Jeraygo

5 mg orally once daily. 4). Missed dose If the patient misses a dose, the patient should be told to resume treatment the next day and not take two doses in the same day. 2). 4). 2). 4). 2). 4). Paediatric population The safety and efficacy of aprocitentan in children and adolescents aged less than 18 years have not been established.

No data are available. Method of administration Oral use. 2). The film-coated tablets are not scored and are designed to be swallowed whole.

4). 1). In this study, 724 patients received aprocitentan, with 633 patients treated for at least 26 weeks, 192 patients for at least 47 weeks, and 99 patients for at least 48 weeks. The frequency of adverse reactions is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).

Table 1:

Adverse reactions System organ class Adverse reaction Frequency Infections and infestations Upper respiratory tract infectiona Common Blood and lymphatic system disorders Haemoglobin decreasedb Common Immune system disorders Hypersensitivityc Common Nervous system disorders Headache Common Vascular disorders Hypotension Uncommon Flushing Uncommon Respiratory, thoracic and mediastinal disorders Dyspnoead Common Hepatobiliary disorders Transaminase increased Uncommon General disorders and administration site conditions Oedema/fluid retentione Very common Investigations Glomerular filtration rate decreased during initial treatment Uncommon 8 Weight increased during initial treatment Uncommon a Upper respiratory tract infection includes pharyngitis, nasopharyngitis.

b Haemoglobin decreased includes anaemia. c Hypersensitivity includes rash, erythema, allergic oedema, dermatitis allergic. d Dyspnoea includes dyspnoea exertional. e Oedema/fluid retention includes mainly oedema peripheral, fluid retention, face oedema.

4% [25 mg] during the 4-week double-blind [DB] treatment. 8% of patients discontinued treatment of aprocitentan 25 mg due to oedema/fluid retention. 4. 2 kg in patients on placebo during the 4-week DB treatment (part 1). This increase disappeared during the 32-week single-blind (SB) treatment (part 2).

9% in placebo patients during the initial 4-week DB treatment (part 1). 5% of patients reported these events during the 32-week SB treatment (part 2) when all subjects received 25 mg. 0% on placebo. There were no reports of patients with ALT and/or AST > 3 × ULN and total bilirubin > 2 × ULN in the study.

6). 6). Hepatotoxicity Elevations of aminotransferases and hepatotoxicity are known effects of other endothelin receptor antagonists (ERAs). 8). 3) and is not recommended in patients with elevated aminotransferases (> 3 × upper limit of normal [ULN]).

Liver enzyme tests should be obtained prior to initiation of JERAYGO. During treatment, monitoring of liver enzymes is recommended. If sustained, unexplained, clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin > 2 × ULN, or by clinical symptoms of hepatotoxicity, JERAYGO should be discontinued.

8). After treatment initiation, patients should be monitored for signs of fluid retention such as oedema or weight gain. If clinically significant fluid retention develops, the patient should be evaluated to determine the cause and the need for additional supportive treatment, including additional diuretics or increase of dose of currently prescribed diuretic (as appropriate), before considering dose reduction or discontinuation of JERAYGO.

In patients treated with loop diuretics before starting therapy with JERAYGO, the loop diuretic should not be switched to a less effective diuretic at initiation. 73 m2) or pre-existing heart failure taking JERAYGO may be at a higher risk of developing fluid retention, as may elderly patients (> 65 years), patients with diabetes, or severely obese patients (body mass index [BMI] ≥ 40 kg/m2).

When switching to 25 mg, the risk of increasing fluid retention, potentially aggravating heart failure or cardiovascular (CV) events, has to be taken into consideration in these patients. Cardiovascular events Aprocitentan has not been studied in patients with unstable or severe cardiac disease, such as uncontrolled symptomatic arrhythmia (including atrial fibrillation), heart failure New York Heart Association stage III–IV or stage II with relevant valve disease, with NT-proBNP plasma concentration ≥ 500 pg/mL, or with recent (within 6 months) unstable angina, myocardial infarction, transient ischemic attack or stroke.

1. 6). 6). 6). 4). 4