August 16, 2016 – Riociguat (Adempas) is a stimulator of soluble guanylate cyclase (sGC). In Canada, it is approved for and indicated in the treatment of pulmonary hypertension (PH) in three forms: inoperable chronic thromboembolic pulmonary hypertension, persistent or recurrent chronic thromboembolic pulmonary hypertension after surgical treatment, and in pulmonary arterial hypertension, as monotherapy or in combination with endothelin receptor antagonists. Generally, pulmonary hypertension (PH) as such is an increase of blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, leg swelling and other symptoms. Pulmonary hypertension can be a severe disease with a markedly decreased exercise tolerance.
A recent clinical study (RISE-IIP) explored the possibility of usage of Riociguat (Adempas) in the treatment of patients with Pulmonary Hypertension Associated with Idiopathic Interstitial Pneumonias (PH-IIP). This study has been terminated early, because interim results of RISE-IIP showed an increased risk of mortality and serious adverse events among patients receiving Riociguat (Adempas) compared to those receiving placebo. The available data indicate that the use of Riociguat (Adempas) in patients with PH-IIP presents greater risks than benefits. As a result, Health Canada has issued, as of August 15, 2016, the following alert to healthcare professionals and hospital clinics who prescribe Riociguat (Adempas) and manage patients with pulmonary hypertension, and to the general public:
- Patients with PH-IIP should not be treated with Riociguat (Adempas). If any patients with PH-IIP are being treated with Riociguat (Adempas), their treatment should be discontinued and their clinical status carefully monitored.
- The RISE-IIP study, which was investigating the effects of Riociguat (Adempas) in patients with pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP), has been terminated early due to an increased risk of mortality and serious adverse events among subjects with PH-IIP receiving Riociguat (Adempas).
- The Canadian Product Monograph will be updated to reflect the contraindication for Riociguat (Adempas) in PH-IIP.
Thus, healthcare professionals should not prescribe Riociguat (Adempas) for patients with PH-IIP. If any patients with PH-IIP are being treated with Riociguat (Adempas) their treatment should be discontinued and their clinical status carefully monitored. The benefit-risk profile of Riociguat (Adempas) in its approved indications remains favourable. Note that a similar alert has recently been issued by the European Medicines Agency (EMA) in June 2016. From the nature of this serious adverse drug effect of Riociguat (Adempas) as detected in this particular clinical study, it is fair to assume that patients worldwide would suffer from this effect when treated with Riociguat (Adempas) for PH-IIP. Therefore, a high degree of caution is implicated.