Erectile Dysfunction Management Using PDE5 Inhibitors

Publication: 18/06/2012  --
Last review: 09/11/2021  
Next review: 09/11/2024  
Clinical Guideline
ID: 2978 
Approved By: Leeds Area Prescribing Committee 
Copyright© Leeds Teaching Hospitals NHS Trust 2021  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Erectile Dysfunction Management using PDE5 Inhibitor

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To improve the management of erectile dysfunction in primary care.
To highlight when it is appropriate to refer patients to a secondary care setting

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Primary Care Investigation

Patient presents to General Practitioner with erectile dysfunction-confirm the diagnosis, assess the patients expectations and complete a full history.

Patient History:

  • Identify causative risk factors;
  • Cardiovascular disease may indicate vascular insufficiency
  • Diabetes (ED may be common)
  • Neurological disease e.g. multiple sclerosis
  • Relationship status (current and past) and sexual orientation
  • Assess previous erection quality (including erections during sexual relations as well as awakening and masturbatory erections), and concomitant ejaculatory and orgasm dysfunction
  • Issues with sexual aversion or pain, or issues for partner (including menopause or vaginal pain)
  • Lifestyle, including use of alcohol, tobacco, and illicit drugs (including cannabis) and treatments already tried
  • Energy levels, loss of libido, loss of body hair or spontaneous hot flushes (symptoms of hypogonadism)

Medication review
Drug therapy may account for erectile dysfunction in a number of presenting cases and may possibly be reversible
when the offending agent is stopped, or a suitable alternative is substituted. It is important that a drug related effect
is considered at the outset, thus avoiding unnecessary investigation and inappropriate use of specific therapies.

Medications which may contribute to erectile dysfunction


Thiazides (e.g. bendroflumethiazide) spironolactone


Methyldopa, clonidine, beta-blockers (e.g. propranolol), verapamil


Clofibrate, gemfibrozil


Phenothiazines (e.g. chlorpromazine), butyrophenones (e.g. haloperidol)

H2 antagonists

Cimetidine, famotidine, nizatidine

Hormones and hormone modifying drugs

Oestrogens, progesterone, corticosteroids, cyproterone acetate, 5-alpha reductase inhibitors


Cyclophosphamide, methotrexate

Anti-arrhythmics and anticonvulsants



Tricyclics , SSRIs

Use doxazosin, indoramin, terazosin, prazosin with caution due to increased risk of postural hypotension unless patient has
finished alpha-blocker dose titration and are on a stable dose.


  • All men should have measurement of body weight, waist circumference, heart rate and blood pressure
  • Examination of the genitalia may reveal hypogonadism or malformation such as Peyronie’s disease.
  • Check for gynaecomastia and reduced body hair
  • A digital rectal examination is recommended to assess prostate if there are genito-urinary or protracted secondary ejaculation symptoms (e.g. suspected prostate problems)


  • Calculate the 10 year cardiovascular risk using Qrisk2 (Qrisk3 where available)
  • Erectile dysfunction is part of a spectrum of generalised arteriopathy and is an early indicator of cardiovascular disease. It may be important to consider preventative treatment (e.g. statins) in those at risk, to reduce morbidity and mortality.
  • Measure serum testosterone in the morning between 8am and 11am. Low testosterone may indicate pituitary disease or testicular failure. If testosterone levels are low repeat the measurement, and also measure follicle-stimulating hormone (FSH) luteinizing hormone (LH) and prolactin levels. Refer patient to urology if patient has two low/borderline test results.
  • For Men with severe cardiovascular disease in whom sexual activity would be unsafe or where PDE5 inhibitors are unsafe, refer to cardiology if appropriate

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Primary Care Investigation

Primary Care Management for all patients
Counsel the patient that erectile dysfunction usually responds well to a combination of lifestyle changes and drug treatment.

  • Advise patient to lose weight, stop smoking, reduce alcohol consumption and increase exercise
  • Undertake optimisation of blood pressure, lipid profile and blood sugar
  • Advise men who cycle for more than 3 hours per week to undertake a trial period without cycling to see if erectile function improves
    • If it is not possible for them to stop cycling, preventative measures such as the use of a properly fitted bicycle
      Seat and riding with the seat in a suitable position, may help prevent impairment of erectile function.
  • Advise the man not to take unlicensed herbal remedies for erectile dysfunction as they may contain prescription-only medicines which may be contraindicated or interact with prescribed medication.
  • Advice and support is also available from the Sexual Dysfunction Association
  • After optimisation management the patient should be assessed for suitability for PDE5 inhibitor therapy. If they are suitable they should be trialed on generic sildenafil by their GP as first line.

Patients presenting in secondary care who are suitable for primary care treatment (Appendix 1) or have had an incomplete trial of PDE5 inhibitors will be referred back to their primary care provider.

Patients suitable for primary care treatment
Patient should be trialed on generic sildenafil as a first line oral agent. If this fails follow the treatment pathway.
Provide the patients with suitable information regarding PDE5 inhibitor therapy.
Patient information leaflets can be found at
Contraindications to PDE5 inhibitor therapy can be checked at
NHS Choices has useful information on Erectile dysfunction
The British Association of Urological Surgeons (BAUS) has produced an information leaflet on Erectile dysfunction.

How do PDE5 inhibitors work?
Normal physiological mechanism responsible for erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. The nitric oxide then activates guanylate cyclase which is an enzyme that causes increase levels of cyclic guanosine monophosphate(cGMP), producing smooth muscle relaxation and allowing blood flow.
Phosphodiesterase type 5 (PDE5) is responsible for degradation of cGMP. Inhibition of PDE5 byPDE5 inhibitors results in increased levels of cGMP in the corpus cavernosum leading to erection. As NO/cGMP pathway is only activated in the presence of sexual stimulation, PDE5 inhibitors for ED have no effect in the absence of sexual stimulation.
A brief summary of dosing is shown below.





Tadalafil once daily

Recommended starting dose

50mg as required (assuming  normal renal function and no contra-indicated co-mobidities).If the patient has a response, dose can be down-titrated to the lowest effective dose.

20mg once a week when required, down-titrated according to response to 10mg once a week.

Vardenafil 20mg once a week as required and then down-titrated according to response to 10mg once a week.

5 mg taken once a day at approximately the same time of day. The dose may be decreased to 2.5 mg once a day based on individual tolerability

Time to take before sexual activity

60 minutes

30 minutes to 12 hours

25 to 60 minutes


Time to max plasma conc

Mean 1 hour (30-120 minutes).  Delayed by 60 minutes if Delayed by 60 minutes if taken with food.

Mean 2 hours, range 30 minutes to 12 hours. Unaffected by food.

30-120 minutes.  15 minutes in some cases.  High fat meal may delay absorption.

Steady-state plasma concentrations are attained within 5 days of once daily dosing. Unaffected by food.

Half life

3-5 hours

17.5 hours

4-5 hours

17.5 hours

Duration of action

Up to 4 hours

Up to 24 hours

Up to 5 hours


Special populations

Consider starting dose of 25mg in patients with reduced renal and hepatic function

Maximum dose of 10mg in eGFR<30 and hepatic impairment

Consider starting dose of 5 mg in those with mild moderate hepatic or severe renal impairment

Once-a-day dosing of 2.5 or 5 mg tadalafil is not recommended in patients with severe renal impairment or hepatic impairment

Patients should have planned follow up review after 3 months of treatment.
If treatment is successful it is up to the primary care providers discretion of how to provide further repeat prescriptions to the patient. Primary care providers should not add PDE5 inhibitors on to repeat prescription until a 3 month review has taken place.

Discussion at follow up reviews

  • Where possible, involve the man's partner in follow-up appointments (bearing in mind the sensitive nature of the condition).
  • Ask about the effectiveness of treatment.
  • If treatment has not been satisfactorily effective:
    • Counsel about the appropriate use of phosphodiesterase-5 (PDE-5) inhibitors. Ensure that the man is aware that PDE-5 inhibitors are not initiators of erection but require sexual stimulation in order to facilitate erection.
    • Reconsider comorbidities and treat where possible. In particular, consider the possibility of hypogonadism (which makes PDE-5 inhibitors ineffective).
    • Consider increasing to the maximum dose or switching to an alternative PDE-5 inhibitor.

PDE5 inhibitors are not licensed for those under the age of 18 years.

Interaction of the PDE5 inhibitors with food, particularly fatty food, is greatest with sildenafil and least with tadalafil.

Use of nitrates (e.g. isosorbide mononitrate or dinitrate, nitroglycerine (GTN), nicorandil including recreational drugs such as amyl nitrates (poppers) in conjunction with PDE5 inhibitors can lead to excessive hypotension and vasodilation. Hence use of nitrates is an absolute contradiction with PDE5 inhibitors.

The combination of sildenafil with ritonavir should be avoided.

Caution should be used in patients taking CYP3A4 inhibitors e.g. erythromycin, azole antifungals, protease inhibitors-

Co-administration of PDE5 inhibitors with antihypertensive agents may result in a small additive drop in blood pressure.

Non responders

  • Approximately 25% of patients do not respond to PDE5 inhibitors
  • Patients should be exposed to preferably 8 doses of the highest tolerated dose of three drugs (taken sequentially not concurrently) with adequate sexual stimulation
  • So called failure may be due to sub-optimal counseling at the initial consultation, which should aim to ensure that the patient understands how to take the medication correctly.

Several methods are described in the literature to salvage patients who are clearly identified as non responders;

  • Counsel again on proper use
  • Optimise treatment of concurrent diseases and frequently evaluate for new risk factors.
  • Consider if the patient needs to be treated for hypogonadism
  • Remember that patients may respond to one drug when another has failed

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Department of Health Service Circular 1999/148 Health Service Circular NHS criteria for erectile dysfunction
Pharmacotherapy (excluding generic sildenafil which can be prescribed on the NHS to any patient with erectile dysfunction regardless of cause, where this is clinically appropriate).

Patients suffering from any of the following;

  • Diabetes
  • Multiple sclerosis
  • Parkinson’s disease
  • Poliomyelitis
  • Prostate cancer
  • Severe pelvic injury
  • Single gene neurological disease
  • Spina bifida
  • Spinal cord injury·
  • Patients receiving treatment for renal failure by dialysis

Patients who have had the following surgery

  • Prostatectomy
  • Radical pelvic surgery
  • Kidney transplant·

Patients who were receiving NHS prescriptions for alprostadil, apomorphine, moxisylyte, sildenafil, tadalafil or thymoxamine HCL on 14th September 1998·

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If a GP believes a patient may be suffering from erectile dysfunction with complications and considered inappropriate to be managed in primary care, they should refer the patient for assessment and advice as per local specialist service.
Reasons for specialist referral may include:

  • Priapism (patients to seek urgent medical advice if erection lasting longer than 4 hours).
  • Underlying cause of erectile dysfunction suspected to be psychogenic. - refer to psychosexual specialist
  • Hypogonadism (abnormal testosterone, follicle-stimulating hormone, luteinizing hormone, or prolactin levels).
  • Severe cardiovascular disease that would make sexual activity unsafe or contraindications to PDE5 use.
  • Recent history of stroke or myocardial infarction
  • Patients with unstable angina or angina suffered during intercourse
  • Patients with New York Heart Association Class 2 or greater heart failure in the last 6 months known hereditary degenerative retinal disorders such as retinitis pigmentosa
  • End stage renal disease requiring dialysis - (for Vardenafil)

Referral form


Record: 2978

To provide evidence-based recommendations for appropriate diagnosis, investigation and management of
erectile dysfunction.

Clinical condition:

Erectile dysfunction

Target patient group: Patients aged over 18 years
Target professional group(s): Primary Care Nurses
Primary Care Doctors
Secondary Care Doctors
Secondary Care Nurses
Adapted from:

Evidence base

Drug Tariff Part XVIIIB-Drugs, Medicines and Other Substances that may be ordered only in certain circumstances.

Erectile Dysfunction Management produced by NHS Clinical knowledge Summaries

Guidelines on the Management of Erectile Dysfunction produced by British Society for Sexual Medicine accessed 01/12/20

Therapeutic Class Summaries - Oral Therapy For Erectile Dysfunction produced by the UK Medicines Information Pharmacist Group accessed 24/05/18

Type 2 Diabetes - The Management of Type 2 Diabetes in Adults NICE Clinical the UK Medicines Information Pharmacist Group accessed 24/05/18
accessed 01/12/20

Items which should be routinely prescribed in primary care
NHSE webpage
Accessed December 2020

Approved By

Leeds Area Prescribing Committee

Document history

LHP version 4.0

Related information

Not supplied

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