Sildenafil Mylan 25 mg, 50 mg & 100 mg film-coated tablets

4.2 Posology and method of administration
Posology
Use in adults
The recommended dose is 50 mg taken as needed approximately one hour before sexual activity.
Based on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg. The
maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once per
day.
Special populations
Elderly patients
Dosage adjustments are not required in elderly patients (≥ 65 years old.

Patients with rRenal impairment
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 25 mg dose should be considered. Based on efficacy and tolerability, the dose may be
increased step-wise to 50 mg up to 100 mg as necessary.
Patients with hHepatic impairment
Since sildenafil clearance is reduced in patients with hepatic impairment (e.g. cirrhosis) a 25 mg dose
should be considered. Based on efficacy and tolerability, the dose may be increased step-wise to
50 mg up to 100 mg as necessary.
Paediatric

In order to minimise the potential for of developing postural hypotension in patients receiving alphablocker
treatment, patients should be stabilised 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).

4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
The co-administration of PDE5 inhibitors, including sildenafil, with guanylate cyclase
stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic
hypotension (see section 4.5).
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).

Concomitant use with other PDE5 inhibitors or other treatments for erectile dysfunction
The safety and efficacy of combinations of sildenafil with other PDE5 Inhibitors inhibitors, or other
pulmonary arterial hypertension (PAH) treatments containing sildenafil, or other treatments for
erectile dysfunction have not been studied. Therefore the use of such combinations is not
recommended.

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 co-administration with nitric oxide
donors or nitrates in any form is therefore contraindicated (see section 4.3).

Riociguat: Preclinical studies showed additive systemic blood pressure lowering effect when
PDE5 inhibitors were combined with riociguat. In clinical studies, riociguat has been shown to
augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favourable clinical
effect of the combination in the population studied. Concomitant use of riociguat with PDE5
inhibitors, including sildenafil, is 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-drug 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 stabilised 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 stabilised on doxazosin therapy, there were
infrequent reports of patients who experienced symptomatic postural hypotension. These reports
included dizziness and light-headedness, but not syncope.

In healthy male volunteers, sildenafil at steady state (80 mg three times daily.t.i.d.) resulted in a 49.8%
increase in bosentan AUC and a 42% increase in bosentan Cmax (125 mg twice daily b.i.d).

4.8 Undesirable effects

Tabulated list of adverse reactions
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 frequency (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), not known
(cannot be estimated from the available data)).
In addition, the frequency of medically important adverse reactions reported from post-marketing
experience is included as not known.
Within each frequency grouping, undesirable effe

*Reported during post-marketing surveillance only
**Visual colour distortions: Chloropsia chloropsia, Chromatopsia chromatopsia,
Cyanopsia cyanopsia, Erythropsia erythropsia and Xanthopsia xanthopsia
***Lacrimation disorders: Dry dry eye, Lacrimal lacrimal disorder and Lacrimation lacrimation
increased
Reporting of suspected adverse

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Urologicals: , Drugs drugs used in erectile dysfunction. ATC Code:
G04B E03.
Mechanism of action
Sildenafil is an oral therapy for

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 aA double blind, placebo controlled exercise stress trial in evaluated 144
patients with erectile dysfunction and chronic stable angina, who regularly received were taking on a
regular basis anti-anginal medications medicinal products (except nitrates). The results

demonstrated no clinically relevant differences between sildenafil and placebo in time to limiting
angina.
Mild and transient

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with
sildenafil the reference medicinal product containing sildenafil in all subsets of the paediatric
population for the treatment of erectile dysfunction. (See see section 4.2 for information on paediatric
use).

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 50 mg single oral dose. The mean
AUC and Cmax of the N-desmethyl metabolite increased up to 126% and up to 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 age-matched volunteers with
no renal impairment. In addition, N-desmethyl metabolite AUC and Cmax values were significantly
increased by 79 200% and 200 79% respectively.
Hepatic

 

6.5 Nature and contents of container

Sildenafil Mylan 25 mg film-coated tablets:
PVC/Aluminium foil blisters in cartons of 1, 2, 4, 8 or 12 tablets.

Sildenafil Mylan 50 mg and 100 mg film-coated tablets:
PVC/Aluminium foil blisters in cartons of 1, 2, 4, 8, 12, 24 or 36 tablets.

Extensive updates to the SmPC in line with the reference product (Viagra) and current QRD template.

In section 6.3, the shelf-life has been changed from 2 to 3 years.
In section 6.4, the storage conditions have changed from "Do not store above 25ºC. Store in the original packaging." to "This medicinal product does not require any special storage conditions."

None provided