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Prescribing Information          

This medicinal product is subject to additional monitoring.

Adempas® Prescribing Information

Composition

Active Ingredient: 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg riociguat. Excipients: cellulose microcrystalline, crospovidone, hypromellose, magnesium stearate, lactose monohydrate, sodium lauril sulfate, hydroxypropylcellulose, hypromellose, propylene glycol and titanium dioxide (E171), ferric oxide yellow (only in 1 mg, 1.5 mg, 2 mg and 2.5 mg tablets), ferric oxide red (only in 2 mg and 2.5 mg tablets).

 

Indications

Chronic thromboembolic pulmonary hypertension (CTEPH):
Treatment of adult patients with WHO functional class II to III with inoperable CTEPH, or persistent or recurrent CTEPH after surgical treatment to improve exercise capacity.

Pulmonary arterial hypertension (PAH):
In monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with PAH with WHO functional class II to III to improve exercise capacity. Efficacy has been shown in a PAH population including etiologies of idiopathic or heritable PAH or PAH associated with connective tissue disease

 

Contraindications

Co-administration with PDE 5 inhibitiors (such as sildenafil, tadalafil, vardenafil); severe hepatic impairment (Child Pugh C); hypersensitivity to the active substance or to any of the excipients; pregnancy; co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form, including recreational drugs called ‘poppers’; patients with systolic blood pressure below 95 mmHg at treatment initiation; patients with pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP).

 

Warnings and Precautions

In PAH, studies with Adempas have been mainly performed in forms related to idiopathic or heritable PAH and PAH associated with connective tissue disease. The use of Adempas in other forms of PAH not studied is not recommended. In CTEPH, pulmonary endarterectomy is the treatment of choice as it is potentially curative. Therefore, an expert assessment of operability should be done prior to treatment with Adempas.

Pulmonary veno-occlusive disease (PVOD): Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Therefore, administration of Adempas to PVOD patients is not recommended. Should signs of pulmonary oedema occur, the possibility of associated PVOD should be considered and treatment with riociguat should be discontinued.

Respiratory tract bleeding: Careful monitoring of patients taking anticoagulants is recommended. The risk of serious and fatal respiratory tract bleeding may be further increased under treatment with Adempas. The use should be avoided in patients with a history of serious hemoptysis or who have previously undergone bronchial arterial embolisation. In case of respiratory tract bleeding, the prescriber should regularly assess the benefit-risk of treatment continuation.

Hypotension: Adempas has vasodilatory properties that may result in lowering of the blood pressure. Before prescribing riociguat, physicians should carefully consider whether patients with certain underlying conditions, could be adversely affected by vasodilatory effects (e.g. patients on antihypertensive therapy or with resting hypotension, hypovolemia, severe left ventricular outflow obstruction or autonomic dysfunction) Adempas must not be used in patients with a systolic blood pressure below 95 mmHg. Patients older than 65 years are at increased risk of hypotension. Therefore, caution should be exercised when administering Adempas in these patients.

Renal impairment: Data in patients with severe renal impairment (creatinine clearance < 30 mL/min) are limited and there are no data for patients on dialysis, therefore Adempas is not recommended in these patients. There is increased Adempas exposure in patients with mild and moderate renal impairment. There is a higher risk of hypotension in these patients particular care should be exercised during individual dose titration.

Hepatic impairment: There is no experience in patients with severe hepatic impairment (Child Pugh C); Adempas is contraindicated in these patients. PK data show that higher Adempas exposure was observed in patients with moderate hepatic impairment (Child Pugh B). Particular care should be exercised during individual dose titration. There is no clinical experience with Adempas in patients with elevated liver aminotransferases (> 3 x Upper Limit of Normal (ULN)) or with elevated direct bilirubin (> 2 x ULN) prior to initiation of treatment; Adempas is not recommended in these patients.

Pregnancy/contraception: Adempas is contraindicated in pregnancy. Therefore, female patients at potential risk of pregnancy must use an effective method of contraception. Monthly pregnancy tests are recommended.

Smokers: Plasma concentrations of Adempas in smokers are reduced compared to non-smokers. Dose adjustment may be necessary in patients who start or stop smoking during treatment with Adempas.

Concomitant use with other medicinal products: The concomitant use of Adempas with strong multi pathway cytochrome P450 (CYP) and P-glycoprotein (P-gp) / breast cancer resistance protein (BCRP) inhibitors such as azole antimycotics (e.g. ketoconazole, itraconazole) or HIV protease inhibitors (e.g. ritonavir) is not recommended, due to the pronounced increase in Adempas exposure. The concomitant use of Adempas with strong CYP1A1 inhibitors, such as the tyrosine kinase inhibitor erlotinib and strong P-glycoprotein (P-gp) / breast cancer resistance protein (BCRP) inhibitors, such as the immuno-suppressive agent cyclosporine A, may increase Adempas exposure. Blood pressure should be monitored and dose reduction of Adempas should be considered.

Pediatric population: The safety and efficacy of Adempas in children and adolescents below 18 years have not been established. The use of Adempas in children and in growing adolescents should be avoided.

Information about excipients: Each 0.5 mg film coated tablet contains 37.8 mg lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

 

Undesirable effects

Very common: headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea and vomiting.

Common: Gastroenteritis, anemia, palpitation, hypotension, hemoptysis epistaxis, nasal congestion, gastritis, gastro-oesophagus reflux disease, dysphagia, gastrointestinal and abdominal pain, constipation, abdominal distension.

Uncommon: Pulmonary hemorrhage (Serious haemoptysis and pulmonary haemorrhage, including cases with fatal outcome have been observed in patients with CTEPH or PAH treated with Adempas).

Classification for supply: Medicinal product subject to medical prescription.

Date of revision of the underlying SmPC: April 2019

Marketing Authorization Holder: Bayer Pharma AG, D-13342 Berlin, Germany

 

Classification for supply: Medicinal product subject to medical prescription.

 

Date of revision of the underlying Prescribing Information: 27.03.2014

Marketing Authorization Holder: Bayer Pharma AG, D-13342 Berlin, Germany