Riociguat
ADEMPAS
What it isSoluble guanylate cyclase stimulator; pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
Why this oneIt is the only approved medical therapy for inoperable CTEPH.
What limits itEmbryo-fetal toxicity under a REMS, and combining it with a PDE5 inhibitor or nitrate causes severe hypotension. Hemoptysis.
FDA-approved for
- pulmonary hypertension (2013)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Pulmonary arterial hypertension (PAH) & chronic thromboembolic pulmonary hypertension (CTEPH) | Adults | 1 mg TID (0.5 mg TID if at risk of hypotension) | up-titrate by 0.5 mg TID as tolerated | 2.5 mg TID |
Titration Increase by 0.5 mg no sooner than every 2 weeks
Renal Not recommended if CrCl <15 mL/min or on dialysis
Hepatic Not recommended in severe (Child-Pugh C) hepatic impairment
Instructions
- May crush and mix with water or soft food (e.g., applesauce) if unable to swallow whole
- If interrupted for 3 days or more, re-titrate
- Smokers may require doses >2.5 mg TID; a dose decrease may be needed on smoking cessation
- Start 0.5 mg TID with strong CYP and P-gp/BCRP inhibitors (e.g., azole antifungals, HIV protease inhibitors)
- Separate from PDE5 inhibitors: stop sildenafil >=24 h and tadalafil >=48 h before starting; stop Adempas >=24 h before a PDE5 inhibitor
Contraindications
- Pregnancy
- Concomitant nitrates or nitric oxide donors (e.g., amyl nitrite) in any form
- Concomitant PDE inhibitors (specific PDE-5 such as sildenafil, tadalafil, vardenafil; nonspecific such as dipyridamole, theophylline)
- Concomitant other soluble guanylate cyclase (sGC) stimulators
- Pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP)
Cautions
- Symptomatic hypotension (reduces blood pressure)
- Bleeding, including serious hemoptysis
- Pulmonary veno-occlusive disease - discontinue if pulmonary edema occurs
Adverse reactions
- Headache
- Dyspepsia/gastritis
- Dizziness
- Nausea
- Diarrhea
- Hypotension
- Vomiting
- Anemia
- GERD
- Constipation
Pregnancy Contraindicated; may cause fetal harm based on animal data.
Lactation Advise not to breastfeed during treatment.
⚠ BOXED WARNING
- Embryo-fetal toxicity
Cost, est. cash$300–$2,500/month
Generic entry2022
Classes and tags
Clinical profile
Legacy pregnancy categoryX
Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.
Mechanism of action: Riociguat ballicule
