Erectile Disfunction


Phosphodiesterase-5 (PDE-5) inhibitors:

  • sildenafil
  • tadalafil
  • vardenafil
  • avanafil

Consider possible causes of erectile dysfunction, such as undiagnosed depression, anxiety, excessive alcohol use and taking certain medicines. Examples of classes of medicines that cause ED include diuretics, anti-hypertensives, corticosteroids, anticonvulsants and recreational drugs. Whilst it may be appropriate to supply the product, provide lifestyle advice and recommend a follow-up 

  1. Rule out red flags
  2. NHS or private?
  3. Assess cardiac risk
  4. Check for interactions
  5. Measure BP
  6. Prescribe correct dose
  7. Counsel patient
    - Onset of effect
    - Adverse effects

1. Red flags

Book patient in for blood test for

  • prolactin
  • LH/FSH
  • testosterone
  • Hba1c
  • TFT

If all these conditions ruled out then can start medication.

If abnormal refer they will need furher investigations by GP.

2. NHS or private?

  • Generic sildenafil can be prescribed without restriction on the NHS
  • Viagra®, tadalafil (Cialis®), vardenafil (Levitra®), and avanafil (Spedra®) can only be prescribed on the NHS for patients who:
    • Have diabetes, multiple sclerosis, Parkinson's disease, poliomyelitis, prostate cancer, severe pelvic injury, single-gene neurological disease (for example 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 kidney transplant.
    • Were receiving Caverject®, Erecnos®, MUSE®, Uprima®, Viagra®, Cialis®, or Viridal® at the expense of the NHS on 14 September 1998.
    • By specialist centres 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.

If above criteria not met then it must be prescribed on a private prescription

3. Assess cardiac risk 

Level of cardiac risk This includes men who have: Who can prescribe 
  • asymptomatic and have less than 3 risk factors for coronary artery disease (CAD, excluding gender).
  • controlled hypertension, mild valvular disease, and left ventricular dysfunction/congestive heart failure (LVD/CHF, New York Heart Association [NYHA] class I and II).
  • had successful coronary revascularisation (for example via coronary artery bypass grafting, stenting, or angioplasty). 
  • implied by the ability to perform exercise of modest intensity without symptoms. 
  • GP
  • No not need for testing or evaluation before the resumption of sexual activity 
  • Three or more risk factors for CAD (excluding gender).
  • Mild or moderate stable angina.
  • Past myocardial infarction (MI, within the last 2–8 weeks) without intervention awaiting exercise electrocardiography.
  • LVD/CHF (NYHA class III).
  • Noncardiac sequelae of atherosclerotic disease (for example peripheral vascular disease and a history of stroke or transient ischemic attack). 
  • Specialist testing or evaluation is recommended before the resumption of sexual activity
  • Unstable or refractory angina.
  • Uncontrolled hypertension.
  • LVD/CHF (NYHA class IV).
  • Recent MI without intervention (within the last 2 weeks).
  • High-risk arrhythmia (exercise-induced ventricular tachycardia, implanted internal cardioverter defibrillator with frequent shocks, and poorly controlled atrial fibrillation).
  • Obstructive hypertrophic cardiomyopathy with severe symptoms.
  • Moderate to severe valve disease (particularly aortic stenosis).
  • Loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure.
  • Referr for cardiac assessment and treatment.
  • Sexual activity should be stopped until the cardiac condition has been stabilized by treatment, or a decision made by the cardiologist that it is safe to resume sexual activity
  • Sildenafil is contraindicated in men with recent history of stroke or myocardial infarction, severe hepatic impairment, and hereditary degenerative retinal disorders (such as retinitis pigmentosa).
  • Tadalafil is contraindicated in men with history of stroke (within the last 6 months) or myocardial infarction (within the last 90 days), New York Heart Association (NYHA) class II or greater heart failure (within the last 6 months), uncontrolled arrhythmias, or uncontrolled hypertension.
  • Vardenafil is contraindicated in men with history of stroke or myocardial infarction (within the last 6 months), severe hepatic impairment, end stage renal disease requiring dialysis, and known hereditary degenerative retinal disorders (such as retinitis pigmentosa).
  • Avanafil is contraindicated in men with a history of stroke, myocardial infarction, life-threatening arrhythmia (within the last 6 months), hypertension (blood pressure greater than 170/100 mmHg), NYHA class II or greater heart failure, severe hepatic impairment (Child-Pugh C), severe renal impairment (creatinine clearance less than 30 mL/minute), and known hereditary degenerative retinal disorders.
  • Prescribe vardenafil with caution to elderly men and men with active peptic ulceration, bleeding disorders, or susceptibility to prolongation of QT interval.
  • Prescribe sildenafil and avanafil with caution to men with active peptic ulceration or bleeding disorders.

4. Check for interactions


concurrent use of PDE-5 inhibitors and organic nitrates (such as nitroglycerine, isosorbide mononitrate, or isosorbide dinitrate), nicorandil, or amyl nitrate ('poppers' used for recreation) are absolutely contraindicated.
  • They result in cyclic guanosine monophosphate (cGMP) accumulation and unpredictable falls in blood pressure and symptoms of hypotension. The duration of interaction between organic nitrates and PDE-5 inhibitors depends on the PDE-5 inhibitor and nitrate used.
  • 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).
  •  concurrent treatment with a PDE-5 inhibitor and an alpha-blocker can increase the risk of postural hypotension as both 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 [ABPI, 2016a].
      • 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 [ABPI, 2017c]. 
      • Tadalafil is not recommended in men taking doxazosin (due to a significant blood pressure lowering effect). For all other alpha-blockers, tadalafil should be used with caution; treatment should be initiated at minimal dosage and progressively adjusted [ABPI, 2017b]. 
      • 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 [ABPI, 2016b].
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 should be done with caution. 
      • Grapefruit — the man should be advised to avoid grapefruit juice within 24 hours prior to taking avanafil.
YP3A4 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.

5. Measure BP

All contraindicated if systolic blood pressure below 50

Avanafil contraindicated in > 170/100

6. Dosage

Medication Initial Dose When to take   Dose range   Hepatic impairment >65 years
Sildenafil 50 mg approximately one hour before sexual activity (or longer if taken with food).   25 mg - 100mg   
  • eGFR < 30 initial dose 25 mg - can be increased to 50 mg, then 100 mg
  • No dose adjustment if mild to moderate 
  • mild to moderate start dose of 25 mg
  • can be increased upto 100mg 
  • avoid in severe 
No dose adjustment is needed
Tadalafil 10mg with or without food) taken at least 30 minutes prior to sexual activity



  • eGFR < 30 max dose 10 mg.
  • No dose adjustment if mild to moderate 
  • benefit/risk evaluation
  • max 10 mg
  • if severe use with caution
 No dose adjustment is needed
Tadalafil daily 2.5 mg and 5 mg  for daily use  for patients expecting sexual activity more than twice per week  
  • Avoid


  •  Use with caution
No dose adjustment is needed
Vardenafil film coated tablets  10mg  at least 25–60 minutes before sexual activity (or longer if taken with a high fat meal)  5-20mg   
  • eGFR < 30 start dose 5mg upto 20mg 
  • No dose adjustment if mild to moderate 
  • start with 5 mg for mild to moderate upto max 10 mg
  • if severe use with caution

No dose adjustment is needed

Avoid max dose

Vardenafil orodispersible tablets  10mg  taken at least 25–60 minutes before sexual activity (not affected by fatty meals) 10mg 
  • eGFR < 30 start dose 5mg upto 20mg 
  • No dose adjustment if mild to moderate 
  • mild- start with 5 mg film-coated tablets. upto 20 mg film-coated tablets, or vardenafil 10 mg orodispersible tablets.
  • Do not use vardenafil orodispersible tablet as a starting dose in any level of hepatic impairment.

Dose adjustments are not required.

Avoid max dose

Avanafil 100mg   approximately 15–30 minutes before sexual activity (or longer if aken with food) 50 - 200mg 
  • eGFR < 30Avoid
  • No dose adjustment if mild to moderate 
  • Do not use avanafil in men with severe hepatic impairment. 
  • In men with mild to moderate hepatic impairment, use the lowest effective initial dose and adjust according to response.

No dose adjustment is needed.

Limited data for its use in men aged 70 years and older.

5. Counselling

  • Medication should be obtained from a reputable pharmacy, as there is a large counterfeit market in PDE-5 inhibitors and the amount of active drug in these medications varies.
  • Lifestyle changes and risk factor modification must precede or accompany treatment - weightloss / exercise, smoking, alcohol / recreational drugs, stress
  • This medication does not initiate erection but requires sexual stimulation in order to facilitate erection.
  • Give adequate information on the drug, including when to take it, time to onset of effect, the duration of action, and the effect of food on the absorption and hence the onset of effect - see dosage and onset of effect tables
  • STOP taking medication and see medical attention IMMEDIATELY if they experience any of the following SERIOUS side effects.
    • Chest pains: If this occurs before, during or after intercourse, they should get into a semi-sitting position and try to relax. Nitrates must NOT be used to treat chest pains
    • A persistent and sometimes painful erection lasting longer than 4 hours
    • A sudden decrease or loss of vision
    • An allergic reaction. Symptoms include sudden wheeziness, difficulty breathing or dizziness, swelling of the eyelids, face, lips or throat
    • Serious skin reactions such as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Syndrome (TEN). Symptoms may include severe peeling and swelling of the skin, blistering of the mouth, genitals and around the eyes, fever
    • Seizures or fits
    • Sudden hearing loss - Stop taking tadalafil and seek prompt medical attention if there is a sudden decrease or loss of hearing.
  • Medicines containing any nitrates (e.g. glyceryl trinitrate, isosorbide mononitrate, isosorbide dinitrate, amyl nitrite also known as ‘poppers’), or nitric oxide donors (e.g. sodium nitroprusside or nicorandil), must NOT be used at the same time as this combination may lead to a dangerous fall in blood pressure
  • Book in for a 4 week review - recheck BP - 

 Onset of effect

  Sildenafil Tadalafil Vardenafil Vardenafil orodispersible Avanafil
Time taken before sexual activity 1 hour At least 30 minutes 25–60 minutes 25–60 minutes 15–30 minutes
Time to reach maximum plasma concentration 30–120 minutes (median 60 minutes) 2 hours (median) 30–120 minutes (median 60 minutes) 45–90 minutes 30–45 minutes (median)
Time to onset of effect 25 minutes (range 12–37 minutes) 16 minutes–36 hours 25 minutes (median range from 15 minutes) 25 minutes (median range from 15 minutes) 15–30 minutes
Duration of action 4–5 hours Up to 36 hours 4–5 hours 4–5 hours Up to 6 hours
Effect of food intake Rate of absorption reduced by mean 60 minutes when taken with food Rate of absorption not affected by food Rate of absorption reduced by median 60 minutes when taken with high fat meals Rate of absorption reduced by median 60 minutes when taken with high fat meals Rate of absorption reduced by mean 75 minutes when taken with high fat meals


Adverse effects

  • All PDE-5 inhibitors
    • Common: back pain, dyspepsia, flushing, migraine, myalgia, nasal congestion, dizziness, nausea, and vomiting.
    • Uncommon but serious: visual disturbances, sudden hearing loss, priapism (persistent erection)
  • Sildenafil
    • Less common: chest pain, drowsiness, dry mouth, epistaxis, fatigue, hypertension, hypoaesthesia, hypotension, painful red eyes, palpitation, tachycardia, tinnitus, and vertigo. 
    • Rare: atrial fibrillation, cerebrovascular accident, facial oedema, hypersensitivity reactions, rash, Stevens-Johnson syndrome, syncope, arrhythmia, myocardial infarction (MI), seizures, and unstable angina.
  • Tadalafil:
    • Less common: hypertension, tachycardia, epistaxis, hypotension, painful red eyes, and palpitation. 
    • Rare: arrhythmia, MI, retinal vascular occlusion, unstable angina, facial oedema, hypersensitivity reactions, rash, Stevens-Johnson syndrome, syncope, abdominal pain, increased sweating, seizures, serious cardiovascular events, and transient amnesia. 
  • Vardenafil:
    • Less common: drowsiness, dyspnoea, epistaxis, hypertension, hypotension, increased lacrimation, painful red eyes, palpitation, photosensitivity, and tachycardia. 
    • Rare: anxiety, facial oedema, hypersensitivity reactions, hypertonia, raised intra-ocular pressure, rash, Stevens-Johnson syndrome, syncope, transient amnesia, arrhythmia, MI, retinal vascular occlusion, seizures, serious cardiovascular events, and unstable angina.
  • Avanafil:
    • Less common: drowsiness, epistaxis, hypertension, hypotension, malaise, painful red eyes, palpitation, and tachycardia. 
    • Rare: abdominal pain, diarrhoea, dry mouth, facial oedema, gastritis, genital irritation, gout, haematuria, hyperactivity, hyperbilirubinaemia, hypersensitivity reactions, increased serum creatinine, insomnia, muscle spasms, peripheral oedema, pollakiuria, rash, Stevens-Johnson syndrome, syncope, weight gain, arrhythmia, MI, retinal vascular occlusion, seizures, serious cardiovascular events, and unstable angina.

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