Treatment of men with erectile dysfunction, which is the inability to achieve or
maintain a penile erection sufficient for satisfactory sexual performance.
In order for Aphrodil® to be effective, sexual stimulation is required.

For oral use.
Use in adults
The recommended dose is 50 mg taken as needed approximately one hour before
sexual activity. Based on efficacy and toleration, the dose may be increased to 100mg
or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum
recommended dosing frequency is once per day. If Aphrodil® is taken with food, the
onset of activity may be delayed compared to the fasted state (see Section 5.2).
Use in the elderly

dosage adjustments are not required in elderly patients.
Use in patients with impaired renal function
The dosing recommendations described in "Use in adults" apply to patients with mild
to moderate renal impairment (creatinine clearance= 30-80 ml/min).
Since sildenafil clearance is reduced in patients with severe renal impairment
(creatinine clearance < 30 ml/min) a 25mg dose should be considered. Based on
efficacy and toleration, the dose may be increased to 50mg and 100mg.
Use in patients with impaired hepatic function
Since sildenafil clearance is reduced in patients with hepatic impairment ( e.g.
cirrhosis) a 25 mg dose should be considered. Based on efficacy and toleration, the
dose may be increased to 50 mg and 100 mg.
Use in children and adolescents
Aphrodil® is not indicated for individuals below 18 years of age.
Use in patients using other medicines
With the exception of ritonavir for which co-administration with sildenafil is not
advised (see Section 4.4) a starting dose of 25 mg should be considered in patients
receiving concomitant treatment with CYP3A4 inhibitors (see Section 4.5).
In order to minimize the potential for developing postural hypotension, patients
should be stable on alpha-blocker therapy prior to initiating sildenafil treatment. In
addition, initiation of sildenafil at a dose of 25 mg should be considered (see Sections
4.4 and 4.5).

Hypersensitivity to the active substance or to any of the excipients. Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway (see Section 5.1), sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form is therefore contraindicated. Agents for the treatment of erectile dysfunction, including sildenafil, should not be used in men for whom sexual activity is inadvisable ( e.g. patients with severe cardiovascular disorders such as unstable angina or severe cardiac failure). AphrodiI® is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (1\AION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure (see section 4.4) The safety of sildenafil has not been studied in the following sub-groups of patients and its use is therefore contraindicated: severe hepatic impairment, hypotension (blood pressure < 90/50 mmHg), recent history of stroke or myocardial infarction and known hereditary degenerative retinal disorders s:uch as retinitis pigmentosa (minorities of these patients have genetic disorders of retinal phosphodiesterases).

A medical history and physical examination should be undertaken to diagnose erectile
dysfunction and determine potential underlying causes, before pharmacological
treatment is considered.
Prior to initiating any treatment for erectile dysfunction, physicians should consider
the cardiovascular status of their patients, since there is a degree of cardiac risk
associated with sexual activity. Sildenafil has vasodilator properties, resulting in mild
and transient decreases in blood pressure (see Section 5.1). Prior to prescribing
sildenafil, physicians should carefully consider whether their patients with certain
underlying conditions could be adversely affected by such vasodilatory effects,
especially in combination with sexual activity. Patients with increased susceptibility
to vasodilators include those with left ventricular outflow obstruction ( e.g., aortic
stenosis, hypertrophic obstructive cardiomyopathy), or those with the rare syndrome
of multiple system atrophy manifesting as severely impaired autonomic control of
blood pressure.
Aphrodil® potentiates the hypotensive effect of nitrates (see Section 4.3).
Serious cardiovascular events, including myocardial infarction, unstable angina,
sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient
ischaemic attack, hypertension and hypotension have been reported post-marketing in
temporal association with the use of Aphrodil®. Most, but not all, of these patients
had pre-existing cardiovascular risk factors. Many events were reported to occur
during or shortly after sexual intercourse and a few were reported to occur shortly
after the use of Aphrodil® without sexual activity. It is not possible to determine
whether these events are related directly to these factors or to other factors.
Agents for the treatment of erectile dysfunction, including sildenafil, should be used
with caution in patients with anatomical deformation of the penis (such as angulation,
cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which
may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or
leukaemia).
The safety and efficacy of combinations of sildenafil with other treatments for erectile
dysfunction have not been studied. Therefore the use of such combinations is not
recommended.
Visual defects and cases of non-arteritic anterior ischaemic optic neuropathy have
been reported in connection with the intake of sildenafil and other PDE5 inhibitors.

the patient should be advised that in case of sudden visual defect, he should stop
taking Aphrodil® and consult a physician immediately (see section 4.3).
Co-administration of sildenafil with ritonavir is not advised (see Section 4.5).
Caution is advised when sildenafil is administered to patients taking an alpha-blocker,
as the coadministration may lead to symptomatic hypotension in a few susceptible
individuals (see Section 4.5). This is most likely to occur within 4 hours post
sildenafil dosing. In order to minimise the potential for developing postural
hypotension, patients should be hemodynamically stable on alpha-blocker therapy
prior to initiating sildenafil treatment. Initiation of sildenafil at a dose of 25 mg should
be considered (see Section 4.2). In addition, physicians should advise patients what to
do in the event of postural hypotensive symptoms.
Studies with human platelets indicate that sildenafil potentiates the antiaggregatory
effect of sodium nitroprusside in vitro. There is no safety information on the
administration of sildenafil to patients with bleeding disorders or active peptic
ulceration. Therefore sildenafil should be administered to these patients only after
careful benefit-risk assessment.
The film coating of the Aphrodil® tablet contains lac':ose. Aphrodil® should not be
administered to men with rare hereditary problems of galactose intolerance, Lapp
lactase deficiency or glucose-galactose malabsorption.
Aphrodil® is not indicated for use by women.

Effects of other medicinal products on sildenafil
In vitro studies:
Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP)
isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these
isoenzymes may reduce sildenafil clearance.
In vivo studies:
Population pharmacokinetic analysis of clinical trial data indicated a reduction in
sildenafil clearance when co-administered with CYP3A4 inhibitors (such as
ketoconazole, erythromycin, and cimetidine). Although no increased incidence of
adverse events was observed in these patients, when sildenafil is administered
concomitantly with CYP3A4 inhibitors, a starting dose of25mg should be considered.
Co-administration of the HIV protease inhibitor ritonavir, which is a highly potent
P450 inhibitor, at steady state (500mg twice daily) with sildenafil (I 00mg single
dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1,000% (II-fold)
increase in sildenafil plasma AUC. At 24 hours, the plasma levels of sildenafil were
still approximately 200ng/ml, compared to approximately 5ng/ml when sildenafil was administered alone. This is consistent with ritonavir's marked effects on a broad range
of P450 substrates. Sildenafil had no effect on ritonavir pharmacokinetics. Based on
these pharmacokinetic results co-administration of sildenafil with ritonavir is not
advised (see Section 4.4) and in any event the maximum dose of sildenafil should
under no circumstances exceed 25mg within 48 hours.
Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at
steady state (1200mg three times a day) with sildenafil (100mg single dose) resulted
in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC.
Sildenafil had no effect on saquinavir pharmacokinetics (see Section 4.2). Stronger
CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have
greater effects.
When a single 100mg dose of sildenafil was administered with erythromycin, a
specific CYP3A4 inhibitor, at steady state (500mg twice daily for 5 days), there was a
182% increase in sildenafil systemic exposure (AUC). In normal healthy male
volunteers, there was no evidence of an effect of azithromycin (500mg daily for 3
days) on the AUC, Cmax, Tmax, elimination rate constant, or subsequent half-life of
sildenafil or its principal circulating metabolite. Cimetidine (800mg), a cytochrome
P450 inhibitor and non-specific CYP3A4 inhibitor, caused a 56% increase in plasma
sildenafil concentrations when co-administered with sildenafil (50mg) to healthy
volunteers.
Grapefruit juice is a weak inhibitor of CYP3A4 gut wall metabolism and may give
rise to modest increases in plasma levels of sildenafil.
Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect
the bioavailability of sildenafil.
Although specific interaction studies were not conducted for all medicinal products,
population pharmacokinetic analysis showed no effect of concomitant medication on
sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as
tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin
reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and
potassium sparing diuretics, angiotensin converting enzyme inhibitors, calcium
channel blockers, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism
(such as rifampicin, barbiturates).
Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate
component it has the potential to have serious interaction with sildenafil.
Effects of sildenafil on other medicinal products
In vitro studies:
Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6,
2El and 3A4 (IC50 > 150 μM). Given sildenafil peak plasma concentrations of
approximately 1 μM after recommended doses, it is unlikely that Aphrodil® will alter
the clearance of substrates of these isoenzymes.

there are no data on the interaction of sildenafil and non-specific phosphodiesterase
inhibitors such as theophylline or dipyridamole.
In vivo studies:
Consistent with its known effects on the nitric oxide/cGMP pathway (see Section 5.1 ),
sildenafil was shown to potentiate the hypotensive effects of nitrates, and its coadministration
with nitric oxide donors or nitrates in any form is therefore
contraindicated (see Section 4.3).
Concomitant administration of sildenafil to patients taking alpha-blocker therapy may
lead to symptomatic hypotension in a few susceptible individuals. This is most likely
to occur within 4 hours post sildenafil dosing (see Sections 4.2 and 4.4). In three
specific drug-drugs interaction studies, the alpha-blocker doxazosin ( 4 mg and 8 mg)
and sildenafil (25 mg, 50 mg, or 100 mg) were administered simultaneously to
patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy. In
these study populations, mean additional reductions of supine blood pressure of 7 /7
mmHg, 9/5 mmHg, and 8/4 mmHg, and mean additional reductions of standing blood
pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were observed.
When sildenafil and doxazosin were administered simultaneously to patients
stabilized on doxazosin therapy, there were infrequent reports of patients who
experienced symptomatic postural hypotension. These reports included dizziness and
light-headedness, but not syncope.
No significant interactions were shown when sildenafil (50mg) was co-administered
with tolbutamide (250mg) or warfarin ( 40mg), both of which are metabolised by
CYP2C9.
Sildenafil (50mg) did not potentiate the increase in bleeding time caused by acetyl
salicylic acid (150mg).
Sildenafil (50mg) did not potentiate the hypotensive effects of alcohol in healthy
volunteers with mean maximum blood alcohol levels of 80 mg/dl.
Pooling of the following classes of antihypertensive medication; diuretics, betablockers,
ACE inhibitors, angiotensin II antagonists, antihypertensive medicinal
products (vasodilator and centrally-acting), adrenergic neurone blockers, calcium
channel blockers and alpha-adrenoceptor blockers, showed no difference in the side
effect profile in patients taking sildenafil compared to placebo treatment. In a specific
interaction study, where sildenafil (100mg) was co-administered with amlodipine in
hypertensive patients, there was an additional reduciion on supine systolic blood
pressure of 8 mmHg. The corresponding additional reduction in supine diastolic blood
pressure was 7 mmHg. These additional blood pressure reductions were of a similar
magnitude to those seen when sildenafil was administered alone to healthy volunteers
(see Section 5.1).
Sildenafil (100mg) did not affect the steady state pharmacokinetics of the HIV
protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.

Aphrodil® is not indicated for use by women.
No relevant adverse effects were found in reproduction studies in rats and rabbits
following oral administration of sildenafil.

No studies on the effects on the ability to drive and use machines have been
performed.
As dizziness and altered v1s10n were reported in clinical trials with sildenafil,
patients should be aware of how they react to Aphrodil®, before driving or
operating machinery.

The safety profile of Aphrodil® is based on 8691 patients who received the
recommended dosing regimen in 67 placebo-controlled clinical studies. The most
commonly reported adverse reactions in clinical studies among sildenafil treated
patients were headache, flushing, dyspepsia, visual disorders, nasal congestion,
dizziness and visual colour distortion.
Adverse reactions from post-marketing surveillance has been gathered covering an
estimated period>9 years. Because not all adverse reactions are reported to the
Marketing Authorisation Holder and included in the safety database, the frequencies
of these reactions cannot be reliably determined.
In the table below all medically important adverse reactions, which occurred in
clinical trials at an incidence greater than placebo are listed by system organ class and
freque:acy (very common(~ 1/10), common(~ 1/100 to <1/10), uncommon(~ 1/1,000
to <1/100), rare(~ 1/10,000 to, 1/1,000).
In addition, the frequency of medically important adverse reactions reported from
post-marketing experience is included as not known.
Within each frequency grouping, undesirable effects are presented m order of
decreasing seriousness.
Table 1: Medically important adverse reactions reported at an incidence greater
than placebo in controlled clinical studies and medically important adverse
reactions reported through post-marketing surveillance

MedDRA System Organ Class	Adverse Reaction
I Immune system disorders
rare	Hypersensitivity reactions
Nervous system disorders
Very common	Headache
Common	Dizziness
Uncommon	, Somnolence, Hypoaesthesia
Rare	Cerebrovascular accident, Syncope
Not known	Transient ischaemic attack, Seizure, Seizure recurrence
Eye disorders
'Common	Visual disorders, Visual colour distortion
Uncommon	Conjunctiva! disorders, Eye disorders, Lacrimation disorders, Other eye disorders
Not known	Non-arteritic anterior ischaemic optic neuropathy (NAION), Retinal vascular occlusion, Visual field defect.
Ear and labyrinth disorders
Uncommon	. Vertigo, Tinnitus
Rare	. Deafness*
Vascular disorders
Common	, Flushing
Rare	Hypertension, Hypotension
Cardiac disorders
Uncommon	Palpitations, Tachycardia
Rare	Myocardial infarction, Atrial fibrillation
Unknown	Ventricular arrhythmia, Unstable angina, Sudden cardiac death
Respiratory, thoracic and mediastinal disorders
Common	Nasal congestion
Rare	Epistaxis
gastrointestinal disorders
Common	Dyspepsia
Uncommon	Vomiting, Nausea, Dry mouth
Skin;subcutaneous and soft tissue disorders
Uncommon	Skin rash
Not Known	Steven Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN)
Musculoskeletal and ' connective tissue disorders
System Organ Class	Adverse Reactions
Uncommon	Myalgia
Reproductive system and · breast disorders
Not known	Priapism, Prolonged erection
General disorders and , administration site conditions
Uncommon	Chest pain, Fatigue
Investigations
Uncommon	Heart rate increased

*Ear disorders: Sudden deafness. Sudden decrease or loss of hearing has been
reported in a small number of post-marketing and clinical trial cases with the use of
all PDE5 inhibitors, including sildenafil.

In single dose volunteer studies of doses up to 800mg, adverse reactions were similar
to those seen at lower doses, but the incidence rates and severities were increased.
Doses of 200mg did not result in increased efficacy but the incidence of adverse
reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision)
was 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 not eliminated in the urine.

Pharmacotherapeutic group: Drugs used in erectile dysfunction. ATC Code: G04B
E03.
Sildenafil is an oral therapy for erectile dysfunction. In the natural setting, i.e. with
sexual stimulation, it restores impaired erectile function by increasing blood flow to
the penis.
The physiological mechanism responsible for erection of the penis involves the
release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation.
Nitric oxide then activates the enzyme guanylate cyclase, which results in increased
levels of cyclic guanosine monophosphate ( cGMP), producing smooth muscle
relaxation in the corpus cavernosum and allowing inflow of blood.
Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase
type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for
degradation of cGMP. Sildenafil has a peripheral site of action on erections.
Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but
potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP
pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by
sildenafil results in increased corpus cavernosum levels of cGMP. Therefore sexual
stimulation is required in order for sildenafil to produce its intended beneficial
pharmacological effects.
Studies in vitro have shown that sildenafil is selective for PDE5, which is involved
in the erection process. Its effect is more potent on PDE5 than on other known
phosphodiesterases. There is a IO-fold selectivity over PDE6 which is involved in
the phototransduction pathway in the retina. At maximum recommended doses,
there is an 80-fold selectivity over PDEl, and over 700-fold over PDE 2, 3, 4, 7, 8,
9, 10 and 11. In particular, sildenafil has greater than 4,000-fold selectivity for
PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the
control of cardiac contractility.
Two clinical studies were specifically designed to assess the time window after
dosing during which sildenafil could produce an erection in response to sexual
stimulation. In a penile plethysmography (RigiScan) study of fasted patients, the
median time to onset for those who obtained erections of 60% rigidity (sufficient
for sexual intercourse) was 25 minutes (range 12-37 minutes) on sildenafil. In a
separate RigiScan study, sildenafil was still able to produce an erection in response
to sexual stimulation 4-5 hours post-dose.
Sildenafil causes mild and transient decreases in blood pressure which, in the
majority of cases, do not translate into clinical effects. The mean maximum
decreases in supine systolic blood pressure following 100mg oral dosing of
sildenafil was 8.4 mmHg. The corresponding change in supine diastolic blood

pressure was 5.5 mmHg. These decreases in blood pressure are consistent with the
vasodilatory effects of sildenafil, probably due to increased cGMP levels in vascular
smooth muscle. Single oral doses of sildenafil up to 100mg in healthy volunteers
produced no clinically relevant effects on ECG.
In a study of the hemodynamic effects of a single oral 100mg dose of sildenafil in
14 patients with severe coronary artery disease (CAD) (>70% stenosis of at least
one coronary artery), the mean resting systolic and diastolic blood pressures
decreased by 7% and 6% respectively compared to baseline. Mean pulmonary
systolic blood pressure decreased by 9%. Sildenafil showed no effect on cardiac
output, and did not impair blood flow through the stenosed coronary arteries.
No clinical relevant differences were demonstrated in time to limiting angina for
sildenafil when compared with placebo in a double blind, placebo controlled
exercise stress trial in 144 patients with erectile dysfunction and chronic stable
angina, who were taking on a regular basis anti-angina! medications ( except
nitrates).
Mild and transient differences in colour discrimination (blue/green) were detected
in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a
100mg dose, with no effects evident after 2 hours post-dose. The postulated
mechanism for this change in colour discrimination is related to inhibition of PDE6,
which is involved in the phototransduction cascade of the retina. Sildenafil has no
effect on visual acuity or contrast sensitivity. In a small size placebo-controlled
study of patients with documented early age-related macular degeneration (n=9),
sildenafil (single dose, 100mg) demonstrated no significant changes in visual tests
conducted (visual acuity, Amsler grid, colour discrimination simulated traffic light,
Humphrey perimeter and photostress).
There was no effect on sperm motility or morphology after single 100mg oral doses
of sildenafil in healthy volunteers.
Further information on clinical trials
In clinical trials sildenafil was administered to more than 8000 patients aged 19-87.
The following patient groups were represented: elderly (19.9%), patients with
hypertension (30.9%), diabetes mellitus (20.3%), ischaemic heart disease (5.8%),
hyperlipidaemia (19.8%), spinal cord injury (0.6%), depression (5.2%),
transurethral resection of the prostate (3.7%), radical prostatectomy (3.3%). The
following groups were not well represented or excluded from clinical trials: patients
with pelvic surgery, patients post-radiotherapy, patients with severe renal or hepatic
impairment and patients with certain cardiovascular conditions (see Section 4.3).
In fixed dose studies, the proportions of patients reporting that treatment improved
their erections were 62% (25mg), 74% (50mg) and 82% (100mg) compared to 25%
on placebo. In controlled clinical trials, the discontinuation rate due to sildenafil
was low and similar to placebo.
Across all trials, the proportion of patients reporting improvement on sildenafil
were as follows: psychogenic erectile dysfunction (84%), mixed erectile

dysfunction (77%), organic erectile dysfunction (68%), elderly (67%), diabetes
mellitus (59%), ischaemic heart disease (69%), hypertension (68%), TURP (61 %),
radical prostatectomy (43%), spinal cord injury (83%), depression (75%). The
safety and efficacy of sildenafil was maintained in long term studies.

Absorption
Sildenafil is rapidly absorbed. Maximum observed plasma concentrations are
reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted
state. The mean absolute oral bioavailability is 41 % (range 25-63%). After oral
dosing of sildenafil AUC and Cmax increase in proportion with dose over the
recommended dose range (25-100mg).
When sildenafil is taken with food, the rate of absorption is reduced with a mean
delay in T max of 60 minutes and a mean reduction in Cmax of 29%.
Distribution
The mean steady state volume of distribution (V ct) for sildenafil is 105 1, indicating
distribution into the tissues. After a single oral dose of 100 mg, the mean maximum
total plasma concentration of sildenafil is approximately 440 ng/ml (CV 40%).
Since sildenafil (and its major circulating N-desmethyl metabolite) is 96% bound to
plasma proteins, this results in the mean maximum free plasma concentration for
sildenafil of 18 ng/ml (38 nM). Protein binding is independent of total drug
concentrations.
In healthy volunteers receiving sildenafil (100mg single dose), less than 0.0002%
(average 188ng) of the administered dose was present in ejaculate 90 minutes after
dosing.
Metabolism
Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9
(minor route) hepatic microsomal isoenzymes. The major circulating metabolite
results from N-demethylation of sildenafil. This metabolite has a phosphodiesterase
selectivity profile similar to sildenafil and an in vitro potency for PDE5
approximately 50% that of the parent drug. Plasma concentrations of this metabolite
are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is
further metabolised, with a terminal half-life of approximately 4 h.
Elimination
The total body clearance of sildenafil is 41 1/h with a resultant terminal phase half
life of 3-5 h. After either oral or intravenous administration, sildenafil is excreted as
metabolites predominantly in the faeces (approximately 80% of administered oral
dose) and to a lesser extent in the urine (approximately 13% of administered oral dose).

Pharmacokinetics in special patient groups
Elderly
Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil,
resulting in approximately 90% higher plasma concentrations of sildenafil and the
active N-desmethyl metabolite compared to those seen in healthy younger
volunteers (18-45 years). Due to age-differences in plasma protein binding, the
corresponding increase in free sildenafil plasma concentration was approximately
40%.
Renal insufficiency
In volunteers with mild to moderate renal impairment ( creatinine clearance = 30-80
ml/min), the pharmacokinetics of sildenafil were not altered after receiving a 50mg
single oral dose. The mean AUC and Cmax of the N-desmethyl metabolite increased
126% and 73% respectively, compared to age-matched volunteers with no renal
impairment. However, due to high inter-subject variability, these differences were
not statistically significant. In volunteers with severe renal impairment ( creatinine
clearance < 30 ml/min), sildenafil clearance was reduced, resulting in mean
increases in AUC and Cmax of 100% and 88% respectively compared to agematched
volunteers with no renal impairment. In addition, N-desmethyl metabolite
AUC and Cmax values were significantly increased 79% and 200% respectively.
Hepatic insufficiency
In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh A and B)
sildenafil clearance was reduced, resulting in increases in AUC (84%) and Cmax
(47%) compared to age-matched volunteers with no hepatic impairment. The
pharmacokinetics of sildenafil in patients with severely impaired hepatic function
have not been studied.

Non-clinical data revealed no special hazard for humans based on
studies of safety pharmacology, repeated dose toxicity, genotoxicity,
potential, and toxicity to reproduction.
 

Composition	Quantity per Tablet
core
Lactose monohydrate	137.000
Croscarmellose sodium	12.000
Magnesium stearate	4.500
Microcrystalline cellulose q.s	300.0001
Coat
Opadry Y-1-7000 white	8.0602
lndigocarmine Eurolake	0.285
Talc	1.510
Propylene glycol	2.145
Methylene chloride	Q.S
Isopropanol liquid	Q.S

1 the weight of microcrystalline cellulose varies according to the base content of
sildenafil citrate.
2 Opadry Y-1-7000 White compositions:

Hypromellose Titanium dioxide Macrogol 400

5.037 2.519 0.504

 

None known.

36 months.

Store between 15-30° C.

Immediate packaging: PVC & Aluminum foil

Outer packaging: Cardboard box

Not applicable.