Endothelin Receptor Antagonist

Macitentan

Approved 5 Aug 2024OralTablet

The FDA lists this product in 11 strengths and forms.

Indications

1.1Pulmonary Arterial Hypertension

Macitentan tablets are an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH. Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of 2 years. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%) [see Clinical Studies (14.1)] .

Contraindications

Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 )

4.1Pregnancy

Macitentan tablets may cause fetal harm when administered to a pregnant woman. Macitentan tablets are contraindicated in females who are pregnant. Macitentan tablets were consistently shown to have teratogenic effects when administered to animals. If macitentan tablets are used during pregnancy, advise the patient of the potential risk to a fetus [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)] .

4.2Hypersensitivity

Macitentan tablets is contraindicated in patients with a history of a hypersensitivity reaction to macitentan or any component of the product [see Adverse Reactions (6.2)] .

Warnings and precautions

EMBRYO-FETAL TOXICITY Macitentan tablets are 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 macitentan tablets. Advise use of effective contraception before the initiation of treatment, during treatment, and for one month after stopping treatment with macitentan tablets [see Dosage and Administration (2.2), Use in Specific Populations (8.3)] .

At a glance

Brand name: Macitentan
Pharmacologic class: Endothelin Receptor Antagonist
Route: Oral
Dosage form: Tablet
Applicant: Torrent
Status: Prescription
FDA approval: 5 Aug 2024
Application: ANDA211107-001

Indications

1.1Pulmonary Arterial Hypertension

Contraindications

Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 )

4.1Pregnancy

4.2Hypersensitivity

Macitentan tablets is contraindicated in patients with a history of a hypersensitivity reaction to macitentan or any component of the product [see Adverse Reactions (6.2)] .

Warnings and precautions

Adverse reactions

Clinically significant adverse reactions that appear in other sections of the labeling include: Embryo-fetal Toxicity [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Fluid Retention [see Warnings and Precautions (5.3)] Decrease in Hemoglobin [see Warnings and Precautions (5.4)] Most common adverse reactions (more frequent than placebo by ≥3%) are anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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 clinical practice. Safety data for macitentan tablets were obtained primarily from one placebo-controlled clinical study in 742 patients with PAH (SERAPHIN study) [see Clinical Studies (14.1)] .

The exposure to macitentan tablets in this trial was up to 3.6 years with a median exposure of about 2 years (N=542 for 1 year; N=429 for 2 years; and N=98 for more than 3 years). The overall incidence of treatment discontinuations because of adverse events was similar across macitentan tablets 10 mg and placebo treatment groups (approximately 11%). Table 2 presents adverse reactions more frequent on macitentan tablets than on placebo by ≥3%.

Table 2: Adverse Reactions Adverse Reaction Macitentan tablets 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

6.2Postmarketing Experience

The following adverse reactions have been identified during post-approval use of macitentan tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders : hypersensitivity reactions (angioedema, pruritus and rash) Vascular disorders : flushing Respiratory, thoracic and mediastinal disorders : nasal congestion Gastrointestinal disorders: Elevations of liver aminotransferases (ALT, AST) and liver injury have been reported with macitentan tablets use; 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 [see Warnings and Precautions (5.2)]. General disorders and administration site conditions : edema/fluid retention. Cases of edema and fluid retention occurred within weeks of starting macitentan tablets, some requiring intervention with a diuretic, fluid management or hospitalization for decompensated heart failure [see Warnings and Precautions (5.3)].

Cardiac disorders : symptomatic hypotension

Macitentan

Indications

1.1Pulmonary Arterial Hypertension

Contraindications

4.1Pregnancy

4.2Hypersensitivity

Warnings and precautions

At a glance

Two medicines in one question?

Macitentan

Indications

1.1Pulmonary Arterial Hypertension

Contraindications

4.1Pregnancy

4.2Hypersensitivity

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

7.1Strong CYP3A4 Inducers

7.2Strong CYP3A4 Inhibitors

7.3Moderate Dual or Combined CYP3A4 and CYP2C9 Inhibitors

Adverse reactions

6.1Clinical Trial Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information