International Journal of Impotence Research (1998) 10, 69–74
`(cid:223) 1998 Stockton Press All rights reserved
`0955-9930/98 $12.00
`http://www.stockton-press.co.uk/ijir
`
`Clinical safety of oral sildenafil citrate (VIAGRATM) in the
`treatment of erectile dysfunction
`
`A Morales1, C Gingell2, M Collins3, PA Wicker4 and IH Osterloh3
`
`1Department of Urology, Queen’s University, Kingston General Hospital, Kingston, Ontario, Canada; 2Urology
`Department, Southmead Hospital, Bristol, UK; 3Pfizer Central Research, Sandwich, UK; and 4Pfizer Central Research,
`Groton, Connecticut, USA
`
`Sildenafil 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 sildenafil, 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 sildenafil in the treatment of
`erectile dysfunction. A total of 4274 patients (2722 sildenafil, 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 sildenafil for up to 1 y. The most commonly reported adverse events (all
`causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and
`dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or
`moderate in nature. These adverse events reflect
`the pharmacology of sildenafil 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
`sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed
`long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a
`well-tolerated oral treatment for erectile dysfunction.
`
`Keywords: erectile dysfunction; sildenafil; phosphodiesterase type 5 inhibitor; safety
`
`Introduction
`
`Sildenafil, 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 flow to the penis, increased
`intracavernosal pressure, and penile erection.4–6
`Sildenafil is a potent inhibitor of cGMP-specific
`phosphodiesterase (PDE)
`type 5, which is the
`predominant PDE isozyme responsible for
`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
`
`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
`sildenafil causes increased concentrations of cGMP
`in the corpus cavernosum. Sexual stimulation is
`required for sildenafil
`to produce its beneficial
`pharmacological effects on erectile function.
`For most patients,
`the recommended dosing
`regimen for sildenafil is 50 mg taken, as needed,
`approximately 1 h before sexual activity. However,
`sildenafil 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.
`Sildenafil
`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 sildenafil is 3–5 h.7
`Sildenafil has been shown to be efficacious 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 sildenafil. Three
`of these studies differed markedly in design from the
`
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`Clinical safety of oral sildenafil citrate (VIAGRATM)
`A Morales et al
`
`70
`
`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 sildenafil 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 sildenafil (with 2355 patients
`receiving doses of 25 mg–100 mg) and 10 long-term,
`open-label studies of sildenafil 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 sildenafil, 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 fixed-dose and
`flexible-dose regimens. The fixed-dose studies as-
`sessed efficacy, safety, and tolerability by dose, and
`the flexible-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 significant concomitant medical
`condition that would impair the patient’s ability to
`participate. Eighty-six percent (2340 out of 2722) of
`the patients treated with sildenafil 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
`sildenafil treatment for up to 1 y, including 1430
`who had received double-blind sildenafil and 769
`who had received double-blind placebo. Nitrate
`
`therapy was excluded in all of these studies since
`sildenafil potentiates the hypotensive effects of
`nitrates. The safety database for these 28 studies
`totalled 1631 y of sildenafil 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 definitely related, uncertain, or not
`related. In all studies, a treatment-related adverse
`event was defined as any event classified as
`definitely related or of uncertain relation to the
`study drug. This classification was also used when
`relationship data were missing. Serious adverse
`events included any event that suggested a signifi-
`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
`(final visit). In two of the placebo-controlled studies,
`electrocardiogram (ECG) recordings were obtained
`within 24 h of dosing.
`
`Results
`
`Adverse events
`
`In PRN flexible-dose, placebo-controlled studies,
`which reflect drug usage in clinical practice, the
`most commonly recorded adverse events of all
`causes reported by patients receiving sildenafil were
`headache (16%), flushing (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 sildenafil than in those receiving placebo.
`
`Table 1 Number of patients treated in Phase II/III studies
`
`Number of patients
`
`Studies (number)
`
`Sildenafil
`
`Placebo
`
`Phase II/III placebo-controlled (18 of 21)a
`PRN dosingb (11)
`Flexible dosing (6)
`Fixed dosing (5)
`Phase II/III open-label extension (10)
`
`2722
`2340
`734
`1606
`2199
`
`1552
`1332
`725
`607
`—
`
`aThree studies are of different designs and are not included in the analysis.
`bPRN dosing(cid:136) as needed.
`
`Page 2
`
`

`

`Table 2 Adverse events of all causes reported by (cid:21)2% of
`patients treated with sildenafil or placebo in PRN flexible-dose,
`placebo-controlled studies
`
`Percentage of patients
`reporting event a
`
`Sildenafil
`(n(cid:136) 734)
`%
`
`Placebo
`(n(cid:136) 725)
`%
`
`16
`10
`7
`4
`3
`3
`3
`2
`2
`
`4
`1
`2
`2
`2
`0
`1
`1
`1
`
`Adverse event
`
`Headache
`Flushing
`Dyspepsia
`Nasal congestion
`Urinary tract infection
`Abnormal visionb
`Diarrhoea
`Dizziness
`Rash
`
`a Other adverse events (respiratory tract infection, back pain, flu
`syndrome, and arthralgia) occurred at a rate of (cid:21)2%, but were
`equally common with placebo.
`bAbnormal 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 sildenafil or placebo in PRN flexible-dose, placebo-
`controlled studies.
`
`Adverse events were predominantly transient and
`mild or moderate in nature (Figure 1), with
`approximately two-thirds of all reports classified as
`mild.
`The overall rate of discontinuation from treat-
`ment due to adverse events of all causes in PRN
`flexible-dose, placebo-controlled studies was com-
`parable for patients in the sildenafil (2.5%) and
`placebo (2.3%) treatment groups. Headache (1.1%),
`flushing (0.4%), and nausea (0.4%) were the most
`common adverse events of all causes leading to
`discontinuation for patients receiving sildenafil.
`Only one patient in 2722 subjects treated with
`sildenafil discontinued treatment due to abnormal
`vision. Headache (0.4%) was the most common
`adverse event (all causes) leading to discontinuation
`for patients receiving placebo.
`
`71
`
`Clinical safety of oral sildenafil citrate (VIAGRATM)
`A Morales et al
`
`In PRN fixed-dose, placebo-controlled studies,
`the majority of the adverse events were also mild or
`moderate and self-limiting in nature for both
`patients receiving sildenafil and those receiving
`placebo.
`In PRN fixed-dose studies,
`the overall
`incidence of treatment-related adverse events and
`the incidences of
`the most commonly reported
`treatment-related adverse events (headache, flush-
`ing, dyspepsia, nasal congestion, abnormal vision,
`and dizziness) increased as the dose of sildenafil
`increased. The incidences of dyspepsia (17%) and
`abnormal vision (11%) were higher at 100 mg than at
`the lower doses of sildenafil in fixed-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 flexible-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 sildenafil 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 fixed-dose studies (0.6% in the
`100 mg sildenafil group).
`In the 10 long-term, open-label studies, 2199
`patients received sildenafil. 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%), flushing (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 efficacy, and
`adverse events. Adverse events of all causes
`accounted for 2% of the withdrawals over a 1 y
`period and lack of efficacy 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
`sildenafil studies.
`
`Additional topics
`
`PDE type 5 occurs in the systemic vasculature and as
`such the incidence of cardiovascular events follow-
`ing sildenafil therapy was of interest. In the 18
`placebo-controlled studies, the incidence of cardio-
`vascular adverse events other than flushing (de-
`scribed above) was 3.0% with sildenafil 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 sildenafil, with a
`
`Page 3
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`

`

`Clinical safety of oral sildenafil citrate (VIAGRATM)
`A Morales et al
`
`72
`
`Table 3 Incidence of serious cardiovascular adverse events and
`myocardial
`infarction in patients treated with sildenafil or
`placebo in Phase II/III studies
`
`Incidence (95% CI ) a
`
`Studies
`
`Sildenafil
`
`Placebo
`
`Phase II/III placebo-controlled
`Serious cardiovascular eventsb
`Myocardial infarction
`Phase II/III open-label extension
`Serious cardiovascular eventsb
`Myocardial infarction
`
`4.1 (2.7–5.5)
`1.7 (0.8–2.6)
`
`5.7 (3.3–8.2)
`1.4 (0.2–2.6)
`
`3.5 (2.3–4.7)
`1.0 (0.3–1.6)
`
`—
`—
`
`aIncidence is expressed as rate per 100 man-years of treatment. CI
`denotes confidence interval.
`bSerious cardiovascular events include myocardial infarction,
`angina, and coronary artery disorder.
`
`similar pattern for placebo. The rate of discontinua-
`tion of
`treatment due to cardiovascular adverse
`events was low and comparable for patients receiv-
`ing sildenafil (0.9%) and those receiving placebo
`(0.9%) in the 18 placebo-controlled studies.
`Of the 2722 patients receiving sildenafil in the 18
`placebo-controlled studies, 885 (33%) were also
`taking antihypertensive medications. The tolerabil-
`ity of sildenafil
`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 sildenafil in
`placebo-controlled studies (4.1; 95% CI 2.6–5.5),
`patients who received sildenafil
`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 sildenafil 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
`sildenafil in open-label extension studies. There
`were no serious adverse events of any type judged to
`be related to sildenafil 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 sildenafil
`group (n(cid:136) 2146) or the placebo group (n(cid:136) 1133).
`There was no evidence of sildenafil-induced
`abnormalities in either ECG parameters or laboratory
`test measurements.
`
`Discussion
`
`Treatment with oral sildenafil was well tolerated,
`with no serious safety concerns identified. Con-
`sistent with its known effects on the NO/cGMP
`
`pathway, sildenafil potentiates the hypotensive
`effects of nitrates. Patients taking organic nitrates
`were excluded from all 28 studies of sildenafil
`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 Sildenafil 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), sildenafil administration was asso-
`ciated with clinically significant decreases in blood
`pressure. Therefore, administration of sildenafil in
`patients who are concurrently using organic nitrates
`in any form is contraindicated.
`The 28 studies reported included more than 3700
`patients who received sildenafil and 1631 total years
`of sildenafil exposure worldwide. The PRN flexible-
`dose studies provide safety information in a situa-
`tion resembling dosing patterns in clinical practice,
`the PRN fixed-dose studies provide insights on the
`safety of sildenafil by dose, and the open-label
`extension studies provide data on the long-term
`safety of sildenafil. 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 sildenafil studies.
`The overall rate of discontinuation of treatment
`due to adverse events was low and comparable for
`patients receiving sildenafil 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 sildenafil therapy and only 2% withdrew due
`to adverse events of any cause. Sildenafil 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 sildenafil in the
`studies reported here. Furthermore, a study in
`which sildenafil 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 sildenafil treatment are related to vasodilation
`(including headache, flushing, and nasal conges-
`tion), gastrointestinal events (dyspepsia), and visual
`effects (abnormal vision). All of these adverse events
`reflect
`the known pharmacological properties of
`sildenafil and, as would be expected, increase in
`incidence with increasing dose. Phase I studies
`showed that sildenafil has modest peripheral vaso-
`dilator properties, which can account
`for
`the
`occurrence of headache and flushing in some
`subjects. Nasal congestion is probably a result of
`
`Page 4
`
`

`

`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, sildenafil 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 sildenafil
`treatment was usually
`described as an occasional burning sensation in
`the epigastrium, suggesting that esophageal reflux
`may be the cause, as would be anticipated from the
`preclinical pharmacology. Although dose-related,
`the dyspepsia associated with sildenafil 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. Sildenafil demonstrates a 10-
`fold selectivity for human PDE type 5 over PDE type
`6.2 In studies in dogs, sildenafil 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 specific 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 sildenafil was a mild, transient change in
`colour discrimination in the blue-green range in
`some subjects. Sildenafil had no effect on other
`objective measures of visual function, including
`visual acuity, contrast sensitivity, intraocular pres-
`sure, Amsler Grid, visual fields, 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 significant change in any visual para-
`meter was noted.
`
`Editorial comment
`
`Clinical safety of oral sildenafil citrate (VIAGRATM)
`A Morales et al
`
`Conclusions
`
`73
`
`Sildenafil is a well-tolerated oral treatment for ED;
`its efficacy, excellent safety profile, lack of signifi-
`cant adverse events, convenient oral administration,
`and low rates of discontinuation from treatment
`suggest that sildenafil 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 Pfizer Inc.
`
`References
`
`1 Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sildenafil, a
`novel effective oral therapy for male erectile dysfunction. Br J
`Urol 1996; 78: 257–261.
`2 Ballard SA et al. Sildenafil, 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. Sildenafil: an orally active type 5 cyclic GMP-
`specific phosphodiesterase inhibitor for the treatment of
`penile erection dysfunction. Int J Impot Res 1996; 8: 47–52.
`8 Goldstein I et al. Oral sildenafil 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. Sildenafil (VIAGRATM), 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.
`
`Clinical safety of oral sildenafil citrate (VIAGRATM) in the treatment of
`erectile dysfunction—by Morales et al
`
`This study clearly demonstrates that sildenafil is a
`safe drug and that
`it will probably gain wide
`acceptance in the population of male patients
`suffering from erectile dysfunction.
`
`in the near future every phys-
`think that
`I
`ician (from the family doctor to the specialist)
`must be
`ready to face
`a potentially over-
`whelming demand for this new drug. A critical
`
`Page 5
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`

`Clinical safety of oral sildenafil citrate (VIAGRATM)
`A Morales et al
`
`74
`
`that
`issue will be to reinforce the concept
`a careful search for the aetiology of erectile dys-
`function is needed in the majority of patients in
`order to identify those who may benefit 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 sildenafil citrate (VIAGRATM) in the treatment of
`erectile dysfunction—by Morales et al
`
`The editorial office 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 first major GCP-study of a
`completely new concept
`it has been regarded
`important
`that
`the safety profile 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 sildenafil. The
`first, 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-profile after five 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 benefited from a permanent
`curative intervention (as mentioned in Dr. Montor-
`si’s comment).
`Globally only a few medically qualified 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 benefit a large group of
`patients as well as enriching the therapeutic
`armamentarium for the clinician.
`
`G Wagner
`Editor
`
`Page 6
`
`