VIAGRA®
(sildenafil citrate)
Tablets
(sildenafil citrate)
Tablets
VIAGRA ®, an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective
inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).
Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1Hpyrazolo[
4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate.
Effects of VIAGRA on Blood Pressure: Single oral doses of sildenafil (100 mg) administered
to healthy volunteers produced decreases in supine blood pressure (mean maximum decrease in
systolic/diastolic blood pressure of 8.4/5.5 mmHg). The decrease in blood pressure was most
notable approximately 1-2 hours after dosing, and was not different than placebo at 8 hours.
Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of VIAGRA,
therefore the effects are not related to dose or plasma levels within this dosage range. Larger
effects were recorded among patients receiving concomitant nitrates.
The results from this pilot study are shown in Table 1; the mean resting systolic and diastolic
blood pressures decreased by 7% and 10% compared to baseline in these patients. Mean resting
values for right atrial pressure, pulmonary artery pressure, pulmonary artery occluded pressure
and cardiac output decreased by 28%, 28%, 20% and 7% respectively. Even though this total
dosage produced plasma sildenafil concentrations which were approximately 2 to 5 times higher
than the mean maximum plasma concentrations following a single oral dose of 100 mg in healthy
male volunteers, the hemodynamic response to exercise was preserved in these patients.
Effects of VIAGRA on Vision: At single oral doses of 100 mg and 200 mg, transient
dose-related impairment of color discrimination (blue/green) was detected using the
Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This
finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the
retina. An evaluation of visual function at doses up to twice the maximum recommended dose
revealed no effects of VIAGRA on visual acuity, intraocular pressure, or pupillometry.
The effectiveness of VIAGRA was evaluated in most studies using several assessment
instruments. The primary measure in the principal studies was a sexual function questionnaire
(the International Index of Erectile Function - IIEF) administered during a 4-week treatment-free
run-in period, at baseline, at follow-up visits, and at the end of double-blind, placebo-controlled,
at-home treatment. Two of the questions from the IIEF served as primary study endpoints;
categorical responses were elicited to questions about (1) the ability to achieve erections
sufficient for sexual intercourse and (2) the maintenance of erections after penetration. The
patient addressed both questions at the final visit for the last 4 weeks of the study. The possible
categorical responses to these questions were (0) no attempted intercourse, (1) never or almost
never, (2) a few times, (3) sometimes, (4) most times, and (5) almost always or always. Also
collected as part of the IIEF was information about other aspects of sexual function, including
information on erectile function, orgasm, desire, satisfaction with intercourse, and overall sexual
satisfaction. Sexual function data were also recorded by patients in a daily diary. In addition,
patients were asked a global efficacy question and an optional partner questionnaire was
administered.
WARNINGS
There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular
disease. Therefore, treatments for erectile dysfunction, including VIAGRA, should not be
generally used in men for whom sexual activity is inadvisable because of their underlying
cardiovascular status.
VIAGRA has systemic vasodilatory properties that resulted in transient decreases in supine blood
pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), (see CLINICAL
PHARMACOLOGY: Pharmacodynamics). While this normally would be expected to be of
little consequence in most patients, prior to prescribing VIAGRA, physicians should carefully
consider whether their patients with underlying cardiovascular disease could be affected
adversely by such vasodilatory effects, especially in combination with sexual activity.
Patients with the following underlying conditions can be particularly sensitive to the actions of
vasodilators including VIAGRA – those with left ventricular outflow obstruction (e.g. aortic
stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic
control of blood pressure.
There is no controlled clinical data on the safety or efficacy of VIAGRA in the following groups;
if prescribed, this should be done with caution.
• Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia
within the last 6 months;
• Patients with resting hypotension (BP <90/50)>170/110);
• Patients with cardiac failure or coronary artery disease causing unstable angina;
• Patients with retinitis pigmentosa (a minority of these patients have genetic disorders of
retinal phosphodiesterases).
Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in
duration) have been reported infrequently since market approval of VIAGRA. In the event of an
erection that persists longer than 4 hours, the patient should seek immediate medical assistance.
If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.
The concomitant administration of the protease inhibitor ritonavir substantially increases serum
concentrations of sildenafil (11-fold increase in AUC). If VIAGRA is prescribed to patients
taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of
sildenafil are limited. Visual disturbances occurred more commonly at higher levels of sildenafil
exposure. Decreased blood pressure, syncope, and prolonged erection were reported in some
healthy volunteers exposed to high doses of sildenafil (200-800 mg). To decrease the chance of
adverse events in patients taking ritonavir, a decrease in sildenafil dosage is recommended (see
Drug Interactions, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).
OVERDOSAGE
In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to
those seen at lower doses but incidence rates were increased.
In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis
is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is
not eliminated in the urine.
DOSAGE AND ADMINISTRATION
For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour
before sexual activity. However, VIAGRA may be taken anywhere from 4 hours to 0.5 hour
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.
The following factors are associated with increased plasma levels of sildenafil: age >65 (40%
increase in AUC), hepatic impairment (e.g., cirrhosis, 80%), severe renal impairment (creatinine
clearance <30>
