Riociguat

BRAND NAMES

Riociguat is marketed under the brand name Adempas. It is available in tablet form for oral administration. The brand is recognized worldwide for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Availability may vary depending on the country or region. It is typically prescribed for adult patients diagnosed with these conditions.

MECHANISM OF ACTION

Riociguat works as a soluble guanylate cyclase (sGC) stimulator. It directly stimulates sGC and enhances the effects of endogenous nitric oxide (NO). This leads to increased cyclic guanosine monophosphate (cGMP) production. Higher cGMP levels promote vasodilation, particularly in the pulmonary arteries. The result is a reduction in pulmonary vascular resistance and lower pulmonary blood pressure.

PHARMACOKINETICS:

Absorption

Riociguat is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1.5 to 2 hours. Its bioavailability is approximately 94%, and absorption is not significantly affected by food.

Distribution

The drug is moderately bound to plasma proteins (about 95%) and distributes into tissues, including the lungs. Its volume of distribution is around 30 L, indicating moderate tissue penetration.

Metabolism

Riociguat is metabolized primarily in the liver by the enzyme CYP1A1, with minor contributions from CYP3A4, CYP2C8, and CYP2J2. Metabolism produces several inactive metabolites.

Excretion

Riociguat is excreted via both urine and feces. Approximately 27–71% of the dose is eliminated as metabolites in urine, and 13–45% in feces. The half-life is around 12 hours in healthy adults.

PHARMACODYNAMICS

Riociguat lowers pulmonary arterial pressure by stimulating sGC and increasing cGMP. It relaxes pulmonary vascular smooth muscle and reduces pulmonary vascular resistance. The drug also improves cardiac output and exercise capacity in patients with PAH and CTEPH. Effects are dose-dependent, and hemodynamic improvements are generally observed within weeks. Riociguat also enhances oxygen delivery by improving pulmonary circulation.

ADMINISTRATION

Riociguat is taken orally in tablet form. It should be administered exactly as prescribed, usually three times daily with or without food. Tablets should be swallowed whole with water and not crushed or chewed. Doses are often adjusted gradually based on blood pressure response. Regular monitoring of blood pressure and clinical symptoms is recommended during treatment.

DOSAGE AND STRENGTH

The usual starting dose for adults is 1 mg three times daily, with gradual titration up to a maximum of 2.5 mg three times daily based on tolerance and blood pressure. Dose adjustments may be needed for renal or hepatic impairment. Tablets are available in strengths of 0.5 mg, 1 mg, and 2 mg. Careful titration minimizes the risk of hypotension. The dose must not be exceeded without medical supervision.

DRUG INTERACTIONS

Riociguat interacts with antihypertensives, PDE5 inhibitors, and CYP1A1/3A4 modulators. Concomitant use with PDE5 inhibitors is contraindicated due to the risk of severe hypotension. Strong CYP inhibitors or inducers can alter riociguat plasma levels. Close monitoring is required when co-administered with anticoagulants or nitrates. Patients should always inform their healthcare provider about all medications they are taking.

FOOD INTERACTIONS

Riociguat can be taken with or without food, as absorption is not significantly affected. Smoking may reduce its plasma concentration due to CYP1A1 induction. Grapefruit and other CYP3A4 modulators may influence drug levels slightly. Alcohol may enhance hypotensive effects. Patients should maintain consistent dietary habits to avoid fluctuations in drug exposure.

CONTRAINDICATIONS

Riociguat is contraindicated in pregnancy due to the risk of fetal harm. It should not be used with PDE5 inhibitors. Severe hypotension, a history of pulmonary veno-occlusive disease, or known hypersensitivity to the drug are also contraindications. Caution is advised in patients with severe hepatic or renal impairment. Breastfeeding women should avoid the drug unless specifically directed by a physician.

SIDE EFFECTS

• Common side effects: Headache, dizziness, low blood pressure (hypotension), nausea, and vomiting.

• Other possible reactions: Dyspepsia (indigestion), diarrhea, and flushing.

• Rare but serious effects: Bleeding, pulmonary edema, and fainting (syncope).

• Reporting: Patients should inform their healthcare provider if side effects are persistent or severe.

• Dose relation: Most side effects are dose-dependent and may improve with gradual dose adjustment.

OVER DOSE

Symptoms of riociguat overdose may include severe hypotension, dizziness, fainting, and tachycardia. Supportive care is essential, including monitoring vital signs and administering intravenous fluids if necessary. Hospitalization may be required for severe cases. There is no specific antidote for riociguat overdose. Immediate medical care is essential to avoid potentially life-threatening complications.                                 

TOXICITY

Riociguat is generally well-tolerated at therapeutic doses. Toxic effects are mainly associated with excessive vasodilation and hypotension. Animal studies have shown reproductive toxicity, which aligns with its contraindication in pregnancy. Long-term toxicity in humans is rare but may include bleeding or syncope. Regular monitoring of blood pressure and organ function helps minimize the risk of toxicity.