Adempas (riociguat) | Condition Facts

SETTING AND TRACKING YOUR PAH PATIENT GOALS

The 2015 ESC/ERS Guidelines recommend follow-up assessments every 3 to 6 months for stable patients with PAH.²Since PAH can progress rapidly, it is critical to monitor your patients often.³

ERS=European Respiratory Society; ESC=European Society of Cardiology; PAH=pulmonary arterial hypertension; WHO=World Health Organization

ASSESS AND MONITOR PATIENT RISK STATUS^2*

Select a risk level:

Low Risk

Intermediate Risk

High Risk

The guidelines above can assist with:

Creating goals and monitoring progress to help guide the course of treatment
Setting goals for your PAH patients that include exercise capacity (6MWD), WHO functional class, and hemodynamics

6MWD=6-minute walk distance;

BNP=brain natriuretic peptide;

CI=cardiac index;

CMR=cardiac magnetic resonance;

NT-proBNP=N-terminal pro-brain natriuretic peptide;

pred.=predicted;

RA=right atrium;

RAP=right atrial pressure;

SvO₂=mixed venous oxygen saturation;

VE/VCO₂=ventilatory equivalents for carbon dioxide;

VO₂=oxygen consumption

*Adempas does not impact all of these measurements.

^†Most of the proposed variables and cut-off values are based on expert opinion. They may provide prognostic information and may be used to guide therapeutic decisions, but application to individual patients must be done carefully. One must also note that most of these variables have been validated mostly for idiopathic PAH and the cut-off levels used above may not necessarily apply to other forms of PAH. Furthermore, the use of approved therapies and their influence on the variables should be considered in the evaluation of the risk.

^‡Occasional syncope during brisk or heavy exercise, or occasional orthostatic syncope in an otherwise stable patient.

^§Repeated episodes of syncope, even with little or regular physical activity.

DOWNLOAD THE ADAPTED ESC/ERS GUIDELINES FOR PAH

CLINICAL DEFINITION

PAH is defined as a mean pulmonary artery pressure (mPAP) >25 mm Hg with a pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg measured by cardiac catheterization.³

TREATMENT LANDSCAPE

The REVEAL Registry evaluated 2525 patients, of whom 2438 were on PAH treatment with ERAs, PCAs, or PDE-5 inhibitors. More than 50% of these patients remained in WHO functional class III or IV.⁴

Evaluation for etiologies other than PAH is appropriate in all instances.
To rule out CTEPH (WHO Group 4), a V/Q scan should be performed.^3,5

CTEPH=chronic thromboembolic pulmonary hypertension; ERA=endothelin receptor antagonist; PCA=prostacyclin analog; PDE-5=phosphodiesterase type 5; V/Q=ventilation/perfusion

WHO GROUP CLASSIFICATION^1,6

Identify which WHO group your PH patients are in.

I. PAH

II. PH due to left heart disease

III. PH due to lung disease and/or hypoxia

IV. CTEPH

V. PH with unclear multifactorial mechanisms

Adempas is approved for adults with PAH (WHO Group 1) and inoperable or persistent/recurrent CTEPH (WHO Group 4) after surgery. Adempas has been studied predominantly in WHO functional class II-III patients.¹

PH=pulmonary hypertension

The guidelines above can assist with:

Creating goals and monitoring progress to help guide the course of treatment
Setting goals for your PAH patients that include exercise capacity (6MWD), WHO functional class, and hemodynamics

6MWD=6-minute walk distance;

BNP=brain natriuretic peptide;

CI=cardiac index;

CMR=cardiac magnetic resonance;

NT-proBNP=N-terminal pro-brain natriuretic peptide;

pred.=predicted;

RA=right atrium;

RAP=right atrial pressure;

SvO₂=mixed venous oxygen saturation;

VE/VCO₂=ventilatory equivalents for carbon dioxide;

VO₂=oxygen consumption

*Adempas does not impact all of these measurements.

^‡Occasional syncope during brisk or heavy exercise, or occasional orthostatic syncope in an otherwise stable patient.

^§Repeated episodes of syncope, even with little or regular physical activity.

DOWNLOAD THE ADAPTED ESC/ERS GUIDELINES FOR PAH

CLINICAL DEFINITION

PAH is defined as a mean pulmonary artery pressure (mPAP) >25 mm Hg with a pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg measured by cardiac catheterization.³

TREATMENT LANDSCAPE

The REVEAL Registry evaluated 2525 patients, of whom 2438 were on PAH treatment with ERAs, PCAs, or PDE-5 inhibitors. More than 50% of these patients remained in WHO functional class III or IV.⁴

Evaluation for etiologies other than PAH is appropriate in all instances.
To rule out CTEPH (WHO Group 4), a V/Q scan should be performed.^3,5

CTEPH=chronic thromboembolic pulmonary hypertension; ERA=endothelin receptor antagonist; PCA=prostacyclin analog; PDE-5=phosphodiesterase type 5; V/Q=ventilation/perfusion

WHO GROUP CLASSIFICATION^1,6

Identify which WHO group your PH patients are in.

I. PAH

II. PH due to left heart disease

III. PH due to lung disease and/or hypoxia

IV. CTEPH

V. PH with unclear multifactorial mechanisms

PH=pulmonary hypertension

MORE IMPORTANT SAFETY INFORMATION LESS IMPORTANT SAFETY INFORMATION

Important Safety Information and Indications

WARNING: EMBRYO-FETAL TOXICITY

Do not administer Adempas (riociguat) tablets to a pregnant female because it may cause fetal harm.

Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and one month after stopping treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment.

For all female patients, Adempas is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program.

Contraindications

Adempas is contraindicated in:

Pregnancy. Based on data from animal reproduction studies, Adempas may cause fetal harm when administered to a pregnant woman and is contraindicated in females who are pregnant. Adempas was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form.
Concomitant administration with specific phosphodiesterase (PDE)-5 inhibitors (such as sildenafil, tadalafil, or vardenafil) or nonspecific PDE inhibitors (such as dipyridamole or theophylline) is contraindicated. Do not administer within 24 hours of sildenafil. Do not administer 24 hours before or within 48 hours after tadalafil.
Patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators.
Patients with Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (PH-IIP).

Warnings and Precautions

Embryo-Fetal Toxicity. Based on data from animal reproduction studies, Adempas may cause embryo-fetal toxicity when administered to a pregnant female and is contraindicated in females who are pregnant. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment, monthly during treatment, and for one month after stopping treatment. Advise females of reproductive potential to use effective contraception during treatment with Adempas and for at least one month after the last dose.

For females, Adempas is only available through a restricted program under the Adempas REMS Program.

Adempas REMS Program. Females can only receive Adempas through the Adempas REMS Program, a restricted distribution program.

Important requirements of the Adempas REMS Program include the following:

Prescribers must be certified with the program by enrolling and completing training.
All females, regardless of reproductive potential, must enroll in the Adempas REMS Program prior to initiating Adempas. Male patients are not enrolled in the Adempas REMS Program.
Female patients of reproductive potential must comply with the pregnancy testing and contraception requirements.
Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive Adempas.

Further information, including a list of certified pharmacies, is available at www.AdempasREMS.com or 1-855-4ADEMPAS.

Hypotension. Adempas reduces blood pressure. Consider the potential for symptomatic hypotension or ischemia in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or concomitant treatment with antihypertensives or strong CYP and P-gp/BCRP inhibitors. Consider a dose reduction if patient develops signs or symptoms of hypotension.

Bleeding. In the placebo-controlled clinical trials, serious bleeding occurred in 2.4% of patients taking Adempas compared to 0% of placebo patients. Serious hemoptysis occurred in 5 (1%) patients taking Adempas compared to 0 placebo patients, including one event with fatal outcome. Serious hemorrhagic events also included 2 patients with vaginal hemorrhage, 2 with catheter-site hemorrhage, and 1 each with subdural hematoma, hematemesis, and intra-abdominal hemorrhage.

Pulmonary Veno-Occlusive Disease. Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Therefore, administration of Adempas to such patients is not recommended. Should signs of pulmonary edema occur, the possibility of associated PVOD should be considered and if confirmed, discontinue treatment with Adempas.

Most Common Adverse Reactions

The most common adverse reactions occurring more frequently (≥3%) on Adempas than placebo were headache (27% vs 18%), dyspepsia/gastritis (21% vs 8%), dizziness (20% vs 13%), nausea (14% vs 11%), diarrhea (12% vs 8%), hypotension (10% vs 4%), vomiting (10% vs 7%), anemia (7% vs 2%), gastroesophageal reflux disease (5% vs 2%), and constipation (5% vs 1%).

Other events that were seen more frequently in Adempas compared to placebo and potentially related to treatment were palpitations, nasal congestion, epistaxis, dysphagia, abdominal distension, and peripheral edema.

Indications

Adempas (riociguat) is indicated for the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
Adempas is indicated for the treatment of adults with pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening.*

Efficacy was shown in patients on Adempas monotherapy or in combination with endothelin receptor antagonists or prostanoids. Studies establishing effectiveness included predominantly patients with WHO functional class II–III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%).

^*Time to clinical worsening was a combined endpoint defined as death (all-cause mortality), heart/lung transplantation, atrial septostomy, hospitalization due to persistent worsening of pulmonary hypertension, start of new PAH-specific treatment, persistent decrease in 6MWD, and persistent worsening of WHO functional class.

For important risk and use information, please see the full Prescribing Information, including Boxed Warning.

References:

Adempas Prescribing Information. Whippany, NJ. Bayer Pharmaceuticals Inc., 2021.
Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016;37(1):67-119.
McLaughlin VV, Archer SL, Badesch BD, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society Inc., and the Pulmonary Hypertension Association. Circulation. 2009;119(16):2250-2294.
Badesch DB, Raskob GE, Elliot CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-387.
Hoeper MM, Barberà JA, Channick RN, et al. Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S85-96.
Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34-D41.

PAH FACTS

Adempas is approved for adults with PAH (WHO Group 1) and has been studied predominantly in WHO functional class II-III patients.¹

WARNING: EMBRYO-FETAL TOXICITY

PAH FACTS

Adempas is approved for adults with PAH (WHO Group 1) and has been studied predominantly in WHO functional class II-III patients.1

WARNING: EMBRYO-FETAL TOXICITY

Adempas is approved for adults with PAH (WHO Group 1) and has been studied predominantly in WHO functional class II-III patients.¹