What Adempas Treats: Main Uses and Benefits

Adempas (Riociguat) is commonly used for adults to help manage specific, severe conditions characterized by significantly elevated blood pressure in the arteries of the lungs. This therapy is relevant for conditions such as Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH). For CTEPH, this therapy is applied when the condition is deemed inoperable or when high pressure persists or returns after surgical clot removal. Its use may be extended to select children aged six years and older with PAH.

The medication assists with managing key symptom clusters that interfere with daily functioning, such as profound fatigue, pronounced dyspnea (shortness of breath) upon physical activity, and episodes of syncope (fainting). It is considered relevant for patients experiencing limitations in physical activity, typically aligning with WHO Functional Class II and III symptoms. The therapy is relevant for easing symptoms that create noticeable physiological strain, which may support improved functional stability.

“This focused use may assist with maintaining day-to-day comfort and physical tolerance during periods of heightened systemic burden.”

Adempas provides supportive relief that is applied in addressing the overall physiological burden of the disease. The therapy is relevant in managing conditions where the overall goal is to support management of conditions where the therapeutic aim is to maintain clinical stability, which is a key long-term benefit for patient stability.

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Quick Fact: Relief for Exertional Limitations

Adempas is applied in clinical settings that involve acute or unstable symptom patterns, helping to ease the impact of symptoms that become more disruptive during exercise. It supports the patient by assisting with the management of shortness of breath and fatigue, which are symptoms related to the elevated pressure in the pulmonary arteries.

Regulatory References

1. European Medicines Agency

Adempas (Riociguat) is strictly a prescription-only medicine with eligibility criteria defined by regulatory bodies. It is approved for adults with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) or Pulmonary Arterial Hypertension (PAH), and for pediatric patients aged six years and older with PAH.

Absolute Prohibitions (Contraindications)

Adempas must not be used in patients who are pregnant due to the risk of fetal harm. It is also contraindicated in patients with Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (PH-IIP) and those with severe hepatic impairment (Child-Pugh C).

Use is also prohibited with certain co-medications, specifically nitrates or nitric oxide donors (in any form) and specific PDE-5 inhibitors (such as sildenafil or tadalafil).

Conditional Use and Restrictions

Population/Condition	Official Eligibility Status
Females of Reproductive Potential	Restricted use: Requires enrollment in a REMS program, with mandatory monthly pregnancy testing and effective contraception.
Severe Renal Impairment	Not recommended ( CrCl < 15 mL/min or on dialysis) due to limited safety data.
Elderly Patients (ge 65 years)	Requires particular care during dose titration due to a higher risk of hypotension.
Smokers	Requires conditional use as plasma concentrations are reduced, potentially necessitating dose adjustments if smoking habits change.

Adempas (riociguat) can interact with several other medicines and substances, which may alter its effectiveness or increase the risk of side effects, particularly dangerously low blood pressure (hypotension). It is essential to discuss all medications, supplements, and lifestyle habits with your healthcare provider.

Contraindicated Combinations

These combinations should be strictly avoided due to the significant risk of severe hypotension:

• Nitrates and Nitric Oxide Donors: Medicines containing nitrates (e.g., nitroglycerin) or nitric oxide donors (e.g., amyl nitrite) in any form.
• Phosphodiesterase-5 (PDE-5) Inhibitors: Medications like sildenafil, tadalafil, or vardenafil, which are used for pulmonary hypertension or erectile dysfunction.
• Non-specific PDE Inhibitors: Medicines such as dipyridamole or theophylline.

Other Significant Interactions

Product Category	Example Medications	Effect on Adempas / Risk	Note
Strong CYP and P-gp/BCRP Inhibitors	Ketoconazole, Itraconazole, Ritonavir	Increases Adempas levels	May require a lower starting dose of Adempas (0.5 mg three times daily) and close monitoring for hypotension.
Strong CYP3A Inducers	Rifampin, Phenytoin, St. John's Wort	Decreases Adempas levels	May make Adempas less effective. Dose adjustment may be necessary.
Antacids	Aluminum hydroxide/magnesium hydroxide	Decreases Adempas absorption	Do not take within one hour before or one hour after taking Adempas.
Smoking	Tobacco products	Decreases Adempas levels	Smoking reduces Adempas effectiveness; higher doses may be considered. Dose reduction may be needed if you stop smoking.

Targeted Stimulation of Soluble Guanylate Cyclase

The active ingredient, Riociguat, functions as a direct stimulator of the Soluble Guanylate Cyclase ( sGC) enzyme, which participates in the regulation of vascular tone. It operates through a dual mechanism: directly binding to sGC to initiate its activity and simultaneously sensitizing the enzyme to endogenous Nitric Oxide ( NO). This potentiation enhances sGC activity even when NO concentrations are reduced.

The activation of sGC increases the production of the secondary messenger cyclic Guanosine Monophosphate ( cGMP) within the pulmonary artery smooth muscle cells. Elevated cGMP concentration triggers a molecular cascade that reduces intracellular calcium levels, resulting in the relaxation of the muscle fibers (vasodilation) and a decrease in Pulmonary Vascular Resistance (PVR).

Beyond immediate relaxation, enhanced cGMP signaling also modulates chronic physiological processes by exerting anti-proliferative and anti-fibrotic effects. This influences the long-term structural integrity of the pulmonary vessels, which physiologically affects the afterload imposed on the right ventricle.

Administration Scope

Route of administration: The medicine is administered via the oral route as film-coated tablets, which are available in multiple strengths, from 0.5 mg up to 2.5 mg. The tablets may be crushed and mixed with water or soft food for immediate consumption by patients who are unable to swallow them whole.

Dosing schedule (Adults): Treatment is initiated at a low starting dose of 1 mg taken three times a day (TID). An alternative starting dose of 0.5 mg TID is specified for patients who may be at risk of not tolerating the dose's effects. The maximum established daily dose is 7.5 mg, which corresponds to 2.5 mg TID.

Frequency and Schedule: Doses must be taken consistently three times a day, spaced approximately 6 to 8 hours apart. The tablets can be taken with or without food.

Procedural Structure: The use involves a mandatory titration phase during which the dose may be increased by 0.5 mg TID at intervals of no less than two weeks. Dose increases are dependent on patient tolerance and specific blood pressure constraints (systolic pressure ge 95 mmHg). If symptoms of hypotension occur at any time, the current dosage must be decreased by 0.5 mg TID. If treatment is interrupted for three days or more, the entire titration sequence must be re-started at the initial 1 mg TID dose.

Special Conditions for Use: Patients who stop smoking require a subsequent dose adjustment. Additionally, specific washout periods (at least 24 or 48 hours) must be observed when transitioning from certain other therapies. If a dose is missed, patients should simply take the next regularly scheduled dose.

Research Evidence / Overview of Studies for Adempas

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Evidence for Use in Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

The clinical evaluation for Riociguat (Adempas) in CTEPH has involved short-term, placebo-controlled clinical trials. These studies included patients whose CTEPH was deemed inoperable or those who still experienced elevated pressure after undergoing pulmonary endarterectomy surgery. Researchers utilized these studies to monitor physiological strain or stress and examine changes in daily functioning or activity level.

Research reports measurements related to the Six-Minute Walk Distance (6MWD), which assesses exercise capacity. Trials also examined pulmonary hemodynamics, which are the pressures within the lung's blood vessels. Data show patterns related to the measured change in these pressures in the observed populations during the study period. While the initial trial provides insight into short-term changes, long-term effects are not fully established compared to a concurrent control group, as sustained observation was primarily conducted in uncontrolled open-label extension studies.

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Evidence for Use in Pulmonary Arterial Hypertension (PAH)

The clinical evaluation for Riociguat in PAH, including idiopathic, heritable, and connective tissue disease-associated forms, has involved initial short-term, placebo-controlled clinical trials. These studies focused on adults with functional limitations related to their condition, examining outcomes reflecting daily functioning and activity level.

In these trials, typically lasting around three months, research examined changes in exercise capacity using the 6MWD. Researchers also examined a composite endpoint called time to clinical worsening, which tracks major events like disease progression. The evidence highlights that while short-term data is available, the pivotal trials were not designed to assess major clinical endpoints such as long-term survival as a standalone primary outcome. Comparative evidence is limited for head-to-head comparisons with some other available advanced PAH therapies.

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Long-Term Research and Evidence Gaps

Beyond the initial controlled trials, Riociguat was observed in long-term open-label extension studies for both PAH and CTEPH, which contribute to the broader evidence landscape by examining how outcomes may change over time. However, long-term effects are not fully established in a blinded, controlled setting, and the evidence quality varies across studies.

Limited research has been studied for its use in specific patient groups, such as children aged six years and older with PAH. For other populations, the data for certain groups remain insufficient. The follow-up durations were limited in the initial controlled trials, meaning long-term outcomes are not well characterized under randomized conditions. Research provides context but not individual predictions; findings describe group patterns, not personal outcomes.

Key Studies & References

1. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a study of 12- and 16-week changes in 6-minute walking distance—the CHEST-1 trial
2. Riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension
3. Riociguat: a new era in the management of pulmonary hypertension

Common questions about Adempas (FAQ)

Q: What is Adempas?

A: Adempas is a prescription medicine with the active substance riociguat. It belongs to a class of medicines called soluble guanylate cyclase (sGC) stimulators.

Q: What is Adempas used to treat?

• Adempas is used to treat adults with two forms of high blood pressure in the lungs, known as pulmonary hypertension:
  • Chronic Thromboembolic Pulmonary Hypertension (CTEPH), for patients who cannot have surgery, or for those whose high blood pressure remains or returns after surgery. The goal is to improve the ability to exercise.
  • Pulmonary Arterial Hypertension (PAH), to improve exercise capacity and other signs of heart function.

Q: How does Adempas work?

• Adempas works by stimulating an enzyme in the blood vessels of the lungs called soluble guanylate cyclase (sGC).
• This stimulation causes the blood vessels in the lungs to relax and widen.
• This action lowers the blood pressure in the lungs, making it easier for the heart to pump blood through the lungs, which helps improve symptoms.

Q: What are the most common side effects of Adempas?

• The most common side effects of Adempas (affecting more than 1 in 10 people in studies) include:

  • Headache
  • Dizziness
  • Dyspepsia (indigestion/heartburn)
  • Nausea
  • Diarrhoea
  • Vomiting
  • Peripheral oedema (swelling, especially of the ankles and feet)

• More serious side effects can include coughing up blood (haemoptysis) and bleeding in the lungs (pulmonary haemorrhage).

Q: Who should not take Adempas?

• You should not take Adempas if you:
  • Are pregnant or planning to become pregnant, as it can cause serious birth defects.
  • Have pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP), a type of scarring of the lungs.
  • Are taking certain other medicines, including:
  • Other soluble guanylate cyclase stimulators.
  • Nitrate medicines to treat high blood pressure or heart disease (e.g., nitroglycerin) or nitric oxide donors.
  • Certain medicines called phosphodiesterase type 5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, or vardenafil).

Q: What is the Adempas REMS program?

• Due to the risk of serious birth defects, Adempas is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program.
• Females who are able to get pregnant must:
  • Enroll in the REMS program.
  • Have a negative pregnancy test before starting treatment, monthly during treatment, and one month after stopping treatment.
  • Use effective contraception during treatment and for one month after stopping.

Q: Can I take antacids while on Adempas?

• If you take an antacid that contains aluminum hydroxide or magnesium hydroxide, you should not take it within 1 hour of taking Adempas, as it can reduce how well Adempas is absorbed by the body.

How to Store and Dispose of Adempas (Riociguat)

Storage Requirement	Official Condition (Regulatory Basis)
Temperature Range	Store at room temperature, between 59 F and 86 F (15 C to 30 C) [Source: FDA/Health Canada].
Environmental Protection	Keep the tablets away from excess heat and moisture and direct light [Source: NIH MedlinePlus].
Prohibited Environment	The medication must be kept from freezing [Source: NIH MedlinePlus].
Container & Packaging	Store the medicine in the container it came in and keep it tightly closed [Source: NIH MedlinePlus].

Handling and Disposal Instructions

Adempas must be stored out of the reach of children [Source: FDA Label]. When medication is outdated or no longer required, it must not be thrown away via wastewater or household waste [Source: SmPC (EU)]. Disposal must be performed in accordance with local requirements by consulting a pharmacist or healthcare professional for guidance [Source: SmPC (UK)].