al 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. The use of Opsumit is not recommended in patients undergoing dialysis (see sections 4.4 and 5.2).
Paediatric population
The safety and efficacy of macitentan in children have not yet been established.
4.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Pregnancy (see section 4.6).
• Women of childbearing potential who are not using reliable contraception (see sections 4.4 and 4.6).
• Breastfeeding (see section 4.6).
• Patients with severe hepatic impairment (with or without cirrhosis) (see section 4.2).
• Baseine values of hepatic aminotransferases (aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 × ULN) (see sections 4.2 and 4.4).
4.4 Special warnings and precautions for use
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). Opsumit is not to be initiated in patients with severe hepatic impairment or elevated aminotransferases (> 3 × ULN) (see sections 4.2 and 4.3), 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. 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 liver injury (e.g., jaundice), Opsumit treatment should be discontinued.
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.
Haemoglobin concentration
As with other ERAs, treatment with macitentan has been associated with a decrease in haemoglobin concentration (see section 4.8). In placebo-controlled studies, macitentan-related decreases in haemoglobin concentration were not progressive, stabilised after the first 4-12 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.
Use in women of childbearing potential
Opsumit treatment should only be initiated in women of childbearing potential when the absence of pregnancy has been verified, appropriate advice o |
