Content uploaded by Alvaro Morales
Author content
All content in this area was uploaded by Alvaro Morales on Dec 15, 2014
Content may be subject to copyright.
Clinical safety of oral sildena®l citrate (VIAGRA
TM
) in the
treatment of erectile dysfunction
A Morales
1
, C Gingell
2
, M Collins
3
, PA Wicker
4
and IH Osterloh
3
1
Department of Urology, Queen's University, Kingston General Hospital, Kingston, Ontario, Canada;
2
Urology
Department, Southmead Hospital, Bristol, UK;
3
P®zer Central Research, Sandwich, UK; and
4
P®zer Central Research,
Groton, Connecticut, USA
Sildena®l citrate has been shown to be effective in a wide range of patients with erectile
dysfunction and has been approved in the United States for this indication. The overall clinical
safety of oral sildena®l, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile
dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure
worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-
controlled studies and from 10 open-label extension studies of sildena®l in the treatment of
erectile dysfunction. A total of 4274 patients (2722 sildena®l, 1552 placebo; age range 19±87 y)
received double-blind treatment over a period of up to six months' duration, and 2199 received
long-term, open-label sildena®l for up to 1 y. The most commonly reported adverse events (all
causes) were headache (16% sildena®l, 4% placebo), ¯ushing (10% sildena®l, 1% placebo), and
dyspepsia (7% sildena®l, 2% placebo) and they were predominantly transient and mild or
moderate in nature. These adverse events re¯ect the pharmacology of sildena®l as a
phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of
discontinuation due to adverse events (all causes) was comparable for patients treated with
sildena®l (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed
long-term sildena®l treatment, with only 2% withdrawing due to adverse events. Sildena®l is a
well-tolerated oral treatment for erectile dysfunction.
Keywords: erectile dysfunction; sildena®l; phosphodiesterase type 5 inhibitor; safety
Introduction
Sildena®l, an oral agent which has proven effective
for the treatment of erectile dysfunction (ED),
enables a natural erectile response to sexual stimu-
lation by enhancing the relaxant effect of nitric
oxide (NO) on the corpus cavernosum.
1,2
Normal
penile erection involves the release of NO from
nonadrenergic-noncholinergic nerves and endothe-
lial cells of the cavernosal bodies.
3±5
NO activates
guanylate cyclase, resulting in increased synthesis
of cyclic guanosine monophosphate (cGMP), which
induces corpus cavernosal smooth muscle relaxa-
tion, increased blood ¯ow to the penis, increased
intracavernosal pressure, and penile erection.
4±6
Sildena®l is a potent inhibitor of cGMP-speci®c
phosphodiesterase (PDE) type 5, which is the
predominant PDE isozyme responsible for the
degradation of cGMP in the corpus cavernosum.
3,7
When the NO/cGMP pathway is activated, as occurs
with sexual stimulation, inhibition of PDE type 5 by
sildena®l causes increased concentrations of cGMP
in the corpus cavernosum. Sexual stimulation is
required for sildena®l to produce its bene®cial
pharmacological effects on erectile function.
For most patients, the recommended dosing
regimen for sildena®l is 50 mg taken, as needed,
approximately 1 h before sexual activity. However,
sildena®l may be taken from 0.5 h±4 h before sexual
activity. Based on effectiveness and toleration, the
dose may be increased to a maximum recommended
dose of 100 mg or decreased to 25 mg. The maximum
recommended dosing frequency is once per day.
Sildena®l is rapidly absorbed, with maximum
observed plasma concentrations reached within
30±120 min (median 60 min) in the fasted state.
The terminal phase half-life of sildena®l is 3±5 h.
7
Sildena®l has been shown to be ef®cacious in the
treatment of ED of various aetiologies.
8
A series of 21
double-blind, placebo-controlled studies evaluated
the overall safety and tolerability of sildena®l. Three
of these studies differed markedly in design from the
Correspondence: Dr A Morales, Department of Urology,
Kingston General Hospital, Victory 4, Kingston, Ontario
K7L2V7, Canada.
Received 27 March 1998; accepted in revised form
14 April 1998
International Journal of Impotence Research (1998) 10, 69±74
ß 1998 Stockton Press All rights reserved 0955
-
9930/98 $12.00
http://www.stockton
-
press.co.uk/ijir
others, thereby preventing their inclusion in the
pooling of the safety data. This article describes the
data from the remaining 18 double-blind, placebo-
controlled studies and 10 long-term, open-label
studies in which sildena®l was administered to
more than 3700 patients (with a total of 1631 years
of exposure worldwide).
Methods
Safety and toleration data were analysed from 18 out
of 21 randomised, double-blind, placebo-controlled
(Phase II/III) studies of sildena®l (with 2355 patients
receiving doses of 25 mg±100 mg) and 10 long-term,
open-label studies of sildena®l in the treatment of
ED of a variety of aetiologies (namely, organic,
psychogenic, or mixed organic/psychogenic). In the
18 placebo-controlled studies, a total of 4274
patients (2722 sildena®l, 1552 placebo; age range
18±87 y) with ED (mean duration 5 y) received
double-blind treatment of up to six months' dura-
tion. The 18 placebo-controlled studies had various
designs (Table 1), and included ®xed-dose and
¯exible-dose regimens. The ®xed-dose studies as-
sessed ef®cacy, safety, and tolerability by dose, and
the ¯exible-dose studies assessed these endpoints in
dosing situations that most closely resemble those
used in clinical practice. Patients were aged 18 y or
older with broad-spectrum ED of more than six
months' duration, including those with concomitant
disease, such as diabetes, hypertension, and depres-
sion, and those who had previous prostate surgery.
The main exclusion criteria were penile anatomical
deformities, treatment with nitrates or anticoagu-
lants, and any signi®cant concomitant medical
condition that would impair the patient's ability to
participate. Eighty-six percent (2340 out of 2722) of
the patients treated with sildena®l took the drug on
an as needed basis (PRN). However, patients were
instructed not to take more than one dose daily. A
total of 2199 patients received long-term, open-label
sildena®l treatment for up to 1 y, including 1430
who had received double-blind sildena®l and 769
who had received double-blind placebo. Nitrate
therapy was excluded in all of these studies since
sildena®l potentiates the hypotensive effects of
nitrates. The safety database for these 28 studies
totalled 1631 y of sildena®l exposure.
In all studies evaluated for this analysis, investi-
gators recorded the occurrence of observed and
patient-reported adverse events throughout the
course of treatment. The nature of the adverse
events (mild, moderate, or severe) and their outcome
were also recorded. Investigators were asked to
classify the relationship of the adverse event to the
study drug as de®nitely related, uncertain, or not
related. In all studies, a treatment-related adverse
event was de®ned as any event classi®ed as
de®nitely related or of uncertain relation to the
study drug. This classi®cation was also used when
relationship data were missing. Serious adverse
events included any event that suggested a signi®-
cant hazard, such as those that were fatal, life-
threatening, permanently disabling, requiring hos-
pitalisation, or that involved cancer, a congenital
anomaly, or a drug overdose. Laboratory tests and
blood pressure measurements were conducted at the
screening visit, at regular intervals during study
drug administration, and at the end of each study
(®nal visit). In two of the placebo-controlled studies,
electrocardiogram (ECG) recordings were obtained
within 24 h of dosing.
Results
Adverse events
In PRN ¯exible-dose, placebo-controlled studies,
which re¯ect drug usage in clinical practice, the
most commonly recorded adverse events of all
causes reported by patients receiving sildena®l were
headache (16%), ¯ushing (10%), and dyspepsia
(7%) (Table 2). Nasal congestion, abnormal vision,
diarrhoea, dizziness, and rash were also reported.
The incidences of the most commonly recorded
adverse events of all causes were higher in patients
receiving sildena®l than in those receiving placebo.
Table 1 Number of patients treated in Phase II/III studies
Number of patients
Studies (number) Sildena®l Placebo
Phase II/III placebo-controlled (18 of 21)
a
2722 1552
PRN dosing
b
(11) 2340 1332
Flexible dosing (6) 734 725
Fixed dosing (5) 1606 607
Phase II/III open-label extension (10) 2199 Ð
a
Three studies are of different designs and are not included in the analysis.
b
PRN dosing as needed.
Clinical safety of oral sildena®l citrate (VIAGRA
TM
)
A Morales
et al
70
Adverse events were predominantly transient and
mild or moderate in nature (Figure 1), with
approximately two-thirds of all reports classi®ed as
mild.
The overall rate of discontinuation from treat-
ment due to adverse events of all causes in PRN
¯exible-dose, placebo-controlled studies was com-
parable for patients in the sildena®l (2.5%) and
placebo (2.3%) treatment groups. Headache (1.1%),
¯ushing (0.4%), and nausea (0.4%) were the most
common adverse events of all causes leading to
discontinuation for patients receiving sildena®l.
Only one patient in 2722 subjects treated with
sildena®l discontinued treatment due to abnormal
vision. Headache (0.4%) was the most common
adverse event (all causes) leading to discontinuation
for patients receiving placebo.
In PRN ®xed-dose, placebo-controlled studies,
the majority of the adverse events were also mild or
moderate and self-limiting in nature for both
patients receiving sildena®l and those receiving
placebo. In PRN ®xed-dose studies, the overall
incidence of treatment-related adverse events and
the incidences of the most commonly reported
treatment-related adverse events (headache, ¯ush-
ing, dyspepsia, nasal congestion, abnormal vision,
and dizziness) increased as the dose of sildena®l
increased. The incidences of dyspepsia (17%) and
abnormal vision (11%) were higher at 100 mg than at
the lower doses of sildena®l in ®xed-dose studies.
The most common description of abnormal vision
was a mild and transient colour tinge to vision. The
overall nature of adverse events was similar to that
observed in the PRN ¯exible-dose studies. The rates
of discontinuation from treatment due to treatment-
related adverse events were comparable at 25 mg
(0.6%) and 50 mg (0.4%) of sildena®l and then
increased at the 100 mg dose (1.2%); the correspond-
ing rate for the placebo group was 1.0%. The most
frequent adverse event causing discontinuation was
headache in the ®xed-dose studies (0.6% in the
100 mg sildena®l group).
In the 10 long-term, open-label studies, 2199
patients received sildena®l. The majority of adverse
events of all causes reported during these open-label
studies were mild or moderate in nature, with the
most common being headache (10%), ¯ushing (9%),
dyspepsia (6%), and respiratory tract infection (6%).
The overall incidence of abnormal vision in open-
label extension studies was low (2%), with no long-
term visual sequelae reported. The incidence and
nature of the visual adverse events were similar in
diabetic and nondiabetic patients. Only 10% of
patients enrolled discontinued treatment prior to
the end of the study for reasons that included loss to
follow up, protocol violation, lack of ef®cacy, and
adverse events. Adverse events of all causes
accounted for 2% of the withdrawals over a 1 y
period and lack of ef®cacy 4%. Headache was the
most common adverse event (all causes) leading to
discontinuation of treatment.
No cases of priapism were reported in any of the
sildena®l studies.
Additional topics
PDE type 5 occurs in the systemic vasculature and as
such the incidence of cardiovascular events follow-
ing sildena®l therapy was of interest. In the 18
placebo-controlled studies, the incidence of cardio-
vascular adverse events other than ¯ushing (de-
scribed above) was 3.0% with sildena®l and 3.5%
with placebo. Overall, 79% of all cardiovascular
adverse events were mild, 16% were moderate, and
only 6% were severe in nature for sildena®l, with a
Table 2 Adverse events of all causes reported by 2% of
patients treated with sildena®l or placebo in PRN ¯exible-dose,
placebo-controlled studies
Percentage of patients
reporting event
a
Sildena®l
(n 734)
Placebo
(n 725)
Adverse event %%
Headache 16 4
Flushing 10 1
Dyspepsia 7 2
Nasal congestion 4 2
Urinary tract infection 3 2
Abnormal vision
b
30
Diarrhoea 3 1
Dizziness 2 1
Rash 2 1
a
Other adverse events (respiratory tract infection, back pain, ¯u
syndrome, and arthralgia) occurred at a rate of 2%, but were
equally common with placebo.
b
Abnormal vision: mild and transient, predominantly colour
tinge to vision, but also increased sensitivity to light or blurred
vision. In these studies, only one patient discontinued due to
abnormal vision.
Figure 1 Severity of adverse events of all causes for patients
treated with sildena®l or placebo in PRN ¯exible-dose, placebo-
controlled studies.
Clinical safety of oral sildena®l citrate (VIAGRA
TM
)
A Morales
et al
71
similar pattern for placebo. The rate of discontinua-
tion of treatment due to cardiovascular adverse
events was low and comparable for patients receiv-
ing sildena®l (0.9%) and those receiving placebo
(0.9%) in the 18 placebo-controlled studies.
Of the 2722 patients receiving sildena®l in the 18
placebo-controlled studies, 885 (33%) were also
taking antihypertensive medications. The tolerabil-
ity of sildena®l treatment was comparable for
patients taking antihypertensive medications and
those not taking these medications.
The incidence rate (per 100 man-years of treat-
ment) of serious cardiovascular adverse events was
comparable for patients who received sildena®l in
placebo-controlled studies (4.1; 95% CI 2.6±5.5),
patients who received sildena®l in open-label
extension studies (3.5; 95% CI 2.3±4.7), and patients
who received placebo (5.7; 95% CI 3.3±8.2) (Table
3). The rate of myocardial infarction was 1.7 per 100
man-years of treatment (95% CI 0.8±2.6) for patients
treated with sildena®l in placebo-controlled studies
compared with 1.4 per 100 man-years (95% CI 0.2±
2.6) for those receiving placebo, and 1.0 per 100
man-years (95% CI 0.3±1.6) for patients taking
sildena®l in open-label extension studies. There
were no serious adverse events of any type judged to
be related to sildena®l treatment.
Pooled data from the 18 placebo-controlled
studies indicated no change from baseline in the
median value for systolic blood pressure, diastolic
blood pressure, or heart rate for either the sildena®l
group (n 2146) or the placebo group (n 1133).
There was no evidence of sildena®l-induced
abnormalities in either ECG parameters or laboratory
test measurements.
Discussion
Treatment with oral sildena®l was well tolerated,
with no serious safety concerns identi®ed. Con-
sistent with its known effects on the NO/cGMP
pathway, sildena®l potentiates the hypotensive
effects of nitrates. Patients taking organic nitrates
were excluded from all 28 studies of sildena®l
reported in this article. In man, basal NO plays an
important role in the regulation of blood pressure
via its arterial vasodilator effect.
9,10
Sildena®l was
well tolerated when administered alone or in
combination with conventional antihypertensive
agents. However, in Phase I studies in the presence
of exogenously administered NO (namely, nitrates
or NO donors), sildena®l administration was asso-
ciated with clinically signi®cant decreases in blood
pressure. Therefore, administration of sildena®l in
patients who are concurrently using organic nitrates
in any form is contraindicated.
The 28 studies reported included more than 3700
patients who received sildena®l and 1631 total years
of sildena®l exposure worldwide. The PRN ¯exible-
dose studies provide safety information in a situa-
tion resembling dosing patterns in clinical practice,
the PRN ®xed-dose studies provide insights on the
safety of sildena®l by dose, and the open-label
extension studies provide data on the long-term
safety of sildena®l. Overall, the adverse events
reported were transient, mild-to-moderate in nature,
and rarely resulted in discontinuation of treatment.
Safety data from the three double-blind, placebo-
controlled studies not included in this analysis
because of design differences were consistent with
those reported here. No case of priapism was
reported in any of the sildena®l studies.
The overall rate of discontinuation of treatment
due to adverse events was low and comparable for
patients receiving sildena®l at the recommended
doses (25 mg±100 mg) and those receiving placebo in
double-blind studies. In open-label extension stud-
ies, 90% of the patients enrolled completed long-
term sildena®l therapy and only 2% withdrew due
to adverse events of any cause. Sildena®l did not
result in increased rates of myocardial infarction or
other serious cardiovascular events during either
short-term or long-term treatment. In fact, there were
no serious adverse events related to sildena®l in the
studies reported here. Furthermore, a study in
which sildena®l was administered as needed for
16 weeks and then withdrawn demonstrated that
there are no adverse effects associated with treat-
ment withdrawal.
11
The majority of the adverse events associated
with sildena®l treatment are related to vasodilation
(including headache, ¯ushing, and nasal conges-
tion), gastrointestinal events (dyspepsia), and visual
effects (abnormal vision). All of these adverse events
re¯ect the known pharmacological properties of
sildena®l and, as would be expected, increase in
incidence with increasing dose. Phase I studies
showed that sildena®l has modest peripheral vaso-
dilator properties, which can account for the
occurrence of headache and ¯ushing in some
subjects. Nasal congestion is probably a result of
Table 3 Incidence of serious cardiovascular adverse events and
myocardial infarction in patients treated with sildena®l or
placebo in Phase II/III studies
Incidence (95% CI )
a
Studies Sildena®l Placebo
Phase II/III placebo-controlled
Serious cardiovascular events
b
4.1 (2.7±5.5) 5.7 (3.3±8.2)
Myocardial infarction 1.7 (0.8±2.6) 1.4 (0.2±2.6)
Phase II/III open-label extension
Serious cardiovascular events
b
3.5 (2.3±4.7) Ð
Myocardial infarction 1.0 (0.3±1.6) Ð
a
Incidence is expressed as rate per 100 man-years of treatment. CI
denotes con®dence interval.
b
Serious cardiovascular events include myocardial infarction,
angina, and coronary artery disorder.
Clinical safety of oral sildena®l citrate (VIAGRA
TM
)
A Morales
et al
72
hyperemia of the nasal mucosa, since PDE type 5 is
located in the blood vessels of this tissue. The
adverse events associated with vasodilation were
generally mild or moderate in nature and rarely
were a reason for discontinuation of treatment. In
preclinical studies, sildena®l was shown to relax the
isolated lower esophageal sphincter of dogs, indi-
cating that PDE type 5 may have a role in maintain-
ing the integrity of the gastro-esophageal junction.
When characterised in clinical trials, the dyspepsia
reported with sildena®l treatment was usually
described as an occasional burning sensation in
the epigastrium, suggesting that esophageal re¯ux
may be the cause, as would be anticipated from the
preclinical pharmacology. Although dose-related,
the dyspepsia associated with sildena®l treatment
was predominantly mild or moderate in nature.
Preclinical studies also indicated that PDE type 6 of
the retina plays an important role in the visual
transduction pathway. Sildena®l demonstrates a 10-
fold selectivity for human PDE type 5 over PDE type
6.
2
In studies in dogs, sildena®l produces a dose-
related reversible effect on hyperpolarization of
retinal tissue in response to light, consistent with
the inhibition of retinal PDE type 6. Long-term
safety studies with a speci®c emphasis on ocular
safety conducted in rats, dogs, and mice have not
revealed any functional or morphological changes in
the retina and optical pathways. Clinical pharma-
cology studies demonstrated that the only acute
effect of sildena®l was a mild, transient change in
colour discrimination in the blue-green range in
some subjects. Sildena®l had no effect on other
objective measures of visual function, including
visual acuity, contrast sensitivity, intraocular pres-
sure, Amsler Grid, visual ®elds, and recovery from a
photostress test. For patients in the placebo-con-
trolled and open-label extension studies, abnormal
vision (usually described as a transient colour tinge
to vision) was generally mild-to-moderate in nature
and resulted in only one case of treatment disconti-
nuation at doses within the recommended range. In
one study in which visual effects were studied
intensively in a small number of patients over a 1 y
period, no signi®cant change in any visual para-
meter was noted.
Conclusions
Sildena®l is a well-tolerated oral treatment for ED;
its ef®cacy, excellent safety pro®le, lack of signi®-
cant adverse events, convenient oral administration,
and low rates of discontinuation from treatment
suggest that sildena®l may be a valuable agent for
the management of patients with ED.
Acknowledgment
We are grateful to all the investigators who partici-
pated in the studies; to Dr. Michael Smith for
assistance with data analysis; and to Dr. Michael
Sweeney and Dr. Patricia Leinen for aid in manu-
script preparation. The studies reported were
funded by P®zer Inc.
References
1 Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sildena®l, a
novel effective oral therapy for male erectile dysfunction. Br J
Urol 1996; 78: 257±261.
2 Ballard SA et al. Sildena®l, an inhibitor of phosphodiesterase
type 5, enhances nitric oxide mediated relaxation of human
corpus cavernosum. Int J Impot Res 1996; 8: 103. Abstract.
3 Rajfer J et al. Nitric oxide as a mediator of relaxation of the
corpus cavernosum in response to nonadrenergic, noncholi-
nergic neurotransmission. N Engl J Med 1992; 326: 90±94.
4 Burnett AL. Nitric oxide in the penis: physiology and
pathology. J Urol 1997; 157: 320±324.
5 Wagner G, Saenz de Tejada I. Update on male erectile
dysfunction. BMJ 1998; 316: 678±682.
6 Andersson K-E, Wagner G. Physiology of penile erection.
Physiol Rev 1995; 75: 191±236.
7 Boolell M et al. Sildena®l: an orally active type 5 cyclic GMP-
speci®c phosphodiesterase inhibitor for the treatment of
penile erection dysfunction. Int J Impot Res 1996; 8: 47±52.
8 Goldstein I et al. Oral sildena®l in the treatment of erectile
dysfunction. N Engl J Med 1998. In press.
9 Das S, Kumar KN. Nitric oxide: its identity and role in blood
pressure control. Life Sci 1995; 57: 1547±1556.
10 Vallance P. Control of the human cardiovascular system by
nitric oxide. J Hum Hypertens 1996; 10: 377±381.
11 Virag R et al. Sildena®l (VIAGRA
TM
), a new oral treatment for
erectile dysfunction (ED): an 8 week double-blind, placebo-
controlled parallel group study. Int J Impot Res 1996; 8: 116.
Abstract.
Editorial comment
Clinical safety of oral sildena®l citrate (VIAGRA
TM
) in the treatment of
erectile dysfunctionÐby Morales et al
This study clearly demonstrates that sildena®l is a
safe drug and that it will probably gain wide
acceptance in the population of male patients
suffering from erectile dysfunction.
I think that in the near future every phys-
ician (from the family doctor to the specialist)
must be ready to face a potentially over-
whelming demand for this new drug. A critical
Clinical safety of oral sildena®l citrate (VIAGRA
TM
)
A Morales
et al
73
issue will be to reinforce the concept that
a careful search for the aetiology of erectile dys-
function is needed in the majority of patients in
order to identify those who may bene®t from some
forms of curative treatment (for example, sex therapy
and vascular surgery) and to identify unknown
medical conditions associated with erectile dys-
function.
A major effort should be made with the media in
order to underline the concept that erectile dysfunc-
tion may be a signal of a serious disease and that
the possiblity of offering a pill must not induce
physicians to forget that the overall health condi-
tions of the patient must primarily deserve the
medical attention.
Francesco Montorsi MD
Editorial comment
Clinical safety of oral sildena®l citrate (VIAGRA
TM
) in the treatment of
erectile dysfunctionÐby Morales et al
The editorial of®ce has given a high priority to a
rapid, peer-reviewed, publication of this paper as
the approval of this new compound by FDA in the
US has occurred after only six months of considera-
tion.
As we are observing the ®rst major GCP-study of a
completely new concept it has been regarded
important that the safety pro®le in short term
studies in a large population with a wide scope in
aetiology and age should be brought to the attention
of the readers of this journal.
Two important questions are so far not addressed
in this or earlier publications on oral sildena®l. The
®rst, which hopefully soon will be studied, is how
effective is the drug going to be in a daily practice
and how accepted will it be by patients in general as
well as compared to other approved therapeutic
medications.
The second question, which obviously will take
several years to be answered: Will there be a
different safety-pro®le after ®ve to ten years of use
and will the compound still be effective after long-
term use, as we know is the case with intracaverno-
sal injections.
These questions will hopefully be studied as
meticulously as the data presented in the present
study, collected by a large number of investigators
around the world.
It seems that most of the involved investigators
have been thoroughly impressed by the immediate
effectiveness of the compound in patients with a
variety of aetiologies and this opens up two different
questions: Who are the patients who do not repond
to this treatment and secondly who are the patients
who might have bene®ted from a permanent
curative intervention (as mentioned in Dr. Montor-
si's comment).
Globally only a few medically quali®ed persons
have been properly trained in taking a thorough
medical/sexological history.
Thus an enormous effort by the manufacturers of
compounds active upon sexual functions as well as
the medical educational institutions still has to be
made in order to make the ``professionals'' profes-
sional in something as elementary as their patients'
sexual health.
Thus the new principle of treatment is highly
interesting and certainly will bene®t a large group of
patients as well as enriching the therapeutic
armamentarium for the clinician.
G Wagner
Editor
Clinical safety of oral sildena®l citrate (VIAGRA
TM
)
A Morales
et al
74
