Adverse reactions : תופעות לוואי

4.8      Undesirable effects

Summary of the safety profile
In the pivotal placebo-controlled study of Revatio in pulmonary arterial hypertension, a total of 207 patients were randomized to and treated with 20 mg, 40 mg, or 80 mg TID doses of Revatio and 70 patients were randomized 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 Revatio 80 mg TID.


In a placebo-controlled study of Revatio as an adjunct to intravenous epoprostenol in pulmonary arterial hypertension, a total of 134 patients were treated with Revatio (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 Revatio 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 Revatio compared to placebo were headache, flushing, dyspepsia, diarrhoea and pain in extremity.


In a study to assess the effects of different dose levels of sildenafil the safety data for sildenafil 20 mg TID (recommended dose) and for sildenafil 80 mg TID (4 times the recommended dose),
were consistent with the established safety profile of sildenafil in previous adult PAH studies.

Tabulated list of adverse reactions
Adverse reactions which occurred in > 1 % of Revatio-treated patients and were more frequent (> 1 % difference) on Revatio in the pivotal study or in the Revatio 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 (≥ 1/1000 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.

Adverse reactions from sildenafil placebo-controlled studies in PAH and post-marketing experience in adults

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 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).


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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/