Adempas

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Adempas have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Adempas are continuously monitored. Side effects reported with Adempas are carefully evaluated and any necessary action taken to protect patients.

Adempas received a marketing authorisation valid throughout the European Union on 27 March 2014.

Adempas can only be obtained with a prescription and treatment should be started and monitored by a doctor who has experience in the treatment of CTEPH or PAH. Adempas is available as tablets. For patients unable to swallow whole tablets, the tablets may be crushed and mixed with water or soft food such as apple sauce.

The usual recommended starting dose is 1 mg three times a day (approximately 6 to 8 hours apart) for two weeks. The dose is then increased every two weeks based on the patients’ systolic blood pressure (blood pressure when the heart is contracting) until the appropriate dose for the individual patient is established. Treatment with the established dose should continue unless patients experience signs and symptoms of low blood pressure, in which case the dose should be reduced.

For more information about using Adempas, see the package leaflet or contact your healthcare provider.

CTEPH and PAH are debilitating diseases where there is severe narrowing of the blood vessels of the lungs. This causes high blood pressure in the vessels taking blood from the heart to the lungs and reduces the blood flow to the lungs. As a result, the amount of oxygen that can get into the blood in the lungs is reduced, making physical activity more difficult.

The active substance in Adempas, riociguat, stimulates an enzyme called ‘soluble guanylate cyclase’ in the blood vessels of the lungs, causing the blood vessels to relax and widen. This helps to lower the blood pressure in the lungs and improve symptoms of CTEPH and PAH.

Adempas has been shown to be effective at improving exercise capacity, measured as the distance patients with CTEPH or PAH could walk in 6 minutes:

• Adempas was compared with placebo (a dummy treatment) in one main study in 262 adult patients with CTEPH who could not have surgery, or in whom CTEPH remained or returned after surgery. Before treatment, the patients could walk an average of 347 metres in 6 minutes. After 16 weeks of treatment with Adempas, patients could walk an average of 46 metres further in 6 minutes than patients taking placebo.

• The medicine was also compared with placebo in another main study in 445 adult patients with PAH. Before treatment, the patients could walk an average of 363 metres in 6 minutes. After 12 weeks, patients treated with Adempas could walk an average of 36 metres further in 6 minutes than patients taking placebo.

• A main study also showed that Adempas can improve walking distance and other signs of heart function in children. Based on evidence from this study, the medicine is expected to work as well in children as it does in adults.

For the full list of side effects and restrictions with Adempas, see the package leaflet.

The most common side effects with Adempas (which may affect more than 1 in 10 people) include headache, dizziness, dyspepsia (heartburn), peripheral oedema (swelling, especially of the ankles and feet), nausea (feeling sick), diarrhoea and vomiting. Serious side effects include haemoptysis (coughing up blood) and pulmonary haemorrhage (bleeding in the lungs).

Adempas must not be used in patients with severely reduced liver function, with low systolic blood pressure (blood pressure when the heart is contracting) or with pulmonary hypertension associated with idiopathic interstitial pneumonia (scarring of the lungs with unknown cause). It must also not be used during pregnancy, or together with certain other medicines used to treat heart conditions.

The European Medicines Agency considered that Adempas led to significant improvements in exercise capacity in patients with CTEPH or PAH. It also noted that no other medicines have been authorised for CTEPH. Regarding safety it considered that side effects of concern, including haemoptysis and pulmonary haemorrhage, have been adequately reflected in the product information and risk management plan. The Agency therefore decided that Adempas’s benefits are greater than its risks and that it can be authorised for use in the EU.