Pharmacological Class:
Soluble guanylate cyclase (sGC) stimulator.
Active Ingredient(s):
Riociguat 0.5mg, 1mg, 1.5mg, 2mg, 2.5mg; tabs.
Company
Bayer Healthcare Pharmaceuticals Inc.
Indication(s):
Treatment of persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), (Who Group 4) after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class. Pulmonary arterial hypertension (PAH), (Who Group 1) to improve exercise capacity, WHO functional class, and to delay clinical worsening.
Pharmacology:
Riociguat has a dual mode of action: it sensitizes sGC to endogenous nitric oxide (NO) by stabilizing the NO-sGC binding. Also, riociguat directly stimulates sGC via a different binding site, independently of NO. Riociguat stimulates the NO-sGC-cGMP pathway and leads to increased cGMP generation with subsequent vasodilation.
Clinical Trials:
CHEST-1, a double-blind, multi-national, multi-center study was conducted in 261 patients with CTEPH. Patients were randomized to Adempas titrated up to 2.5mg three daily (n=173) or placebo (n=88).
The primary endpoint was change from baseline in six minute walking distance (6MWD) after 16 weeks based on imputed values. Improvements in walking distance were apparent from Week 2 onward. At Week 16, the placebo adjusted mean increase in 6MWD within the Adempas group was 46m (95% CI: 25m–67m; P<0.0001). The median difference in 6MWD was 39m (95% CI: 25m–54m). Patients treated with Adempas (83%) experienced an improvement in 6MWD vs. placebo (57%).
An open-label extension study, CHEST-2, included 237 patients who had completed CHEST-1. The mean treatment duration for the total population was 582 days (+/− 317 days). The probabilities of survival at 1 and 2 years were 97% and 94%, respectively.
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
Initially 1mg three times daily; if intolerant, consider starting at 0.5mg three times daily. Increase dose by 0.5mg (three times daily) at intervals of ≥2 weeks as tolerated (SBP >95mmHg and no hypotension); max 2.5mg three times daily. If intolerant at any time, decrease dose by 0.5mg three times daily. Smokers: consider titrating to doses >2.5mg three times daily; may require dose reduction after smoking cessation. Concomitant strong CYP450 and P-gp/BCRP inhibitors: initiate at 0.5mg three times daily.
Children:
Not established.
Contraindication(s):
Pregnancy (Category X). Concomitant nitrates or nitric oxide donors in any form, specific or non-specific phosphodiesterase (PDE) inhibitors (eg, sildenafil, tadalafil, vardenafil, dipyridamole, theophylline).
Warnings/Precautions:
In females of reproductive potential, exclude pregnancy prior to starting, monthly during, and for 1 month after treatment discontinuation; must use acceptable methods of contraception. Risk of hypotension or ischemia in hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction; consider dose reduction if signs/symptoms occur. Bleeding risk. Pulmonary veno-occlusive disease: not recommended; discontinue if confirmed. Severe hepatic (Child Pugh C) or renal impairment (CrCl<15mL/min), or on dialysis: not recommended. Nursing mothers: not recommended.
Interaction(s)
See Contraindications. Potentiated by strong CYP450 and P-gp/BCRP inhibitors (eg, ketoconazole, itraconazole, ritonavir); monitor for hypotension. Antagonized by smoking. May be antagonized by strong CYP3A inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort). Separate dosing of antacids by ≥1 hour of riociguat.
Adverse Reaction(s)
Headache, dizziness, dyspepsia/gastritis, nausea, diarrhea, vomiting, anemia, gastroesophageal reflux, constipation.
Notes:
For all female patients: available only through the Adempas REMS program. To enroll call (855) 4ADEMPAS or www.AdempasREMS.com.
How Supplied:
Tabs—42, 90
LAST UPDATED:
12/13/2013
