What is the half-life of sildenafil? The half-life of sildenafil (Viagra) is approximately 3 to 5 hours in most adults, meaning the drug's concentration in the bloodstream reduces by half during this period. This phosphodiesterase type 5 (PDE5) inhibitor is widely prescribed for erectile dysfunction in the UK. Whilst the half-life indicates how quickly the body processes the medication, therapeutic effects typically last 4 to 6 hours. Understanding sildenafil's pharmacokinetics helps patients and clinicians optimise dosing, timing, and safety. Factors such as age, liver function, and drug interactions can significantly influence how long sildenafil remains active in your system.

What Is the Half-Life of Sildenafil?

The half-life of sildenafil, commonly known by the brand name Viagra, is approximately 3 to 5 hours in most adults. This pharmacokinetic parameter refers to the time it takes for the concentration of the drug in the bloodstream to reduce by half. Understanding this concept is important for both patients and healthcare professionals when considering dosing schedules and the duration of therapeutic effect.

Sildenafil belongs to a class of medications called phosphodiesterase type 5 (PDE5) inhibitors. It works by blocking the enzyme PDE5, which normally breaks down cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of blood vessels. By inhibiting this enzyme, sildenafil allows cGMP to accumulate, leading to relaxation of smooth muscle and increased blood flow to the penis during sexual stimulation. This mechanism is what enables the drug to treat erectile dysfunction effectively.

Whilst the half-life is 3 to 5 hours, it is important to note that this does not mean the drug stops working after this time. The therapeutic effects of sildenafil can persist for longer than the half-life suggests, typically remaining effective for 4 to 6 hours after administration. Peak plasma concentrations are usually reached within 30 to 120 minutes of oral administration, though this can vary depending on whether the medication is taken with food.

In the UK, most sildenafil products are prescription-only medicines (POM). The exception is Viagra Connect 50mg, which is available as a Pharmacy (P) medicine following assessment by a pharmacist. All other strengths (25mg and 100mg) and most generic sildenafil products remain prescription-only.

How Long Does Sildenafil Stay in Your System?

Although sildenafil has a half-life of 3 to 5 hours, the drug does not leave your system immediately after this period. Following the principles of pharmacokinetics, it typically takes four to five half-lives for a medication to be almost completely eliminated from the body. This means sildenafil is generally cleared from the system within approximately 15 to 25 hours after a single dose.

The primary route of elimination for sildenafil is through hepatic (liver) metabolism, predominantly via the cytochrome P450 enzyme system, specifically CYP3A4 and, to a lesser extent, CYP2C9. The drug is converted into several metabolites, with the main active metabolite (N-desmethyl sildenafil) having similar PDE5 inhibitory properties to the parent compound, though it is less potent. Approximately 80% of the administered dose is excreted in faeces, whilst around 13% is eliminated in urine.

For most healthy adults, this elimination process occurs efficiently, and the drug does not accumulate with standard dosing regimens. While laboratory tests may detect sildenafil or its metabolites for a period after administration, such testing is not routinely performed in clinical practice. It's worth noting that haemodialysis is not expected to enhance sildenafil clearance due to its high protein binding.

It is important to understand that whilst the drug may remain in the system for this duration, the clinical effects typically diminish well before complete elimination occurs. Patients should not expect therapeutic benefits beyond 6 to 8 hours after taking a dose, even though trace amounts remain in the bloodstream.

Factors That Affect Sildenafil Half-Life

Several physiological and external factors can significantly influence how quickly sildenafil is metabolised and eliminated from the body. Understanding these variables is essential for optimising treatment and minimising the risk of adverse effects.

Age is an important consideration. Older adults (aged 65 years and above) typically experience a prolonged half-life of sildenafil, with plasma concentrations potentially 40% higher than in younger adults. This is due to age-related decline in hepatic function and reduced clearance capacity. The starting dose of 25mg is often recommended for elderly patients.

Hepatic impairment substantially affects sildenafil metabolism. Patients with moderate to severe liver disease (Child-Pugh class B or C) show significantly reduced clearance, leading to increased plasma concentrations and prolonged half-life. In these patients, a starting dose of 25mg should be considered, with careful titration if needed.

Renal function also plays a role, though to a lesser extent than hepatic function. Severe renal impairment (creatinine clearance <30 mL/min) can increase sildenafil exposure, and dose reduction may be necessary. Patients with significant kidney disease should discuss appropriate dosing with their healthcare provider.

Food intake, particularly high-fat meals, can delay the absorption of sildenafil by up to an hour and reduce peak plasma concentrations by approximately 29%. This does not significantly alter the half-life but does affect the onset of action.

Drug interactions are particularly important. Medications that inhibit CYP3A4 enzymes—such as ketoconazole, itraconazole, erythromycin, and ritonavir—can substantially increase sildenafil concentrations and prolong its half-life. Conversely, CYP3A4 inducers like rifampicin may reduce sildenafil effectiveness. Grapefruit juice can also inhibit CYP3A4 and should be avoided when taking sildenafil. Patients should always inform their GP or pharmacist about all medications they are taking.

When to Take Sildenafil for Best Results

Optimal timing of sildenafil administration is crucial for achieving the desired therapeutic effect whilst minimising inconvenience and potential side effects. The standard recommendation is to take sildenafil approximately 30 to 60 minutes before anticipated sexual activity. This timeframe allows the medication to be absorbed, reach peak plasma concentrations, and begin exerting its therapeutic effect.

For most men, sildenafil reaches maximum plasma concentration within 60 minutes when taken on an empty stomach. However, individual variation exists, and some patients may experience effects as early as 20 to 30 minutes after administration, whilst others may require up to 2 hours. Patients are advised to trial the medication on separate occasions to understand their individual response pattern.

Taking sildenafil with food requires additional consideration. Whilst food does not prevent the drug from working, a high-fat meal can delay absorption and reduce peak concentrations. If taking sildenafil after a substantial meal, patients should allow an additional 30 to 60 minutes for the medication to take effect. For optimal and predictable results, taking sildenafil on an empty stomach or after a light meal is generally recommended.

It is important to emphasise that sildenafil does not cause automatic erections. Sexual stimulation is required for the medication to work, as it enhances the natural erectile response rather than initiating it independently. The drug facilitates the physiological processes that occur during arousal but cannot substitute for it.

Frequency of use should also be considered. The maximum recommended dosing frequency is once per 24-hour period. Taking sildenafil more frequently does not enhance effectiveness and increases the risk of adverse effects. Excessive alcohol consumption should be avoided as it can reduce efficacy and increase the risk of dizziness and hypotension.

Patients taking alpha-blockers for benign prostatic hyperplasia or hypertension should ensure they are stable on alpha-blocker therapy before starting sildenafil. They should start with the 25mg dose and consider separating the timing of sildenafil and alpha-blocker doses by at least 4 hours to reduce the risk of postural hypotension.

Sildenafil Dosing and Timing Considerations

Sildenafil is available in the UK in several strengths: 25mg, 50mg, and 100mg tablets. The standard starting dose for most adult men is 50mg, taken as needed approximately one hour before sexual activity. Based on efficacy and tolerability, the dose may be increased to a maximum of 100mg or decreased to 25mg. These adjustments should only be made following consultation with a healthcare professional.

For older adults (aged 65 and over) and patients with hepatic or renal impairment, the recommended starting dose is 25mg. This lower dose accounts for reduced drug clearance and higher plasma concentrations in these populations. Dose escalation should be approached cautiously and only under medical supervision.

Patients taking certain concomitant medications require special dosing considerations. Those on alpha-blockers should be stabilised on alpha-blocker therapy before initiating sildenafil, starting with the 25mg dose and separating administration times by at least 4 hours. With moderate CYP3A4 inhibitors (such as erythromycin), a 25mg starting dose should be considered with cautious titration if needed. With potent CYP3A4 inhibitors (such as ritonavir), the dose should not exceed 25mg, and dosing frequency should be reduced to once every 48 hours.

Sildenafil is contraindicated in patients taking nitrates or nitric oxide donors (such as glyceryl trinitrate or 'poppers') due to the risk of severe hypotension. It is also contraindicated with guanylate cyclase stimulators such as riociguat. The drug should be used with caution in patients with severe cardiovascular disease, recent stroke or myocardial infarction, or hypotension.

Common adverse effects of sildenafil include headache, facial flushing, dyspepsia, nasal congestion, and visual disturbances (such as a blue tinge to vision or increased light sensitivity). These effects are generally mild to moderate and transient. Patients should report suspected side effects via the MHRA Yellow Card Scheme.

Patients should seek immediate medical attention if they experience:

• Priapism (an erection lasting more than 4 hours)

• Sudden vision loss in one or both eyes

• Sudden hearing loss or decrease in hearing

• Chest pain during or after sexual activity (and should not take nitrates; call 999)

• Severe dizziness or fainting

Frequently Asked Questions