OPSUMIT^® (macitentan) has a well-studied safety and tolerability profile

Adverse reactions in the SERAPHIN study¹

Adverse reactions more frequent with OPSUMIT^® 10 mg vs placebo by ≥3%	OPSUMIT^® 10 mg (n=242)	Placebo (n=249)
Anemia	13%	3%
Nasopharyngitis /pharyngitis	20%	13%
Bronchitis	12%	6%
Headache	14%	9%
Influenza	6%	2%
Urinary tract infection	9%	6%

The overall incidence of treatment discontinuations due to adverse events with OPSUMIT® (approximately 11%) was similar to placebo (approximately 12%)^1,2

Additional adverse events of special interest^1-3

	OPSUMIT® 10 mg (n=242)	Placebo (n=249)
Hypotension	7.0%	4.4%
Edema	21.9%	20.5%
Peripheral edema	18.2%	18.1%

Incidence of elevated aminotransferases/decreases in hemoglobin^1,2

	OPSUMIT® 10 mg (n=242)	Placebo (n=249)
ALT/AST elevations >3 x ULN	3.4%	4.5%
ALT/AST elevations >8 x ULN	2.1%	0.4%
Patients with Hgb <10 g/dL	8.7%	3.4%

Drug-drug interactions¹

MEDICATION	EFFECT
Strong inducers of CYP3A4 (eg, rifampin)	Significantly reduce macitentan exposure Concomitant use of OPSUMIT® with strong CYP3A4 inducers should be avoided
Strong inhibitors of CYP3A4 (eg, ketoconazole)	Approximately double macitentan exposure Concomitant use of OPSUMIT® with strong CYP3A4 inhibitors should be avoided Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment (eg, ritonavir)
Moderate dual inhibitors of CYP3A4 and CYP2C9 (eg, fluconazole and amiodarone)	Predicted to increase macitentan exposure approximately 4-fold Concomitant use of OPSUMIT® with moderate dual inhibitors of CYP3A4 and CYP2C9 should be avoided
Combined moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor	Concomitant use of OPSUMIT® with both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor should be avoided

Postmarketing experience with OPSUMIT®¹

Because these following adverse reactions are reported voluntarily during post-approval use of OPSUMIT® from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions (angioedema, pruritus, and rash)
Flushing
Nasal congestion
Elevations of liver aminotransferases (ALT, AST) and liver injury; in most cases alternative causes could be identified (heart failure, hepatic congestion, autoimmune hepatitis). Endothelin receptor antagonists have been associated with elevations of aminotransferases, hepatotoxicity, and cases of liver failure
Edema/fluid retention. Cases of edema and fluid retention occurred within weeks of starting OPSUMIT®, some requiring intervention with a diuretic, fluid management, or hospitalization for decompensated heart failure
Symptomatic hypotension

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ALT=alanine aminotransferase; AST=aspartate aminotransferase; CYP=cytochrome P450; Hgb=hemoglobin; HIV=human immunodeficiency virus; PAH=pulmonary arterial hypertension; SERAPHIN=Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve CliNical Outcome; ULN=upper limit of normal.

References: 1. OPSUMIT® (macitentan) full Prescribing Information. Actelion Pharmaceuticals US, Inc. 2. Pulido T, Adzerikho I, Channick RN, et al; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809-818 and suppl 1-21. doi:10.1056/NEJMoa1213917 3. US Dept of Health and Human Services, US Food and Drug Administration, Center for Drug Evaluation and Research. Opsumit® (macitentan) NDA 204410. Accessed July 19, 2024. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000MedR.pdf

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OPSUMIT® (macitentan) has a well-studied safety and tolerability profile

Adverse reactions in the SERAPHIN study1

Additional adverse events of special interest1-3

Incidence of elevated aminotransferases/decreases in hemoglobin1,2

Drug-drug interactions1

Postmarketing experience with OPSUMIT®1