Prescribing information For Healthcare Professionals Only

ACTIVE INGREDIENT(S): Macitentan

Please refer to the Summary of Product Characteristics (SmPC) before prescribing.

INDICATION(S): Mono or combination therapy for long-term treatment of pulmonary arterial hypertension (PAH), in adults of WHO Functional Class (FC) II & III. Efficacy shown in idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease.

DOSAGE & ADMINISTRATION: Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. To be administered orally, once daily with/without food. The film-coated tablets are not breakable, and are to be swallowed whole, with water. Elderly patients: No dose adjustment required in patients >65 years. Paediatric patients: Safety and efficacy not yet established in children and adolescents below 18 years. Hepatic impairment: Mild: no dose adjustment. Moderate: not recommended. Severe: contraindicated. Elevated hepatic aminotransferase (AST/ALT) >3X upper limit of normal (ULN): contraindicated. Renal impairment: Caution advised in PAH patients with severe renal impairment. Not recommended in dialysis patients. 

CONTRAINDICATIONS: Hypersensitivity to active substance, soya or to any of the excipients. Pregnancy, women of childbearing potential not using reliable contraception, breastfeeding, severe hepatic impairment or baseline hepatic AST/ ALT >3X ULN.

SPECIAL WARNINGS & PRECAUTIONS: Benefit/risk not established in WHO FC I. Patients with rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption or hypersensitivity to soya, should not take macitentan. Hepatic insufficiency: Record baseline hepatic AST/ALT prior to therapy, monthly monitoring recommended. If sustained AST/ALT elevation including increase in bilirubin >2X ULN or signs of clinical hepatic injury, discontinue treatment. Treatment may be recommenced in patients with no clinical hepatic injury, following hepatologist advice and normalisation of liver tests. Renal impairment: Patients with renal impairment may run a higher risk of experiencing hypotension and anaemia during treatment with macitentan. Therefore, monitoring of blood pressure and haemoglobin should be considered. Haemoglobin (Hb): Record baseline Hb and monitor as clinically indicated. As with other ERA treatment a non-progressive decrease in Hb (1g/dL) has been observed, with stabilisation and maintenance after 4-12 weeks of treatment. Cases of anaemia requiring blood cell transfusion have been reported with macitentan and other ERAs. Treatment not recommended in patients with severe anaemia.

Pulmonary veno-occlusive disease (PVOD): If signs of pulmonary oedema, consider possibility of PVOD. Women of child bearing potential: Only initiate treatment in women of childbearing potential, using reliable contraception, who have a negative pregnancy test immediately prior to treatment and thereafter monthly during treatment. Women should not become pregnant for 1 month after discontinuation of treatment. Ability to drive and use machines: Headache and hypotension are known side effects and may have a minor influence on the ability to drive and use machinery.

SIDE EFFECTS: Very common: nasopharyngitis, bronchitis, headache, anaemia, haemoglobin decrease, oedema, fluid retention. Common: pharyngitis, influenza, urinary tract infection, leukopenia, thrombocytopenia, AST/ALT elevations, hypotension, flushing, nasal congestion. Other side effects: hypersensitivity. Refer to SmPC for other side effects.

PREGNANCY AND FERTILITY: Opsumit is contraindicated during pregnancy and in women of childbearing potential who are not using reliable contraception. Animal studies have shown reproductive toxicity. Decreases in sperm count have been observed in patients taking ERAs. Macitentan, like other ERAs, may have an adverse effect on spermatogenesis in men.

LACTATION: Opsumit is contraindicated during breastfeeding.

INTERACTIONS: CYP3A4 inducers/inhibitors: Avoid concomitant use with strong CYP3A4 inducers (e.g. rifampicin, St. John’s wort, carbamazepine, and phenytoin) as efficacy could be reduced. Use caution with concomitant use of strong CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir). Macitentan does not affect the exposure to CYP3A4 substrates. no affect on the pharmacokinetic of an oral  contraceptive pill (norethisterone 1 mg and ethinyl estradiol 35 µg). Refer to SmPC for full details of interactions. Dual/combined CYP3A4 and CYP2C9 inhibitors: Use caution with concomitant use of moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g., fluconazole and amiodarone). Use caution with concomitant use of both a moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole, piperine).  

LEGAL CATEGORY: Prescription Only Medicine (POM).

MARKETING AUTHORISATION HOLDERS:

Northern Ireland: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.

Great Britain: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.

FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.

Prescribing information last revised: December 2022