What are the precautions for Opsynvi (Macitentan and Tadalafil)?

In clinical studies of Opsynvi (Macitentan and Tadalafil), warnings and precautions such as embryonic-fetal toxicity, hepatotoxicity, hypotension, decreased hemoglobin, worsening of pulmonary veno-occlusive disease, vision loss, hearing loss, fluid retention, and prolonged erection have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Embryo-Fetotoxicity: Use during pregnancy may cause harm to the fetus, and use in pregnant women is prohibited. For females of reproductive potential, rule out pregnancy before initiating treatment, ensure the use of an acceptable method of contraception, and take monthly pregnancy tests. Opsynvi is available to females through the Macitentan-Containing Products REMS program.

2. Hepatotoxicity: Endothelin receptor antagonists (ERA): may lead to elevated transaminases, hepatotoxicity and liver failure. Perform liver enzyme testing before starting Opsynvi and repeat testing during treatment as clinically indicated. Symptoms of liver damage include nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever or itching. Discontinue Opsynvi if clinically relevant aminotransferase elevations occur, or if the elevation is accompanied by an increase in bilirubin >2 times the ULN, or if there are clinical signs of hepatotoxicity. Do not use Opsynvi in u200bu200bpatients with elevated transaminases at baseline (>3 times the upper limit of normal [ULN]). OPSYNVI should be avoided in patients with severe cirrhosis (Child-Pugh class C).

3. Hypotension:Opsynvi tablets have vasodilatory properties that can cause a temporary drop in blood pressure. Before prescribing Opsynvi tablets, careful consideration should be given to whether patients with underlying cardiovascular disease may be adversely affected by such vasodilatory effects. Patients with preexisting hypotension, autonomic dysfunction, and left ventricular outflow tract obstruction may be particularly sensitive to the effects of vasodilators.

4. Decreased hemoglobin: After taking other endothelin receptor antagonists (ERA), hemoglobin concentration and hematocrit decreased, and were observed in clinical studies of Opsynvi and Macitentan. These declines occur early on and then stabilize. A decrease in hemoglobin rarely requires a blood transfusion. It is not recommended that patients with severe anemia start using Opsynvi. Measure hemoglobin before initiating treatment and repeat measurements during treatment as clinically indicated.

5. Vision loss: Non-arteritic anterior ischemic optic neuropathy (NAION) is a cause of vision loss, including permanent blindness, and has been reported post-marketing to be temporally associated with the use of PDE5 inhibitors (including Tadalafil). It occurs in most, but not all, of these patientsPotential anatomic or vascular risk factors for NAION include age over 50 years, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. Use of Opsynvi is not recommended in these patients.

6. Worsened pulmonary veno-occlusive disease (PVOD): Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease. Since there are no clinical data on the use of this product in patients with veno-occlusive disease, its use in these patients is not recommended. If symptoms of pulmonary edema occur while taking this product, the possibility of associated skin shadow should be considered. If confirmed, stop Opsynvi.

7. Hearing loss: It has been reported that patients taking Tadalafil may experience sudden hearing loss or loss, which may be accompanied by tinnitus and dizziness. It was not possible to determine whether these events were directly related to the use of PDE5 inhibitors or other factors.

8. Fluid Retention: Peripheral edema and fluid retention are known clinical consequences of PAH, and known effects of ERA and heart failure have been reported in patients taking Opsynvi. Patients with underlying left ventricular dysfunction are particularly susceptible to significant fluid retention after initiation of ERA therapy. Monitor for signs of fluid retention after Opsynvi is started. If clinically significant fluid retention occurs, evaluate the patient to determine the cause, such as Opsynvi or underlying heart failure, and the possible need to discontinue Opsynvi.

9. Combination with otherPDE5 inhibitors:Tadalafil is also suitable for erectile dysfunction. The safety and effectiveness of Tadalafil tablets when combined with another PDE5 inhibitor or other medications used to treat erectile dysfunction have not been studied. Instruct patients taking Opsynvi tablets not to take other PDE5 inhibitors.

10. Reduced sperm count:Macitentan, like other ERAs, may have adverse effects on spermatogenesis. Men are advised to be aware of the potential effects on fertility.

11. Prolonged erections: ForPDE5 inhibitors such asTadalafil, prolonged erections exceeding 4 hours and priapism (painful erection lasting more than 6 hours) have been reported. The risk is higher in patients with conditions that may cause priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformations of the penis (such as angulation, cavernous fibrosis, or Peyronie's disease). If left untreated, priapism can cause irreversible damage to erectile tissue. Patients who have an erection lasting more than 4 hours, whether painful or not, should seek emergency medical attention.