The Challenge of Pulmonary Hypertension
Pulmonary hypertension (PH) is a serious and progressive condition characterized by high blood pressure in the arteries of the lungs [1.3.3]. This increased pressure forces the right side of the heart to work harder to pump blood through the lungs, which can lead to right heart failure and is associated with a substantially increased mortality risk [1.11.2, 1.11.3]. PH is broadly categorized into five groups based on its cause. Adempas (riociguat) is a targeted oral therapy approved by the FDA to treat two of these specific types [1.2.2, 1.3.5].
What are CTEPH and PAH?
Adempas is specifically used for adults with:
- Chronic Thromboembolic Pulmonary Hypertension (CTEPH, WHO Group 4): This form of PH is caused by old blood clots in the lungs that have turned into scar-like tissue, blocking or narrowing the pulmonary arteries [1.2.3]. Adempas is prescribed for patients whose CTEPH is inoperable, or for those who have persistent or recurrent PH after undergoing surgical removal of the clots (pulmonary thromboendarterectomy) [1.2.1, 1.2.3].
- Pulmonary Arterial Hypertension (PAH, WHO Group 1): In PAH, the small arteries in the lungs become narrowed, thickened, or stiff, leading to increased resistance to blood flow. Adempas is used to improve exercise ability, improve WHO functional class, and delay clinical worsening [1.7.1]. It can be used as a standalone therapy or in combination with other PAH treatments like endothelin receptor antagonists (ERAs) or prostanoids [1.8.1].
The Unique Mechanism of Action: What Does Adempas Do?
To understand what Adempas does, it's essential to look at its unique pharmacological action. Adempas is the first-in-class soluble guanylate cyclase (sGC) stimulator [1.8.4].
In a healthy person, a chemical called nitric oxide (NO) is produced by cells lining the blood vessels. NO binds to and activates the sGC enzyme, which then produces another molecule called cyclic guanosine monophosphate (cGMP) [1.3.3]. cGMP acts as a signaling molecule that tells the smooth muscle of the artery walls to relax, causing vasodilation (widening of the blood vessels) [1.3.3, 1.3.4]. In patients with PAH and CTEPH, the NO-sGC-cGMP pathway is impaired due to insufficient NO production [1.3.3].
Adempas has a dual mode of action to restore this pathway [1.3.5]:
- Direct Stimulation of sGC: It directly stimulates the sGC enzyme, independent of nitric oxide. This means it can still work even when NO levels are very low [1.3.3].
- Sensitization to Nitric Oxide: It also makes the sGC enzyme more sensitive to the body's own naturally occurring NO. This allows even small amounts of NO to have a greater effect [1.3.2, 1.3.5].
By restoring the function of this pathway, Adempas leads to increased cGMP, vasodilation in the pulmonary arteries, reduced pressure in the lungs, and an increased supply of blood, which ultimately reduces the strain on the heart [1.2.1, 1.2.2]. Clinical studies have shown that this leads to significant improvements in exercise capacity, measured by how far a person can walk in 6 minutes [1.2.4, 1.2.5].
Important Safety Information and Side Effects
Black Box Warning
Adempas carries a boxed warning for embryo-fetal toxicity. It must not be used in females who are pregnant because it can cause serious birth defects [1.4.1, 1.6.2]. Because of this risk, all female patients, regardless of reproductive potential, must enroll in a special restricted distribution program called the Adempas REMS (Risk Evaluation and Mitigation Strategy) Program. This program requires regular pregnancy testing before, during, and for one month after treatment [1.7.1, 1.7.3].
Common and Serious Side Effects
The most common side effects reported in clinical trials (affecting 10% or more of patients) include headache, indigestion (dyspepsia), dizziness, nausea, diarrhea, and low blood pressure (hypotension) [1.5.1, 1.5.5].
More serious side effects can include:
- Bleeding: There is an increased risk of bleeding, including serious events like coughing up blood (hemoptysis) [1.5.2, 1.6.5].
- Severe Hypotension: The vasodilating effect can lead to a significant drop in blood pressure, causing dizziness or fainting [1.5.2].
- Pulmonary Edema in PVOD patients: Patients with a rare condition called Pulmonary Veno-Occlusive Disease (PVOD) may experience a dangerous buildup of fluid in the lungs [1.5.2].
Adempas vs. Other PH Treatments
Adempas works differently from other common oral PH medications like PDE-5 inhibitors.
| Feature | Adempas (Riociguat) | PDE-5 Inhibitors (e.g., Sildenafil, Tadalafil) |
|---|---|---|
| Drug Class | Soluble Guanylate Cyclase (sGC) Stimulator [1.3.5] | Phosphodiesterase 5 (PDE-5) Inhibitor [1.4.1] |
| Mechanism | Directly stimulates sGC and increases its sensitivity to nitric oxide to produce cGMP [1.3.2, 1.3.3]. | Prevents the breakdown of cGMP, thereby increasing its availability. Relies on existing nitric oxide to initiate the process [1.4.1]. |
| Use Together? | Contraindicated. Taking them together can cause a dangerous drop in blood pressure [1.4.1, 1.6.2]. | Contraindicated. Must have a washout period of at least 24-48 hours before switching between these drug classes [1.4.1]. |
| Key Indications | CTEPH (inoperable or persistent/recurrent) and PAH [1.2.1]. | Primarily PAH. Not approved for CTEPH [1.4.1, 1.10.1]. |
Conclusion
So, what does Adempas do? It provides a unique therapeutic option for patients with specific, severe forms of pulmonary hypertension. By directly stimulating the sGC enzyme to relax and widen the blood vessels of the lungs, it improves blood flow, enhances exercise capacity, and eases the significant burden placed on the heart [1.2.2, 1.2.4]. Its distinct mechanism of action sets it apart from other treatments like PDE-5 inhibitors and makes it the only medication approved for patients with inoperable or persistent CTEPH [1.8.4]. However, due to significant risks, such as embryo-fetal toxicity and dangerous drug interactions, its use requires careful medical supervision and adherence to safety programs like the Adempas REMS [1.7.1].
For more information from the manufacturer, visit: https://www.adempas-us.com/ [1.7.2]
