Instructions for Opsynvi (Macitentan and Tadalafil)

1. Name:Opsynvi, Macitentan and Tadalafil

2. Indications:

Opsynvi (Macitentan and Tadalafil) is a combination of Macitentan and Tadalafil, indicated for the chronic treatment of adults with pulmonary arterial hypertension (PAH, WHO group I and WHO functional class II-III). On an individual basis, Macitentan reduced the risk of clinical worsening events and hospitalization, and Tadalafil improved exercise capacity.

3. Usage and dosage:

1. Before treatment: Before receiving Opsynvi treatment, every month during treatment and one month after stopping treatment, a pregnancy test should be performed on women of reproductive potential. Start Opsynvi treatment in women of reproductive potential only after a negative pregnancy test

2. Recommended dosage:

(1) For patients who have not received any specific treatment for pulmonary arterial hypertension (PAH) or are transitioning from endothelin receptor antagonist (ERA) monotherapy, the recommended starting dose of Opsynvi is one 10 mg/20 mg tablet taken orally once daily for one week; if tolerated, increase it to one 10 mg/40 mg tablet taken orally once daily as a maintenance dose.

(2) For patients transitioning from phosphodiesterase 5 (PDE5) inhibitor monotherapy or PDE5 inhibitor and ERA combination therapy, the recommended dose of Opsynvi is one 10 mg/40 mg tablet taken orally once daily.

3. Medication management: Opsynvi is taken orally once a day, with or without food. Swallow the tablets whole with water. Do not cut, crush, or chew tablets. If a patient misses a dose of Opsynvi, tell the patient to take it as soon as possible and then take the next dose at the regularly scheduled time. If a dose is missed, tell the patient not to take both doses at the same time.

4. Adverse reactions:

In clinical studies of Opsynvi, the most common adverse reactions were edema/fluid retention, anemia, and headache/migraine; the most common adverse reactions leading to discontinuation were anemia and hemoglobin reduction, and peripheral edema and peripheral swelling.

5. Supply and storage:

Opsynvi is available in 10mg/20mg and 10mg/40mg combination tablets. It can be stored at 20°C to 25°C (68°F to 77°F); the tolerance is between 15°C and 30°C (59°F and 86°F). It can be stored and packaged in the original packaging to prevent moisture. Do not discard the desiccant.

6. Taboo:

1. Pregnancy: Pregnant women taking itOpsynvi may cause harm to the fetus. Opsynvi is contraindicated in pregnant women. Macitentan has been shown to be teratogenic when used in animals; If Opsynvi is used during pregnancy, inform patients of the potential risk to the fetus.

2. Allergy: Opsynvi is contraindicated in patients with a history of allergic reaction to Macitentan, Tadalafil or any ingredients of this product. There have been reports of allergic reactions. There have been reports of Stevens-Johnson syndrome and exfoliative dermatitis with Tadalafil.

3. Concomitant organic nitrates: Opsynvi is contraindicated in patients who regularly or intermittently use any form of organic nitrates. Do not use nitrates within 48 hours of taking your last dose of Opsynvi. Tadalafil potentiates the antihypertensive effect of nitrate, This potentiation is thought to be caused by the combined effects of nitrate andTadalafil on the nitric oxide/cGMP pathway.

4. Concomitant use of guanylyl cyclase (GC) stimulators: It is prohibited to combine guanylyl cyclase (GC) stimulators (such as riociguat) with Opsynvi. Tadalafil may enhance the antihypertensive effects of GC stimulants.

7. Mechanism of action:

Macitentan in Opsynvi is an endothelin receptor antagonist that inhibits the binding of ET-1 to ETA and ETB receptors. Macitentan exhibits high affinity and sustained occupancy of ET receptors in human pulmonary artery smooth muscle cells. A metabolite of Macitentan also has pharmacological activity at the ET receptor, and its in vitro efficacy is estimated to be about 20% of the parent drug. The clinical impact of dual endothelin blockade is unknown.

Tadalafil in Opsynvi is an inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for degrading cyclic guanosine monophosphate (cGMP). PAH is associated with impaired nitric oxide release from the vascular endothelium and subsequent reduction in cGMP concentration in pulmonary vascular smooth muscle. PDE5 is the major phosphodiesterase in the pulmonary vasculature. Inhibition of PDE5 by tadalafil increases cGMP concentrations, leading to relaxation of pulmonary vascular smooth muscle cells and vasodilation in the pulmonary vascular bed.