Last reviewed 2026-04-20 · How we verify

Macitentan and Tadalafil

Macitentan and Tadalafil, marketed by Humanis Saglık Anonim Sirketi, is a chronic treatment for pulmonary arterial hypertension (PAH) with a key composition patent expiring in 2028. The drug's key strength lies in its dual mechanism of action, combining an endothelin receptor antagonist with a phosphodiesterase-5 inhibitor, which may offer enhanced efficacy and patient compliance. The primary risk is the upcoming patent expiry in 2028, which could lead to increased competition from generic alternatives.

At a glance

Approved indications

• Chronic treatment of PAH

Boxed warnings

• WARNING: EMBRYO-FETAL TOXICITY OPSYNVI is contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications (4.1) , Warnings and Precautions (5.1) , Use in Specific Populations (8.1) ]. Therefore, for females of reproductive potential, exclude pregnancy before the start of treatment with OPSYNVI. Advise use of effective contraception before the initiation of treatment, during treatment, and for one month after stopping treatment with OPSYNVI [see Dosage and Administration (2.2) , Use in Specific Populations (8.3) ]. When pregnancy is detected, discontinue OPSYNVI as soon as possible [see Warnings and Precautions (5.1) ] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Based on animal data, OPSYNVI may cause fetal harm if used during pregnancy ( 4.1 , 5.1 , 8.1 ). Females of reproductive potential: exclude pregnancy before start of treatment. Prevent pregnancy prior to initiation of treatment, during treatment and for one month after treatment by using effective methods of contraception ( 2.2 , 8.3 ). When pregnancy is detected, discontinue OPSYNVI as soon as possible ( 5.1 ).

Common side effects

• edema/fluid retention
• anemia
• headache/migraine
• abdominal pain
• hypotension
• myalgia
• nasopharyngitis
• nausea
• increased uterine bleeding
• back pain
• flushing
• vomiting

Drug interactions

• Nitrates
• Strong CYP3A4 Inducers (e.g., rifampin)
• Strong CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir, itraconazole)
• Moderate Dual or Combined CYP3A4 and CYP2C9 Inhibitors (e.g., fluconazole, amiodarone)
• Alpha-Blockers (e.g., doxazosin)
• Antihypertensives (e.g., amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalapril, metoprolol)
• Alcohol

Key clinical trials

• A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (PHASE3)
• Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (PHASE3)
• Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM) - PDE5
• A Study to Compare the Macitentan-tadalafil Fixed Dose Combination Tablet Relative to the Concomitant Administration of the Reference Tablets of Macitentan and Tadalafil in Healthy Subjects (PHASE1)
• A Study of Macitentan and Tadalafil as a Fixed Dose Combination and the Free Combination in Healthy Adult Participants (PHASE1)
• The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (PHASE3)
• A Study of Macitentan/Tadalafil Combination Administered a Fixed-dose Combination Formulation Compared to the Reference Free Combination of Macitentan and Tadalafil (PHASE1)
• A Study of Fixed Dose Combination of Macitentan/Tadalafil (10 mg/20 mg) Compared to the Reference Free Combination of Macitentan and Tadalafil in Healthy Adult Participants (PHASE1)

Primary sources

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