Opsynvi

Long-term treatment of pulmonary arterial hypertension (PAH) in adults w/ PAH (WHO FC II or III), who are already treated w/ macitentan & tadalafil or medications w/in the same classes, in accordance w/ medical practices.

Patients who are treatment-naïve to any PAH specific therapy or transitioning from ERA monotherapy Initially one 10/20 mg-tab once daily for 1 wk. If tolerated, up-titrate to one 10/40 mg-tab once daily as maintenance dose. Patients transitioning from PDE5 inhibitor monotherapy or PDE5 inhibitor & ERA combination therapy One 10/40 mg-tab once daily. Mild (CrCl 51-80 mL/min) to moderate (CrCl 30-50 mL/min) renal impairment & mild to moderate hepatic impairment (Child-Pugh Class A or B) Maintain adult dosing.

May be taken with or without food: Swallow whole. Do not cut, crush, or chew.

History of hypersensitivity. Concomitant use w/ organic nitrates; guanylate cyclase stimulators eg, riociguat. Administration of nitrates w/in 48 hr after last dose of therapy. Pregnancy.

Discontinue treatment if pulmonary veno-occlusive disease (PVOD) is confirmed; clinically relevant aminotransferase elevations occur, or if elevations are accompanied by increase in bilirubin >2x ULN, or by clinical symptoms of hepatotoxicity. Not to be initiated in patients w/ severe hepatic impairment or clinically significant elevated hepatic aminotransferases (>3x ULN) at baseline. Not recommended in patients w/ severe anemia; PVOD; known hereditary degenerative retinal disorders, including retinitis pigmentosa. Aminotransferase elevations, hepatotoxicity, liver failure; transient BP decrease; decrease in Hb conc & hematocrit. May significantly worsen CV status of patients w/ PVOD. Non-arteritic anterior ischemic optic neuropathy which causes decreased vision including permanent loss of vision. Sudden decrease or loss of hearing, which may be accompanied by tinnitus & dizziness. Peripheral edema & fluid retention; heart failure. Prolonged erections >4 hr & priapism. Patients w/ underlying CV disease; pre-existing hypotension, autonomic dysfunction, left ventricular outflow obstruction; left ventricular dysfunction; conditions predisposing to priapism (eg, sickle cell anemia, multiple myeloma or leukemia), or anatomical deformation of penis (eg, angulation, cavernosal fibrosis or Peyronie's disease). Obtain liver enzyme tests; measure Hb prior to initiation & during treatment as clinically indicated. Monitor for signs of fluid retention after treatment initiation. Evaluate patient if clinically significant fluid retention develops. Not to be taken concomitantly w/ other PDE5 inhibitors. Not recommended in patients undergoing dialysis. Avoid use in patients w/ severe renal impairment (CrCl 15-29 mL/min); severe hepatic cirrhosis. May cause decreased sperm count; affect male fertility. Obtain pregnancy test prior to treatment initiation. Use effective contraception before initiation, during, & for 1 mth after stopping treatment. May cause fetal harm. Discontinue use as soon as pregnancy is detected. Lactation. Childn.

Edema/fluid retention, anemia, headache/migraine, decreased Hb, peripheral edema & swelling. Abdominal pain, hypotension, myalgia, nasopharyngitis, nausea, increased uterine bleeding, back pain, flushing, vomiting, palpitations, pain in extremity, epistaxis.

Increased exposure of strong CYP3A4 inhibitors eg, ketoconazole. Avoid concomitant use w/ strong CYP3A4 inhibitors eg, ritonavir, ketoconazole & itraconazole. Increased potential for orthostatic signs & symptoms, including increase in heart rate, decrease in standing BP, dizziness & headache w/ alcohol (≥5 u). Macitentan: Reduced exposure w/ strong CYP3A4 inducers (eg, rifampin). Increased exposure w/ moderate dual CYP3A4 & CYP2C9 inhibitors eg, fluconazole. Tadalafil: May lead to symptomatic hypotension w/ concomitant α₁-blockers. Small BP reductions w/ amlodipine, ARBs, bendroflumethiazide, enalapril & metoprolol.

Other Antihypertensives

C02KX54 - macitentan and tadalafil ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.

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