This is a summary of the European public assessment report (EPAR) for Revatio. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Revatio.
- What is Revatio?
Revatio is a medicine that contains the active substance sildenafil. It is available as tablets (20 mg), a solution for injection (0.8 mg/ml) and a powder to be made up into an oral suspension (10 mg/ml).
- What is Revatio used for?
Revatio is used to treat adults and children aged one to 17 with pulmonary arterial hypertension (PAH, abnormally high blood pressure in the arteries of the lungs). In adults, Revatio is used in patients with class-II (slight limitation of physical activity) or class-III (marked limitation of physical activity) PAH.
Revatio has been shown to be effective in PAH with no identified cause in adults and in children, in PAH caused by connective tissue disease in adults, and in PAH caused by congenital (inborn) heart disease in children.
The solution for injection is for adults who cannot take Revatio tablets or oral suspension for a short period, but whose condition is stable.
Because the number of patients with PAH is low, the disease is considered ‘rare’, and Revatio was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 12 December 2003.
The medicine can only be obtained with a prescription.
- How is Revatio used?
Revatio treatment should only be started and monitored by a doctor who has experience in the treatment of PAH.
In adults, Revatio is taken at a dose of 20 mg three times a day. The solution for injection is for adults who temporarily cannot take Revatio tablets or oral suspension and is injected into a vein by a doctor or nurse at a dose of 10 mg (12.5 ml) three times a day. The same doses are used in patients with kidney or liver problems, and should only be lowered if the patient does not tolerate the normal dose. Different doses of Revatio may be needed in patients taking some medicines that affect the way that Revatio is broken down in the body.
In children aged one to 17, the recommended dose is 10 mg three times a day in children weighing less than 20 kg, or 20 mg three times a day in those over 20 kg. Higher doses should not be used.
- How does Revatio work?
PAH is a debilitating disease where there is severe constriction (narrowing) of the blood vessels of the lungs. This leads to high blood pressure in the vessels taking blood from the heart to the lungs and reduces the amount of oxygen that can get into the blood in the lungs, making physical activity more difficult. The active substance in Revatio, sildenafil, belongs to a group of medicines called ‘phosphodiesterase-type-5 (PDE5) inhibitors’, which means that it blocks the PDE5 enzyme. This enzyme is found in the blood vessels of the lungs. When it is blocked, a substance called ‘cyclic guanine monophosphate’ (cGMP) cannot be broken down, so that it remains in the vessels where it causes relaxation and widening of the blood vessels. In patients with PAH, sildenafil widens the blood vessels of the lungs, which lowers the blood pressure and improves symptoms.
- How has Revatio been studied?
Three doses of Revatio tablets (20, 40 and 80 mg three times a day) were compared with placebo (a dummy treatment) in one main study involving 277 adults with PAH, most of whom had class-II or class-III disease. The main measure of effectiveness was the change in the distance patients could walk in six minutes after 12 weeks of treatment. This is a way of measuring the change in exercise capacity.
In children, Revatio was compared with placebo in one main study involving 235 children aged one to 17 with PAH. Revatio was given three times a day at three different doses according to the children’s weight. The main measure of effectiveness was the change in the maximum volume of oxygen used during exercise after 16 weeks of treatment, in children able to perform the exercise tests. This is another way of measuring the change in exercise capacity.
The company also presented the results of studies showing that the tablets were equivalent to the oral suspension (produced similar levels of sildenafil in the blood), and that the 10 mg injections were equivalent to the 20 mg tablets.
- What benefit has Revatio shown during the studies?
Revatio was more effective than placebo at improving exercise capacity. Before treatment, adults with class-II disease could walk an average of 379 m in six minutes. After 12 weeks, this distance had increased by 49 m more in the patients taking 20 mg Revatio than in the patients taking placebo. Adults with class-III disease could walk an average of 325 m at the start of the study. This distance had increased by 45 m more in the patients taking 20 mg Revatio than in those taking placebo after 12 weeks. As the three doses of Revatio had similar effects, the lowest dose (20 mg three times a day) was chosen for use in adults.
In the study in children, the maximum volume of oxygen the patients used during exercise increased by 10.2% on average after 16 weeks of Revatio treatment, while it increased by 0.5% on average for patients given placebo. The medium dose showed the best results.
- What is the risk associated with Revatio?
The most common side effects with Revatio in adults (seen in more than 1 patient in 10) are headache, flushing (reddening of the skin), dyspepsia (heartburn), diarrhoea and limb (arm or leg) pain. Side effects are similar with the solution for injection. In children, the most common side effects (seen in between 1 and 10 patients in 100) are vomiting, cough, pyrexia (fever), nausea (feeling sick), abdominal pain and photophobia (increased sensitivity of the eyes to light). For the full list of all side effects reported with Revatio, see the package leaflet.
Revatio must not be used in people who are hypersensitive (allergic) to sildenafil or any of the other ingredients. It must not be taken by patients who 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). Revatio must not be taken with nitrates (a group of medicines used to treat angina), or with medicines that could affect the way that Revatio is broken down in the body, such as ketoconazole or itraconazole (antifungal medicines) and ritonavir (used to treat HIV infection). It must not be used in patients with severe liver disease or severe hypotension (very low blood pressure) at initiation of treatment, or who have recently had a stroke or myocardial infarction (heart attack), because Revatio has not been studied in these groups of patients.
- Why has Revatio been approved?
The CHMP concluded that Revatio provides an alternative treatment option for PAH. The Committee decided that Revatio’s benefits are greater than its risks and recommended that it be given marketing authorisation.
Revatio was originally authorised under ‘exceptional circumstances’, because, as the disease is rare, limited information was available at the time of approval. As the company had supplied the additional information requested, the ‘exceptional circumstances’ ended on 25 August 2008.
- What measures are being taken to ensure the safe use of Revatio?
The company that makes Revatio will agree with each European Union Member State on how the solution for injection will be distributed. It will also ensure that doctors and pharmacists who will prescribe or dispense the solution for injection in each Member State receive information about how it should be used and how to report side effects such as low blood pressure.
- Other information about Revatio
The European Commission granted a marketing authorisation valid throughout the European Union for Revatio on 28 October 2005.
For more information about treatment with Revatio, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
|Name||Language||First published||Last updated|
|Revatio : EPAR - Summary for the public||BG = bălgarski||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||ES = español||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||CS = čeština||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||DA = dansk||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||DE = Deutsch||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||ET = eesti keel||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||EL = elliniká||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||EN = English||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||FR = français||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||IT = italiano||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||LV = latviešu valoda||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||LT = lietuvių kalba||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||HU = magyar||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||MT = Malti||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||NL = Nederlands||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||PL = polski||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||PT = português||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||RO = română||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||SK = slovenčina||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||SL = slovenščina||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||FI = suomi||17/08/2009||03/04/2012|
|Revatio : EPAR - Summary for the public||SV = svenska||17/08/2009||03/04/2012|
This EPAR was last updated on 10/04/2013 .
13/12/2012 Revatio -EMEA/H/C/000638 -II/48
|Name||Language||First published||Last updated|
|Revatio : EPAR - Product Information||BG = bălgarski||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||ES = español||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||CS = čeština||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||DA = dansk||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||DE = Deutsch||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||ET = eesti keel||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||EL = elliniká||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||EN = English||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||FR = français||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||IT = italiano||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||LV = latviešu valoda||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||LT = lietuvių kalba||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||HU = magyar||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||MT = Malti||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||NL = Nederlands||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||PL = polski||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||PT = português||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||RO = română||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||SK = slovenčina||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||SL = slovenščina||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||FI = suomi||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||SV = svenska||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||IS = Islenska||17/08/2009||10/04/2013|
|Revatio : EPAR - Product Information||NO = Norsk||17/08/2009||10/04/2013|
- Annex I - Summary of product characteristics
- Annex IIA - Manufacturing-authorisation holder responsible for batch release
- Annex IIB - Conditions of the marketing authorisation
- Annex IIIA - Labelling
- Annex IIIB - Package leaflet
Please note that the size of the above document can exceed 50 pages.
You are therefore advised to be selective about which sections or pages you wish to print.
Treatment of adult patients with pulmonary arterial hypertension classified as World Health Organization (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.
Treatment of paediatric patients aged one 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.
Revatio solution for injection is for the treatment of adult patients with pulmonary arterial hypertension who are currently prescribed oral Revatio and who are temporarily unable to take oral therapy, but are otherwise clinically and haemodynamically stable.
Revatio (oral) is indicated for 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.
Changes since initial authorisation of medicine
|Name||Language||First published||Last updated|
|Revatio : EPAR - Procedural steps taken and scientific information after authorisation||(English only)||17/08/2009||10/04/2013|
|CHMP post-authorisation summary of positive opinion for Revatio||(English only)||18/03/2011|
|Revatio-H-C-638-P46-40 : EPAR - Assessment Report||(English only)||10/04/2013|
|Revatio-H-C-638-X-37 : EPAR - Assessment Report - Extension||(English only)||03/04/2012|
|Revatio-H-C-638-A45-20 : EPAR - Assessment Report||(English only)||02/04/2012|
|Revatio-H-C-638-II-28 : EPAR - Assessment Report - Variation||(English only)||21/06/2011|
|Revatio-H-C-638-X-19 : EPAR - Assessment Report - Extension||(English only)||20/01/2010|
|Revatio-H-C-638-II-21 : EPAR - Assessment Report - Variation||(English only)||17/08/2009|
Initial marketing-authorisation documents
|Name||Language||First published||Last updated|
|Revatio : EPAR - Scientific Discussion||(English only)||11/10/2006|
|Revatio : EPAR - Procedural steps taken before authorisation||(English only)||11/10/2006|
This medicine is approved for use in the European Union