OPSYNVI

What it is

OPSYNVI 10/40 contains 10 mg macitentan and 40 mg tadalafil. It is a film-coated tablet, white to almost-white, oblong, and debossed with "1040" on one side and "MT" on the other side. OPSYNVI should be taken orally once daily with or without food, and the film-coated tablets must be swallowed whole, with water, and must not be chewed, divided or crushed.

Approved indications

— Maintenance treatment of pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1) in adult patients of WHO functional class (FC) II and III whose PAH is idiopathic, heritable or associated with connective tissue disease or congenital heart disease with repaired shunts. OPSYNVI is intended as substitution treatment only for patients currently treated concomitantly with stable doses of macitentan 10 mg and tadalafil 40 mg (20 mg x 2) as separate tablets.

Dosing overview

The recommended dose of OPSYNVI is one tablet taken once daily. Treatment with OPSYNVI should only be initiated and monitored by a physician experienced in the treatment of PAH.

Key safety warnings

OPSYNVI is not indicated as initial combination therapy in treatment-naïve patients or as a step-up therapy in patients already taking ERA or PDE5i monotherapies. In the ADUE study, combination therapy with macitentan and tadalafil was associated with increased adverse events, in particular hypotension, oedema and anaemia compared to monotherapies. Elderly patients (>65 years) may be at increased risk of adverse events when using combination therapy. Cases of pulmonary oedema have been reported with vasodilators when used in patients with pulmonary veno-occlusive disease. If signs of pulmonary oedema occur when OPSYNVI is administered in patients with PAH, the possibility of pulmonary veno-occlusive disease should be considered. Discontinuation of OPSYNVI should be considered in patients with treatment-related pulmonary veno-occlusive disease. Hepatic enzyme elevations, and in some cases serious hepatic events, potentially related to therapy have been observed with endothelin receptor antagonists. The incidence of aminotransferase elevations (ALT/AST) > 3 × ULN was 3.4% on macitentan 10 mg and 4.5% on placebo in a double-blind study in patients with PAH. The incidence of elevations in ALT > 3 × ULN were 3.4% on macitentan 10 mg and 1.6% on placebo. The incidence of ALT > 8 × ULN were 2.1% on macitentan 10 mg and 0.4% on placebo. Liver enzyme tests should be obtained prior to initiation of macitentan and monthly monitoring of aminotransferases during treatment with macitentan is recommended. Decreases in haemoglobin concentration and haematocrit have occurred following administration of other ERAs and were observed in clinical studies with macitentan. 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. Nitrates and tadalafil must not be used concomitantly. Co-administration of tadalafil with nitric oxide donors, organic nitrates or organic nitrites in any form either regularly or intermittently is contraindicated. Drugs which must not be used concomitantly include glyceryl trinitrate (injection, tablets, sprays or patches), isosorbide salts, sodium nitroprusside, amyl nitrite, nicorandil or organic nitrates in any form. In clinical studies, tadalafil was shown to potentiate the hypotensive effects of both acute and chronic nitrate administration. Physicians should advise patients to stop use of all PDE5 inhibitors, including tadalafil, and seek medical attention in the event of any sudden visual defect including loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischaemic optic neuropathy (NAION), a cause of decreased vision, including permanent loss of vision that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors.

Contraindications

Macitentan is contraindicated in women who are or may become pregnant and in women of child-bearing potential who are not using reliable contraception. Women must not become pregnant for at least 3 months after stopping treatment with macitentan. OPSYNVI is contraindicated in patients with severe hepatic impairment, with or without cirrhosis (Child-Pugh Class C), or clinically significant elevated hepatic aminotransferases (greater than 3 times the Upper Limit of Normal (> 3 × ULN)). Nitrates and tadalafil must not be used concomitantly. Co-administration of tadalafil with nitric oxide donors, organic nitrates or organic nitrites in any form either regularly or intermittently is contraindicated. Administration of tadalafil to patients who are using any form of organic nitrate is contraindicated. Tadalafil is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. The following groups of patients with cardiovascular disease were not included in tadalafil clinical trials and the use of tadalafil is therefore contraindicated: patients who had acute myocardial infarction within the last 90 days, patients with severe hypotension (< 90/50 mmHg), patients with unstable angina, patients with uncontrolled arrhythmias, patients with uncontrolled hypertension, and patients with a stroke within the last 6 months. The combination of tadalafil and guanylate cyclase stimulators such as riociguat, is contraindicated, as it may potentially lead to symptomatic hypotension.

PBS listing

OPSYNVI was recommended by the PBAC in November 2024 for pulmonary arterial hypertension (continuing treatment for patients on stable doses of macitentan and tadalafil as combination therapy) under Section 100 (Highly Specialised Drug Program) with Authority Required (Written) listing. The cost was minimised against dual therapy components prices.

Regulatory history

OPSYNVI 10/40 (macitentan 10 mg / tadalafil 40 mg film-coated tablet) was first listed on the ARTG on 16 September 2024. OPSYNVI was approved by the TGA on 11 September 2024 for the maintenance treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO functional class II and III, as a substitution for those already on stable doses of macitentan and tadalafil. The PBAC recommended listing in November 2024.