Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Cialis (Eli Lilly)
10 mg and 20 mg tablets
Approved indication: erectile dysfunction
Australian Medicines Handbook section 13.3
The treatment of impotence changed when sildenafil was launched in 1998.Over 17 million men have been prescribed sildenafil and in 2001 it generated sales of US$1.5 billion. There is therefore a large potential market for oral treatments of erectile dysfunction.
Although it has a different structure, tadalafil acts in the same way assildenafil. It inhibits the phosphodiesterase type 5 enzyme to reduce the inactivation of cyclic guanosine monophosphate (cGMP). This inhibition helps to maintain the smooth muscle relaxation, in the corpus cavernosum of the penis, which produces an erection. As the production of cGMP requires the release of nitricoxide in response to sexual arousal, tadalafil will have no effect in the absence of sexual stimulation.
Tadalafil is more slowly absorbed than sildenafil. The median time to the maximum concentration is two hours compared to one hour. In addition, tadalafil has a much longer half-life than sildenafil (17.5 hours versus 4 hours). It can still be effective 36 hours after a dose. Tadalafil is mainly eliminated by metabolism. This metabolism involves cytochrome P450 3A4 so there is a potential for interactions with drugs which inhibit or induce this enzyme.
Few of the clinical trials of tadalafil have been published in full. Overall the efficacy of tadalafil 20 mg for successful sexual intercourse is 75% compared with a placebo response of 32%. The efficacy is likely to be less in patients with diabetes.
Only 1.7% of patients in clinical trials stopped treatment because of adverse events, but 26% had at least one adverse effect. Headache and dyspepsia are the commonest adverse effects. As tadalafil causes vasodilatation it can provoke flushing and falls in blood pressure. It may therefore potentiate the effect of antihypertensive drugs. Tadalafil is contraindicated in patients taking nitrates. As the clinical trials excluded men with unstable cardiovascular disease, tadalafil should not be prescribed for these patients. These contraindications include men with a recent history of stroke, heart failure or myocardial infarction and those with unstable angina or uncontrolled hypertension or arrhythmia.
Although tadalafil is a more potent inhibitor of phosphodiesterase type 5than sildenafil is, the clinical relevance is uncertain. There appear to be no published trials which compare the two drugs or investigate if patients who do not respond to one drug will respond to the other. As tadalafil causes fewer ocular adverse effects it may have a role in patients who have developed abnormal vision while taking sildenafil, however there are no reports of this usage.