Opsynvi Drug Interactions

Nitrates: Administration of nitrates within 48 hours after the last dose of OPSYNVI is contraindicated [see Concomitant Organic Nitrates under Contraindications].
Strong CYP3A4 Inducers: Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Use of OPSYNVI with strong CYP3A4 inducers should be avoided [see Pharmacology: Pharmacokinetics under Actions].
Strong CYP3A4 Inhibitors: Concomitant use of strong CYP3A4 inhibitors like ketoconazole increase exposure to both macitentan and tadalafil. Avoid concomitant use of OPSYNVI with strong CYP3A4 inhibitors such as ritonavir, ketoconazole and itraconazole. Use other PAH treatment options when strong CYP3A4 inhibitors are needed [see Pharmacology: Pharmacokinetics under Actions].
Moderate Dual or Combined CYP3A4 and CYP2C9 Inhibitors: Concomitant use of moderate dual inhibitors of CYP3A4 and CYP2C9 such as fluconazole is predicted to increase macitentan exposure approximately 4-fold. Avoid concomitant use of OPSYNVI with moderate dual inhibitors of CYP3A4 and CYP2C9 (such as fluconazole and amiodarone) [see Pharmacology: Pharmacokinetics under Actions].
Concomitant treatment of both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor with OPSYNVI should also be avoided [see Pharmacology: Pharmacokinetics under Actions].
Alpha-Blockers: PDE5 inhibitors, including tadalafil, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. In patients who are taking alpha₁ blockers, concomitant administration of tadalafil may lead to symptomatic hypotension in some patients. Therefore, the combination of OPSYNVI and doxazosin is not recommended [see Hypotension under Precautions and Pharmacology: Pharmacodynamics under Actions].
Antihypertensives: PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. Clinical pharmacology studies were conducted to assess the effect of tadalafil on the potentiation of the blood-pressure-lowering effects of selected antihypertensive medications (amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalapril, and metoprolol). Small reductions in blood pressure occurred following coadministration of tadalafil with these agents compared with placebo [see Pharmacology: Pharmacodynamics under Actions].
Alcohol: Both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Substantial consumption of alcohol (e.g., 5 units or greater) in combination with OPSYNVI can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Tadalafil (10 mg or 20 mg) did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations [see Pharmacology: Pharmacodynamics under Actions].