Adempas

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. In patients taking certain medicines, including some medicines for HIV infection, tuberculosis or fungal infections, the doctor may recommend a lower starting dose. The dose is then increased every two weeks until the appropriate dose for the individual patient is established. The maximum dose should not exceed 2.5 mg three times a day. 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 doctor or pharmacist.

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 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 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.

The most common side effects with Adempas (which may affect more than 1 in 10 people) are 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). For the full list of side effects with Adempas, see the package leaflet.

Adempas must not be used in patients with severely reduced liver function, with systolic blood pressure (blood pressure when the heart is contracting) below 95 mmHg before starting treatment 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 medicines called ‘PDE 5 inhibitors’ (a class of medicines used for PAH or erectile dysfunction), with nitrates or nitric oxide donors (often used to treat high blood pressure, chest pain and heart disease, or as recreational drugs) or with other soluble guanylate cyclase stimulators. For the full list of restrictions, see the package leaflet.

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.

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.