Erectile dysfunction pde5 inhibitors
ERECTILE DYSFUNCTION (ED) AND
PDE5 INHIBITOR PRESCRIBING
In the UK there are now 3 ‘on-demand’ PDE5 oral inhibitors; sildenafil, vardenafil and tadalafil and one ‘daily’ PDE5 oral inhibitor, tadalafil once daily. The Warrington and Halton Hospitals Foundation Trust Drug and Therapeutics Committee recently gave approval for the once daily tadalafil 2.5mg and 5mg tablets according to the recommendations below:
1st choice Sildenafil (currently Viagra but a generic may soon be available) 2nd Vardenafil or Tadalafil on-demand 3rd/4th Tadalafil once a day ( tadalafil on-demand should have been tried prior to this) Occasionally patients may respond to one drug when another has failed.
Tadalafil one a day tablets are licensed for patients 18yrs and over who have already responded to an on-demand PDE 5 inhibitor but who require use at least twice weekly. The recommended dose is 5mg once a day at the same time each day. This dose can be decreased to 2.5mg once a day if tolerability is a problem. Once daily tadalafil 2.5mg or 5mg is less expensive per annum than tadalafil 10mg or 20mg taken three times a week but more expensive than tadalafil 10mg or 20mg taken twice a week.
How do the oral PDE 5 inhibitors work?
Sexual stimulation causes the local release of nitric oxide. Inhibition of PDE 5 produces increased levels of cyclic GMP in the corpus cavernosum. This results in smooth muscle relaxation and inflow of blood into the penile tissues, producing an erection. PDE5 inhibitors for ED have no effect in the absence of sexual stimulation.
How do the oral PDE 5 inhibitors differ from each other?
Sildenafil and vardenafil are efficacious for about 6-8hrs post dose (terminal half-life 3-5hrs) Tadalafil on-demand is efficacious for up to 36hrs (terminal half-life 17.5hrs). Food may affect the absorption of sildenafil and a fatty meal affects the absorption of vardenafil. Tadalafil is less affected by food. Although most patients will experience onset of action for all 3 drugs within 30 minutes of ingestion, a longer delay is usually required; 60mins for sildenafil and vardenafil and 2hrs for tadalafil. For further information consult the SPCs for the individual products http://www.medicines.org.uk/
Non-responder to PDE5 inhibitors? (1)
Approximately 25% of patients do not respond to PDE5 inhibitors. Patients should be exposed to a minimum of 4 (preferably 8) of the highest tolerated dose of at least two drugs (taken sequentially, not concurrently) with adequate sexual stimulation. Patients should be followed up, ideally within 6 weeks of commencing therapy. So-called failure may be due to suboptimal counselling at the initial consultation, which should aim to ensure that the patient understands how to take the tablets properly and to return to the doctor if they are dissatisfied.
Several measures are described in the literature to salvage patients, clearly identified as non
Counsel again on proper use
Optimise treatment of concurrent diseases and frequently re-evaluate for new risk factors
Consider treatment of concurrent hypogonadism. It is well established that testosterone regulates the
expression of PDE5 and the responsiveness of PDE5 inhibitors in the corpus cavernosum. Several studies
have shown that patients can be salvaged by treating low or low-normal levels of testosterone.
Remember that occasionally patients may respond to one drug when another has failed.
Treatment for Impotence: Health Service Circular 1999/148 (amended 2009)
‘One treatment per week will be appropriate for most patients being treated for erectile dysfunction. If the GP in
exercising his clinical judgement considers that more than one treatment a week is appropriate he should
prescribe that amount on the NHS.’
This guidance is only appropriate to those men who are listed as eligible to receive the treatment on the NHS. PDE-5 inhibitors are NOT available as an NHS prescription except in men who:
Have diabetes, multiple sclerosis, Parkinson's disease, poliomyelitis, prostate cancer, severe pelvic
injury, single-gene neurological disease (e.g. Huntington's disease), spina bifida, or spinal cord injury.
Are receiving renal dialysis for renal failure.
Have had radical pelvic surgery, prostatectomy (including transurethral resection of the prostrate), or a
Were receiving Caverject®, Erecnos®, MUSE®, Viagra®, or Viridal® at the expense of the NHS on 14 September 1998.
In addition, specialist centres can prescribe PDE-5 inhibitors if the man is 'suffering severe distress as
a result of impotence' that causes:
Significant disruption to normal social and occupational activities.
A marked effect on mood, behaviour, social, and environmental awareness.
A marked effect on interpersonal relationships.
Amendment to the Health Service Circular 2009
‘In exercising their clinical judgement, GPs may consider a daily dose treatment for a small
number of patients’.
Warrington and Halton Hospitals NHS Foundation Trust currently runs two erectile dysfunction clinics (Urology
The hospital can only prescribe PDE5 inhibitors for patients who are confirmed as 'suffering severe distress
as a result of impotence'.
1. British Society for Sexual Medicine (BSSM) Guidelines on the Management of Erectile Dysfunction 2007.
Approved by Joint Medicines Management Group September 2009
Warrington and Halton Hospitals NHS Foundation Trust
Review date: September 2010
Halton & St Helens Primary Care NHS Trust
5 Boroughs Partnership NHS Trust
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