PDE5 inhibitors are recommended first line therapy
The PDE5 inhibitors currently available are; sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). They
improve erectile function by inhibiting type 5 cGMP phosphodiesterase, thereby increasing penile cyclic guanosine monophosphate
(cGMP) which mediates relaxation of cavernosal smooth-muscle cells.7
The main difference between the PDE5 inhibitors is the longer half-life of tadalafil at approximately 18 hours compared
with approximately four hours for sildenafil and vardenafil.8
There is insufficient evidence to support the superiority of one agent over the others and patient preference will usually
The PDE5 inhibitors are not funded and vary in price from approximately $80 to $115 for a pack of four tablets.
PDE5 inhibitors are contraindicated in patients taking organic nitrates
PDE5 inhibitors potentiate the hypotensive effects of organic nitrates and therefore the concomitant use of nitrates
is contraindicated.8 The safe time interval, if nitrates need to be used in a medical emergency, has not been
determined. Most recommendations suggest withholding nitrate therapy for 24 hours after sildenafil and vardenafil, and
48 hours after tadalafil have been taken.7
If the patient requires nitrates after taking a PDE5 inhibitor a cardiologist should be consulted immediately.
PDE5 inhibitors require sexual stimulation to have an effect
PDE5 inhibitors do not cause erections in the absence of sexual stimulation. It is essential for the doctor prescribing
PDE5 inhibitors to educate men in the need for sexual stimulation to ensure the drug is effective. Some men who initially
fail to respond to a PDE5 inhibitor can be successful with these medications after being correctly educated about their
use.7 As anxiety can over-ride the effect of a PDE5 inhibitor, a patient should not be considered to have
failed in the use of a particular PDE5 inhibitor until they have tried them on five to six occasions.
PDE5 inhibitors need to be taken at least 30 minutes to one hour before sexual activity and taking sildenafil with fatty
food and/or alcohol may delay its onset of action.
Monitor for adverse effects and therapeutic response
Common adverse effects such as headache, flushing, gastric upset, diarrhoea, nasal congestion, and light-headedness
are similar for all three PDE5 inhibitors and are often the result of PDE inhibition in other parts of the body.7
Sildenafil and vardenafil have some cross-reactivity with PDE6 and produce visual side effects on rare occasions.
PDE5 inhibitors tend to be less effective in the presence of reduced neural nitric oxide release as is the case in men
Testosterone therapy is not usually indicated for ED in men with normal testosterone levels.8
Testosterone replacement is appropriate when a man with ED is established to have hypogonadism.1 Gynaecomastia,
increased haematocrit, alterations in lipid profile, hypertension, and infertility are some side effects associated
with exogenous testosterone therapy.
It also is possible that testosterone may increase the risk of prostate cancer and the risk of treatment versus benefit
should be considered and discussed with the patient.
N.B. Hyperprolactinaemia of any cause may result in ED and appropriate management of the raised prolactin may restore
Injection therapies are usually second line treatments
If oral therapy with PDE5 inhibitors fails or if they are contraindicated or not tolerated, injection therapy
may be required.
These agents act by directly relaxing smooth muscle in the corpora cavernosum and result in an erection.10 Unlike
PDE5 inhibitors, they do not require sexual stimulation to work.
Side effects include pain at the injection site and priapism, and long term use can result in scarring of the tunica
albuginea with potential curvature and shortening of the penis.2
It is generally recommended that the first dose be administered under medical supervision because of the small risk
of priapism and the importance of detailed education in the technique of self-injection.5
Alprostadil (Caverject) is the most commonly used agent in New Zealand. Other injectable agents include; an aviptadil
and phentolamine combination (Invicorp) and papaverine. Caverject and Invicorp are not funded, however the papaverine
injection is. Papaverine is associated with a higher incidence of priapism and scarring of the tunica albuginea and should
only be used as a second-line therapy by experienced practitioners.
Penile devices may be suitable for men who fail to respond to other therapies
Vacuum constriction devices and penile prosthetic devices are options for men who fail to respond to other therapies.
Vacuum devices draw blood into the penis by means of a vacuum and a constriction band is applied to retain the blood.
Adverse effects include pain, numbness, bruising, a cold blue penis and difficulty with ejaculation. These devices require
significant education in their use and the constriction band should not be applied for any longer than 30 minutes.
Penile prostheses are usually malleable or inflatable devices which are surgically implanted into the penis. They are
expensive and should only be implanted by an experienced surgeon who is regularly performing the procedure. Due to their
permanence they must not be considered until all less invasive options have been tried and failed.2