Sildenafil, commonly prescribed for erectile dysfunction and pulmonary arterial hypertension, is generally safe for the kidneys. Many patients wonder: does sildenafil affect the kidneys, particularly those with existing renal impairment? Whilst sildenafil is primarily metabolised by the liver and excreted mainly through faeces, approximately 13% is eliminated via the kidneys. There is no evidence that sildenafil causes direct kidney damage in individuals with normal renal function. However, patients with severe kidney impairment may require dose adjustments due to reduced drug clearance. Understanding how sildenafil interacts with kidney function is essential for safe prescribing and patient care.

How Sildenafil Works in the Body

Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor primarily prescribed for erectile dysfunction and pulmonary arterial hypertension. The medication works by blocking the enzyme PDE5, which normally breaks down cyclic guanosine monophosphate (cGMP) in smooth muscle cells. By inhibiting this enzyme, sildenafil allows cGMP levels to rise, leading to smooth muscle relaxation and increased blood flow to specific tissues—most notably the corpus cavernosum in the penis and the pulmonary vasculature.

Once taken orally, sildenafil is absorbed through the gastrointestinal tract and reaches peak plasma concentrations within 30 to 120 minutes. Absorption may be delayed when taken with a high-fat meal. The drug undergoes extensive first-pass metabolism in the liver, primarily via the cytochrome P450 enzyme CYP3A4, with a smaller contribution from CYP2C9. This hepatic metabolism produces an active metabolite (N-desmethyl sildenafil) that also contributes to the therapeutic effect, though to a lesser extent than the parent compound.

The elimination of sildenafil occurs predominantly through hepatic metabolism with biliary/faecal excretion. Approximately 80% of the administered dose is excreted in faeces, whilst only about 13% is eliminated through the kidneys in urine. Both the parent drug and its metabolites are excreted renally to a limited extent.

The terminal half-life of sildenafil in healthy adults is approximately 3 to 5 hours. This can be prolonged in individuals with severe kidney impairment (creatinine clearance <30 mL/min), potentially leading to higher drug concentrations in the bloodstream. Understanding this pharmacokinetic profile is essential for safe prescribing, particularly in patients with pre-existing renal conditions.

Using Sildenafil with Kidney Disease

Patients with chronic kidney disease (CKD) can generally use sildenafil, but consideration of their renal function may be necessary in some cases. There is no evidence that sildenafil causes direct nephrotoxicity in individuals with normal renal function, although rare cases of acute kidney injury have been reported in specific contexts (such as severe hypotension).

In individuals with mild to moderate renal impairment (creatinine clearance 30–80 mL/min), sildenafil pharmacokinetics are not significantly altered, and no dose adjustment is typically required. However, in patients with severe renal impairment (creatinine clearance <30 mL/min), the area under the concentration-time curve (AUC) can increase by approximately 100%. This elevation occurs because the kidneys are less efficient at eliminating the drug and its active metabolites, leading to prolonged exposure.

For patients on dialysis, including haemodialysis, sildenafil is not significantly removed during the dialysis process due to its high protein binding (approximately 96%). This means that standard dialysis sessions will not substantially reduce drug levels in the bloodstream, and dosing adjustments should be based on the patient's residual renal function rather than dialysis timing.

Clinicians should assess renal function where clinically indicated before prescribing sildenafil. It is important to note that sildenafil is contraindicated with nitrates (used for angina) and riociguat (used for pulmonary hypertension) due to the risk of severe hypotension. Caution is also needed when co-prescribing with alpha-blockers; patients should be stable on alpha-blocker therapy before starting sildenafil, and a lower starting dose of sildenafil may be appropriate.

Patients with kidney disease should always inform their GP or prescriber about their condition to ensure appropriate dosing and monitoring. Grapefruit juice should be avoided as it can inhibit CYP3A4 and increase sildenafil levels.

Dosage Adjustments for Kidney Impairment

Dosage modifications may be necessary for patients with significant renal impairment to minimise the risk of adverse effects whilst maintaining therapeutic efficacy. For erectile dysfunction, the standard starting dose in adults with normal kidney function is 50 mg taken approximately one hour before sexual activity.

For patients with mild to moderate renal impairment (creatinine clearance 30–80 mL/min), no dose adjustment is required according to UK guidance, and the standard 50 mg starting dose can be used. In cases of severe renal impairment (creatinine clearance <30 mL/min), a reduced starting dose of 25 mg is generally recommended. The dose may be adjusted based on individual response and tolerability, but should not exceed 100 mg in any 24-hour period. It is important to note that sildenafil should be taken no more than once daily, regardless of renal function.

For pulmonary arterial hypertension, the typical dose is 20 mg three times daily. According to the UK Summary of Product Characteristics for Revatio (sildenafil for PAH), no dose adjustment is required in patients with renal impairment, including those with severe impairment. However, treatment should always be under specialist supervision.

Key considerations include:

• Assess renal function where clinically indicated before prescribing

• Start with the lowest effective dose in severe renal impairment

• Monitor for adverse effects, particularly hypotension and visual disturbances

• Review concurrent medications for potential drug interactions

• Sildenafil is contraindicated with nitrates and riociguat

• Use with caution in patients taking alpha-blockers; ensure patients are stable on alpha-blocker therapy first and consider starting sildenafil at 25 mg

Healthcare professionals should consult current NICE guidance, the electronic Medicines Compendium (eMC), and the British National Formulary (BNF) for the most up-to-date prescribing information.

When to Seek Medical Advice

Patients taking sildenafil should be aware of situations that warrant prompt medical attention. Whilst sildenafil is generally well-tolerated, certain symptoms may indicate complications or interactions that require professional assessment.

Call 999 or go to A&E immediately if you experience:

• Chest pain or irregular heartbeat, particularly during or after sexual activity

• Sudden vision loss or changes in vision, which may indicate non-arteritic anterior ischaemic optic neuropathy (NAION)

• Signs of a serious allergic reaction including breathing difficulties, swelling of the face, lips, tongue or throat

• Severe dizziness or fainting, which may indicate significant hypotension

• Priapism—a painful erection lasting more than 4 hours, which requires emergency treatment to prevent permanent damage

Stop taking sildenafil and seek urgent medical help if you experience:

• Sudden hearing loss or ringing in the ears (tinnitus), which has been reported rarely with PDE5 inhibitors

Contact your GP or prescriber if you notice:

• Worsening kidney function symptoms, such as reduced urine output, swelling in the legs or ankles, or unexplained fatigue

• New or worsening side effects, including persistent headaches, facial flushing, indigestion, or nasal congestion

• The medication is not working as expected, as this may require dose adjustment or investigation of underlying causes

Patients with pre-existing kidney disease should attend regular monitoring appointments to assess renal function through blood tests (serum creatinine and eGFR). Any deterioration in kidney function should be discussed with your healthcare team, as this may necessitate dose adjustment or consideration of alternative treatments.

It is essential to inform all healthcare professionals about sildenafil use, particularly before surgery or when starting new medications. Sildenafil can interact with nitrates (used for angina), riociguat (used for pulmonary hypertension), alpha-blockers (used for prostate problems or hypertension), and certain antifungal or antibiotic medications. Your pharmacist can provide advice on potential drug interactions.

If you experience any suspected side effects, report them to the MHRA Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for 'MHRA Yellow Card' in the Google Play or Apple App Store.

Frequently Asked Questions