creatinine clearance under 30 mL/min)	Exposure about double
Taking erythromycin or a strong CYP3A4 inhibitor	About 3 times the exposure with erythromycin or saquinavir; more expected with ketoconazole or itraconazole; 11 times with ritonavir, which has its own limit
Taking an alpha blocker	Additive fall in blood pressure; the label says start at 25 mg

Age alone is handled differently in the EU, where no dose adjustment is required for men 65 and over. Both labels agree the dose can then be moved up to 100 mg or down to 25 mg depending on how well it works and how well it is tolerated. The sildenafil guide sets out what each step buys in success rate and costs in side effects.

If you are in a 25 mg group, a 25 mg tablet such as Cenforce 25 or Fildena 25 gives the dose directly rather than relying on splitting a larger tablet.

Taking the tablet, step by step

1. Take one tablet about an hour before sex. The label allows 30 minutes to 4 hours. Swallow it with water.
2. Keep it to once a day. That is the label's maximum dosing frequency, whatever happened with the first dose.
3. Mind heavy meals. A high fat meal delays the peak by about an hour and lowers it by 29%. Take the tablet earlier or on a lighter stomach rather than taking more.
4. Allow for arousal. Sildenafil has no effect without sexual stimulation. Nothing happening while you wait is expected.
5. Give it several tries. A single attempt tells you little. If the dose you were advised to take does not work after several correct attempts, see a doctor rather than raising it yourself.
6. Note what you took and when. If something goes wrong, the time of the dose matters to whoever treats you.

How long the effect lasts, and what happens if sex is later than planned, is covered in our guide on how long sildenafil lasts.

Alpha blockers for the prostate

Many men with ED also take an alpha blocker for an enlarged prostate: doxazosin, terazosin, tamsulosin, alfuzosin, silodosin or prazosin. Both drug classes widen blood vessels, and together they can lower blood pressure enough to cause dizziness or fainting. The FDA label is specific about how to combine them:

• Be stable on the alpha blocker before starting sildenafil. Men whose blood pressure is unstable on the alpha blocker alone are at higher risk.
• Start sildenafil at 25 mg.
• If you are already on a settled sildenafil dose and are starting an alpha blocker, the alpha blocker should start at its lowest dose. Each increase in the alpha blocker dose may lower blood pressure further.

The reason is visible in the three doxazosin studies in the FDA label. Older men with an enlarged prostate who had taken doxazosin for at least two weeks were given a single sildenafil dose. The number whose standing systolic blood pressure fell below 85 mmHg rose with the sildenafil dose. Large drops of more than 30 mmHg, however, happened at every dose, including 25 mg.

Sildenafil dose with doxazosin	Standing systolic below 85 mmHg	Standing systolic drop over 30 mmHg after sildenafil only	Placebo-subtracted fall in standing systolic pressure (mmHg)
25 mg (17 men)	0	3	6.0
50 mg (20 men)	2, both with moderately severe hypotension starting about 1 hour and resolving about 7.5 hours after the dose	1	11.6 (19 men with a placebo comparison)
100 mg (20 men)	3, with mild symptoms	4	4.3

The first study had originally given 100 mg to four men. One had postural hypotension with symptoms lasting 8 hours, and two of the four fell below 85 mmHg (both had low or unstable blood pressure before the dose), after which the study switched to 25 mg. At 50 mg, one more man left the study with hypotension (he was also taking minoxidil), and one man screened for the 100 mg study had symptomatic hypotension on 50 mg; the 100 mg study then enrolled only men who had tolerated 50 mg. These were small, separate studies, so the averages do not rise neatly with dose. The consistent message is the label's: be stable on the alpha blocker and start at 25 mg. These data are for doxazosin; the label applies the same caution to all alpha blockers.

Blood pressure medicines

Sildenafil can lower blood pressure further in men already treated for high blood pressure. In hypertensive patients taking amlodipine 5 or 10 mg, adding sildenafil 100 mg lowered supine blood pressure by a mean additional 8/7 mmHg.

That is similar to the effect of sildenafil alone, and a retrospective look at the clinical trial safety data, which the label notes was not designed to detect differences, found no apparent difference in side effects between men taking and not taking blood pressure medicines. Men on several blood pressure drugs, or who get dizzy standing up, should start low and stand up slowly for the first few hours after a dose.

Medicines that raise sildenafil levels

Sildenafil is cleared mainly by the liver enzyme CYP3A4. Anything that blocks that enzyme raises sildenafil levels and makes side effects and blood pressure falls more likely.

Medicine or food	Effect on sildenafil	What the label advises
Ritonavir (HIV)	Exposure 11 times higher, peak 4 times higher	US: no more than 25 mg in 48 hours. EU: combination not advised
Ketoconazole, itraconazole (antifungals)	Expected to be greater than saquinavir	Consider starting at 25 mg
Saquinavir (HIV)	Exposure 210% higher	Consider starting at 25 mg
Erythromycin (antibiotic)	Exposure 182% higher	Consider starting at 25 mg
Cimetidine (acid-reducing H2 blocker)	Levels 56% higher with 800 mg cimetidine	Named as raising levels
Grapefruit juice	EU: may cause modest increases	No specific advice

The US patient information also names indinavir, atazanavir, clarithromycin and telithromycin. Other strong CYP3A4 inhibitors, such as HIV medicines boosted with cobicistat, would be expected to act the same way. If you take any regular medicine, check with a pharmacist before your first dose.

Medicines that lower it, and ones that do not matter

Drugs that speed up CYP3A4 do the opposite. Bosentan, used for pulmonary hypertension, cut sildenafil exposure by 63% in one study (using sildenafil 80 mg three times a day, a pulmonary hypertension dose), and the label expects strong inducers such as rifampin to cut it further. A tablet that seems not to work may simply be being cleared too fast.

Several common medicines were tested and did not change sildenafil levels in a meaningful way:

• Azithromycin: no clinically significant effect on sildenafil levels.
• Antacids (magnesium or aluminium hydroxide): no effect on absorption.
• Warfarin and tolbutamide: no significant interaction.
• Aspirin: sildenafil did not change bleeding time alone or with aspirin.
• SSRI and tricyclic antidepressants, thiazide diuretics, ACE inhibitors and calcium channel blockers: no effect on sildenafil blood levels in trial patients. The blood pressure medicines among them can still add to the fall in blood pressure, as the amlodipine data show.

Alcohol

The FDA label tested sildenafil 50 mg with alcohol at 0.5 g/kg, enough to reach a mean peak blood alcohol of 0.08%. The systolic fall in blood pressure was almost the same with or without sildenafil, 18.5 against 17.4 mmHg. The diastolic fall was larger with sildenafil, 17.2 against 11.1 mmHg. No one had dizziness on standing.

The label summarises this as sildenafil not potentiating alcohol's effect, but the diastolic numbers show the combination is not neutral, and 100 mg was not tested. Heavier drinking was not tested either. Alcohol also works against erections on its own. A drink or two is not a contraindication. A heavy night plus 100 mg is untested territory.

Never combine with other ED medicines

The label says combinations of sildenafil with other PDE5 inhibitors (the class that also includes tadalafil, vardenafil and avanafil), with Revatio or other pulmonary hypertension products containing sildenafil, or with other ED treatments have not been studied, may lower blood pressure further, and are not recommended.

Products that combine sildenafil with a second active drug, such as dapoxetine for premature ejaculation, are outside that label warning, but in our view they call for the same care: they carry the risks of both medicines, and the second drug has interactions of its own. Our sildenafil and dapoxetine guide covers what is known about them.

Why more than 100 mg is not safer or better

The maximum recommended dose is 100 mg. Tablets of 120, 150 and 200 mg are sold online, including by us, so we are direct about what the evidence says about them.

• The EU product information states that doses of 200 mg did not increase efficacy but did increase headache, flushing, dizziness, indigestion, nasal congestion and altered vision.
• In healthy volunteers given single doses up to 800 mg, side effects were of the same kinds as at lower doses but more frequent and more severe.
• Even within the approved range, side effects climb steeply. Headache went from 21% at 50 mg to 28% at 100 mg, indigestion from 9% to 17%, and vision changes from 2% to 11%.

If 100 mg does not work, the next step is a doctor's review of the cause, a different drug such as tadalafil, or a different treatment. It is not a bigger tablet. Our Cenforce strengths comparison explains where each strength sits against the label.

Side effects to expect

In flexible-dose trials, where men took 25 to 100 mg as needed, these side effects were more common than on placebo:

Side effect	Sildenafil (n=734)	Placebo (n=725)
Headache	16%	4%
Flushing	10%	1%
Indigestion	7%	2%
Nasal congestion	4%	2%
Abnormal vision	3%	0%
Dizziness	2%	1%
Rash	2%	1%

The vision effects are usually a blue or other colour tinge, more sensitivity to light, or blurring, described as mild and temporary. They come from sildenafil's effect on PDE6, an enzyme in the retina. Across placebo-controlled trials, 2.5% of men stopped sildenafil because of side effects, against 2.3% on placebo.

In the label's blood pressure study the effect was gone by 8 hours, and the vision changes are described as transient. Side effects that last beyond the day, or that stop you using the tablet, are a reason to lower the dose or see a doctor.

Warning signs: stop and get help

• An erection lasting more than 4 hours. Get medical help immediately. Priapism, a painful erection lasting over 6 hours, can permanently damage the penis if not treated quickly.
• Sudden loss of vision in one or both eyes. Stop all PDE5 inhibitors and get urgent care.
• Sudden loss or reduction of hearing, sometimes with ringing or dizziness. Stop and get prompt medical attention.
• Chest pain, fainting or severe dizziness during or after sex. Call emergency services. Tell them you took sildenafil and when, so you are not given a nitrate.
• Rash, hives or swelling of the face can be an allergic reaction. Rash and hives have been reported, and allergy to sildenafil is a contraindication.

Vision loss and NAION in more detail

NAION (non-arteritic anterior ischemic optic neuropathy) is a loss of blood supply to the optic nerve that causes sudden, sometimes permanent, vision loss. It is rare. The FDA label cites an annual incidence of 2.5 to 11.8 cases per 100,000 men aged 50 and over, regardless of any medicine.

Observational study	Risk of NAION with PDE5 inhibitor use shortly before onset	95% confidence interval
First case-crossover study	2.15 times	1.06 to 4.34
Second, similar study	2.27 times	0.99 to 5.20

Both suggest roughly double the risk, though the second result could be chance, and the label states that neither the reports nor these studies establish that PDE5 inhibitors cause NAION. Most men with NAION after these drugs had risk factors: a "crowded" optic disc, age over 50, diabetes, high blood pressure, coronary artery disease, high cholesterol or smoking.

The practical points: if you have had NAION in one eye, the EU label contraindicates sildenafil and the FDA label calls for caution because the risk of recurrence is higher. Anyone with sudden vision loss after a dose should stop and be seen urgently.

If you do not have ED

Some young men take sildenafil to perform better. A randomised trial of 60 healthy men aged 20 to 40 with no ED tested 25 mg against placebo at home. Erection quality improved in 12 of 30 on sildenafil and 10 of 30 on placebo, which was no real difference. The authors concluded sildenafil should not be given to young healthy men to improve erections.

Taking it recreationally still carries every risk above, and combining it with poppers can be dangerous. If erections are a problem at a young age, the cause is often worth finding. Our guide to erectile dysfunction in young men covers the common ones.

Make sure the tablet is what it says

All the safety data above assume the tablet contains the stated dose of sildenafil and nothing else. Online, that cannot be taken for granted.

In a study run by Pfizer, researchers ordered what was sold as Pfizer Viagra from 22 websites found through top search results in March 2011. None required a prescription. 17 of the 22 orders (77%) were counterfeit and contained 30% to 50% of the labelled sildenafil. Four were authentic and one was an illegal generic.

A 2010 review of counterfeit ED drugs found contents ranging from no active ingredient to more than twice the labelled dose, with contaminants including talcum powder, paint and printer ink. In one analysis it cited, only 10.1% of samples were within 10% of the labelled strength.

SafeRxPills sells generic sildenafil made by Indian manufacturers, including Centurion Laboratories (Cenforce) and Fortune Healthcare (Fildena). These are not FDA-approved products. Whoever you buy from, check that you can see the manufacturer, strength, batch number and expiry date on the strip, and that the seller will answer questions about them. Our guides to checking an online pharmacy and what WHO GMP certification means go through the checks.

What sildenafil does not do

• It does not protect against sexually transmitted infections, including HIV.
• It is not an aphrodisiac and does not create desire on its own. It works only with sexual stimulation.
• It is not approved for premature ejaculation.
• It is not approved for women in the US, UK or EU.
• It does not treat the cause of ED. If there is an underlying problem such as diabetes or vascular disease, it is still there.

When to see a doctor

Before starting, see a doctor if anything in the checklist above applies to you, if you take any regular medicines, or if your ED came on suddenly or with other symptoms. After starting, see one if 100 mg used correctly on several occasions does not work, if side effects persist, or after any of the warning signs above.

ED often shares its causes with heart disease and diabetes, and it can appear years before them. Our erectile dysfunction page covers the causes and treatments, and the tadalafil versus sildenafil comparison covers the main alternative tablet.

Sources

• VIAGRA (sildenafil citrate) tablets, US prescribing information, sections 2, 4, 5, 6, 7, 8, 10 and 12, and patient information. DailyMed
• Viagra EPAR product information (EU SmPC), sections 4.2, 4.3, 4.4, 4.5 and 4.9. European Medicines Agency
• Campbell N et al. Internet-ordered Viagra (sildenafil citrate) is rarely genuine. J Sex Med 2012;9(11):2943-51. PMID 22925379.
• Jackson G et al. Counterfeit phosphodiesterase type 5 inhibitors pose significant safety risks. Int J Clin Pract 2010;64(4):497-504. PMID 20088883.
• Mondaini N et al. Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time. Int J Impot Res 2003;15(3):225-8. PMID 12904810.

This article is for information only and is not medical advice. Sildenafil is a prescription medicine. Talk to a doctor or pharmacist before starting, stopping or changing any treatment.