Mysildecard

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Mysildecard 20 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 20 mg of sildenafil (as citrate).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet.  
 
A white, round, biconvex film-coated tablet (approximately 6.5 mm diameter), debossed with M on 
one side of the tablet and SL over 20 on the other side.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Adults 
Treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II 
and III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension 
and pulmonary hypertension associated with connective tissue disease. 
 
Paediatric population 
Treatment of paediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension. 
Efficacy in terms of improvement of exercise capacity or pulmonary haemodynamics has been shown 
in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart 
disease (see section 5.1). 
 
4.2 Posology and method of administration 
 
Treatment should only be initiated and monitored by a physician experienced in the treatment of 
pulmonary arterial hypertension. In case of clinical deterioration in spite of Mysildecard treatment, 
alternative therapies should be considered. 
 
Posology 
 
Adults 
The recommended dose is 20 mg three times a day (TID). Physicians should advise patients who 
forget to take Mysildecard to take a dose as soon as possible and then continue with the normal dose. 
Patients should not take a double dose to compensate for the missed dose. 
 
Paediatric population (1 year to 17 years) 
For paediatric patients aged 1 year to 17 years old, the recommended dose in patients ≤ 20 kg is 10 mg 
three times a day and for patients > 20 kg is 20 mg three times a day. Higher than recommended doses 
should not be used in paediatric patients with PAH (see also sections 4.4 and 5.1). The 20 mg tablet 
should not be used in cases where 10 mg TID should be administered in younger patients. Other 
pharmaceutical forms are available for administration to patients ≤ 20 kg and other younger patients 
who are not able to swallow tablets. 
 



 

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Patients using other medicinal products 
In general, any dose adjustment should be administered only after a careful benefit-risk assessment. A 
downward dose adjustment to 20 mg twice daily should be considered when sildenafil is 
co-administered to patients already receiving CYP3A4 inhibitors like erythromycin or saquinavir. A 
downward dose adjustment to 20 mg once daily is recommended in case of co-administration with 
more potent CYP3A4 inhibitors clarithromycin, telithromycin and nefazodone. For the use of 
sildenafil with the most potent CYP3A4 inhibitors, see section 4.3. Dose adjustments for sildenafil 
may be required when co-administered with CYP3A4 inducers (see section 4.5). 
 
Special populations 
 
Elderly (≥ 65 years) 
Dose adjustments are not required in elderly patients. Clinical efficacy as measured by 6-minute walk 
distance could be less in elderly patients. 
 
Renal impairment  
Initial dose adjustments are not required in patients with renal impairment, including severe renal 
impairment (creatinine clearance < 30 ml/min). A downward dose adjustment to 20 mg twice daily 
should be considered after a careful benefit-risk assessment only if therapy is not well-tolerated. 
 
Hepatic impairment 
Initial dose adjustments are not required in patients with hepatic impairment (Child-Pugh class A and 
B). A downward dose adjustment to 20 mg twice daily should be considered after a careful 
benefit-risk assessment only if therapy is not well-tolerated. 
 
Sildenafil is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) (see 
section 4.3). 
 
Paediatric population 
The safety and efficacy of sildenafil in children below 1 year of age has not been established. No data 
are available. 
 
Discontinuation of treatment 
Limited data suggests that the abrupt discontinuation of sildenafil is not associated with rebound 
worsening of pulmonary arterial hypertension. However to avoid the possible occurrence of sudden 
clinical deterioration during withdrawal, a gradual dose reduction should be considered. Intensified 
monitoring is recommended during the discontinuation period. 
 
Method of administration 
Mysildecard is for oral use only. Tablets should be taken approximately 6 to 8 hours apart with or 
without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form due to the 
hypotensive effects of nitrates (see section 5.1).  
 
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). 
 
Combination with the most potent of the CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, 
ritonavir) (see section 4.5).  
 



 

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Patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic 
neuropathy (NAION), 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, 
 Recent history of stroke or myocardial infarction, 
 Severe hypotension (blood pressure < 90/50 mmHg) at initiation. 
 
4.4 Special warnings and precautions for use 
 
The efficacy of sildenafil has not been established in patients with severe pulmonary arterial 
hypertension (functional class IV). If the clinical situation deteriorates, therapies that are 
recommended at the severe stage of the disease (e.g. epoprostenol) should be considered (see section 
4.2). The benefit-risk balance of sildenafil has not been established in patients assessed to be at WHO 
functional class I pulmonary arterial hypertension. 
 
Studies with sildenafil have been performed in forms of pulmonary arterial hypertension related to 
primary (idiopathic), connective tissue disease associated or congenital heart disease associated forms 
of PAH (see section 5.1). The use of sildenafil in other forms of PAH is not recommended. 
 
In the long term paediatric extension study, an increase in deaths was observed in patients 
administered doses higher than the recommended dose. Therefore, doses higher than the recommended 
doses should not be used in paediatric patients with PAH (see also sections 4.2 and 5.1). 
 
Retinitis pigmentosa 
The safety of sildenafil has not been studied in patients with known hereditary degenerative retinal 
disorders such as retinitis pigmentosa (a minority of these patients have genetic disorders of retinal 
phosphodiesterases) and therefore its use is not recommended. 
 
Vasodilatory action  
When prescribing sildenafil, physicians should carefully consider whether patients with certain 
underlying conditions could be adversely affected by sildenafil’s mild to moderate vasodilatory 
effects, for example patients with hypotension, patients with fluid depletion, severe left ventricular 
outflow obstruction or autonomic dysfunction (see section 4.4). 
 
Cardiovascular risk factors 
In post-marketing experience with sildenafil for male erectile dysfunction, serious cardiovascular 
events, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, 
cerebrovascular haemorrhage, transient ischaemic attack, hypertension and hypotension have been 
reported in temporal association with the use of sildenafil. 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 sildenafil without sexual 
activity. It is not possible to determine whether these events are related directly to these factors or to 
other factors.  
 
Priapism 
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). 
 
Prolonged erections and priapism have been reported with sildenafil in post-marketing experience. 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 (see section 4.8). 
 



 

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Vaso-occlusive crises in patients with sickle cell anaemia  
Sildenafil should not be used in patients with pulmonary hypertension secondary to sickle cell 
anaemia. In a clinical study events of vaso-occlusive crises requiring hospitalisation were reported 
more commonly by patients receiving sildenafil than those receiving placebo leading to the premature 
termination of this study. 
 
Visual events 
Cases of visual defects have been reported spontaneously in connection with the intake of sildenafil 
and other PDE5 inhibitors. Cases of non-arteritic anterior ischaemic optic neuropathy, a rare condition, 
have been reported spontaneously and in an observational study in connection with the intake of 
sildenafil and other PDE5 inhibitors (see section 4.8). In the event of any sudden visual defect, the 
treatment should be stopped immediately and alternative treatment should be considered (see section 
4.3). 
 
Alpha-blockers 
Caution is advised when sildenafil is administered to patients taking an alpha-blocker as the 
co-administration may lead to symptomatic hypotension in susceptible individuals (see section 4.5). In 
order to minimise the potential for developing postural hypotension, patients should be 
haemodynamically stable on alpha-blocker therapy prior to initiating sildenafil treatment. Physicians 
should advise patients what to do in the event of postural hypotensive symptoms. 
 
Bleeding disorders 
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. 
 
Vitamin K antagonists 
In pulmonary arterial hypertension patients, there may be a potential for increased risk of bleeding 
when sildenafil is initiated in patients already using a Vitamin K antagonist, particularly in patients 
with pulmonary arterial hypertension secondary to connective tissue disease.  
 
Veno-occlusive disease  
No data are available with sildenafil in patients with pulmonary hypertension associated with 
pulmonary veno-occlusive disease. However, cases of life threatening pulmonary oedema have been 
reported with vasodilators (mainly prostacyclin) when used in those patients. Consequently, should 
signs of pulmonary oedema occur when sildenafil is administered in patients with pulmonary 
hypertension, the possibility of associated veno-occlusive disease should be considered. 
 
Use of sildenafil with bosentan 
The efficacy of sildenafil in patients already on bosentan therapy has not been conclusively 
demonstrated (see sections 4.5 and 5.1).  
 
Concomitant use with other PDE5 inhibitors  
The safety and efficacy of sildenafil when co-administered with other PDE5 inhibitor products, 
including the combined use of sildenafil for erectile dysfunction has not been studied in PAH patients 
and such concomitant use is not recommended (see section 4.5). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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 and inducers of these isoenzymes may increase sildenafil clearance. For dose 
recommendations, see sections 4.2 and 4.3.  



 

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In vivo studies 
Co-administration of oral sildenafil and intravenous epoprostenol has been evaluated (see sections 4.8 
and 5.1).  
 
The efficacy and safety of sildenafil co-administered with other treatments for pulmonary arterial 
hypertension (e.g. ambrisentan, iloprost) has not been studied in controlled clinical trials. Therefore, 
caution is recommended in case of co-administration.  
 
The safety and efficacy of sildenafil when co-administered with other PDE5 inhibitors has not been 
studied in pulmonary arterial hypertension patients (see section 4.4).  
 
Population pharmacokinetic analysis of pulmonary arterial hypertension clinical trial data indicated a 
reduction in sildenafil clearance and/or an increase of oral bioavailability when co-administered with 
CYP3A4 substrates and the combination of CYP3A4 substrates and beta-blockers. These were the 
only factors with a statistically significant impact on sildenafil pharmacokinetics in patients with 
pulmonary arterial hypertension. The exposure to sildenafil in patients on CYP3A4 substrates and 
CYP3A4 substrates plus beta-blockers was 43% and 66% higher, respectively, compared to patients 
not receiving these classes of medicines. Sildenafil exposure was 5-fold higher at a dose of 80 mg 
three times a day compared to the exposure at a dose of 20 mg three times a day. This concentration 
range covers the increase in sildenafil exposure observed in specifically designed drug interaction 
studies with CYP3A4 inhibitors (except with the most potent of the CYP3A4 inhibitors e.g. 
ketoconazole, itraconazole, ritonavir).  
 
CYP3A4 inducers seemed to have a substantial impact on the pharmacokinetics of sildenafil in 
pulmonary arterial hypertension patients, which was confirmed in the in-vivo interaction study with 
CYP3A4 inducer bosentan.  
 
Co-administration of bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) 
125 mg twice daily with sildenafil 80 mg three times a day (at steady state) concomitantly 
administered during 6 days in healthy volunteers resulted in a 63% decrease of sildenafil AUC. A 
population pharmacokinetic analysis of sildenafil data from adult PAH patients in clinical trials 
including a 12 week study to assess the efficacy and safety of oral sildenafil 20 mg three times a day 
when added to a stable dose of bosentan (62.5 mg – 125 mg twice a day) indicated a decrease in 
sildenafil exposure with bosentan co-administration, similar to that observed in healthy volunteers (see 
sections 4.4 and 5.1).  
 
Efficacy of sildenafil should be closely monitored in patients using concomitant potent CYP3A4 
inducers, such as carbamazepine, phenytoin, phenobarbital, St John’s wort and rifampicine.  
 
Co-administration of the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at 
steady state (500 mg twice daily) with sildenafil (100 mg single dose) resulted in a 300% 
(4-fold)increase in sildenafil Cmax and a 1,000% (11-fold) increase in sildenafil plasma AUC. At 
24 hours, the plasma levels of sildenafil were still approximately 200 ng/ml, compared to 
approximately 5 ng/ml when sildenafil was administered alone. This is consistent with ritonavir’s 
marked effects on a broad range of P450 substrates. Based on these pharmacokinetic results 
co-administration of sildenafil with ritonavir is contraindicated in pulmonary arterial hypertension 
patients (see section 4.3).  
 
Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at steady state 
(1200 mg three times a day) with sildenafil (100 mg single dose) resulted in a 140% increase in 
sildenafil Cmax and a 210% increase in sildenafil AUC. Sildenafil had no effect on saquinavir 
pharmacokinetics. For dose recommendations, see section 4.2.  
 
When a single 100 mg dose of sildenafil was administered with erythromycin, a moderate CYP3A4 
inhibitor, at steady state (500 mg twice daily for 5 days), there was a 182% increase in sildenafil 
systemic exposure (AUC). For dose recommendations, see section 4.2. In healthy male volunteers, 



 

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there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, Tmax, 
elimination rate constant, or subsequent half-life of sildenafil or its principal circulating metabolite. 
No dose adjustment is required. Cimetidine (800 mg), a cytochrome P450 inhibitor and a non-specific 
CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered 
with sildenafil (50 mg) to healthy volunteers. No dose adjustment is required.  
 
The most potent of the CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected 
to have effects similar to ritonavir (see section 4.3). CYP3A4 inhibitors like clarithromycin, 
telithromycin and nefazodone are expected to have an effect in between that of ritonavir and CYP3A4 
inhibitors like saquinavir or erythromycin, a seven-fold increase in exposure is assumed. Therefore 
dose adjustments are recommended when using CYP3A4 inhibitors (see section 4.2). 
 
The population pharmacokinetic analysis in pulmonary arterial hypertension patients suggested that 
co-administration of beta-blockers in combination with CYP3A4 substrates might result in an 
additional increase in sildenafil exposure compared with administration of CYP3A4 substrates alone. 
 
Grapefruit juice is a weak inhibitor of CYP3A4 gut wall metabolism and may give rise to modest 
increases in plasma levels of sildenafil. No dose adjustment is required but the concomitant use of 
sildenafil and grapefruit juice is not recommended. 
 
Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability 
of sildenafil.  
 
Co-administration of oral contraceptives (ethinyloestradiol 30 μg and levonorgestrel 150 μg) did not 
affect the pharmacokinetics of sildenafil.  
 
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 (see section 4.3).  
 
Effects of sildenafil on other medicinal products 
 
In-vitro studies  
Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 
(IC50 > 150 μM).  
 
There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as 
theophylline or dipyridamole.  
 
In-vivo studies  
No significant interactions were shown when sildenafil (50 mg) was co-administered with tolbutamide 
(250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9. 
 
Sildenafil had no significant effect on atorvastatin exposure (AUC increased 11%), suggesting that 
sildenafil does not have a clinically relevant effect on CYP3A4. 
 
No interactions were observed between sildenafil (100 mg single dose) and acenocoumarol. 
 
Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid 
(150 mg). 
 
Sildenafil (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with 
mean maximum blood alcohol levels of 80 mg/dl. 
 
In a study of healthy volunteers sildenafil at steady state (80 mg three times a day) resulted in a 50% 
increase in bosentan AUC (125 mg twice daily). A population pharmacokinetic analysis of data from a 
study of adult PAH patients on background bosentan therapy (62.5 mg – 125 mg twice a day) 
indicated an increase (20% (95% CI: 9.8 - 30.8)) of bosentan AUC with co-administration of 



 

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steadystate sildenafil (20 mg three times a day) of a smaller magnitude than seen in healthy volunteers 
when co-administered with 80 mg sildenafil three times a day (see sections 4.4 and 5.1). 
 
In a specific interaction study, where sildenafil (100 mg) was co-administered with amlodipine in 
hypertensive patients, there was an additional reduction 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. 
 
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) stabilised on doxazosin therapy. In these study populations, mean 
additional reductions of supine systolic and diastolic blood pressure of 7/7 mmHg, 9/5 mmHg, and 
8/4 mmHg, respectively, 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 stabilised on doxazosin therapy, there were infrequent reports 
of patients who experienced symptomatic postural hypotension. These reports included dizziness and 
lightheadedness, but not syncope. Concomitant administration of sildenafil to patients taking 
alpha-blocker therapy may lead to symptomatic hypotension in susceptible individuals (see section 
4.4). 
 
Sildenafil (100 mg single dose) did not affect the steady state pharmacokinetics of the HIV protease 
inhibitor saquinavir, which is a CYP3A4 substrate/inhibitor. 
 
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). 
 
Sildenafil had no clinically significant impact on the plasma levels of oral contraceptives 
(ethinyloestradiol 30 µg and levonorgestrel 150 µg).  
 
Paediatric population 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential and contraception in males and females 
Due to lack of data on effects of sildenafil in pregnant women, Mysildecard is not recommended for 
women of childbearing potential unless also using appropriate contraceptive measures.  
 
Pregnancy 
There are no data from the use of sildenafil in pregnant women. Animal studies do not indicate direct 
or indirect harmful effects with respect to pregnancy and embryonal/foetal development. Studies in 
animals have shown toxicity with respect to postnatal development (see section 5.3).  
 
Due to lack of data, Mysildecard should not be used in pregnant women unless strictly necessary.  
 
Breast-feeding 
There are no adequate and well controlled studies in lactating women. Data from one lactating woman 
indicate that sildenafil and its active metabolite N-desmethylsildenafil are excreted into breast milk at 
very low levels. No clinical data are available regarding adverse events in breast-fed infants, but 



 

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amounts ingested would not be expected to cause any adverse effects. Prescribers should carefully 
assess the mother’s clinical need for sildenafil and any potential adverse effects on the breast-fed 
child.  
 
Fertility 
Non-clinical data revealed no special hazard for humans based on conventional studies of fertility (see 
section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Mysildecard has moderate influence on the ability to drive and use machines.  
 
As dizziness and altered vision were reported in clinical trials with sildenafil, patients should be aware 
of how they might be affected by Mysildecard, before driving or using machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In the pivotal placebo-controlled study of sildenafil in pulmonary arterial hypertension, a total of 207 
patients were randomised to and treated with 20 mg, 40 mg, or 80 mg TID doses of sildenafil and 70 
patients were randomised to placebo. The duration of treatment was 12 weeks. The overall frequency 
of discontinuation in sildenafil treated patients at doses of 20 mg, 40 mg and 80 mg TID was 2.9%, 
3.0% and 8.5% respectively, compared to 2.9% with placebo. Of the 277 subjects treated in the pivotal 
study, 259 entered a long-term extension study. Doses up to 80 mg three times a day (4 times the 
recommended dose of 20 mg three times a day) were administered and after 3 years 87% of 183 
patients on study treatment were receiving sildenafil 80 mg TID.  
 
In a placebo-controlled study of sildenafil as an adjunct to intravenous epoprostenol in pulmonary 
arterial hypertension, a total of 134 patients were treated with sildenafil (in a fixed titration starting 
from 20 mg, to 40 mg and then 80 mg, three times a day, as tolerated) and epoprostenol, and 131 
patients were treated with placebo and epoprostenol. The duration of treatment was 16 weeks. The 
overall frequency of discontinuations in sildenafil/epoprostenol treated patients due to adverse events 
was 5.2% compared to 10.7% in the placebo/epoprostenol treated patients. Newly reported adverse 
reactions, which occurred more frequently in the sildenafil/ epoprostenol group, were ocular 
hyperaemia, vision blurred, nasal congestion, night sweats, back pain and dry mouth. The known 
adverse reactions headache, flushing, pain in extremity and oedema were noted in a higher frequency 
in sildenafil/epoprostenol treated patients compared to placebo/epoprostenol treated patients. Of the 
subjects who completed the initial study, 242 entered a long-term extension study. Doses up to 80 mg 
TID were administered and after 3 years 68% of 133 patients on study treatment were receiving 
sildenafil 80 mg TID.  
 
In the two placebo-controlled studies adverse events were generally mild to moderate in severity. The 
most commonly reported adverse reactions that occurred (greater or equal to 10%) on sildenafil 
compared to placebo were headache, flushing, dyspepsia, diarrhoea and pain in extremity.  
 
Tabulated list of adverse reactions 
 
Adverse reactions which occurred in > 1% of sildenafil-treated patients and were more frequent (> 1% 
difference) on sildenafil in the pivotal study or in the sildenafil combined data set of both the 
placebo-controlled studies in pulmonary arterial hypertension, at doses of 20, 40 or 80 mg TID are 
listed in the table below by class and frequency grouping (very common (≥1/10), common (≥1/100 to 
< 1/10), uncommon (≥1 /1,000 to < 1/100) and not known (cannot be estimated from the available 
data). Within each frequency grouping, adverse reactions are presented in order of decreasing 
seriousness.  
 
Reports from post-marketing experience are included in italics. 



 

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MedDRA system organ class (V.14.0) Adverse reaction 
Infections and infestations  
Common  cellulitis, influenza, bronchitis, sinusitis, rhinitis, 

gastroenteritis 
Blood and lymphatic system disorders
Common  anaemia 
Metabolism and nutrition disorders 
Common  fluid retention 
Psychiatric disorders 
Common  insomnia, anxiety 
Nervous system disorders 
Very common  headache 
Common  migraine, tremor, paraesthesia, burning sensation, 

hypoaesthesia 
Eye disorders 
Common  retinal haemorrhage, visual impairment, vision 

blurred, photophobia, chromatopsia, cyanopsia, 
eye irritation, ocular hyperaemia  

Uncommon  visual acuity reduced, diplopia, abnormal sensation 
in eye 

Not known  Non-arteritic anterior ischaemic optic neuropathy 
(NAION)*, Retinal vascular occlusion*, Visual 
field defect*

Ear and labyrinth disorders 
Common  vertigo 
Not known  sudden hearing loss
Vascular disorders 
Very common  flushing 
Not Known  hypotension
Respiratory, thoracic and mediastinal disorders
Common  epistaxis, cough, nasal congestion  
Gastrointestinal disorders 
Very common  diarrhoea, dyspepsia 
Common  gastritis, gastrooesophageal reflux disease, 

haemorrhoids, abdominal distension, dry mouth 
Skin and subcutaneous tissue disorders
Common  alopecia, erythema, night sweats  
Not known  rash
Musculoskeletal and connective tissue disorders
Very common  pain in extremity 
Common  myalgia, back pain 
Renal and urinary disorders 
Uncommon haematuria
Reproductive system and breast disorders 
Uncommon  penile haemorrhage, haematospermia, 

gynaecomastia 



 

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MedDRA system organ class (V.14.0) Adverse reaction 
Not known  priapism, erection increased 
General disorders and administration site 
conditions 

  

Common  pyrexia 
*These adverse events/reactions have been reported in patients taking sildenafil for the treatment of 
male erectile dysfunction (MED). 
 
Paediatric population 
 
In the placebo-controlled study of sildenafil in patients 1 to 17 years of age with pulmonary arterial 
hypertension, a total of 174 patients were treated three times a day with either low (10 mg in patients 
> 20 kg; no patients ≤ 20 kg received the low dose), medium (10 mg in patients ≥ 8-20 kg; 20 mg in 
patients ≥ 20-45 kg; 40 mg in patients > 45 kg) or high dose (20 mg in patients ≥ 8-20 kg; 40 mg in 
patients ≥ 20-45 kg; 80 mg in patients > 45 kg) regimens of sildenafil and 60 were treated with 
placebo. 
 
The adverse reactions profile seen in this paediatric study was generally consistent with that in adults 
(see table above). The most common adverse reactions that occurred (with a frequency ≥ 1%) in 
sildenafil patients (combined doses) and with a frequency > 1% over placebo patients were pyrexia, 
upper respiratory tract infection (each 11.5%), vomiting (10.9%), erection increased (including 
spontaneous penile erections in male subjects) (9.0%), nausea, bronchitis (each 4.6%), pharyngitis 
(4.0%), rhinorrhoea (3.4%), and pneumonia, rhinitis (each 2.9%). 
 
Of the 234 paediatric subjects treated in the short-term, placebo-controlled study, 220 subjects entered 
the long-term extension study. Subjects on active sildenafil therapy continued on the same treatment 
regimen, while those in the placebo group in the short-term study were randomly reassigned to 
sildenafil treatment. 
 
The most common adverse reactions reported across the duration of the short-term and long-term 
studies were generally similar to those observed in the short-term study. Adverse reactions reported in 
>10% of 229 subjects treated with sildenafil (combined dose group, including 9 patients that did not 
continue into the long-term study) were upper respiratory infection (31%), headache (26%), vomiting 
(22%), bronchitis (20%), pharyngitis (18%), pyrexia (17%), diarrhoea (15%), and influenza, epistaxis 
(12% each). Most of these adverse reactions were considered mild to moderate in severity.  
 
Serious adverse events were reported in 94 (41%) of the 229 subjects receiving sildenafil. Of the 94 
subjects reporting a serious adverse event, 14/55 (25.5%) subjects were in the low dose group, 35/74 
(47.3%) in the medium dose group, and 45/100 (45%) in the high dose group. The most common 
serious adverse events that occurred with a frequency ≥ 1% in sildenafil patients (combined doses) 
were pneumonia (7.4%), cardiac failure, pulmonary hypertension (each 5.2%), upper respiratory tract 
infection (3.1%), right ventricular failure, gastroenteritis (each 2.6%), syncope, bronchitis, 
bronchopneumonia, pulmonary arterial hypertension (each 2.2%), chest pain, dental caries (each 
1.7%), and cardiogenic shock, gastroenteritis viral, urinary tract infection (each 1.3%). 
 
The following serious adverse events were considered to be treatment related, enterocolitis, 
convulsion, hypersensitivity, stridor, hypoxia, neurosensory deafness and ventricular arrhythmia.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 



 

12 

4.9 Overdose 
 
In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at 
lower doses, but the incidence rates and severities were increased. At single doses of 200 mg the 
incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, and 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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Urologicals, Drugs used in erectile dysfunction, ATC code: G04BE03  
 
Mechanism of action 
Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP) specific 
phosphodiesterase type 5 (PDE5), the enzyme that is responsible for degradation of cGMP. Apart from 
the presence of this enzyme in the corpus cavernosum of the penis, PDE5 is also present in the 
pulmonary vasculature. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth 
muscle cells resulting in relaxation. In patients with pulmonary arterial hypertension this can lead to 
vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic 
circulation. 
 
Pharmacodynamic effects  
Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 
than on other known phosphodiesterases. There is a 10-fold selectivity over PDE6 which is involved 
in the phototransduction pathway in the retina. There is an 80-fold selectivity over PDE1, 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. 
 
Sildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of 
cases, do not translate into clinical effects. After chronic dosing of 80 mg three times a day to patients 
with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was 
a decrease of 9.4 mmHg and 9.1 mm Hg respectively. After chronic dosing of 80 mg three times a day 
to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were 
observed (a reduction in both systolic and diastolic pressure of 2 mmHg). At the recommended dose of 
20 mg three times a day no reductions in systolic or diastolic pressure were seen. Single oral doses of 
sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG. After 
chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no 
clinically relevant effects on the ECG were reported. 
 
In a study of the hemodynamic effects of a single oral 100 mg 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. 
 
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 100 mg 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, 100 mg) 



 

13 

demonstrated no significant changes in visual tests conducted (visual acuity, Amsler grid, colour 
discrimination simulated traffic light, Humphrey perimeter and photostress).  
 
Clinical efficacy and safety 
 
Efficacy in adult patients with pulmonary arterial hypertension (PAH) 
A randomised, double-blind, placebo-controlled study was conducted in 278 patients with primary 
pulmonary hypertension, PAH associated with connective tissue disease, and PAH following surgical 
repair of congenital heart lesions. Patients were randomised to one of four treatment groups: placebo, 
sildenafil 20 mg, sildenafil 40 mg or sildenafil 80 mg, three times a day. Of the 278 patients 
randomised, 277 patients received at least 1 dose of study drug. The study population consisted of 68 
(25%) men and 209 (75%) women with a mean age of 49 years (range: 18-81 years) and baseline 
6-minute walk test distance between 100 and 450 metres inclusive (mean: 344 metres). 175 patients 
(63%) included were diagnosed with primary pulmonary hypertension, 84 (30%) were diagnosed with 
PAH associated with connective tissue disease and 18 (7%) of the patients were diagnosed with PAH 
following surgical repair of congenital heart lesions. Most patients were WHO Functional Class II 
(107/277, 39%) or III (160/277, 58%) with a mean baseline 6-minute walking distance of 378 meters 
and 326 meters respectively; fewer patients were Class I (1/277, 0.4%) or IV (9/277, 3%) at baseline. 
Patients with left ventricular ejection fraction < 45% or left ventricular shortening fraction < 0.2 were 
not studied. 
 
Sildenafil (or placebo) was added to patients’ background therapy which could have included a 
combination of anticoagulation, digoxin, calcium channel blockers, diuretics or oxygen. The use of 
prostacyclin, prostacyclin analogues and endothelin receptor antagonists was not permitted as add-on 
therapy, and neither was arginine supplementation. Patients who previously failed bosentan therapy 
were excluded from the study. 
 
The primary efficacy endpoint was the change from baseline at week 12 in 6-minute walk distance 
(6MWD). A statistically significant increase in 6MWD was observed in all 3 sildenafil dose groups 
compared to those on placebo. Placebo corrected increases in 6MWD were 45 metres (p < 0.0001), 
46 metres (p < 0.0001) and 50 metres (p < 0.0001) for sildenafil 20 mg, 40 mg and 80 mg TID 
respectively. There was no significant difference in effect between sildenafil doses. For patients with a 
baseline 6MWD < 325 m improved efficacy was observed with higher doses (placebo-corrected 
improvements of 58 metres, 65 metres and 87 metres for 20 mg, 40 mg and 80 mg doses TID, 
respectively). 
 
When analysed by WHO functional class, a statistically significant increase in 6MWD was observed 
in the 20 mg dose group. For class II and class III, placebo corrected increases of 49 metres (p = 
0.0007) and 45 metres (p = 0.0031) were observed respectively. 
 
The improvement in 6MWD was apparent after 4 weeks of treatment and this effect was maintained at 
weeks 8 and 12. Results were generally consistent in subgroups according to aetiology (primary and 
connective tissue disease-associated PAH), WHO functional class, gender, race, location, mean PAP 
and PVRI. 
 
Patients on all sildenafil doses achieved a statistically significant reduction in mean pulmonary arterial 
pressure (mPAP) and pulmonary vascular resistance (PVR) compared to those on placebo. 
Placebo-corrected treatment effects with mPAP were –2.7 mmHg (p = 0.04), -3.0 mmHg (p = 0.01) 
and -5.1 mmHg (p < 0.0001) for sildenafil 20 mg, 40 mg and 80 mg TID respectively. 
Placebo-corrected treatment effects with PVR were -178 dyne.sec/cm5 (p=0.0051), -195 dyne.sec/cm5 
(p=0.0017) and -320 dyne.sec/cm5 (p<0.0001) for sildenafil 20 mg, 40 mg and 80 mg TID, 
respectively. The percent reduction at 12 weeks for sildenafil 20 mg, 40 mg and 80 mg TID in PVR 
(11.2%, 12.9%, 23.3%) was proportionally greater than the reduction in systemic vascular resistance 
(SVR) (7.2%, 5.9%, 14.4%). The effect of sildenafil on mortality is unknown. 
 
A greater percentage of patients on each of the sildenafil doses (i.e. 28%, 36% and 42% of subjects 
who received sildenafil 20 mg, 40 mg and 80 mg TID doses, respectively) showed an improvement by 



 

14 

at least one WHO functional class at week 12 compared to placebo (7%). The respective odds ratios 
were 2.92 (p=0.0087), 4.32 (p=0.0004) and 5.75 (p<0.0001).  
 
Long-term survival data in naive population 
Patients enrolled into the pivotal study were eligible to enter a long term open label extension study. 
At 3 years 87% of the patients were receiving a dose of 80 mg TID. A total of 207 patients were 
treated with sildenafil in the pivotal study, and their long term survival status was assessed for a 
minimum of 3 years. In this population, Kaplan-Meier estimates of 1, 2 and 3 year survival were 96%, 
91% and 82%, respectively. Survival in patients of WHO functional class II at baseline at 1, 2 and 
3 years was 99%, 91%, and 84% respectively, and for patients of WHO functional class III at baseline 
was 94%, 90%, and 81%, respectively.  
 
Efficacy in adult patients with PAH (when used in combination with epoprostenol) 
A randomised, double-blind, placebo controlled study was conducted in 267 patients with PAH who 
were stabilised on intravenous epoprostenol. The PAH patients included those with Primary 
Pulmonary Arterial Hypertension (212/267, 79%) and PAH associated with connective tissue disease 
(55/267, 21%). Most patients were WHO Functional Class II (68/267, 26%) or III (175/267, 66%); 
fewer patients were Class I (3/267, 1%) or IV (16/267, 6%) at baseline; for a few patients (5/267, 2%), 
the WHO Functional Class was unknown. Patients were randomised to placebo or sildenafil (in a fixed 
titration starting from 20 mg, to 40 mg and then 80 mg, three times a day as tolerated) when used in 
combination with intravenous epoprostenol. 
 
The primary efficacy endpoint was the change from baseline at week 16 in 6-minute walk distance. 
There was a statistically significant benefit of sildenafil compared to placebo in 6-minute walk 
distance. A mean placebo corrected increase in walk distance of 26 metres was observed in favour of 
sildenafil (95% CI: 10.8, 41.2) (p = 0.0009). For patients with a baseline walking distance ≥ 
325 metres, the treatment effect was 38.4 metres in favour of sildenafil; for patients with a baseline 
walking distance < 325 metres, the treatment effect was 2.3 metres in favour of placebo. For patients 
with primary PAH, the treatment effect was 31.1 metres compared to 7.7 metres for patients with PAH 
associated with connective tissue disease. The difference in results between these randomisation 
subgroups may have arisen by chance in view of their limited sample size. 
 
Patients on sildenafil achieved a statistically significant reduction in mean Pulmonary Arterial 
Pressure (mPAP) compared to those on placebo. A mean placebo-corrected treatment effect 
of -3.9 mmHg was observed in favour of sildenafil (95% CI: -5.7, -2.1) (p = 0.00003). Time to clinical 
worsening was a secondary endpoint as defined as the time from randomisation to the first occurrence 
of a clinical worsening event (death, lung transplantation, initiation of bosentan therapy, or clinical 
deterioration requiring a change in epoprostenol therapy). Treatment with sildenafil significantly 
delayed the time to clinical worsening of PAH compared to placebo (p = 0.0074). 23 subjects 
experienced clinical worsening events in the placebo group (17.6%) compared with 8 subjects in the 
sildenafil group (6.0%).  
 
Long-term Survival Data in the background epoprostenol study 
Patients enrolled into the epoprostenol add-on therapy study were eligible to enter a long term open 
label extension study. At 3 years 68% of the patients were receiving a dose of 80 mg TID. A total of 
134 patients were treated with sildenafil in the initial study, and their long term survival status was 
assessed for a minimum of 3 years. In this population, Kaplan-Meier estimates of 1, 2 and 3 year 
survival were 92%, 81% and 74%, respectively.  
 
Efficacy and safety in adult patients with PAH (when used in combination with bosentan) 
A randomised, double-blind, placebo controlled study was conducted in 103 clinically stable subjects 
with PAH (WHO FC II and III) who were on bosentan therapy for a minimum of three months. The 
PAH patients included those with primary PAH, and PAH associated with connective tissue disease. 
Patients were randomised to placebo or sildenafil (20 mg three times a day) in combination with 
bosentan (62.5-125 mg twice a day). The primary efficacy endpoint was the change from baseline at 
Week 12 in 6MWD. The results indicate that there is no significant difference in mean change from 



 

15 

baseline on 6MWD observed between sildenafil (20 mg three times a day) and placebo (13.62 m (95% 
CI: -3.89 to 31.12) and 14.08 m (95% CI: -1.78 to 29.95), respectively). 
 
Differences in 6MWD were observed between patients with primary PAH and PAH associated with 
connective tissue disease. For subjects with primary PAH (67 subjects), mean changes from baseline 
were 26.39 m (95% CI: 10.70 to 42.08) and 11.84 m (95% CI: -8.83 to 32.52) for the sildenafil and 
placebo groups, respectively. However, for subjects with PAH associated with connective tissue 
disease (36 subjects) mean changes from baseline were -18.32 m (95% CI: -65.66 to 29.02) and 
17.50 m (95% CI: -9.41 to 44.41) for the sildenafil and placebo groups, respectively. 
 
Overall, the adverse events were generally similar between the two treatment groups (sildenafil plus 
bosentan vs. bosentan alone), and consistent with the known safety profile of sildenafil when used as 
monotherapy (see sections 4.4 and 4.5).  
 
Paediatric population 
A total of 234 subjects aged 1 to 17 years were treated in a randomised, double-blind, multi-centre, 
placebo controlled parallel group, dose ranging study. Subjects (38% male and 62% female) had a 
body weight ≥8 kg, and had primary pulmonary hypertension (PPH) [33%], or PAH secondary to 
congenital heart disease [systemic-to-pulmonary shunt 37%, surgical repair 30%]. In this trial, 63 of 
234 (27%) patients were < 7 years old (sildenafil low dose = 2; medium dose = 17; high dose = 28; 
placebo = 16) and 171 of 234 (73%) patients were 7 years or older (sildenafil low dose = 40; medium 
dose = 38; and high dose = 49; placebo = 44). Most subjects were WHO Functional Class I (75/234, 
32%) or II (120/234, 51%) at baseline; fewer patients were Class III (35/234, 15%) or IV (1/234, 
0.4%); for a few patients (3/234, 1.3%), the WHO Functional Class was unknown. 
 
Patients were naïve for specific PAH therapy and the use of prostacyclin, prostacyclin analogues and 
endothelin receptor antagonists was not permitted in the study, and neither was arginine 
supplementation, nitrates, alpha-blockers and potent CYP450 3A4 inhibitors. 
 
The primary objective of the study was to assess the efficacy of 16 weeks of chronic treatment with 
oral sildenafil in paediatric subjects to improve exercise capacity as measured by the Cardiopulmonary 
Exercise Test (CPET) in subjects who were developmentally able to perform the test, n = 115). 
Secondary endpoints included haemodynamic monitoring, symptom assessment, WHO functional 
class, change in background treatment, and quality of life measurements. 
 
Subjects were allocated to one of three sildenafil treatment groups, low (10 mg), medium (10-40 mg) 
or high dose (20-80 mg) regimens of sildenafil given three times a day, or placebo. Actual doses 
administered within a group were dependent on body weight (see Section 4.8). The proportion of 
subjects receiving supportive medicinal products at baseline (anticoagulants, digoxin, calcium channel 
blockers, diuretics and/or oxygen) was similar in the combined sildenafil treatment group (47.7%) and 
the placebo treatment group (41.7%). 
 
The primary endpoint was the placebo-corrected percentage change in peak VO2 from baseline to 
week 16 assessed by CPET testing in the combined dose groups (Table 2). A total of 106 out of 234 
(45%) subjects were evaluable for CPET, which comprised those children ≥ 7 years old and 
developmentally able to perform the test. Children < 7 years (sildenafil combined dose = 47; placebo = 
16) were evaluable only for the secondary endpoints. Mean baseline peak volume of oxygen 
consumed (VO2) values were comparable across the sildenafil treatment groups (17.37 to 
18.03 ml/kg/min), and slightly higher for the placebo treatment group (20.02 ml/kg/min). The results 
of the main analysis (combined dose groups versus placebo) were not statistically significant (p = 
0.056) (see Table 2). The estimated difference between the medium sildenafil dose and placebo was 
11.33% (95% CI: 1.72 to 20.94) (see Table 2).  
 



 

16 

Table 2: Placebo Corrected % Change from Baseline in Peak VO2 by Active Treatment Group  
 
Treatment group Estimated difference 95% confidence interval
Low dose  
(n=24) 

3.81  -6.11, 13.73  

Medium dose  
(n=26) 

11.33  1.72, 20.94  

High dose  
(n=27) 

7.98  -1.64, 17.60  

Combined dose groups  
(n=77) 

7.71  
(p = 0.056) 

-0.19, 15.60  

 
n=29 for placebo group 
 
Estimates based on ANCOVA with adjustments for the covariates baseline peak VO2, etiology and 
weight group  
 
Dose related improvements were observed with pulmonary vascular resistance index (PVRI) and mean 
pulmonary arterial pressure (mPAP). The sildenafil medium and high dose groups both showed PVRI 
reductions compared to placebo, of 18% (95% CI: 2% to 32%) and 27% (95% CI: 14% to 39%), 
respectively; whilst the low dose group showed no significant difference from placebo (difference of 
2%). The sildenafil medium and high dose groups displayed mPAP changes from baseline compared 
to placebo, of -3.5 mmHg (95% CI: -8.9, 1.9) and -7.3 mmHg (95% CI: -12.4, -2.1), respectively; 
whilst the low dose group showed little difference from placebo (difference of 1.6 mmHg). 
Improvements were observed with cardiac index with all three sildenafil groups over placebo, 10%, 
4% and 15% for the low, medium and high dose groups respectively. 
 
Significant improvements in functional class were demonstrated only in subjects on sildenafil high 
dose compared to placebo. Odds ratios for the sildenafil low, medium and high dose groups compared 
to placebo were 0.6 (95% CI: 0.18, 2.01), 2.25 (95% CI: 0.75, 6.69) and 4.52 (95% CI: 1.56, 13.10), 
respectively. 
 
Long term extension data 
Of the 234 paediatric subjects treated in the short-term, placebo-controlled study, 220 subjects entered 
the long-term extension study. Subjects who had been in the placebo group in the short-term study 
were randomly reassigned to sildenafil treatment; subjects weighing ≤ 20 kg entered the medium or 
high dose groups (1:1), while subjects weighing > 20 kg entered the low, medium or high dose groups 
(1:1:1). Of the total 229 subjects who received sildenafil, there were 55, 74, and 100 subjects in the 
low, medium and high dose groups, respectively. Across the short-term and long-term studies, the 
overall duration of treatment from start of double-blind for individual subjects ranged from 3 to 
3129 days. By sildenafil treatment group, median duration of sildenafil treatment was 1696 days 
(excluding the 5 subjects who received placebo in double-blind and were not treated in the long-term 
extension study). 
 
Kaplan-Meier estimates of survival at 3 years in patients > 20 kg in weight at baseline were 94%, 93% 
and 85% in the low, medium and high dose groups, respectively; for patients ≤ 20 kg in weight at 
baseline, the survival estimates were 94% and 93% for subjects in the medium and high dose groups 
respectively (see sections 4.4 and 4.8). 
 
During the conduct of the study, there were a total of 42 deaths reported, whether on treatment or 
reported as part of the survival follow-up. 37 deaths occurred prior to a decision taken by the Data 
Monitoring Committee to down titrate subjects to a lower dosage, based on an observed mortality 
imbalance with increasing sildenafil doses. Among these 37 deaths, the number (%) of deaths was 
5/55 (9.1%), 10/74 (13.5%), and 22/100 (22%) in the sildenafil low, medium, and high dose groups, 
respectively. An additional 5 deaths were reported subsequently. The causes of deaths were related to 



 

17 

PAH. Higher than recommended doses should not be used in paediatric patients with PAH (see 
sections 4.2 and 4.4). 
 
Peak VO2 was assessed 1 year after the start of the placebo-controlled study. Of those sildenafil treated 
subjects developmentally able to perform the CPET 59/114 subjects (52%) had not shown any 
deterioration in Peak VO2 from start of sildenafil. Similarly 191 of 229 subjects (83%) who had 
received sildenafil had either maintained or improved their WHO Functional Class at 1 year 
assessment. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
sildenafil in newborns with pulmonary arterial hypertension (see section 4.2 for information on 
paediatric use).  
 
5.2 Pharmacokinetic properties 
 
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 three times a day dosing of sildenafil, AUC and Cmax 
increase in proportion with dose over the dose range of 20-40 mg. After oral doses of 80 mg three 
times a day a more than dose proportional increase in sildenafil plasma levels has been observed. In 
pulmonary arterial hypertension patients, the oral bioavailability of sildenafil after 80 mg three times a 
day was on average 43% (90% CI: 27% - 60%) higher compared to the lower doses. 
 
When sildenafil is taken with food, the rate of absorption is reduced with a mean delay in Tmax of 
60 minutes and a mean reduction in Cmax of 29% however, the extent of absorption was not 
significantly affected (AUC decreased by 11%).  
 
Distribution 
The mean steady state volume of distribution (Vss) for sildenafil is 105 l, indicating distribution into 
the tissues. After oral doses of 20 mg three times a day, the mean maximum total plasma concentration 
of sildenafil at steady state is approximately 113 ng/ml. Sildenafil and its major circulating 
N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is 
independent of total drug concentrations.  
 
Biotransformation 
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. The N-desmethyl metabolite is further 
metabolised, with a terminal half-life of approximately 4 h. In patients with pulmonary arterial 
hypertension, plasma concentrations of N-desmethyl metabolite are approximately 72% those of 
sildenafil after 20 mg three times a day dosing (translating into a 36% contribution to sildenafil’s 
pharmacological effects). The subsequent effect on efficacy is unknown.  
 
Elimination 
The total body clearance of sildenafil is 41 l/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 



 

18 

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 50 mg single oral dose. 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 200% and 79% respectively in subjects with severe renal impairment compared 
to subjects with normal renal function.  
 
Hepatic insufficiency 
In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh class A and B) sildenafil clearance 
was reduced, resulting in increases in AUC (85%) and Cmax (47%) compared to age-matched 
volunteers with no hepatic impairment. In addition, N-desmethyl metabolite AUC and Cmax values 
were significantly increased by 154% and 87%, respectively in cirrhotic subjects compared to subjects 
with normal hepatic function. The pharmacokinetics of sildenafil in patients with severely impaired 
hepatic function have not been studied.  
 
Population pharmacokinetics 
In patients with pulmonary arterial hypertension, the average steady state concentrations were 20-50% 
higher over the investigated dose range of 20–80 mg three times a day compared to healthy volunteers. 
There was a doubling of the Cmin compared to healthy volunteers. Both findings suggest a lower 
clearance and/or a higher oral bioavailability of sildenafil in patients with pulmonary arterial 
hypertension compared to healthy volunteers.  
 
Paediatric population 
From the analysis of the pharmacokinetic profile of sildenafil in patients involved in the paediatric 
clinical trials, body weight was shown to be a good predictor of drug exposure in children. Sildenafil 
plasma concentration half-life values were estimated to range from 4.2 to 4.4 hours for a range of 10 to 
70 kg of body weight and did not show any differences that would appear as clinically relevant. Cmax 
after a single 20 mg sildenafil dose administered PO was estimated at 49, 104 and 165 ng/ml for 70, 
20 and 10 kg patients, respectively. Cmax after a single 10 mg sildenafil dose administered PO was 
estimated at 24, 53 and 85 ng/ml for 70, 20 and 10 kg patients, respectively. Tmax was estimated at 
approximately 1 hour and was almost independent from body weight. 
 
5.3 Preclinical safety data 
 
Non-clinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential, toxicity to 
reproduction and development. 
 
In pups of rats which were pre- and postnatally treated with 60 mg/kg sildenafil, a decreased litter size, 
a lower pup weight on day 1 and a decreased 4-day survival were seen at exposures which were 
approximately fifty times the expected human exposure at 20 mg three times a day. Effects in 
non-clinical studies were observed at exposures considered sufficiently in excess of the maximum 
human exposure indicating little relevance to clinical use. 
 
There were no adverse reactions, with possible relevance to clinical use, seen in animals at clinically 
relevant exposure levels which were not also observed in clinical studies. 
 
 



 

19 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Microcrystalline cellulose (PH 102) 
Anhydrous calcium hydrogen phosphate 
Croscarmellose sodium 
Magnesium stearate 
 
Film coat: 
Hypromellose 6 mPas 
Titanium dioxide (E171) 
Triacetin 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage condition. 
 
6.5 Nature and contents of container 
 
PVC-Al blister packs containing 90 or 300 film-coated tablets.  
PVC-Al blisters unit dose perforated blister pack containing 90 x 1 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
No special requirements for disposal. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Mylan S.A.S 
117 Allee des parcs 
69800 Saint Priest 
France 
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
EU/1/16/1134/001 
EU/1/16/1134/002 
EU/1/16/1134/003 
 
 



 

20 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: DD month YYYY 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
  



 

21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
B.  CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



 

22 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Mylan Hungary Kft. 
Mylan utca 1., Komárom,  
2900  
Hungary 
 
Mylan Germany GmbH 
Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 
Bad Homburg v. d. Hoehe 
Hessen, 61352,  
Germany 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are 
set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines 
web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
 Risk Management Plan (RMP) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicine Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



 

23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 

24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



 

25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Mysildecard 20 mg film-coated tablets 
sildenafil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each film-coated tablet contains 20 mg of sildenafil (as citrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
90 film-coated tablets 
300 film-coated tablets 
90 x 1 film-coated tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



 

26 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Mylan S.A.S 
117 Allee des parcs 
69800 Saint Priest 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1134/001  
EU/1/16/1134/002  
EU/1/16/1134/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription.  
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Mysildecard 20 mg  tablets  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA  
 
PC: 
SN:  
NN:   



 

27 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Mysildecard 20 mg film-coated tablets 
sildenafil 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Mylan S.A.S 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
  



 

28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

29 

Package leaflet: Information for the patient 
 

Mysildecard 20 mg film-coated tablets 
sildenafil 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Mysildecard is and what it is used for  
2. What you need to know before you take Mysildecard 
3. How to take Mysildecard 
4. Possible side effects  
5. How to store Mysildecard 
6. Contents of the pack and other information 
 
 
1. What Mysildecard is and what it is used for 
 
Mysildecard contains the active substance sildenafil which belongs to a group of medicines called 
phosphodiesterase type 5 (PDE5) inhibitors.  
Mysildecard brings down blood pressure in the lungs by widening the blood vessels in the lungs.  
Mysildecard is used to treat adults and children and adolescents from 1 to 17 years old with high blood 
pressure in the blood vessels in the lungs (pulmonary arterial hypertension). 
 
 
2. What you need to know before you take Mysildecard  
 
Do not take Mysildecard: 
 if you are allergic to sildenafil or any of the other ingredients of this medicine (listed in section 

6). 
 if you are taking medicines containing nitrates, or nitric oxide donors such as amyl nitrate 

(“poppers”). These medicines are often given for relief of chest pain (or “angina pectoris”). 
Mysildecard can cause a serious increase in the effects of these medicines. Tell your doctor if 
you are taking any of these medicines. If you are not certain, ask your doctor or pharmacist. 

 if you are taking riociguat. This drug is used to treat pulmonary arterial hypertension (i.e. high 
blood pressure in the lungs) and chronic thromboembolic pulmonary hypertension (i.e. high 
blood pressure in the lungs secondary to blood clots).PDE5 inhibitors, such as sildenafil have 
been shown to increase the hypotensive effects of this medicine. If you are taking riociguat or 
are unsure tell your doctor. 

 if you have recently had a stroke, a heart attack or if you have severe liver disease or very low 
blood pressure (<90/50 mmHg). 

 if you are taking a medicine to treat fungal infections such as ketoconazole or itraconazole or 
medicines containing ritonavir (for HIV). 

 if you have ever had loss of vision because of a problem with blood flow to the nerve in the eye 
called non-arteritic anterior ischaemic optic neuropathy (NAION). 

 



 

30 

Warnings and precautions  
Talk to your doctor before taking Mysildecard if you: 
  
 have a disease due to a blocked or narrow vein in the lungs rather than a blocked or narrow 

artery.  
 have a severe heart problem.  
 have a problem with the pumping chambers of your heart.  
 have high blood pressure in the blood vessels in the lungs.  
 have low blood pressure at rest.  
 lose a large amount of body fluids (dehydration) which can occur when you sweat a lot or do 

not drink enough liquids. This can happen if you are sick with a fever, vomiting, or diarrhoea.  
 have a rare inherited eye disease (retinitis pigmentosa).  
 have an abnormality of red blood cells (sickle cell anaemia), cancer of blood cells (leukaemia), 

cancer of bone marrow (multiple myeloma), or any disease or deformity of the penis.  
 currently have a stomach ulcer, a bleeding disorder (such as haemophilia) or problems with nose 

bleeds.  
 take medicines for erectile dysfunction.  
 
When used to treat male erectile dysfunction (ED), the following visual side effects have been 
reported with PDE5 inhibitors, including sildenafil at an unknown frequency; partial, sudden, 
temporary, or permanent decrease or loss of vision in one or both eyes.  
 
If you experience sudden decrease or loss of vision, stop taking Mysildecard and contact your 
doctor immediately (see also section 4).  
 
Prolonged and sometimes painful erections have been reported in men after taking sildenafil. If you 
have an erection, which lasts continuously for more than 4 hours, stop taking Mysildecard and 
contact your doctor immediately (see also section 4).  
 
Special considerations for patients with kidney or liver problems  
You should tell your doctor if you have kidney or liver problems, as your dose may need to be 
adjusted. 
 
Children 
Mysildecard should not be given to children below 1 year of age. 
 
Other medicines and Mysildecard 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
 Medicines containing nitrates, or nitric oxide donors such as amyl nitrate (“poppers”). These 

medicines are often given for relief of angina pectoris or “chest pain” (see section 2. Before you 
take Mysildecard) 

 Tell your doctor or pharmacist if you are already taking riociguat (see section 2). 
 Therapies for pulmonary hypertension (e.g. bosentan, iloprost) 
 Medicines containing St. John’s Wort (herbal medicinal product), rifampicin (used to treat 

bacterial infections), carbamazepine, phenytoin and phenobarbital (used, among others, to treat 
epilepsy) 

 Blood thinning medicines (for example warfarin) although these did not result in any side effect. 
 Medicines containing erythromycin, clarithromycin, telithromycin (these are antibiotics used to 

treat certain bacterial infections), saquinavir (for HIV) or nefazodone (for mental depression), as 
your dose may need to be adjusted. 

 Alpha-blocker therapy (e.g. doxazosin) for the treatment of high blood pressure or prostate 
problems, as the combination of the two medicines may cause symptoms resulting in the 
lowering of your blood pressure (e.g. dizziness, light headedness). 

 



 

31 

Mysildecard with food and drink 
You should not drink grapefruit juice while you are being treated with Mysildecard. 
 
Pregnancy and breast-feeding 
If you are pregnant, or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. Mysildecard should not be used 
during pregnancy unless strictly necessary.  
Mysildecard should not be given to women of child bearing potential unless using appropriate 
contraceptive methods.  
Mysildecard passes into your breast milk at very low levels and would not be expected to harm your 
baby.   
 
Driving and using machines 
Mysildecard can cause dizziness and can affect vision. You should be aware of how you react to the 
medicine before you drive or use machines. 
 
 
3. How to take Mysildecard 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
For adults, the recommended dose is 20 mg three times a day (taken 6 to 8 hours apart) taken with or 
without food. 
 
Use in children and adolescents 
For children and adolescents aged 1 year to 17 years old, the recommended dose is either 10 mg three 
times a day for children and adolescents ≤ 20 kg or 20 mg three times a day for children and 
adolescents > 20 kg, taken with or without food. Higher doses should not be used in children. This 
medicine should be used only in case of administration of 20 mg three times a day. Other 
pharmaceutical forms may be more appropriate for administration to patients ≤ 20 kg and other 
younger patients who are not able to swallow tablets. 
 
If you take more Mysildecard than you should 
You should not take more medicine than your doctor tells you to.  
If you take more medicine than you have been told to take contact your doctor immediately. Taking 
more Mysildecard than you should may increase the risk of known side effects. 
 
If you forget to take Mysildecard 
If you forget to take Mysildecard, take a dose as soon as you remember, then continue to take your 
medicine at the usual times. Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking Mysildecard  
Suddenly stopping your treatment with Mysildecard may lead to your symptoms getting worse. Do not 
stop taking Mysildecard unless your doctor tells you to. Your doctor may tell you to reduce the dose 
over a few days before stopping completely.  
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you experience any of the following side effects you should stop taking Mysildecard and contact a 
doctor immediately (see also section 2):  



 

32 

if you experience sudden decrease or loss of vision (frequency not known)  
if you have an erection, which lasts continuously for more than 4 hours. Prolonged and sometimes 
painful erections have been reported in men after taking sildenafil (frequency not known).  
 
Adults  
Side effects reported very commonly (may affect more than 1 in 10 people) were headache, facial 
flushing, indigestion, diarrhoea and pain in the arms or legs.  
 
Side effects reported commonly (may affect up to 1 in 10 people) included: infection under the skin, 
flu-like symptoms, inflammation of the sinuses, reduced number of red blood cells (anaemia), fluid 
retention, difficulty sleeping, anxiety, migraine, shaking, “pins and needles”-like sensation, burning 
sensation, reduced sense of touch, bleeding at the back of the eye, effects on vision, blurred vision and 
light sensitivity, effects on colour vision, eye irritation, bloodshot eyes /red eyes, vertigo, bronchitis, 
nosebleed, runny nose, cough, stuffy nose, stomach inflammation, gastroenteritis, heartburn, piles, 
abdominal distension, dry mouth, hair loss, redness of the skin, night sweats, muscle aches, back pain 
and increased body temperature.  
 
Side effects reported uncommonly (may affect 1 in 100 people) included: reduced sharpness of vision, 
double vision, abnormal sensation in the eye, penile bleeding, presence of blood in semen and/or 
urine, and breast enlargement in men.  
 
Skin rash and sudden decrease or loss of hearing and decreased blood pressure have also been reported 
at an unknown frequency (frequency cannot be estimated from the available data).  
 
Children and adolescents  
The following serious adverse events have been reported commonly (may affect up to 1 in 10 people); 
pneumonia, heart failure, right heart failure, heart related shock, high blood pressure in the lungs, chest 
pain, fainting, respiratory infection, bronchitis, viral infection in the stomach and intestines, urinary 
tract infections and tooth cavities. 
 
The following serious adverse events were considered to be treatment related and were reported 
uncommonly (may affect up to 1 in 100 people), allergic reaction (such as skin rash, swelling of the 
face, lips and tongue, wheezing, difficulty breathing or swallowing), convulsion, irregular heart-beat, 
hearing impairment, shortness of breath, inflammation of the digestive tract, wheezing due to 
disrupted airflow. 
 
Side effects reported very commonly (may affect more than 1 in 10 people) were headache, vomiting, 
infection of the throat, fever, diarrhoea, flu and nosebleed. 
 
Side effects reported commonly (may affect up to 1 in 10 people) were nausea, increased erections, 
pneumonia and runny nose. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Mysildecard 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date 
refers to the last day of that month. 
 



 

33 

This medicinal product does not require any special storage condition. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Mysildecard contains  
- The active substance is sildenafil. Each tablet contains 20 mg of sildenafil (as the citrate).  
- The other ingredients are: 

Tablet core: microcrystalline cellulose (PH 102), calcium hydrogen phosphate anhydrous, 
croscarmellose sodium and magnesium stearate. 
Film coat: hypromellose (6mPas), titanium dioxide (E171) and triacetin. 

 
What Mysildecard looks like and contents of the pack 
 
Mysildecard film-coated tablets are white and round in shape. The tablets are marked with M on one 
side and SL over 20 on the other. The tablets are provided in blisters in packs containing 90, 300 and 
(90 x 1) tablets. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
Mylan S.A.S 
117 Allee des parcs 
69800 Saint Priest 
France 
 
Manufacturer: 
Mylan Hungary Kft. 
Mylan utca 1,  
Komárom,  
2900,  
Hungary 
 
Mylan Germany GmbH 
Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 
Bad Homburg v. d. Hoehe 
Hessen, 61352,  
Germany 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 32 02 658 61 00 

Lietuva 
BGP Products UAB  
Tel: +370 5 205 1288 

България 
Майлан ЕООД 
Тел: +359 2 44 55 400 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tel: + 32 02 658 61 00 
(Belgique/Belgien) 



 

34 

Česká republika 
Mylan Healthcare CZ  
Tel: + 420 222 004 400 

Magyarország 
Mylan EPD Kft 
Tel: + 36 1 465 2100 

Danmark 
Mylan Denmark ApS 
Tel: +45 28 11 69 32 
 

Malta 
V.J. Salomone Pharma Ltd 
Tel: + 356 21 22 01 74 

Deutschland 
Mylan Healthcare GmbH 
Tel: +49 800 0700 800 
 

Nederland 
Mylan BV 
Tel: +31 (0)20 426 3300 
 

Eesti 
BGP Products Switzerland GmbH Eesti filiaal  
Tel: + 372 6363 052 
 

Norge 
Mylan Healthcare Norge AS 
Tel: + 47 66 75 33 00 
 

Ελλάδα 
Generics Pharma Hellas ΕΠΕ 
Τηλ: +30 210 993 6410 
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 2418 

España 
Mylan Pharmaceuticals, S.L 
Tel: + 34 900 102 712 

Polska 
Mylan Healthcare Sp. z.o.o. 
Tel: + 48 22 546 64 00 

France 
Mylan S.A.S 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Tel: + 351 21 412 72 56 

Hrvatska 
Mylan Hrvatska d.o.o.   
Tel: +385 1 23 50 599 
 
 
Ireland 
Mylan Ireland Limited 
Tel:  +353 (0) 87 1694982 
 

România 
BGP Products SRL 
Tel: +40 372 579 000 
 
 
Slovenija 
Mylan Healthcare d.o.o. 
Tel: + 386 1 23 63 180 

Ísland 
Icepharma hf  
Tel: +354 540 8000  
 
 

Slovenská republika 
Mylan s.r.o. 
Tel: +421 2 32 199 100 

Italia 
Mylan Italia S.r.l. 
Tel: + 39 02 612 46921 

Suomi/Finland 
Mylan Finland OY 
Puh/Tel: +358 20 720 9555 

Κύπρος 
Varnavas Hadjipanayis Ltd Τηλ: +357 2220 7700 
 

Sverige 
Mylan AB 
Tel: + 46 855 522 750 

Latvija 
Mylan Healthcare SIATel: +371 676 055 80 
 

United Kingdom 
Generics [UK] Ltd 
Tel: +44 1707 853000 

 
 
This leaflet was last revised in 



 

35 

 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.  


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET