Sildenafil Citrate Tablets: What the Medication Is and How It Treats ED

• Sildenafil citrate is the salt form of sildenafil, and MHRA documentation states each tablet contains "sildenafil citrate equivalent to 50 mg of sildenafil"
• The drug class is PDE5 inhibitor, described by MHRA as a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 in the corpus cavernosum
• Selectivity is over 4,000-fold against the cardiac isoenzyme PDE3 but only 10-fold against retinal PDE6, which is the postulated reason for blue and green colour changes
• Generic sildenafil 50mg is from £3.99 for 4 tablets at EveryDayMeds, a standard price

Sildenafil citrate tablets are an oral prescription medicine for erectile dysfunction. Sildenafil citrate is the salt form of sildenafil, and the two names describe the same medicine.

This page is the pharmacology of the tablet rather than a how to take it guide. It covers what the substance is, the drug class it belongs to, how the mechanism of action works step by step, what the selectivity figures mean, what is physically in the tablet, how the body handles it and what that explains about the side effects.

Two numbers reframe most of the rest. MHRA documentation describes sildenafil as having greater than 4,000-fold selectivity for PDE5 over PDE3, the enzyme involved in cardiac contractility, but only 10-fold selectivity over PDE6, which sits in the retina. Together they explain why the medicine does not act on heart muscle directly and why a temporary blue or green tinge to vision is a recognised effect.

When people search for ED medication, sildenafil is usually the first name they meet. Understanding what is actually in the tablet makes the consultation that follows a better one. Results vary between individuals.

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Key things to know

• Sildenafil citrate is the salt form; the strength on the box refers to sildenafil, not to the salt
• The drug class is phosphodiesterase type 5 inhibitor, shortened to PDE5 inhibitor
• Licensed UK strengths for erectile dysfunction are 25mg, 50mg and 100mg film-coated oral tablets.
• Mean absolute oral bioavailability is 41%, with a range of 25 to 63%.
• Sildenafil and its major circulating metabolite are 96% bound to plasma proteins.
• It is cleared predominantly by CYP3A4, with CYP2C9 as a minor route.
• About 80% is excreted as metabolites in the faeces and about 13% in the urine.
• Headache is very common, affecting more than 1 in 10 people.
• Nitrates, nitric oxide donors and riociguat are absolute contraindications.
• It is a prescription only medicine, with one narrow pharmacy exception at a single strength.
• Sildenafil is also used to treat pulmonary arterial hypertension, a serious medical condition affecting blood flow in the lungs.
• The prescribed dose must be adhered to carefully to avoid adverse events such as irregular heartbeat or painful erection.
• Grapefruit juice should be avoided during treatment as it can increase blood levels of sildenafil, leading to heightened effects or side effects.
• Patients with medical conditions such as pulmonary veno occlusive disease, retinitis pigmentosa, sickle cell anaemia, multiple myeloma, or bleeding disorders should inform their healthcare provider before using sildenafil.
• Taking too much sildenafil or missing a dose requires guidance from a healthcare provider to maintain a regular dosing schedule and avoid complications.
• The effects of sildenafil depend on sexual stimulation to increase blood flow and improve erectile function; it does not cause an erection without this stimulation.
• Sildenafil must not be combined with amyl nitrate or butyl nitrate (street drugs) due to the risk of severe blood pressure drops.
• Elderly patients may require dose adjustments due to changes in metabolism and increased sensitivity to the medication.

What is sildenafil citrate?

Sildenafil citrate is the chemical salt of sildenafil, the active substance that treats erectile dysfunction. It is what is physically weighed out and pressed into the tablet.

A salt form is a version of a drug combined with an acid or a base to make it stable and suitable for manufacturing. Most oral medicines are formulated this way, and the salt changes how the substance behaves as a powder rather than what it does in the body.

Sildenafil citrate vs sildenafil: why both names appear

The two names appear on the same pack because they describe two different things: the ingredient that goes in, and the amount of active substance that comes out.

MHRA documentation states it precisely: "Each tablet contains sildenafil citrate equivalent to 50 mg of sildenafil."

Read that carefully, because it answers a question people ask and rarely get answered. The number on the box is the sildenafil, not the sildenafil citrate. A 50mg tablet contains more than 50mg of sildenafil citrate by weight, because the citrate part has weight of its own. The stated 50mg strength refers to the amount of sildenafil equivalent, rather than the total weight of sildenafil citrate. Different products may use different formulations and excipients.

The practical consequence is simple. Sildenafil citrate tablets and sildenafil tablets at the same stated strength are the same medicine at the same dose. There is nothing to compare between them.

Sildenafil generic name and brand names

Sildenafil is the generic name, the internationally recognised name for the active substance, and it is what appears on a generic pack and on a dispensing label. Viagra is the brand name under which sildenafil was first marketed in the UK. A brand name belongs to a specific product from a specific manufacturer; the generic name belongs to the substance itself.

Discussions of sildenafil brand names sometimes give the impression that different brands are different medicines. They are not. A UK generic must contain the same active substance as the reference medicinal product, in the same pharmaceutical form, and must be shown to be bioequivalent to it. What differs is the name, the manufacturer, the appearance, the inactive ingredients and the price.

Sildenafil drug class

The sildenafil drug class is phosphodiesterase type 5 inhibitor, usually shortened to PDE5 inhibitor.

MHRA documentation describes it as "a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum". Every part of that phrase does work:

• Potent means it acts at low concentrations
• Selective means it acts on PDE5 far more than on the related enzymes
• cGMP specific identifies which signalling molecule the enzyme breaks down
• In the corpus cavernosum identifies the tissue, which is the erectile tissue of the penis

Other medicines in the same class include tadalafil, vardenafil and avanafil. They share a mechanism but differ in how long they act and in the regimens they are licensed for.

Sildenafil mechanism of action

Sildenafil works by blocking PDE5, the enzyme that breaks down cGMP, so that cGMP persists and the blood vessels in erectile tissue stay relaxed and open for longer.

MHRA documentation sets out the natural pathway: "Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood."

Put in sequence:

1. Stimulation causes nerve endings and endothelium to release nitric oxide
2. Nitric oxide activates guanylate cyclase, an enzyme
3. Guanylate cyclase produces cGMP
4. cGMP relaxes the smooth muscle of the corpus cavernosum, so blood flows in
5. PDE5 breaks cGMP down, which ends the response
6. Sildenafil blocks step 5, so the response from steps 1 to 4 lasts longer

Step 1 is the one that gets missed. Sildenafil does not start the pathway, it prevents the pathway being switched off. If nitric oxide is not released, there is no cGMP for sildenafil to protect, and the tablet has nothing to act on. Sexual stimulation is required for sildenafil to produce its intended effect. If adequate sexual stimulation does not occur, an erection may not result.

How selective is sildenafil?

Very selective against some related enzymes and much less so against others, and the difference explains the side effect profile.

PDE5 is one of a family of phosphodiesterase enzymes that sit in different tissues and break down different signalling molecules. A drug aimed at one of them will always touch the others to some degree. The published selectivity figures show by how much.

What those numbers explain

The PDE3 figure is reassuring and the PDE6 figure is informative, and both are the same kind of fact.

Greater than 4,000-fold selectivity for PDE5 over PDE3 means sildenafil is much more potent against PDE5 than PDE3. Sildenafil nevertheless has vasodilator effects and can lower blood pressure, so this selectivity does not mean that cardiovascular effects are impossible.

Ten-fold selectivity over PDE6 is a much narrower margin, and PDE6 sits in the phototransduction pathway of the retina, which is how the eye converts light into a nerve signal. MHRA documentation reports that "mild and transient differences in colour discrimination (blue/green) were detected in some subjects" and states plainly that "the postulated mechanism for this change in colour discrimination is related to inhibition of PDE6".

That is a rare thing in medicines information: a specific, temporary, recognised side effect with a stated mechanism behind it. A blue or green tinge to vision is not a mystery and not a warning sign in itself. Sudden loss of vision is an entirely different event and is covered further down.

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Sildenafil citrate uses

Sildenafil citrate uses in the UK, in the tablets this page covers, are limited to erectile dysfunction in men aged 18 and over.

Sildenafil is also formulated under different licences at different doses for conditions unrelated to erectile dysfunction. Those are separate products with separate marketing authorisations, and nothing on this page applies to them.

Sildenafil products licensed for erectile dysfunction should be used only according to their authorised indication and prescribing instructions. Sildenafil is also licensed in different formulations and doses for pulmonary arterial hypertension

Sildenafil tablets for ED treat the difficulty itself for a period of hours. They do not treat what is causing it, which is why an assessment matters as much as the prescription. Erectile dysfunction can be an early indicator of cardiovascular disease or diabetes, so the consultation has value beyond the tablet.

Sildenafil medication guide: the tablet at a glance

This is a summary of the medicine as MHRA documentation describes it, in one place.

What is in a sildenafil oral tablet

A sildenafil oral tablet is a film-coated tablet, meaning a compressed core with a thin outer coating.

For the specific product MHRA documentation describes, the core contains microcrystalline cellulose, calcium hydrogen phosphate (anhydrous), croscarmellose sodium and magnesium stearate. The film coat contains hypromellose, titanium dioxide (E171), lactose, triacetin and indigo carmine aluminium lake (E132). That product is a blue, rounded diamond-shaped tablet supplied in PVC and aluminium foil blisters in cartons of 2, 4 or 8.

Two cautions belong with that list. It describes one product. Generic sildenafil citrate tablets from different manufacturers contain different inactive ingredients and look different, so appearance is not a way to judge whether a tablet is genuine or what strength it is.

Lactose appears in that film coat. Anyone who avoids lactose should raise it at consultation and check the leaflet in the pack they are actually supplied.

Sildenafil citrate dosage

MHRA documentation records the dose as one tablet taken as needed, approximately 1 hour beforehand, with a maximum of one tablet in any 24 hour period.

Sildenafil citrate dosage is not something to set for yourself. Treatment suitability depends on an individual clinical assessment, and your prescriber will determine the appropriate treatment. There is no dose escalation plan on this page.

Do not take more than the prescribed dose or more than one sildenafil dose in 24 hours. Do not combine tablets to create a higher dose unless specifically instructed by a prescriber.

Sildenafil citrate 50mg tablets

Sildenafil citrate 50mg tablets are the strength the published efficacy data describes and the strength involved in the 2017 reclassification decision.

In the trial data MHRA records, 74% of men taking sildenafil 50mg reported an improvement in their erections, against 25% of men on placebo. More than 8,000 patients received sildenafil across the studies referred to, at doses ranging from 25 to 100mg.

That 74% figure belongs to 50mg. Moving it to another strength would be an attribution error rather than a comparison.

Sildenafil citrate 100mg tablets

Sildenafil citrate 100mg tablets are a licensed UK strength, listed in the MHRA products database as sildenafil 100mg film-coated tablets. 100mg is the upper end of the dose range studied in the trials described above.

The MHRA sources used here do not publish a separate efficacy percentage for 100mg alongside the 50mg figure, so this page does not quote one. That is an absence in these sources rather than a statement about how the strength performs.

A higher strength is not automatically a better result and is not somewhere to move because a first tablet disappointed. Which strength is appropriate is a prescriber decision made after assessment.

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How the body handles sildenafil

Only about 41% of a swallowed dose reaches the bloodstream, and what does arrive is almost entirely bound to plasma proteins.

MHRA documentation records mean absolute oral bioavailability as 41%, with a range of 25 to 63%. That range matters as much as the average, because it means the same tablet does not deliver the same blood concentration in every person. Sildenafil and its major circulating metabolite are then 96% bound to plasma proteins.Sildenafil and its major circulating metabolite are highly bound to plasma proteins; the unbound fraction is pharmacologically available to tissues.

Clearance is where the interaction warnings come from. Sildenafil is cleared predominantly by CYP3A4, a liver enzyme, with CYP2C9 as a minor route. That single fact is the reason potent CYP3A4 inhibitors carry a caution: a medicine that slows that enzyme leaves more sildenafil in circulation for longer. It is why a newly started antibiotic or antifungal is worth mentioning at consultation.

The main metabolite, formed by N-demethylation, has a phosphodiesterase selectivity profile similar to sildenafil and an in vitro potency for PDE5 of approximately 50% that of the parent drug, so the medicine leaves behind something still partly active.

Excretion is mostly not through the kidneys. About 80% of an oral dose is excreted as metabolites in the faeces and about 13% in the urine.

Sildenafil citrate side effects

Headache is the only side effect of MHRA documentation classes as it is very common, meaning it may affect more than 1 in 10 people.

Most of that list traces directly back to the mechanism. Blood vessels widening in erectile tissue also widen elsewhere, which produces headache, flushing and nasal congestion. The visual effects trace to PDE6 in the retina, as set out above.

Men with erectile dysfunction should be advised to have appropriate medical review, particularly if symptoms persist or worsen or if underlying cardiovascular risk factors have not been assessed.

Who must not take this medicine

Sildenafil is contraindicated, meaning it must not be taken, by anyone who:

• Takes nitrates or nitric oxide donors, including medicines for chest pain or heart failure
• Takes riociguat
• Takes ritonavir
• Is allergic to sildenafil or any of the other ingredients
• Has been advised to avoid exertion because of a heart or blood vessel problem, including a heart attack or stroke within the last 6 months, unstable angina or severe cardiac failure
• Has ever had loss of vision from damage to the optic nerve, such as non-arteritic anterior ischaemic optic neuropathy
• Sildenafil is contraindicated in patients with hypotension below 90/50 mmHg, severe hepatic impairment, recent stroke or myocardial infarction, certain hereditary retinal disorders, previous NAION-related loss of vision in one eye, and in those taking nitrates, nitric oxide donors, riociguat or, for relevant products, ritonavir.
• Has a severe liver problem
• Caution or medical assessment is required in patients with uncontrolled hypertension, anatomical penile deformity such as Peyronie's disease, or conditions that may predispose them to priapism.

The nitrate interaction is the most serious. Both nitrates and sildenafil lower blood pressure, and together the drop can be severe.

Further caution, and a prescriber conversation first, applies to anyone taking alpha blockers or CYP3A4 inhibitors, and anyone with mild to moderate liver disease or severe kidney problems. This medicine should only be used under the supervision of an appropriately qualified prescriber.

Sildenafil prescription medication: how it is supplied in the UK

Sildenafil is a prescription only medicine in the UK, with one narrow exception at a single strength.

In November 2017 the MHRA reclassified a sildenafil 50mg product from prescription only medicine to pharmacy medicine, making that specific product available without a prescription for men over 18 with erectile dysfunction, after a pharmacist consultation. It is not sold to people with severe cardiovascular disorders, those at high cardiovascular risk, those with liver failure or severe kidney failure, or those taking certain interacting medicines.

For anyone buying online the rule is unchanged. Sildenafil supplied legally through a UK pharmacy is subject to the applicable pharmacy and prescribing requirements. Patients should check that an online pharmacy is registered with the appropriate regulator and avoid websites supplying medicines without the required checks.

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When to seek urgent help

• An erection lasting longer than 4 hours needs immediate medical attention
• Sudden loss of vision in one or both eyes, or sudden loss or reduction of hearing, means stopping the medicine and being seen urgently
• Chest pain during or after use is an emergency, and you must say that you have taken sildenafil, because nitrates must not be given
• Fainting or collapse needs assessment

Medical Disclaimer

This article is for general information only and is not medical advice. It does not replace an assessment by a qualified healthcare professional. Treatment suitability depends on an individual clinical assessment. Your prescriber will determine the appropriate treatment. This medicine should only be used under the supervision of an appropriately qualified prescriber. Results vary between individuals.

Nothing here instructs you to take a particular strength, quantity or frequency, or to change an existing regimen, and there is no dose escalation plan on this page. The guidance here does not replace the instructions on your dispensing label or in the patient information leaflet supplied with your pack, and where they differ you should follow your prescriber and your leaflet.

The pharmacology figures on this page, including selectivity ratios, bioavailability, protein binding, metabolic route and excretion, are taken from MHRA documentation relating to sildenafil for erectile dysfunction and do not apply to sildenafil products licensed for other conditions. The efficacy figure of 74% against 25% on placebo relates to sildenafil 50mg, in studies in which more than 8,000 patients received doses of 25 to 100mg, and it is not transferable to another strength. No matching percentage for 25mg or 100mg appears in the sources used here, which is an absence rather than a statement about how those strengths perform.

The excipient list, tablet appearance and pack sizes described relate to one specific product and are not generalisable. Inactive ingredients differ between manufacturers, the leaflet in your own pack is the authority on what it contains, and appearance is not a way to verify a tablet's identity, strength or authenticity. Prices quoted are standard prices at the time of writing, shown per pack and per tablet. They are not promotional or first order prices, every per tablet figure is calculated from the pack price shown, and prices may change. Cost is not a basis on which to choose a strength.

Do not start, stop or change the strength or frequency of any prescribed medicine because of this page. Never take more than one tablet in any 24 hour period, and never take two tablets of a lower strength to make a higher one. Never combine sildenafil with a nitrate, a nitric oxide donor or riociguat. Suspected side effects can be reported through the MHRA Yellow Card scheme. Seek immediate medical help for an erection lasting longer than 4 hours, chest pain, fainting, or sudden loss of vision or hearing.