Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Adempas

Adempas 0.15 mg/mL granules for oral suspension · Abschnitt 4.5 · PDF-Seite 30–31

HOS-129073 · Präparat HOS-096659

30 PDE5 inhibitors Preclinical studies in animal models showed additive systemic blood pressure lowering effect when riociguat was combined with either sildenafil or vardenafil. With increased doses, over additive effects on systemic blood pressure were observed in some cases. In an exploratory interaction study in 7 patients with PAH on stable sildenafil treatment (20 mg 3 times daily) single doses of riociguat (0.5 mg and 1 mg sequentially) showed additive haemodynamic effects. Doses above 1 mg riociguat were not investigated in this study. A 12 week combination study in 18 patients with PAH on stable sildenafil treatment (20 mg 3 times daily) and riociguat (1.0 mg to 2.5 mg 3 times daily) compared to sildenafil alone was performed. In the long term extension part of this study (non controlled) the concomitant use of sildenafil and riociguat resulted in a high rate of discontinuation, predominately due to hypotension. There was no evidence of a favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors (such as sildenafil, tadalafil, vardenafil) is contraindicated (see sections 4.2 and 4.3). RESPITE was a 24-week, uncontrolled study to investigate switching from PDE5 inhibitors to riociguat, in 61 adult PAH patients on stable PDE5 inhibitors. All patients were WHO Functional Class III and 82% received background therapy with an endothelin receptor antagonist (ERA). For the transition from PDE5 inhibitors to riociguat, median treatment-free time for sildenafil was 1 day and for tadalafil 3 days. Overall, the safety profile observed in the study was comparable with that observed in the pivotal trials, with no serious adverse reactions reported during the transition period. Six patients (10%) experienced at least one clinical worsening event, including 2 deaths unrelated to study drug. Changes from baseline suggested beneficial effects in selected patients, e.g. improvement in 6MWD (+31 m), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels (-347 pg/mL), percent distribution of WHO FC I/II/III/IV (2% / 52% / 46% / 0%), and cardiac index (+0.3 L/min/m2).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tadalafil (HOS-086316) sildenafil (HOS-086162) vardenafil (HOS-086163)