the longest duration of action.
Its half-life of 17.5 hours gives a 36-hour "window of opportunity" for
patients with erectile dysfunction(ED) to achieve sexual intercourse, says
urologist Dr. Gerald Brock.
Brock, who is from the University of Western Ontario, Canada, was in Kuala
Lumpur recently as a guest speaker at the launch of tadalafil(CialisTM, Eli Lilly).
According to him, 80 percent of all attempts at intercourse in 4 to 36 hours
after a 20 mg tadalafil dose was taken were successful.
Although the drug reaches peak levels in the body about 2 hours after
consumption [Int J Impot Res 2002;14(S1):S57~S64], this does not mean that
the drug has a slow onset, Brock said.
In fact, among men who tried to have sex within 30 minutes of taking
tadalafil, 52 percent of those attempts resulted in a sustained erection that
led to successful intercourse with orgasm and ejaculation. A third of the men
had an erection and successful intercourse just 16 minutes after taking
tadalafil [J Urol 2002;168:1332~1336].
Tadalafil`s efficacy is dose-related and the most effective dose is 20 mg. This
is the dose available in Malaysia."This drug has no food or alcohol interaction
and therefore may provide additional freedom to the couple allowing for a
maximally spontaneous, intimate encounter, not having to plan their meal and
the drug."
Tadalafil has also been shown to improve erectile function in patients with
hypertension and diabetes.
An integrated analysis of five randomized, placebo-controlled clinical trials
that involved 1,100 patients with average age of 59 years showed that 75
percent of successful attempts at intercourse were reported with 20 mg of
tadalafil [J Urol 2002;168:1332~1336]. A third of the patients had
hypertension while a fifth had diabetes. The severity of ED ranged from mild to
severe, which was representative of ED patients in a typical clinical practice,
Brock said.
In a diabetic population, 64 percent of men on 20 mg tadalafil were found to
have improved erectile function [Diab Care 2002;25:2159~2164].
In the study of 1,100 patients, the number of patients who discontinued
treatment due to adverse events in the tadalafil arm did not differ significantly
from that of the placebo group(2 percent vs 1.3 percent)[J Urol
2002;168:1332~336].
The side effects of tadalafil are typical of phosphodiesterase-5(PDE-5)
inhibitors in general. Headache is a common complaint affecting 14 percent of
the men compared with 6 percent of men taking placebo. Other side effects
include dyspepsia, back pain, rhinitis, myalgia and flushing.
Compared to other PDE-5 inhibitors, there are more complaints of myalgia,
muscle ache and back pain with tadalafil.
Brock explained that this could be related to dilatation of the blood vessels
about 12 hours after taking tadalafil. However, the pain goes away after
patients start moving about, he assured. Furthermore, those patients who
report back pain generally respond to acetaminophen.
The drop-out rate was less than 1 percent attributable to this side effect,
meaning it was not significant even among those who reported myalgia.
Among the patients who reported headaches, the rate of headache actually
declined by 50 percent within 3 months of continued use of tadalafil.
Tadalafil selectively inhibits PDE-5 which is important for erection, with an
almost 800-fold selectivity over PDE-6. Therefore, visual side effects that occur
with other ED drugs are predictably absent with tadalafil.
Tadalafil also partially inhibits PDE-11 but without any clinically significant
impact.
"Even in men who took Cialis 20㎎daily for 6 months, we could not measure
any difference in their sperm analysis, pituitary hormones or any clinical
consequences of this partial PDE-11 inhibition."
This drug is a mild vasodilator but there was no clinically significant change in
the diastolic and systolic blood pressure of healthy volunteers given tadalafil
10 and 20㎎.
An absolute contraindication for the use of tadalafil is the use of
nitroglycerines or nitrates of any type. Systolic hypotension may result from
the interaction between nitrates and tadalafil, which is typical of PDE-5
inhibitors.
This was demonstrated in a study where healthy volunteers of at least 40
years of age were given sublingual nitroglycerin (NTG) following daily doses of
tadalafil 20 mg or placebo for 7 days [J Am Coll Cardiol 2003; 42: 1855~1860].
A systolic blood pressure of less than 85㎜ Hg was observed when a single
dose of 0.4㎎ NTG was given at 2, 4, 8, 24 hours and beyond. After 48 hours,
systolic hypotension was not detectable.
Therefore, Brock cautioned that patients who have chest pains within 48
hours of taking tadalafil should be treated with other resuscitating options,
such as oxygen, morphine and beta blockers, for a further 48 hours. However,
nitrates can be used in a controlled setting if those options fail.
A clinical trial of patients with cardiovascular disease who were able to walk
up stairs and did not use nitrates showed that the incidence of hypotension
with tadalafil is not significantly different from that with placebo.
Nevertheless, patients with severe vascular disease who are taking nitrates
and cannot walk up stairs should not take any treatment for ED and instead
should be optimized with respect to cardiovascular function, he stressed.
On the other hand, the incidence of myocardial infarction(MI) in men who
took tadalafil is significantly lower than that of the placebo group in clinical
trials.
Similar results were found in trials of other PDE-5 inhibitors. PDE-5 inhibitors
have not been shown to increase the risk of MI but instead may be proven in
the future to be cardioprotective, Brock said.
■ 기사 요지
메디메디아아시아 발간 메디칼트리뷴 아시아판에 게재된 내용으로 대표적 발기부전치료제
시알리스의 지속성 효과를 주제로 하고 있다.
시알리스의 가장 큰 특징은 36시간의 지속성 효과로 발기부전환자의 성공적 성행위를 보장
한다는 것이다. 평균 59세 연령층의 발기부전환자 1,100명을 대상으로 한 무작위·대조군시
험들을 통합분석 한 결과, 시알리스 20㎎을 통해 성공적인 성행위를 경험한 비율이 75%에
달했다.
당뇨병환자의 경우는 64%에서 발기부전효과가 확인됐다. 부작용 또한 위약군과 큰 차이
를 보이지 않아, 효과와 안전성이 동시에 검증되고 있다. 정리·이상돈 기자
sdlee@kimsonline.co.kr