Opsumit

Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. Posology Adults and paediatric patients aged less than 18 years of age weighing at least 40 kg The recommended dose is 10 mg once daily.

Opsumit should be taken every day at about the same time. If the patient misses a dose of Opsumit, the patient should be told to take it as soon as possible and then take the next dose at the regularly scheduled time. The patient should be told not to take two doses at the same time if a dose has been missed.

The 10 mg film-coated tablets are only recommended in paediatric patients weighing at least 40 kg. 5 mg is available. Please refer to the Opsumit dispersible tablets Summary of Product Characteristics. 2). 2). However, there is no clinical experience with the use of macitentan in PAH patients with moderate or severe hepatic impairment.

4). Renal impairment Based on PK data, no dose adjustment is required in patients with renal impairment. There is no clinical experience with the use of macitentan in PAH patients with severe renal impairment. 2). Paediatric population Dosing and efficacy of macitentan in children below 2 years of age have not been established.

2 but no recommendation on a posology can be made. Method of administration The film-coated tablets are not breakable and are to be swallowed whole, with water. They may be taken with or without food.

Summary of the safety profile. 4). Tabulated list of adverse reactions The safety of macitentan has been evaluated in a long-term placebo-controlled trial of 742 adult and adolescent patients with symptomatic PAH (SERAPHIN study). 3 weeks in the placebo group.

Adverse reactions associated with macitentan obtained from this clinical study are tabulated below. Post-marketing adverse reactions are also included. Frequencies are defined as: 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).

, angioedema, pruritus, rash)1 Nervous system disorders Very common Headache Vascular disorders Common Hypotension,2 flushing Respiratory, thoracic and mediastinal disorders Common Nasal congestion1 Hepatobiliary disorders Common Aminotransferase elevations4 Reproductive system and breast disorders Common Increased uterine bleeding8 General disorders and administration site conditions Very common Oedema, fluid retention3 1 Data derived from pooled placebo-controlled studies.

8 Includes PTs of heavy menstrual bleeding, abnormal uterine bleeding, intermenstrual bleeding, uterine/vaginal haemorrhage, polymennorhoea and menstruation irregular. Frequency based on exposure in females. Description of selected adverse reactions 2 Hypotension has been associated with the use of ERAs including macitentan.

4% of patients on macitentan 10 mg and placebo, respectively. 7 events / 100 patient-years on placebo. 3 Oedema/fluid retention has been associated with the use of ERAs including macitentan. 5%, respectively. 8%, respectively. 5% in the placebo groups.

5% on placebo in SERAPHIN, a double-blind study in patients with PAH. 5% of patients on macitentan 10 mg versus 2% of patients on placebo. 5 Haemoglobin In SERAPHIN, a double-blind study in patients with PAH, macitentan 10 mg was associated with a mean decrease in haemoglobin versus placebo of 1 g/dL.

The benefit/risk balance of macitentan has not been established in patients with WHO class I functional status of pulmonary arterial hypertension. Liver function Elevations of liver aminotransferases (AST, ALT) have been associated with PAH and with endothelin receptor antagonists (ERAs).

3) and is not recommended in patients with moderate hepatic impairment. Liver enzyme tests should be obtained prior to initiation of Opsumit. Patients should be monitored for signs of hepatic injury and monthly monitoring of ALT and AST is recommended.

, jaundice), Opsumit treatment should be discontinued. 4 Reinitiation of Opsumit may be considered following the return of hepatic enzyme levels to within the normal range in patients who have not experienced clinical symptoms of liver injury.

The advice of a hepatologist is recommended. 8). In placebo-controlled studies, macitentan-related decreases in haemoglobin concentration were not progressive, stabilised after the first 4 to 12 weeks of treatment and remained stable during chronic treatment.

Cases of anaemia requiring blood cell transfusion have been reported with macitentan and other ERAs. Initiation of Opsumit is not recommended in patients with severe anaemia. It is recommended that haemoglobin concentrations be measured prior to initiation of treatment and tests repeated during treatment as clinically indicated.

Pulmonary veno-occlusive disease Cases of pulmonary oedema have been reported with vasodilators (mainly prostacyclins) when used in patients with pulmonary veno-occlusive disease. Consequently, if signs of pulmonary oedema occur when macitentan is administered in patients with PAH, the possibility of pulmonary veno-occlusive disease should be considered.

6). Women should not become pregnant for 1 month after discontinuation of Opsumit. Monthly pregnancy tests during treatment with Opsumit are recommended to allow the early detection of pregnancy. Concomitant use with strong CYP3A4 inducers In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur.

1. 6). 6). 6). 2). 4).