Previous changes

September 2025  — minor update. Minor typographical error corrected.

October 2024 — minor update. Central Serous Chorioretinopathy (CSCR) added as an adverse effect of avanafil.

June 2024 — minor update. A typographical error has been corrected. 

April 2024 — minor update. Typographical error corrected. 

January 2024 — minor update. Broken link removed. 

May 2023 — minor update. Information on prescribing PDE-5 inhibitors on the NHS has been updated and a link to the NHS Electronic Drug Tariff added. 

March 2023 — reviewed. A literature search was conducted in November 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. The topic has undergone minor restructuring to improve clarity and navigation. No major changes to clinical recommendations have been made. Detail about phosphodiesterase-5 (PDE-5) inhibitor dose escalation if initial treatment is ineffective or unsatisfactory has been added in the section on Follow-up.

July 2020 — minor update. Additional information regarding prostate cancer as a cause of erectile dysfunction has been included.

August 2019 — minor update. The topic has been updated in line with the British Society for Sexual Medicine (BSSM) Guidelines on the management of erectile dysfunction (BSSM, 2017).

December 2017 — reviewed. A literature search was conducted in October 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. No major changes to clinical recommendations have been made. However, a prescribing information section for avanafil (Spedra^®) has been added, and the topic has been restructured.

November 2016 — minor update. The contraindications and interactions sections have been updated to include information that guanylate cyclase stimulators, such as riociguat, are contraindicated in men receiving phosphodiesterase-5-inhibitors (PDE-5 inhibitors), as concomitant use may lead to symptomatic hypotension.

December 2014 — minor update. Change to the text with regards to sildenafil to improve clarity.

November 2014 — minor update. Removal of Selected List Scheme (SLS) status for generic sildenafil products.

January 2013  — reviewed. A literature search was conducted in December 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. No major changes to clinical recommendations have been made.

January 2012 — minor update to clarify the term 'protracted secondary ejaculation' in response to an enquiry. 

September 2011  — minor update to the treatment of erectile dysfunction to include advice from the Medicines and Healthcare products Regulatory Agency (MHRA) on the use of unlicensed herbal remedies.

October 2009 — minor update. A link to the Sexual Dysfunction Association website has been added. 

June 2009 — minor update to include advice from the MHRA on PDE-5-inhibitors and non-selective alpha-blockers. 

March 2009 — minor update to include hypopituitarism following traumatic brain injury as a possible cause of erectile dysfunction.

July to October 2008 — this is a new CKS topic. The evidence base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines have been published since 1 November 2022. 

HTAs (Health Technology Assessments)

No new HTAs since 1 November 2022. 

Economic appraisals

No new economic appraisals relevant to England since 1 November 2022. 

Systematic reviews and meta-analyses

No new systematic reviews published since 1 November 2022. 

Primary evidence

No new randomized trials published since 1 November 2022. 

New policies

No new national policies or guidelines since 1 November 2022. 

New safety alerts

No new safety alerts since 1 November 2022. 

Changes in product availability

• New product Hezkue (sildenafil) 12.5 mg/actuation, is licensed for use in adult men with erectile dysfunction. See more here.
• New product Viagra Connect Melts, (sildenafil citrate) 50 mg Orodispersible film, offers a discreet and more convenient alternative to conventional tablets, while retaining the same mechanism of action and median onset of 30 minutes. See more here.

Cardiac risk stratification

Men with erectile dysfunction can be stratified into low-, intermediate-, or high-risk cardiovascular categories, depending on cardiovascular risk factors and co-morbidities [Nehra, 2012; Hackett, 2018; EAU, 2022].

• Low risk
  • Asymptomatic; able to perform exercise of modest intensity without symptoms; less than 3 risk factors for coronary artery disease (CAD, excluding sex).
  • Mild, stable angina.
  • Uncomplicated previous myocardial infarction (MI).
  • Previous successful coronary revascularization.
  • Reduced ejection fraction heart failure (New York Heart Association [NYHA] class I and II).
  • Controlled hypertension.
  • Mild valvular heart disease (VHD).
     
• Intermediate risk 
  • Three or more risk factors for CAD (excluding sex).
  • Moderate stable angina.
  • Recent MI (within the last 2–6 weeks).
  • Reduced ejection fraction heart failure (NYHA class III).
  • Peripheral arterial disease, stroke disease.
• High risk
  • Unstable or refractory angina.
  • Recent MI (within the last 2 weeks).
  • Reduced ejection fraction heart failure (NYHA class IV).
  • Uncontrolled hypertension.
  • High-risk arrhythmia (exercise-induced ventricular tachycardia, implanted internal cardioverter defibrillator with frequent shocks, and poorly controlled atrial fibrillation).
  • Hypertrophic obstructive or other cardiomyopathy.
  • Moderate-to-severe VHD.

Basis for recommendation

The recommendations on assessment are largely based on the British Society for Sexual Medicine (BSSM) Guidelines on the management of erectile dysfunction in men-2017 [Hackett, 2018], the European Association of Urology (EAU) publication EAU Guidelines on sexual and reproductive health [EAU, 2022], the US consensus document The Princeton III consensus recommendations for the management of erectile dysfunction and cardiovascular disease [Nehra, 2012], and expert opinion in review articles on erectile dysfunction [Muneer, 2014; Rew, 2016; Nguyen, 2017].

Clinical features on history-taking

• These recommendations are largely based on the BSSM guidelines [Hackett, 2018], the EAU guidelines [EAU, 2022], and expert opinion in review articles [Muneer, 2014; Rew, 2016; Nguyen, 2017].
  • The recommendation to assess with a partner if possible ensures that any co-existing issues with sexual function affecting the partner can also be addressed [Hackett, 2018].
  • The information about typical clinical features of organic and psychogenic causes is based on expert opinion in review articles [Muneer, 2014; Nguyen, 2017].
  • The recommendation to consider using a validated patient questionnaire is based on the BSSM guidelines, the EAU guidelines, and expert opinion in a review article [Rew, 2016]. 
  • The recommendation to assess the cardiac risk of sexual activity is based on the BSSM guidelines [Hackett, 2018] and the EAU guidelines [EAU, 2022].
    • Assessment of erectile dysfunction may provide an opportunity for early diagnosis and management of underlying condition(s) such as cardiovascular or endocrine disease with important implications for men's health [Hackett, 2018].
    • The EAU guidelines highlight the importance of identifying any cardiovascular disease which is sufficiently severe or unstable such that sexual activity carries a significant risk. They also state it is possible to estimate the risk of sexual activity in most men from their level of exercise tolerance on history-taking.
  • The BSSM guidelines note that the severity of lower urinary tract symptoms (LUTS) is closely linked to the severity of erectile dysfunction, and treatment of one condition may impact the symptoms of the other [Hackett, 2018].

Clinical features on examination

• These recommendations are largely based on the BSSM guidelines [Hackett, 2018], the EAU guidelines [EAU, 2022], and expert opinion in a review article [Muneer, 2014].
  • Examination provides an opportunity to detect potentially reversible causes of erectile dysfunction, including cardiovascular or endocrine disease. Erectile dysfunction in an otherwise asymptomatic man may be a marker of underlying coronary artery disease [Hackett, 2018].
  • The recommendation to assess for any testicular abnormalities if there are symptoms is extrapolated from the BSSM guidelines [Hackett, 2018] and is also pragmatic, based on what CKS considers to be good clinical practice.

Arranging investigations

• These recommendations are largely based on the BSSM guidelines [Hackett, 2018], the EAU guidelines [EAU, 2022], and expert opinion in review articles [Muneer, 2014; Rew, 2016; Nguyen, 2017].
  • The recommendation to assess serum HbA1c and lipid profile is based on the fact erectile dysfunction in an otherwise asymptomatic man may be a marker of underlying coronary artery or endocrine disease, or other modifiable risk factors [Hackett, 2018].
  • The recommendation to assess the serum total testosterone level is based on the BSSM and EAU guidelines. The recommendation to arrange additional hormone profile tests if the initial serum total testosterone level is low or borderline is based on the BSSM guidelines and expert opinion in a review article [Rew, 2016].
    • Serum-free testosterone is a more reliable measure of androgen status. A reasonable estimate of free and bioavailable testosterone levels can be calculated from total testosterone, sex hormone binding globulin, and albumin levels [Hackett, 2018].
    • The BSSM guidelines note that testosterone deficiency is potentially reversible and low testosterone may be a reason for failure to respond to phosphodiesterase-5 (PDE-5) inhibitor drug treatment.
    • If the serum testosterone is low, other hormone tests can help to differentiate between primary and secondary causes of hypogonadism [Rew, 2016].
    • High prolactin levels suppress luteinizing hormone production and cause hypogonadism. Men with raised prolactin levels are often resistant to testosterone therapy [Hackett, 2018].
  • The recommendation to consider checking the prostate-specific antigen (PSA) level is based on the BSSM and EAU guidelines.
  • The recommendation to consider checking thyroid function tests is based on the BSSM guidelines and expert opinion in review articles [Muneer, 2014; Nguyen, 2017]. Hyperthyroidism can affect erectile function by increasing sex hormone binding globulin and reducing free testosterone levels [Muneer, 2014; Hackett, 2018].
  • The recommendation to consider checking liver and renal function tests is extrapolated from the BSSM and EAU guidelines, and is also pragmatic, based on what CKS considers to be good clinical practice.

When should I refer a man with erectile dysfunction?

If a man presents with erectile dysfunction following initial assessment:

• Arrange emergency hospital admission if there is evidence of priapism (painful prolonged erection for more than 4 hours — may be a rare adverse effect of specialist treatments for erectile dysfunction).
• Arrange referral to a urology specialist if:
  • The man is young or has a lifelong history of difficulty in obtaining or maintaining an erection (possible primary erectile dysfunction).
  • There is a history of pelvic, perineal, or genital trauma.
  • There is a penile structural abnormality or abnormal testicular examination. See the CKS topics on  Scrotal pain and swelling and Urological cancers - recognition and referral for more information.
• Arrange referral to an endocrinologist if:
  • A diagnosis of hypogonadism is suspected (low serum testosterone level) or there are other abnormalities of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or prolactin levels.
  • Testosterone replacement is being considered.
• Arrange referral to a cardiologist or seek specialist advice if:
  • The man is at high cardiac risk (or intermediate cardiac risk, depending on clinical judgement), where sexual activity may be unsafe or phosphodiesterase-5 (PDE-5) inhibitor use is contraindicated.
    • Advise stopping all sexual activity until specialist assessment, and a decision has been made that further cardiac assessment and management is needed, or it is safe to resume sexual activity. See the sections on Cardiac risk stratification and Contraindications and cautions in Prescribing information for more information.
• Arrange referral to mental health services, psychosexual or relationship counselling, depending on clinical judgement, if:
  • There is a suspected psychogenic or relationship cause for symptoms.
  • There is a complex or severe mental health condition which cannot be managed in primary care. See the CKS topics on Depression, Generalized anxiety disorder, Post-traumatic stress disorder, and Psychosis and schizophrenia for more information.

How should I manage a man with erectile dysfunction in primary care?

Offer management of erectile dysfunction symptoms in primary care following initial assessment.

• Arrange hospital admission or specialist referral if clinically indicated. See the section on Referral for more information.
• Advise on sources of information and support, such as: 
  • The NHS information Erectile dysfunction.
  • The British Association of Urological Surgeons (BAUS, website www.baus.org.uk) information on Erectile dysfunction, including information on specialist treatments including penile injections, medicated urethral system for erection (MUSE), and vacuum erection assistance devices (VEDs).
• Advise about lifestyle modification that may help, including:
  • Weight loss, if indicated, and regular exercise. See the CKS topic on Obesity for more information.
  • Smoking cessation, if indicated. See the CKS topic on Smoking cessation for more information.
  • Alcohol reduction to recommended levels, if indicated. See the CKS topic on Alcohol - problem drinking for more information.
  • Stopping all sexual activity until specialist cardiology assessment, if a man is at high cardiac risk from sexual activity (or intermediate risk, depending on clinical judgement). See the sections on Cardiac risk stratification and Referral for more information.
  • Stopping cycling for a trial period, if a man regularly cycles for more than 3 hours a week. If this is not possible, advise to use a properly fitted bicycle seat and ride with the seat in a suitable position.
• Optimize management of any reversible or modifiable risk factors or conditions, such as diabetes, hypertension, and dyslipidaemia.
• If a drug cause is suspected, consider stopping medication if the onset of erectile dysfunction correlated with starting a specific drug and a causative relationship seems likely, depending on clinical judgement.
  • Be aware that for most men, management of any underlying condition with appropriate drug treatment is more likely to be beneficial than changes to potentially contributory drugs.
• Do not recommend the use of unlicensed herbal preparations or complementary medicines.
  • Advise these may contain pharmacological substances which may be contraindicated or interact with other prescribed medication(s).
• For men not at high cardiac risk of sexual activity, consider prescribing drug treatment with a phosphodiesterase-5 (PDE-5) inhibitor, irrespective of the suspected underlying cause(s). Drug choice depends on the frequency of intercourse, speed of onset, duration of action, dosing regimen, personal experience and preference, adverse effect profile, cost, and local prescribing guidelines.
  • Options include sildenafil (Viagra^®), tadalafil (Cialis^®), vardenafil (Levitra^®), and avanafil (Spedra^®).
    
    • Advise that sildenafil 50 mg tablets (Viagra Connect^®) can be purchased over-the-counter from pharmacies and do not need a prescription.
    • See the section on Patient advice in Prescribing information for more information on how to take medication correctly. The BAUS leaflet Phosphodiesterase type-5 inibitors for erectile dysfunction may be helpful.
  • Before prescribing a PDE-5 inhibitor, assess whether the man qualifies for an NHS prescription. If not, offer a private prescription. See the section on NHS prescription criteria in Prescribing information for more information.
    • If prescribing Viagra^®, tadalafil (Cialis^®), vardenafil (Levitra^®), or avanafil (Spedra^®) on the NHS, endorse with 'SLS' (Selected List Scheme). Generic sildenafil does not need to be endorsed with 'SLS'.
    • See the sections on Contraindications and cautions, Adverse effects, Drug interactions, and Dosing regimen in Prescribing information for more information.
• Arrange follow-up 6–8 weeks after starting treatment, to assess its efficacy, tolerability, and patient satisfaction. See the section on Follow-up for more information.

How should I follow up with a man with erectile dysfunction?

When reviewing a man with erectile dysfunction following initial management in primary care:

• If initial treatment is effective, reinforce lifestyle modification advice and arrange review depending on clinical judgement. See the section on Management for more information.
• If initial treatment is ineffective or unsatisfactory, reassess for underlying cause(s) and risk factor(s) and manage appropriately, including arranging specialist referral if clinically indicated.
  • Be aware that hypogonadism and a low testosterone level may result in a reduced response or non-response to phosphodiesterase-5 (PDE-5) inhibitor drug treatment.
• If the man is using PDE-5 inhibitor drug treatment, ensure it is taken correctly and advise on possible dose and drug regimen changes.
  • Advise about the importance of dose timing and the fact drug treatment requires sexual stimulation in order to facilitate erection. See the section on Patient advice in Prescribing information for more information.
  • Consider increasing to the maximum dose depending on symptom response and adverse effects. Advise to try each PDE-5 inhibitor 4–8 times at the maximum tolerated dose before switching to an alternative drug.
  • Suggest a trial of at least two different PDE-5 inhibitors taken sequentially before being classed as a 'non-responder'.
  • Consider increasing the dose frequency, such as switching to once daily (rather than 'on-demand') dosing if taking tadalafil, depending on clinical judgement. See the section on Dosing regimen in Prescribing information for more information on once-daily dosing regimens.
• If PDE-5 inhibitor drug or other treatment is ineffective, not tolerated, or contraindicated, offer referral to a urology specialist.
  
  • Specialist treatment options may include vacuum erection assistance devices (VEDs), alprostadil penile intracavernous injections (Caverject^®, Viridal^®), medicated urethral system for erection (MUSE^®), vacuum erection assistance devices (VEDs), vascular surgery/angioplasty, or penile prostheses. The British Association of Urological Surgeons (BAUS, website www.baus.org.uk) information on Erectile dysfunction includes information on specialist treatments.
     

Contraindications and cautions

• Do not prescribe a phosphodiesterase-5 (PDE-5) inhibitor to a man with:
  • Unstable angina or angina occurring during sexual intercourse. See the section on Cardiac risk stratification for more information.
  • Regular or intermittent use of nitrates in any form — risk of severe, life-threatening hypotension. The manufacturer advises that prescribers should avoid concomitant prescribing. 
  • Hypotension (systolic blood pressure below 90 mmHg).
  • History of non-arteritic anterior ischaemic optic neuropathy (NAION).
  • Recent history of myocardial infarction (within 90 days for tadalafil).
  • Recent history of stroke.
  • Heart failure (mild to severe, tadalafil, and avanafil).
  • Uncontrolled arrhythmias (tadalafil and avanafil).
  • Uncontrolled hypertension (tadalafil and avanafil).
  • Severe hepatic impairment (sildenafil, vardenafil film-coated tablets, and avanafil); moderate-to-severe (vardenafil orodispersible tablets).
  • Renal impairment (creatinine clearance less than 30 mL/min, avanafil).
  • A hereditary degenerative retinal disorder, such as retinitis pigmentosa (sildenafil, vardenafil, and avanafil).
• Prescribe a PDE-5 inhibitor with caution to a man with:
  • Cardiovascular disease. See the section on Cardiac risk stratification for more information. 
  • Left ventricular outflow obstruction (for example aortic stenosis and idiopathic hypertrophic subaortic stenosis).
  • Anatomical deformity of the penis (for example angulation, cavernosal fibrosis, or Peyronie's disease).
  • A predisposition to priapism (for example sickle-cell disease, multiple myeloma, or leukaemia).
  • Active peptic ulceration or bleeding disorders (sildenafil, vardenafil, and avanafil).
  • Hepatic impairment (sildenafil — consider initial dose reduction if mild-to-moderate impairment); severe hepatic impairment (tadalafil); mild-to-moderate (caution if vardenafil film-coated tablets or avanafil); mild (caution if vardenafil orodispersible tablets).
  • Renal impairment (creatinine clearance less than 30 mL/min, sildenafil and vardenafil — consider initial dose reduction); severe renal impairment (tadalafil — avoid regular once-daily dosing and consider dose reduction for intermittent use).
  • Susceptibility to prolongation of QT interval, or older age (vardenafil).
  • Autonomic dysfunction.
• Prescribe sildenafil with caution to men taking sacubitril/valsartan — a single dose of sildenafil in people with hypertension significantly reduces blood pressure. 

 [Hackett, 2018; BNF, 2022; ABPI, 2023]

Adverse effects

Possible adverse effects of phosphodiesterase-5 (PDE-5) inhibitors include:

• Most common — headache, flushing, dyspepsia, nasal congestion (sildenafil, tadalafil, avanafil, vardenafil), back pain, and myalgia (with tadalafil) [Hatzimouratidis, 2016; BNF, 2022].
• Common — alopecia, anaemia, anxiety, cough, diarrhoea, dizziness, fluid retention, gastrointestinal discomfort, increased risk of infection, insomnia, nausea, night sweats, pain, skin reactions, tremor, and vision disorders (sildenafil) [BNF, 2022].
• Rare — optic neuropathy, retinal occlusion (sildenafil, tadalafil, vardenafil — discontinue if sudden visual impairment), and priapism (persistent erection) [BNF, 2022].
• Unknown frequency —  central Serous Chorioretinopathy (avanafil) [EMC, 2024]. 

Drug interactions

Possible drug interactions with phosphodiesterase-5 (PDE-5) inhibitors include:

• Nitrates — concurrent use of PDE-5 inhibitors and organic nitrates (such as isosorbide mononitrate or isosorbide dinitrate), nicorandil, or amyl nitrate ('poppers') are absolutely contraindicated due to the risk of hypotension.
  • If a PDE-5 inhibitor is taken and the man develops chest pain, organic nitrates should not be used for at least 24 hours for sildenafil and possibly vardenafil (half-life 4 hours), 48 hours for tadalafil (due to its longer half-life of 17.5 hours), and at least 12 hours for avanafil (half-life 6–17 hours).
• Alpha-blockers — concurrent use of PDE-5 inhibitors and alpha-blockers can increase the risk of postural hypotension as both drugs are vasodilators. 
  • PDE-5 inhibitors should not be used by men taking non-selective alpha blockers (such as doxazosin, indoramin, terazosin, or prazosin) unless they have finished alpha-blocker dose titration and are on a stable dose. The manufacturers also state that:
    • Sildenafil should be used with caution in men taking an alpha-blocker (especially doxazosin). Hypotension is more likely to occur within four hours following treatment with an alpha-blocker. A sildenafil starting dose of 25 mg is recommended.
    • Vardenafil should be initiated at the lowest starting dose of 5 mg (if the man has been stabilised on his alpha-blocker treatment). Vardenafil may be given at any time with tamsulosin or alfuzosin but with other alpha-blockers, a time separation of dosing should be considered. In men already taking an optimized dose of vardenafil, alpha-blocker treatment should be initiated at the lowest dose.
    • Tadalafil is not recommended in men taking doxazosin. For all other alpha-blockers, tadalafil should be used with caution; treatment should be initiated at the minimum dose and progressively adjusted.
    • Avanafil should be initiated at the lowest dose of 50 mg. Conversely in men already taking an optimal dose of avanafil, alpha-blocker treatment should be initiated at the lowest dose.
• Cytochrome P450 (CYP) 3A4 and 2C9 inhibitors — may reduce the clearance of PDE-5 inhibitors, as PDE-5 inhibitors are metabolized by this enzyme.
  • Sildenafil 
    • With ritonavir — co-administration should be avoided if possible, otherwise a maximum dose of 25 mg of sildenafil within 48 hours must not be exceeded.
    • With all other CYP3A4 inhibitors (such as ketoconazole, itraconazole, erythromycin, cimetidine, and grapefruit juice) — a sildenafil starting dose of 25 mg should be considered.
  • Vardenafil
    • HIV protease inhibitors (such as ritonavir and indinavir; very potent inhibitors of CYP3A4) — co-administration is contraindicated.
    • Potent CYP3A4 inhibitors (such as clarithromycin and oral ketoconazole and itraconazole) — co-administration is contraindicated in men older than 75 years and should be avoided in all other men.
    • Moderate CYP3A4 inhibitors (such as erythromycin) — vardenafil dose adjustment may be necessary.
    • Grapefruit — co-administration should be avoided as concomitant intake of grapefruit or grapefruit juice is expected to increase the plasma concentrations of vardenafil.
  • Tadalafil 
    • Co-administration with CYP3A4 should be avoided if possible, otherwise tadalafil should be initiated at the lowest recommended starting dose.
  • Avanafil
    • Very potent and potent CYP3A4 inhibitors (such as itraconazole, clarithromycin, saquinavir, and indinavir) — co-administration is contraindicated.
    • Moderate CYP3A4 inhibitors (such as erythromycin) — a maximum dose of 100 mg of avanafil within 48 hours must not be exceeded.
    • Other CYP3A4 inhibitors — co-administration with caution. 
    • Grapefruit — the man should be advised to avoid grapefruit juice within 24 hours prior to taking avanafil.
• CYP3A4 inducers (such as rifampin, phenobarbital, phenytoin, and carbamazepine) — may enhance the clearance of PDE-5 inhibitors.
  • Co-administration should be avoided if possible, otherwise higher doses of the PDE-5 inhibitor may be required.
• Sacubitril/valsartan — a single dose of sildenafil in people with hypertension significantly reduces blood pressure. Prescribe sildenafil to these people with caution. 

[ABPI, 2020; ABPI, 2021; ABPI, 2022a; ABPI, 2022b; BNF, 2022; ABPI, 2023]

Dosing regimen

Phosphodiesterase-5 (PDE-5) inhibitor drugs are usually taken intermittently as needed. The drug tadalafil may be prescribed once daily in specific circumstances, depending on clinical judgement.

• In general, PDE-5 inhibitors are prescribed as one treatment dose per week on the NHS, based on research evidence on the frequency of sexual intercourse in study populations. However, if more than one treatment per week is considered to be clinically appropriate, this may be prescribed on the NHS [Hackett, 2018].
• Sildenafil
  • Dosage
    • Advise taking 50 mg approximately one hour before sexual activity (or longer if taken with food). Based on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg, to be taken as a single dose. The maximum recommended dose is 100 mg. The maximum recommended dosing is once per 24 hours.
  • Renal impairment
    • If the creatinine clearance is less than 30 mL/min, use an initial dose of 25 mg. This can be increased to 50 mg, then 100 mg based on efficacy and tolerability.
  • Hepatic impairment
    • In men with mild-to-moderate hepatic impairment, consider a starting dose of 25 mg. This can be increased to 50 mg, then 100 mg based on efficacy and tolerability.
    • Avoid in men with severe hepatic impairment.
• Tadalafil
  • Dosage
    • Advise taking 10 mg (with or without food) taken at least 30 minutes prior to sexual activity. Based on efficacy and tolerability, this can be increased to the maximum dose of 20 mg. The maximum dose frequency is once per 24 hours.
    • For men who prefer spontaneous (rather than planned) sexual activity, or who anticipate frequent sexual activity (at least twice a week), consider prescribing tadalafil 5 mg once daily, reduced to 2.5 mg once daily, dose adjusted according to response.
       
  • Renal impairment
    • If severe impairment, use a maximum dose of 10 mg for intermittent use. Avoid regular once-daily dosing regimen.
  • Hepatic impairment 
    • A maximum daily dose of 10 mg once daily should be considered for intermittent use.
    • Use with caution in severe hepatic impairment and in regular once-daily dosing regimens.
• Vardenafil (film-coated and orodispersible formulations available)
  • Dosage
    • For film-coated tablets — 10 mg (with or without food) taken at least 25–60 minutes before sexual activity (or longer if taken with a high fat meal). Based on efficacy and tolerability, this can be increased to the maximum recommended daily dose of 20 mg or decreased to 5 mg. The maximum recommended dosing frequency is once per 24 hours.
    • For orodispersible tablets — 10 mg (with or without food) taken at least 25–60 minutes before sexual activity (not affected by fatty meals). The maximum recommended dose is 10 mg a day. The maximum recommended dosing frequency is once per 24 hours.
  • Renal impairment 
    • For film-coated tablets — if severe renal impairment (creatinine clearance less than 30mL/min), a starting dose of 5 mg should be considered. This can be increased to 10 mg, then 20 mg based on tolerability and efficacy.  
    • For orodispersible tablets — if severe renal impairment (creatinine clearance less than 30 mL/min), a starting dose of vardenafil 5 mg film-coated tablets should be considered. Based on tolerability and efficacy, the dose may be increased to vardenafil 10 mg and 20 mg film-coated tablets, or vardenafil 10 mg orodispersible tablets. Do not use orodispersible tablets in men with end-stage kidney disease.
  • Hepatic impairment
    • For film-coated tablets — a starting dose of 5 mg should be considered in men with mild-to-moderate hepatic impairment. Based on tolerability and efficacy, the dose may subsequently be increased. The maximum dose recommended in moderate hepatic impairment is 10 mg.
    • For orodispersible tablets — in mild hepatic impairment, use a starting dose of vardenafil 5 mg film-coated tablets. Based on tolerability and efficacy, the dose may be increased to vardenafil 10 mg and 20 mg film-coated tablets, or vardenafil 10 mg orodispersible tablets. Do not use orodispersible tablets as a starting dose in men with mild hepatic impairment and in men with moderate or severe hepatic impairment.
  • Elderly men (aged 65 years and older) 
    • A dose increase to the maximum of 20 mg should be used cautiously, depending on individual tolerability.
• Avanafil
  • Dosage
    • The recommended dose is 100 mg (with or without food) taken as needed approximately 15–30 minutes before sexual activity (or longer if taken with food). Based on individual efficacy and tolerability, the dose may be increased to a maximum dose of 200 mg or decreased to 50 mg. The maximum recommended dosing frequency is once per 24 hours. 
  • Renal impairment
    • If the creatinine clearance is less than 30 mL/min, do not use.
  • Hepatic impairment 
    • If severe hepatic impairment, do not use. 
    • In men with mild-to-moderate hepatic impairment, use the lowest effective initial dose and adjust according to response.
  • Elderly men (aged 65 years and older) 
    • No dose adjustment is needed, however, there are limited data for its use in men aged 70 years and older.

[ABPI, 2020; ABPI, 2021; ABPI, 2022a; ABPI, 2022b; BNF, 2022; EAU, 2022]

Patient advice

• Give advice on how to obtain phosphodiesterase-5 (PDE-5) inhibitors safely and how to take drug treatment correctly.
  • Advise obtaining medication from a pharmacy, as counterfeit drugs from unauthorized sources may not contain the amount or type of drug claimed by the product packaging, and may contain pharmacological substances which are illegal and potentially dangerous [Hatzimouratidis, 2016; EAU, 2022].
  • Advise that PDE-5 inhibitors are not initiators of erection but require sexual stimulation in order to facilitate erection [Hackett, 2018; EAU, 2022].
  • See Table 1 for information on when to take it, the time to onset of effect, the duration of action, and the effect of food on drug absorption (and hence the onset of effect).

Table 1. Pharmacokinetic comparison of phosphodiesterase-5 (PDE-5) inhibitors.

NHS prescription criteria

• Generic sildenafil, tadalafil, vardenafil and avanafil can be prescribed without restriction on the NHS in England.
• Viagra^®, Cialis^®, Levitra^®, and Spedra^® are not prescribable on the NHS unless the prescription is endorsed 'Selective List Scheme' (SLS) and the man has one of the following specific medical condition(s) or previous treatment(s) [Hackett, 2018; BNF, 2022]:
  • Has diabetes, multiple sclerosis, Parkinson's disease, poliomyelitis, prostate cancer, severe pelvic injury, single-gene neurological disease (for example Huntington's disease), spina bifida, spinal cord injury.
  • Is receiving treatment for renal failure by dialysis. 
  • Has had the following surgery: prostatectomy, radical pelvic surgery, renal failure treated by transplant. 
  • Was receiving a course of NHS drug treatment for erectile dysfunction on 14 September 1998.
  • Is experiencing 'severe distress' due to erectile dysfunction (needs to be diagnosed by a specialist who has ongoing responsibility for providing prescriptions). Note: this only applies in Wales. 
• For up-to-date information on which PDE-5 inhibitors are prescribable on the NHS, see the NHS Electronic Drug Tariff.