For doctors

What is it?

Revatio is a medicine that contains the active substance sildenafil. It is available as round, white tablets (20 mg) and as a solution for injection (0.8 mg/ml).

What is it used for?

Revatio tablets are used to treat adults with pulmonary arterial hypertension (PAH) to improve exercise capacity (the ability to carry out physical activity). PAH is abnormally high blood pressure in the arteries of the lungs. Revatio is used in patients with class II or III disease. The ‘class’ reflects the seriousness of the disease: ‘class II’ involves slight limitation of physical activity and ‘class III’ involves marked limitation of physical activity. Revatio has been shown to be effective in PAH with no identified cause and in PAH caused by connective tissue disease.

Revatio solution for injection is for patients who cannot take their Revatio tablets 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 it used?

Revatio treatment should only be started and monitored by a doctor who has experience in the treatment of PAH.

Revatio is taken as one tablet three times a day, about six to eight hours apart. The solution for injection 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.

How does it work?

PAH is a debilitating disease where there is severe constriction (narrowing) of the blood vessels of the lungs. It causes high blood pressure in the vessels taking blood from the heart to the lungs. This pressure 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 it been studied?

Three doses of Revatio tablets (20, 40 and 80 mg three times a day) have been compared with placebo (a dummy treatment) in one main study involving 277 patients 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.

The company also presented the results of studies to show that the 10 mg injections produce similar levels of sildenafil in the blood as the 20 mg tablets.

What benefits has it shown during the studies?

Revatio was more effective than placebo at improving exercise capacity. Before treatment, the patients 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. The patients 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 patients.

What is the risk associated?

The most common side effects with Revatio tablets (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. For the full list of all side effects reported with Revatio, see the package leaflet.

Revatio should not be used in people who may be 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), 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 it 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.

How has it been studied?

The company that makes Revatio will agree on how the solution for injection will be distributed in each European Union Member State. 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.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Revatio to Pfizer Limited on 28 October 2005. The marketing authorisation is valid for an unlimited period.

For more information about treatment with Revatio, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

The summary of opinion of the Committee for Orphan Medicinal Products for Revatio is available here.

This summary was last updated in 08-2010.

Name

Revatio 20mg film-coated tablets

Composition

Each film-coated tablet contains 20mg of sildenafil (as citrate). Revatio tablets also contain lactose. For a full list of excipients, see section 6.1.

Pharmaceutical Form

Film-coated tablet.

White, round, biconvex film-coated tablets marked “PFIZER” on one side and “RVT 20”on the other.