OPSYNVI Dosage & Rx Info | Uses, Side Effects

Opsynvi Generic Name & Formulations

Legal Class

General Description

Macitentan, tadalafil; 10mg/20mg, 10mg/40mg; tabs.

Pharmacological Class

Endothelin receptor antagonist + phosphodiesterase 5 (PDE5) inhibitor (cGMP-specific).

How Supplied

Tabs (10mg/20mg)—7, 30; (10mg/40mg)—10, 30

Storage

Store at 20ºC to 25ºC (68ºF to 77ºF); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Manufacturer

Janssen Pharmaceuticals, Inc.

Generic Availability

Mechanism of Action

Macitentan is an endothelin receptor antagonist that inhibits the binding of ET-1 to both ETA and ETB receptors. Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells.

Tadalafil is an inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Pulmonary arterial hypertension is associated with impaired release of nitric oxide by the vascular endothelium and consequent reduction of cGMP concentrations in the pulmonary vascular smooth muscle. Inhibition of PDE5 by tadalafil increases the concentrations of cGMP resulting in relaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed.

Opsynvi Indications

Indications

Chronic treatment of adults with pulmonary arterial hypertension (PAH, WHO Group I and WHO Functional Class II–III).

Opsynvi Dosage and Administration

Adult

Swallow whole. Treatment-naïve to PAH-specific therapy or transitioning from ERA monotherapy: 10mg/20mg once daily for 1 week; titrate up to 10mg/40mg once daily if tolerated. Transitioning from PDE5 inhibitor monotherapy or PDE5 inhibitor + ERA combination therapy: 10mg/40mg once daily.

Children

Not established.

Opsynvi Contraindications

Contraindications

Pregnancy. Concomitant organic nitrates, guanylate cyclase stimulators (eg, riociguat).

Opsynvi Boxed Warnings

Boxed Warning

Embryo-fetal toxicity.

Opsynvi Warnings/Precautions

Warnings/Precautions

Embryo-fetal toxicity: in females of reproductive potential, exclude pregnancy prior to initiation, monthly during, and for 1 month after treatment discontinuation; must use acceptable methods of contraception. Obtain LFTs prior to initiation and repeat during treatment as clinically indicated. Discontinue if clinically relevant ALT/AST elevations or if elevations accompanied by bilirubin >2×ULN, or by symptoms of hepatotoxicity occur. If >3×ULN at baseline, severe hepatic cirrhosis (Child-Pugh Class C), severe anemia, pulmonary veno-occlusive disease, hereditary degenerative retinal disorders (eg, retinitis pigmentosa), undergoing dialysis: not recommended. Preexisting hypotension, autonomic dysfunction, left ventricular outflow obstruction. Measure Hgb prior to initiation and repeat during treatment as clinically indicated. Discontinue if confirmed pulmonary veno-occlusive disease. History of non-arteritic anterior ischemic optic neuropathy (NAION). "Crowded" optic disc. Underlying left ventricular dysfunction. Monitor for fluid retention after initiation; evaluate if develops. Anatomical penile deformation. Predisposition to priapism. Male infertility. Avoid in severe renal impairment (CrCl 15–29mL/min) or severe hepatic impairment. Nursing mothers: not recommended.

REMS

YES

Opsynvi Pharmacokinetics

Distribution

Macitentan:

Apparent volume of distribution: 50 L.
Plasma protein bound: >99%.

Tadalafil:

Apparent volume of distribution: ~77 L.
Plasma protein bound: 94%.

Metabolism

Macitentan: primarily by oxidative depropylation of the sulfamide (mainly CYP3A4, minor with CYP2C8, CYP2C9, CYP2C19).

Tadalafil: primarily CYP3A.

Elimination

Macitentan: renal (~50%), fecal (~24%); half-life: ~16 hours.

Tadalafil: renal, fecal; half-life: 11 hours.

Opsynvi Interactions

Not Applicable

Opsynvi Adverse Reactions

Adverse Reactions

Edema/fluid retention, anemia, headache/migraine; hypersensitivity, hepatotoxicity, hypotension, decreased hemoglobin, sudden visual or hearing loss, NAION, prolonged erection, priapism.

Opsynvi Clinical Trials

Clinical Trials

The approval of Opsynvi was based on data from the phase 3 A DUE trial (ClinicalTrials.gov Identifier: NCT03904693), which compared the efficacy and safety of Opsynvi to monotherapy with macitentan or tadalafil in 187 patients with PAH (WHO FC II-III), who were treatment naïve or on a stable dose of an ERA or a PDE5 inhibitor for at least 3 months. Patients with pulmonary vascular resistance (PVR) of at least 240 dyn·s/cm⁵ were randomly assigned to receive Opsynvi (n=108), macitentan 10mg (n=35), or tadalafil 40mg (n=44) once daily.

The primary endpoint was PVR measured 16 weeks after treatment initiation (expressed as the ratio of geometric means to baseline). Findings showed treatment with Opsynvi led to a statistically significantly greater reduction in PVR compared with macitentan (treatment effect ratio, -29% [95% CI, -39%, -18%; P <.0001]), and vs tadalafil (treatment effect ratio, -28% [95% CI, -36%, -20%]; P <.0001). This effect was found to be consistent among treatment-naïve patients as well as those who were previously exposed to an ERA or PDE5 inhibitor.

Opsynvi Note

Notes

For all female patients: available only through the Macitentan-Containing Products REMS program. To enroll call (888) 572-2934 or www.MacitentanREMS.com.

Opsynvi Patient Counseling

See Literature

Opsynvi

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