Opsynvi Adverse Reactions

Clinically significant adverse reactions that appear in other sections include: Hypersensitivity [see Hypersensitivity under Contraindications]; Embryo-fetal Toxicity [see Use in Pregnancy: Embryo-fetal Toxicity under Precautions]; Hepatotoxicity [see Hepatotoxicity under Precautions]; Hypotension [see Hypotension under Precautions]; Decrease in Hemoglobin [see Hemoglobin Decrease under Precautions]; Visual Loss [see Visual Loss under Precautions and Patient Counselling Information]; Hearing loss [see Hearing Impairment under Precautions]; Fluid Retention [see Fluid Retention under Precautions]; Prolonged Erection [see Prolonged Erection under Precautions].
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The overall safety profile of OPSYNVI is based on data from a double-blind, active-controlled, phase 3 clinical study (A DUE) and an open-label extension study, in patients with PAH [see Pharmacology: Clinical Studies under Actions]. In the double-blind portion of the study, a total of 107 patients were treated with OPSYNVI 10 mg/40 mg, 35 patients were treated with 10 mg macitentan monotherapy, and 44 patients were treated with 40 mg tadalafil monotherapy. The duration of exposure to OPSYNVI during the double-blind portion was 16 weeks.
The most common adverse reactions (occurring in ≥10% of the OPSYNVI-treated patients) from the double-blind study data were edema/fluid retention (21%), anemia (19%), and headache/migraine (18%). The incidence of treatment discontinuations due to adverse events among patients receiving OPSYNVI in the double-blind phase of the study was 8%. The most frequent adverse reactions leading to discontinuation were anemia and hemoglobin decreased (2% grouped) and peripheral edema and peripheral swelling (2% grouped). Table 4 presents adverse reactions seen in patients treated for 16 weeks during the double-blind portion of A DUE. (See Table 4.)

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One-hundred eighty-five patients received OPSYNVI in the double-blind or open-label phase of the study. The median exposure to OPSYNVI during the combined double-blind/open-label extension was 59.9 weeks with a mean exposure of 63.2 weeks. Adverse reactions from the combined double-blind/open-label study data were similar to those observed in the double-blind study.
The following adverse reactions have been reported during clinical trials with the individual components of OPSYNVI but were not observed in 3% or more of subjects treated with OPSYNVI in the A DUE clinical trial: Macitentan: bronchitis, pharyngitis, transaminases increased, influenza, urinary tract infection.
Tadalafil: lower respiratory tract infection, prolonged erections, gastroesophageal reflux disease, vision blurred, tinnitus, swelling face, chest pain.
Postmarketing Experience: Additional adverse reactions have been identified during post-approval use of tadalafil. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Macitentan: liver injury, symptomatic hypotension, hypersensitivity reactions (angioedema, pruritus, and rash).
Tadalafil: Cardiovascular and cerebrovascular events including myocardial infarction, sudden cardiac death, stroke, and tachycardia; Nervous system events including, seizure, transient amnesia; Hypersensitivity reactions including urticaria, Stevens-Johnson syndrome, and exfoliative dermatitis; visual field defect, NAION, retinal vascular occlusion; sudden hearing loss, priapism.