CTEPH FACTS

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

WHAT IS CTEPH?

CTEPH is a form of pulmonary hypertension (PH) and is designated as WHO Group 4. Diagnosis of CTEPH is based on the following after 3 months of anticoagulation^1-3

PVR ≥3 WU or 240 dyn•sec•cm^-5
Mean pulmonary arterial pressure (mPAP) >20 mm Hg
Pulmonary artery wedge pressure (PAWP) ≤15 mm Hg
The presence of multiple chronic/organized occlusive thrombi/emboli in the elastic pulmonary arteries as indicated by mismatched perfusion defects on lung scan and specific signs of occlusion on imaging

CTEPH=chronic thromboembolic pulmonary hypertension; WHO=World Health Organization; WU=Wood units.

EVALUATING CTEPH PATIENTS FOR TREATMENT

All patients should be evaluated by CTEPH experts for pulmonary thromboendarterectomy (PTE) surgery.⁴

Regular follow-up is recommended, including invasive assessment with
RHC 3-6 months after the intervention to support consideration of a multimodal treatment approach.³

Adempas is the first and only FDA-approved therapy to treat adults with inoperable or persistent/recurrent CTEPH.
Adempas was predominantly studied in WHO functional class II-III patients.¹

V/Q=ventilation/perfusion.

PATHOGENESIS

CTEPH may be caused by either single or recurrent pulmonary emboli that incompletely resolve, resulting in endothelialized residua that obstruct or significantly narrow pulmonary arteries.⁸

CTEPH results from persistent macrovascular obstruction, often associated with vasoconstrictor response, which leads to a secondary small vessel arteriopathy. Small vessel arteriopathy is characterized by medial hypertrophy, intimal proliferation and thickening, microthrombi formation, and plexiform lesions.⁸

WHO PH CLASSIFICATION^3,9

Identify which WHO group your PH patients are in.

I.PAH

II.PH associated with left heart disease

III.PH associated with lung disease and/or hypoxia

IV.ICTEPH

V.PH with unclear and/or multifactorial mechanism

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

PAH=pulmonary arterial hypertension; PH=pulmonary hypertension.

WHAT IS CTEPH?

CTEPH is a form of pulmonary hypertension (PH) and is designated as WHO Group 4. Diagnosis of CTEPH is based on the following after 3 months of anticoagulation^1-3

PVR ≥3 WU or 240 dyn•sec•cm^-5
Mean pulmonary arterial pressure (mPAP) >20 mm Hg
Pulmonary artery wedge pressure (PAWP) ≤15 mm Hg
The presence of multiple chronic/ organized occlusive thrombi/emboli in the elastic pulmonary arteries as indicated by mismatched perfusion defects on lung scan and specific signs of occlusion on imaging

CTEPH=chronic thromboembolic pulmonary hypertension; WHO=World Health Organization; WU=Wood units.

EVALUATING CTEPH PATIENTS FOR TREATMENT

All patients should be evaluated by CTEPH experts for pulmonary thromboendarterectomy (PTE) surgery.⁴

SEE INOPERABLE CTEPH SEE OPERABLE CTEPH

Regular follow-up is recommended, including invasive assessment with RHC 3-6 months after the intervention to support consideration of a multimodal treatment approach.³

Adempas is the first and only FDA-approved therapy to treat adults with inoperable or persistent/ recurrent CTEPH.
Adempas was predominantly studied in WHO functional class II-III patients.¹

V/Q=ventilation/perfusion.

PATHOGENESIS

CTEPH may be caused by either single or recurrent pulmonary emboli that incompletely resolve, resulting in endothelialized residua that obstruct or significantly narrow pulmonary arteries.⁸

WHO PH CLASSIFICATION^3,9

Identify which WHO group your PH patients are in.

I.PAH

II.PH associated with left heart disease

III.PH associated with lung disease and/or hypoxia

IV.ICTEPH

V.PH with unclear and/or multifactorial mechanism

PAH=pulmonary arterial hypertension; 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.
Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):180913.
Humbert M, Kovacs G, Hoeper M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;00:1-114.
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.
Freed DH, et al. Survival after pulmonary thromboendarterectomy: effect of residual pulmonary hypertension. J Thorac Cardiovasc Surg. 2011;141(2):383-387.
Kim NH, Delcroix M, Jenkins DP, et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D92–D99.
Condliffe R, Kiely DG, Gibbs SR, et al. Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2008;177(10):1122-1127.
Piazza G, Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2011;364(4):351-360.
Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–D41.

CTEPH FACTS

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

WARNING: EMBRYO-FETAL TOXICITY

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