Adempas Riociguat Tablets

1. Indications and Usage
Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Treatment of adult patients with inoperable chronic thromboembolic pulmonary hypertension (WHO Group 4) or persistent/recurrent CTEPH after surgery, to improve exercise capacity and WHO functional class.
Pulmonary Arterial Hypertension (PAH): Treatment of adult patients with pulmonary arterial hypertension (WHO Group 1) to improve exercise capacity and delay clinical worsening.
2. Dosage and Administration
Administration: Oral administration, three times daily (every 6–8 hours). Can be taken with or without food.
Starting Dose: 1 mg three times daily. If not tolerated (e.g., hypotension), start at 0.5 mg three times daily.
Titration: Increase dose by 0.5 mg increments no more frequently than every 2 weeks, based on tolerability (maintaining systolic BP ≥95 mmHg and absence of hypotension symptoms).
Target/Max Dose: The maximum recommended dose is 2.5 mg three times daily.
Missed Dose: If a dose is missed, do not take it; resume with the next scheduled dose. If treatment has been interrupted for ≥3 days, restart titration from 1 mg three times daily.
3. Mechanism of Action
sGC Stimulator: Riociguat is a soluble guanylate cyclase (sGC) stimulator.
Dual Mechanism: It has a dual mode of action: it sensitizes sGC to endogenous nitric oxide (NO), and it directly stimulates sGC independent of NO. This leads to increased cGMP production, resulting in pulmonary and systemic vasodilation and inhibition of vascular smooth muscle cell proliferation.
4. Safety and Warnings
Embryo-Fetal Toxicity: Contraindicated in pregnancy. May cause fetal harm. Pregnancy tests are required before starting, monthly during treatment, and for 1 month after discontinuation. Effective contraception is mandatory.
Hypotension: Symptomatic hypotension may occur. Not recommended for use in patients with resting hypotension or severe left ventricular outflow obstruction.
Bleeding Risk: May increase the risk of bleeding, including severe pulmonary hemorrhage.
Pulmonary Venous Occlusive Disease (PVOD): Do not use if PVOD is suspected or diagnosed, as it may cause severe pulmonary edema.
5. Adverse Reactions
Most Common: Headache, dyspepsia, dizziness, nausea, diarrhea, vomiting, hypotension, peripheral edema, and anemia.
6. Drug Interactions
Contraindicated Combinations:
Nitrates/NO Donors: (e.g., nitroglycerin, amyl nitrite) due to additive hypotensive effects.
PDE-5 Inhibitors: (e.g., sildenafil, tadalafil, vardenafil) due to potential severe hypotension. A washout period is required when switching between these drugs.
CYP/P-gp Inhibitors: Strong inhibitors (e.g., ketoconazole, ritonavir) may increase riociguat exposure; start at 0.5 mg three times daily.
Smoking: Smoking decreases plasma concentrations of riociguat. Dose adjustment may be needed when smoking status changes.
7. Pharmaceutical Information
Chemical Name: (3-[1-(2-butoxyethoxy)benzyl]-7-fluoro-5-methyl-1H-pyrrolo[2,3-b]pyridin-6-yl)-(2,4-difluorophenyl)methanone.
Storage: Store below 30°C. Keep container tightly closed to protect from moisture.