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Opsumit macitentan 10 mg Tablet, Film Coated, 30-count — NDC 66215-501-30 (Billing 66215-0501-30)

by Actelion Pharmaceuticals US, Inc. · 1 BOTTLE in 1 CARTON / 30 TABLET, FILM COATED in 1 BOTTLE

This is a package of 30 tablets of Opsumit macitentan 10 mg Tablet, Film Coated from Actelion Pharmaceuticals US, Inc., marketed since Nov 2013 and currently FDA-listed. It is the main listing for this product, which comes in 2 package sizes.

NDC 66215-0501-30
🏷️ FDA NDC (as labeled) 66215-501-30 billing pads the product segment with a zero
This package
Contains30-count Medicaid pays$426.28 / unit · 12 mo Per package$12,788.44 / 30 tablets · Medicaid Pack sizes2 compare ↓
Also priced by: Part D plans $450.76/unit — full pricing hub ↓
Main listing for product 66215-501 · Also comes in: 15 tablets 66215-501-15
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 66215-501-30 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
66215 labeler · 501 product · 30 package
Package marketed since
Nov 4, 2013
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
30 EA per package
Barcode (UPC-A, from the NDC)
3 6621550130 6
Medicaid fills, this package
17,706 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 66215-501-30
Product NDC 66215-501
11-digit billing NDC 66215050130
NCPDP billing unit EA — each (per item)
RxCUI 1442137, 1442143
UNII Z9K9Y9WMVL
Application # NDA204410
SPL Set ID 1e484a50-55db-4b85-8c57-6cd1b0353abd
Established class (EPC) Endothelin Receptor Antagonist
Mechanism of action Endothelin Receptor Antagonists
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2013-11-04
Route ORAL
Dosage form TABLET, FILM COATED
Substance MACITENTAN
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 40160050000320
GPI class Opsumit
GCN Seq No 071567
GCN 35443
HICL code 040677
Ingredient (HICL) Macitentan
HIC1 code B
Therapeutic class — broad (HIC1) Respiratory System
HIC2 code B1
Therapeutic class — intermediate (HIC2) Affect Primarily Lungs
HIC3 code B1B
Therapeutic class — specific (HIC3) Pulmonary Anti-Htn, Endothelin Receptor Antagonist
AHFS code 24:12.92.00
AHFS class Vasodilating Agents, Miscellaneous
FDB label name OPSUMIT 10 MG TABLET
FDB brand name Opsumit
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 071567
  • GCN: 35443
  • GPI-14 (Medi-Span): 40160050000320
  • HICL (First Databank): 040677
  • AHFS class code: 24:12.92.00
  • RxCUI (RxNorm): 1442137
Why two NDCs? The FDA registers this code as 66215-501-30 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 66215-0501-30. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Endothelin Receptor Antagonist class.

Pharmacologic class Endothelin Receptor Antagonist
Drug family (ATC) Antihypertensives for pulmonary arterial hypertension
How it works Endothelin Receptor Antagonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name OPSUMIT 10 MG TABLET Ingredient Macitentan
📗 Our plain-language guide HelloPharmacist
  • Macitentan works by blocking a protein called endothelin-1 that causes the blood vessels in your lungs to narrow and stiffen — that's what drives pulmonary arterial hypertension. B...
  • What exactly does macitentan do, and why do I need to take it every day?
  • Good news — you can take macitentan with or without food. Studies showed that even a high-fat meal doesn't meaningfully change how much of the drug gets into your system. The most...
  • Can I take this pill with food, or do I need to take it on an empty stomach?
📖 Read our full Macitentan guide →
1
Nutrient depletion considerations

Macitentan may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Macitentan nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $426.28 $12,788.44 / 30 tablets
Medicare drug plans payPart D · Q2 2026 $450.76 $13,522.75 / 30 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
66215-0501-15 66215-501-15 1 BLISTER PACK in 1 CARTON / 15 TABLET, FILM COATED in 1 BLISTER PACK 2013-11-04 — Active
66215-0501-30 You're viewing this Main listing 1 BOTTLE in 1 CARTON / 30 TABLET, FILM COATED in 1 BOTTLE 2013-11-04 — Active

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 30-count package — 1 bottle in 1 carton / 30 tablet, film coated in 1 bottle.
How does this package differ from NDC 66215-0501-15?
Both are Opsumit macitentan 10 mg Tablet, Film Coated — the drug itself is identical. This page's package is the 30-count one, while NDC 66215-0501-15 is the 15 tablets package.
What NDC number is used to bill for this package of Opsumit macitentan 10 mg Tablet, Film Coated?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Macitentan 10 mg 00378-0606-93 Mylan 30 tablets — AB FDA listed —
macitentan 10 mg 00480-0915-56 Teva 30 tablets — AB FDA listed —
macitentan 10 mg 00781-8135-31 Sandoz 30 tablets — AB FDA listed —
Macitentan 10 mg 13668-0542-05 Torrent 500 tablets — AB FDA listed —
Macitentan 10 mg 42385-0907-15 Laurus 15 tablets — AB FDA listed —
Macitentan 10 mg 46708-0373-30 Alembic 30 tablets — AB FDA listed —
Macitentan 10 mg 47335-0070-15 Sun 3 tablets — AB FDA listed —
Macitentan 10 mg 59651-0147-30 Aurobindo 30 tablets — AB FDA listed —
macitentan 10 mg 60505-4644-03 Apotex 30 tablets — AB FDA listed —
Macitentan 10 mg 62332-0373-30 Alembic 30 tablets — AB FDA listed —
Opsumit 10 mgthis 66215-0501-30 Actelion 30 tablets — AB FDA listed —
Macitentan 10 mg 69238-1327-03 Amneal 30 tablets — AB FDA listed —
Macitentan 10 mg 70710-1166-03 Zydus 30 tablets — AB FDA listed —
Macitentan 10 mg 82293-0041-10 Novugen 15 tablets — AB FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2013
First FDA approval
Oct 2013
📍
2026
Currently FDA-listed
13 years listed
🛡️
2029
Latest patent/protection listed
not a guaranteed launch date
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Oct 2029. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Oct 18, 2013 AB TE-rated RLD RS ⏳ ~3 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 8268847 — method of use (U-1446)
US 9265762 — method of use (U-1820)
US 10946015 — method of use (U-1445)
US 8367685 — method of use (U-1445)
US 7094781 — drug substance
US 8268847*PED — drug product
US 7094781*PED — drug product
US 8367685*PED — drug product
US 9265762*PED — drug product
US 10946015*PED — drug product
Exclusivity M-187
Exclusivity PED
2013 2015 2017 2019 2021 2023 2025 2027 2029
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (10)
PatentTypeUse codeExpires
US 8268847 ↗ Method of use U-1446 Apr 18, 2029
US 9265762 ↗ Method of use U-1820 May 29, 2027
US 10946015 ↗ Method of use U-1445 Sep 11, 2026
US 8367685 ↗ Method of use U-1445 Oct 4, 2028
US 7094781 ↗ Drug substance — Dec 5, 2025
US 8268847*PED ↗ Drug product — Oct 18, 2029
US 7094781*PED ↗ Drug product — Jun 5, 2026
US 8367685*PED ↗ Drug product — Apr 4, 2029
US 9265762*PED ↗ Drug product — Nov 29, 2027
US 10946015*PED ↗ Drug product — Mar 11, 2027
FDA exclusivity
CodeWhat it grantsExpires
M-187New indication / labeling change (3-year)Feb 28, 2028
PEDPediatric Exclusivity (+6 months)Aug 28, 2028
Common questions
Is there a generic version of OPSUMIT 10 MG TABLET?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for OPSUMIT 10 MG TABLET. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Macitentan inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerActelion Pharmaceuticals US, Inc.
Application holderACTELION PHARMACEUTICALS US INC
FDA applicationNDA204410 (NDA)
Labeler code66215
First marketedNov 2013
Product typeHuman Prescription Drug
Portfolio21 products on file

More NDCs from Actelion Pharmaceuticals US, Inc. labeler code 66215

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 179 words ▾

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

When pregnancy is detected, discontinue OPSUMIT 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, OPSUMIT 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 OPSUMIT as soon as possible ( 5.1 ).

🎯 Indications and Usage 130 words ▾

1 INDICATIONS AND USAGE OPSUMIT is 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 ( 1.1 ).

1.1Pulmonary Arterial Hypertension OPSUMIT is 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) ] .

⏱️ Dosage and Administration 106 words ▾

2 DOSAGE AND ADMINISTRATION 10 mg once daily . Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended ( 2.1 ).

2.1Recommended Dosage The recommended dosage of OPSUMIT is 10 mg once daily for oral administration. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended.

2.2Pregnancy Testing in Females of Reproductive Potential Exclude pregnancy before initiating treatment with OPSUMIT in females of reproductive potential [see Boxed Warning , Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.3) ] .

💊 Dosage Forms and Strengths 25 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: 10 mg, bi-convex film-coated, round, white, and debossed with "10" on both sides. Tablet: 10 mg ( 3 )

⛔ Contraindications 100 words ▾

4 CONTRAINDICATIONS Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 )

4.1Pregnancy OPSUMIT may cause fetal harm when administered to a pregnant woman. OPSUMIT is contraindicated in females who are pregnant. OPSUMIT was consistently shown to have teratogenic effects when administered to animals. If OPSUMIT is 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 OPSUMIT 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 Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS ERAs cause hepatotoxicity and liver failure. Obtain baseline liver enzymes and monitor as clinically indicated ( 5.2 ). Fluid retention may require intervention ( 5.3 ). Decreases in hemoglobin ( 5.4 ). Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment ( 5.5 ). Decreases in sperm count have been observed in patients taking ERAs ( 5.6 ).

5.1Embryo-fetal Toxicity Based on data from animal reproduction studies, OPSUMIT may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for ERAs do not establish the presence or absence of major birth defects related to the use of OPSUMIT. Advise patients who can become pregnant of the potential risk to a fetus.

Obtain a pregnancy test prior to initiation of therapy with OPSUMIT. Advise patients who can become pregnant to use effective contraceptive methods prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with OPSUMIT. When pregnancy is detected, discontinue use as soon as possible [see Dosage and Administration (2.2) , Contraindications (4.1) , and Use in Specific Populations (8.1 , 8.3) ] .

5.2Hepatotoxicity ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. The incidence of elevated aminotransferases in the study of OPSUMIT in PAH is shown in Table 1. Table 1: Incidence of Elevated Aminotransferases in the SERAPHIN Study OPSUMIT 10 mg (N=242) Placebo (N=249) >3 × ULN 3.4% 4.5% >8 × ULN 2.1% 0.4% In the placebo-controlled study of OPSUMIT, discontinuations for hepatic adverse events were 3.3% in the OPSUMIT 10 mg group vs.

1.6% for placebo. Obtain liver enzyme tests prior to initiation of OPSUMIT and repeat during treatment as clinically indicated [see Adverse Reactions (6.2) ] . Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching).

If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 × ULN, or by clinical symptoms of hepatotoxicity, discontinue OPSUMIT. Consider re-initiation of OPSUMIT when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity.

5.3Fluid Retention Peripheral edema and fluid retention are known clinical consequences of PAH and known effects of ERAs. In the placebo-controlled study of OPSUMIT in PAH, the incidence of edema was 21.9% in the OPSUMIT 10 mg group and 20.5% in the placebo group. Patients with underlying left ventricular dysfunction may be at particular risk for developing significant fluid retention after initiation of ERA treatment.

In a small study of OPSUMIT in patients with pulmonary hypertension because of left ventricular dysfunction, more patients in the OPSUMIT group developed significant fluid retention and had more hospitalizations because of worsening heart failure compared to those randomized to placebo. Postmarketing cases of edema and fluid retention occurring within weeks of starting OPSUMIT, some requiring intervention with a diuretic or hospitalization for decompensated heart failure, have been reported [see Adverse Reactions (6.2) ] .

Monitor for signs of fluid retention after OPSUMIT initiation. If clinically significant fluid retention develops, evaluate the patient to determine the cause, such as OPSUMIT or underlying heart failure, and the possible need to discontinue OPSUMIT.

5.4Hemoglobin Decrease Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and were observed in clinical studies with OPSUMIT. These decreases occurred early and stabilized thereafter. In the placebo-controlled study of OPSUMIT in PAH, OPSUMIT 10 mg caused a mean decrease in hemoglobin from baseline to up to 18 months of about 1.0 g/dL compared to… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 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 Actelion at 1-800-526-7736 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 OPSUMIT were obtained primarily from one placebo-controlled clinical study in 742 patients with PAH (SERAPHIN study) [see Clinical Studies (14.1) ]. The exposure to OPSUMIT 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 OPSUMIT 10 mg and placebo treatment groups (approximately 11%). Table 2 presents adverse reactions more frequent on OPSUMIT than on placebo by ≥3%. Table 2: Adverse Reactions Adverse Reaction 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

6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of OPSUMIT. 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 OPSUMIT 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 OPSUMIT, some requiring intervention with a diuretic, fluid management or hospitalization for decompensated heart failure [see Warnings and Precautions (5.3) ].

Cardiac disorders: symptomatic hypotension

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with OPSUMIT ( 7.1 , 12.3 ). Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . Moderate dual CYP3A4 and CYP2C9 inhibitors (fluconazole, amiodarone) or use of combined CYP3A4 and CYP2C9 inhibitors may increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.3 , 12.3 ).

7.1Strong CYP3A4 Inducers Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Concomitant use of OPSUMIT with strong CYP3A4 inducers should be avoided [see Clinical Pharmacology (12.3) ] .

7.2Strong CYP3A4 Inhibitors Concomitant use of strong CYP3A4 inhibitors like ketoconazole approximately double macitentan exposure. Many HIV drugs like ritonavir are strong inhibitors of CYP3A4. Avoid concomitant use of OPSUMIT with strong CYP3A4 inhibitors [see Clinical Pharmacology (12.3) ] . Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment [see Clinical Pharmacology (12.3) ] .

7.3Moderate 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 based on physiologically based pharmacokinetic (PBPK) modeling. Avoid concomitant use of OPSUMIT with moderate dual inhibitors of CYP3A4 and CYP2C9 (such as fluconazole and amiodarone) [see Clinical Pharmacology (12.3) ] . Concomitant treatment of both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor with OPSUMIT should also be avoided [see Clinical Pharmacology (12.3) ].

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )

8.1Pregnancy Risk Summary Based on data from animal reproduction studies, OPSUMIT may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy. There are risks to the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see Clinical Considerations ] . Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as OPSUMIT have not identified an increased risk of major birth defects; however, these data are limited.

Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use. Macitentan was teratogenic in rabbits and rats at all doses tested.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the risk to a fetus [see Contraindications (4.1) ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk In patients with pulmonary arterial hypertension, pregnancy is associated with an increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction and premature labor. Data Animal Data In both rabbits and rats, there were cardiovascular and mandibular arch fusion abnormalities.

Administration of macitentan to female rats from late pregnancy through lactation caused reduced pup survival and impairment of the male fertility of the offspring at all dose levels tested.

8.2Lactation Risk Summary There are no data on the presence of macitentan in human milk, the effects on the breastfed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breastfed infants from OPSUMIT advise women not to breastfeed during treatment with OPSUMIT.

8.3Females and Males of Reproductive Potential Based on data from animal reproductive toxicity studies, OPSUMIT can cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1) , and Use in Specific Populations (8.1) ]. Pregnancy Testing Verify that patients who can become pregnant are not pregnant prior to initiating OPSUMIT. The patient should contact their physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected.

If the pregnancy test is positive, the physician and patient should discuss the risks to the pregnancy, and the fetus. Contraception Patients who can become pregnant who are using OPSUMIT should use an effective method of contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with OPSUMIT to prevent pregnancy [see Warnings and Precautions (5.1) ] . Infertility Based on findings in animals, OPSUMIT may impair fertility in males of reproductive potential.

It is not known whether effects on fertility would be reversible [see Warnings and Precautions (5.6) , Adverse Reactions (6.1) , and Nonclinical Toxicology (13.1) ] .

8.4Pediatric Use The safety and effectiveness of OPSUMIT in pediatric patients have not been established for the treatment of PAH. OPSUMIT was evaluated in 148 pediatric patients 2 to 17 years… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on data from animal reproduction studies, OPSUMIT may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy. There are risks to the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see Clinical Considerations ] . Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as OPSUMIT have not identified an increased risk of major birth defects; however, these data are limited.

Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use. Macitentan was teratogenic in rabbits and rats at all doses tested.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the risk to a fetus [see Contraindications (4.1) ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk In patients with pulmonary arterial hypertension, pregnancy is associated with an increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction and premature labor. Data Animal Data In both rabbits and rats, there were cardiovascular and mandibular arch fusion abnormalities.

Administration of macitentan to female rats from late pregnancy through lactation caused reduced pup survival and impairment of the male fertility of the offspring at all dose levels tested.

🧒 Pediatric Use 111 words ▾

8.4Pediatric Use The safety and effectiveness of OPSUMIT in pediatric patients have not been established for the treatment of PAH. OPSUMIT was evaluated in 148 pediatric patients 2 to 17 years of age with PAH in a single open-label, randomized trial with an extension period in which all patients received treatment. The trial did not demonstrate a clinical benefit of OPSUMIT compared with standard of care in the treatment of PAH.

It cannot be ruled out that a trial with a different design would demonstrate a clinical benefit in this patient population. Adverse reactions observed in the trial were similar in nature to those reported in clinical trials in adults.

🧓 Geriatric Use 37 words ▾

8.5Geriatric Use Of the total number of subjects in the clinical study of OPSUMIT for PAH, 14% were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

🆘 Overdosage 59 words ▾

10 OVERDOSAGE OPSUMIT has been administered as a single dose of up to and including 600 mg to healthy subjects (60 times the approved dosage). Adverse reactions of headache, nausea and vomiting were observed. In the event of an overdose, standard supportive measures should be taken, as required. Dialysis is unlikely to be effective because macitentan is highly protein-bound.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Endothelin (ET)-1 and its receptors (ET A and ET B ) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. In disease conditions such as PAH, the local ET system is upregulated and is involved in vascular hypertrophy and in organ damage. Macitentan is an endothelin receptor antagonist that inhibits the binding of ET-1 to both ET A and ET B receptors.

Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro . The clinical impact of dual endothelin blockage is unknown.

12.2Pharmacodynamics Pulmonary Hemodynamics The clinical efficacy study in patients with pulmonary arterial hypertension assessed hemodynamic parameters in a subset of patients after 6 months of treatment. Patients treated with OPSUMIT 10 mg (N=57) achieved a median reduction of 37% (95% CI 22–49) in pulmonary vascular resistance and an increase of

0.6L/min/m 2 (95% CI 0.3–0.9) in cardiac index compared to placebo (N=67). Cardiac Electrophysiology In a randomized, placebo-controlled four-way crossover study with a positive control in healthy subjects, repeated doses of macitentan 10 and 30 mg (3 times the recommended dosage) had no significant effect on the QTc interval.

12.3Pharmacokinetics The pharmacokinetics of macitentan and its active metabolite have been studied primarily in healthy subjects. The pharmacokinetics of macitentan are dose proportional over a range from 1 mg to 30 mg after once daily administration. A cross study comparison shows that the exposures to macitentan and its active metabolite in patients with PAH are similar to those observed in healthy subjects.

Absorption and Distribution The maximum plasma concentration of macitentan is achieved about 8 hours after oral administration. The absolute bioavailability after oral administration is not known. In a study in healthy subjects, the exposure to macitentan and its active metabolite were unchanged after a high fat breakfast.

Macitentan may therefore be taken with or without food. Macitentan and its active metabolite are highly bound to plasma proteins (>99%), primarily to albumin and to a lesser extent to alpha-1-acid glycoprotein. The apparent volumes of distribution (Vss/F) of macitentan and its active metabolite were about 50 L and 40 L respectively in healthy subjects.

Metabolism and Elimination Following oral administration, the apparent elimination half-lives of macitentan and its active metabolite are approximately 16 hours and 48 hours, respectively. Macitentan is metabolized primarily by oxidative depropylation of the sulfamide to form the pharmacologically active metabolite. This reaction is dependent on the cytochrome P450 (CYP) system, mainly CYP3A4 with minor contributions of CYP2C8, CYP2C9, and CYP2C19.

At steady state in PAH patients, the systemic exposure to the active metabolite is 3-times the exposure to macitentan and is expected to contribute approximately 40% of the total pharmacologic activity. In a study in healthy subjects with radiolabeled macitentan, approximately 50% of radioactive drug material was eliminated in urine but none was in the form of unchanged drug or the active metabolite. About 24% of the radioactive drug material was recovered from feces.

Special Populations There are no clinically relevant effects of age, sex, or race on the pharmacokinetics of macitentan and its active metabolite. Renal Impairment Exposure to macitentan and its active metabolite in patients with severe renal impairment (CrCl 15–29 mL/min) compared to healthy subjects was increased by 30% and 60%, respectively. This increase is not considered clinically relevant.

Hepatic Impairment Exposure to macitentan was decreased by 21%, 34%, and… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 128 words ▾

12.1Mechanism of Action Endothelin (ET)-1 and its receptors (ET A and ET B ) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. In disease conditions such as PAH, the local ET system is upregulated and is involved in vascular hypertrophy and in organ damage. Macitentan is an endothelin receptor antagonist that inhibits the binding of ET-1 to both ET A and ET B receptors.

Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro . The clinical impact of dual endothelin blockage is unknown.

📦 How Supplied / Storage and Handling 84 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING OPSUMIT ® (macitentan) tablets are 10 mg white, film-coated, bi-convex debossed with "10" on both sides and supplied as follows: 15 count /PVC/ PE/PVDC aluminum foil blisters in carton (NDC 66215-501-15) 30 count white high-density polyethylene bottle in carton (NDC 66215-501-30) Store at 20 ºC to 25 ºC (68 ºF to 77 ºF). Excursions are permitted between 15 °C and 30 °C (59 °F and 86 °F). [See USP Controlled Room Temperature] . Keep out of reach of children.

📦 Storage and Handling 38 words ▾

Store at 20 ºC to 25 ºC (68 ºF to 77 ºF). Excursions are permitted between 15 °C and 30 °C (59 °F and 86 °F). [See USP Controlled Room Temperature] . Keep out of reach of children.

📋 Description 132 words ▾

11 DESCRIPTION OPSUMIT ® (macitentan) is an endothelin receptor antagonist. The chemical name of macitentan is N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide. It has a molecular formula of C 19 H 20 Br 2 N 6 O 4 S and a molecular weight of 588.27.

Macitentan is achiral and has the following structural formula: Macitentan is a crystalline powder that is insoluble in water. In the solid state macitentan is very stable, is not hygroscopic, and is not light sensitive. OPSUMIT is available as a 10 mg film-coated tablet for once daily oral administration.

The tablets include the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 80, povidone, and sodium starch glycolate Type A. The tablets are film-coated with a coating material containing polyvinyl alcohol, soya lecithin, talc, titanium dioxide, and xanthan gum. Chemical Structure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise patient to read FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity Counsel female patients of reproductive potential about the need to use effective methods of contraception prior to initiation of treatment with OPSUMIT, during treatment and for one month after treatment discontinuation. Females of reproductive potential should have a negative pregnancy test prior to treatment with OPSUMIT [see Contraindications (4.1) , and Use in Specific Populations (8.1 , 8.3) ] .

Patients should be instructed to contact their physician if they suspect they may be pregnant. Patients should seek additional contraceptive advice from a gynecologist or similar expert as needed. Educate and counsel females of reproductive potential on the use of emergency contraception in the event of unprotected sex or contraceptive failure.

Advise pre-pubertal females to report any changes in their reproductive status immediately to her prescriber. Review the Medication Guide with female patients. Lactation Advise women not to breastfeed during treatment with OPSUMIT [see Use in Specific Populations (8.2) ] .

Hepatotoxicity Some members of this pharmacological class are hepatotoxic. Educate patients on signs of hepatotoxicity. Advise patients that they should contact their doctor if they have unexplained nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching [see Warnings and Precautions (5.2) ].

Fluid Retention Educate patients on signs of fluid retention. Advise patients that they should contact their doctor if they have unusual weight increase or swelling of the ankles or legs [see Warnings and Precautions (5.3) ] .

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE OPSUMIT ® (OP-sum-it) (macitentan) tablets This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 4/2025 Read this Medication Guide for OPSUMIT before you start taking OPSUMIT and each time you get a refill.

There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is the most important information I should know about OPSUMIT?

Serious birth defects. OPSUMIT can cause serious birth defects if taken during pregnancy. Females should not be pregnant when they start taking OPSUMIT or become pregnant during treatment with OPSUMIT.

Females who are able to get pregnant should have a negative pregnancy test before beginning treatment with OPSUMIT. Talk to your healthcare provider about your menstrual cycle. Your healthcare provider will decide when to do the pregnancy test and will order a pregnancy test for you depending on your menstrual cycle.

Females who are able to get pregnant are females who: have entered puberty, even if they have not started their menstrual period, and have a uterus, and have not gone through menopause. Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed. Females who are not able to get pregnant are females who: have not yet entered puberty, or do not have a uterus, or have gone through menopause.

Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed, or are infertile for other medical reasons and this infertility is permanent and cannot be reversed. Females who are able to get pregnant should use effective birth control before starting treatment with OPSUMIT, during treatment, and for one month after stopping OPSUMIT because the medicine may still be in the body. Talk with your healthcare provider or gynecologist (a doctor who specializes in female reproduction) to find out about options for acceptable birth control that you may use to prevent pregnancy during treatment with OPSUMIT.

If you decide that you want to change the form of birth control that you use, talk with your healthcare provider or gynecologist to be sure that you choose another acceptable form of birth control. Do not have unprotected sex. Talk to your healthcare provider or pharmacist right away if you have unprotected sex or if you think your birth control has failed.

Your healthcare provider may talk with you about using emergency birth control. Tell your healthcare provider right away if you miss a menstrual period or think you may be pregnant. If you are the parent or caregiver of a female child who started taking OPSUMIT before reaching puberty, you should check your child regularly to see if she is developing signs of puberty.

Tell your healthcare provider right away if you notice that she is developing breast buds or any pubic hair. Your healthcare provider should decide if your child has reached puberty. Your child may reach puberty before having her first menstrual period.

If you are a female who can get pregnant, you should talk to your healthcare provider to understand the benefits and risks of OPSUMIT. What is OPSUMIT? OPSUMIT is a prescription medicine used to treat pulmonary arterial hypertension (PAH), which is high blood pressure in the arteries of your lungs.

OPSUMIT can improve your ability to exercise, improve some of your symptoms, and help slow down the progression of your disease. OPSUMIT can also lower your chance of being hospitalized for PAH. It is not known if OPSUMIT is safe and effective in children.

Who should not take OPSUMIT? Do not take OPSUMIT if you are pregnant, plan to become pregnant, or become pregnant during treatment with OPSUMIT. OPSUMIT can cause serious birth defects (see the Medication Guide section above called " What is the most important information I shoul… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The pharmacokinetics of macitentan and its active metabolite have been studied primarily in healthy subjects. The pharmacokinetics of macitentan are dose proportional over a range from 1 mg to 30 mg after once daily administration. A cross study comparison shows that the exposures to macitentan and its active metabolite in patients with PAH are similar to those observed in healthy subjects.

Absorption and Distribution The maximum plasma concentration of macitentan is achieved about 8 hours after oral administration. The absolute bioavailability after oral administration is not known. In a study in healthy subjects, the exposure to macitentan and its active metabolite were unchanged after a high fat breakfast.

Macitentan may therefore be taken with or without food. Macitentan and its active metabolite are highly bound to plasma proteins (>99%), primarily to albumin and to a lesser extent to alpha-1-acid glycoprotein. The apparent volumes of distribution (Vss/F) of macitentan and its active metabolite were about 50 L and 40 L respectively in healthy subjects.

Metabolism and Elimination Following oral administration, the apparent elimination half-lives of macitentan and its active metabolite are approximately 16 hours and 48 hours, respectively. Macitentan is metabolized primarily by oxidative depropylation of the sulfamide to form the pharmacologically active metabolite. This reaction is dependent on the cytochrome P450 (CYP) system, mainly CYP3A4 with minor contributions of CYP2C8, CYP2C9, and CYP2C19.

At steady state in PAH patients, the systemic exposure to the active metabolite is 3-times the exposure to macitentan and is expected to contribute approximately 40% of the total pharmacologic activity. In a study in healthy subjects with radiolabeled macitentan, approximately 50% of radioactive drug material was eliminated in urine but none was in the form of unchanged drug or the active metabolite. About 24% of the radioactive drug material was recovered from feces.

Special Populations There are no clinically relevant effects of age, sex, or race on the pharmacokinetics of macitentan and its active metabolite. Renal Impairment Exposure to macitentan and its active metabolite in patients with severe renal impairment (CrCl 15–29 mL/min) compared to healthy subjects was increased by 30% and 60%, respectively. This increase is not considered clinically relevant.

Hepatic Impairment Exposure to macitentan was decreased by 21%, 34%, and 6% and exposure to the active metabolite was decreased by 20%, 25%, and 25% in subjects with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C), respectively. This decrease is not considered clinically relevant. Drug Interactions In Vitro Studies At plasma levels obtained with dosing at 10 mg once daily, macitentan has no relevant inhibitory or inducing effects on CYP enzymes.

Macitentan is not a substrate or inhibitor of multi-drug resistance protein (P-gp, MDR-1). The active metabolite of macitentan also is not an inhibitor of P-gp/MDR-1 at clinically relevant concentrations. Macitentan and its active metabolite are not expected to have significant interaction with drug transporters such as organic anion transporting polypeptide (OATP1B1, OATP1B3), multidrug and toxin extrusion protein (MATE-1, MATE-2K), bile salt export pump (BSEP), sodium-taurocholate co-transporting polypeptide (NTCP), organic cation transporter (OCT-1, OCT-3), organic anion transporter (OAT-1, OAT-3) or BCRP transporter at clinically relevant plasma concentrations.

In Vivo Studies Effect of other drugs on macitentan The effect of other drugs on macitentan and its active metabolite are studied in healthy subjects and are shown in Figure 1 below. Figure 1 Effects of other strong CYP3A4 inhibitors such as ritonavir on macitentan were not studied, but are likely to result in an increase in macitentan exposure at steady state similar to that seen with ketoconazole [see Drug Interactions (… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 101 words ▾

12.2Pharmacodynamics Pulmonary Hemodynamics The clinical efficacy study in patients with pulmonary arterial hypertension assessed hemodynamic parameters in a subset of patients after 6 months of treatment. Patients treated with OPSUMIT 10 mg (N=57) achieved a median reduction of 37% (95% CI 22–49) in pulmonary vascular resistance and an increase of

0.6L/min/m 2 (95% CI 0.3–0.9) in cardiac index compared to placebo (N=67). Cardiac Electrophysiology In a randomized, placebo-controlled four-way crossover study with a positive control in healthy subjects, repeated doses of macitentan 10 and 30 mg (3 times the recommended dosage) had no significant effect on the QTc interval.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Pulmonary Arterial Hypertension The effect of macitentan on progression of PAH was demonstrated in a multi-center, long-term (average duration of exposure approximately 2 years), placebo-controlled study in 742 patients with symptomatic [WHO functional class (FC) II–IV] PAH who were randomized to placebo (n=250), 3 mg macitentan (n=250), or 10 mg macitentan (n=242) once daily. Patients were treated with OPSUMIT monotherapy or in combination with phosphodiesterase-5 inhibitors or inhaled prostanoids. The primary study endpoint was time to the first occurrence of death, a significant morbidity event, defined as atrial septostomy, lung transplantation, initiation of IV or subcutaneous (SC) prostanoids, or "other worsening of PAH" during double-blind treatment plus 7 days.

Other worsening was defined as all of the following: 1) a sustained ≥15% decrease from baseline in 6 minute walk distance (6MWD), 2) worsening of PAH symptoms (worsening of WHO FC), and 3) need for additional treatment for PAH. All of these other worsening events were confirmed by an independent adjudication committee, blinded to treatment allocation. A critical secondary endpoint was time to PAH death or PAH hospitalization.

The mean patient age was 46 years (14% were age 65 or above). Most patients were white (55%) or Asian (29%) and female (77%). Approximately 52%, 46%, and 2% of patients were in WHO FC II, III, and IV, respectively.

Idiopathic or heritable PAH was the most common etiology in the study population (57%) followed by PAH caused by connective tissue disorders (31%), PAH caused by congenital heart disease with repaired shunts (8%), and PAH caused by other etiologies [drugs and toxins (3%) and HIV (1%)]. At baseline, the majority of enrolled patients (64%) were being treated with a stable dose of specific therapy for PAH, either oral phosphodiesterase inhibitors (61%) and/or inhaled/oral prostanoids (6%). Study results are described for the placebo and OPSUMIT 10 mg groups.

The median treatment durations were 101 and 118 weeks in the placebo and OPSUMIT 10 mg groups, respectively, up to a maximum of 188 weeks. Treatment with OPSUMIT 10 mg resulted in a 45% reduction (HR 0.55, 97.5% CI 0.39–0.76; logrank p<0.0001) in the occurrence of the primary endpoint up to end of double-blind treatment compared to placebo (Table 3 and Figure 2). The beneficial effect of OPSUMIT 10 mg was primarily attributable to a reduction in clinical worsening events (deterioration in 6MWD and worsening of PAH symptoms and need for additional PAH treatment).

Figure 2 Kaplan-Meier Estimates of the Occurrence of the Primary Endpoint Event in the SERAPHIN Study Table 3: Summary of Primary Endpoint Events Placebo N=250 n (%) OPSUMIT 10 mg N=242 n (%) Patients with a primary endpoint event No patients experienced an event of lung transplantation or atrial septostomy in the placebo or OPSUMIT 10 mg treatment groups. 116 (46.4) 76 (31.4) Component as first event Worsening PAH 93 (37.2) 59 (24.4) Death 17 (6.8) 16 (6.6) IV/SC prostanoid 6 (2.4) 1 (0.4) Subgroup analyses were performed to examine their influence on outcome as shown in Figure 3.

Consistent efficacy of OPSUMIT 10 mg on the primary endpoint was seen across subgroups of age, sex, race, etiology, by monotherapy or in combination with another PAH therapy, baseline 6MWD, and baseline WHO FC. Figure 3 Subgroup Analysis of the SERAPHIN Study Eo = Number of events OPSUMIT 10 mg; No = Number of patients randomized to OPSUMIT 10 mg Ep = Number of events placebo; Np = Number of patients randomized to placebo PAH related death or hospitalization for PAH was assessed as a secondary endpoint. The risk of PAH related death or hospitalization for PAH was reduced by 50% in patients receiving OPSUMIT 10 mg compared to placebo (HR 0.50, 97.5% CI 0.34–0.75; logrank p<0.0001) (Table 4 and Figure 4).

Figure 4 Kaplan-Meier Estimates of the Occurrence of Death due to PAH or Hospitalization for PAH in SERAPHIN Table 4:… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies of 2 years' duration did not reveal any carcinogenic potential at exposures 75-fold and 140-fold the human exposure (based on AUC) in male and female mice, respectively, and 8.3- and 42-fold in male and female rats, respectively. Mutagenesis Macitentan was not genotoxic in a standard battery of in vitro and in vivo assays that included a bacterial reverse mutation assay, an assay for gene mutations in mouse lymphoma cells, a chromosome aberration test in human lymphocytes, and an in vivo micronucleus test in rats.

Impairment of Fertility Reversible testicular tubular dilatation was observed in chronic toxicity studies at exposures greater than 7-fold and 23-fold the human exposure in rats and dogs, respectively. After 2 years of treatment, tubular atrophy was seen in rats at 4-fold the human exposure. Macitentan did not affect male or female fertility at exposures ranging from 19- to 44-fold the human exposure, respectively, and had no effect on sperm count, motility, and morphology in male rats.

No testicular findings were noted in mice after treatment up to 2 years.

13.2Animal Toxicology In dogs, macitentan decreased blood pressure at exposures similar to the therapeutic human exposure. Intimal thickening of coronary arteries was observed at 17-fold the human exposure after 4 to 39 weeks of treatment. Due to the species-specific sensitivity and the safety margin, this finding is considered not relevant for humans.

There were no adverse liver findings in long-term studies conducted in mice, rats, and dogs at exposures of 12- to 116-fold the human exposure.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 182 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies of 2 years' duration did not reveal any carcinogenic potential at exposures 75-fold and 140-fold the human exposure (based on AUC) in male and female mice, respectively, and 8.3- and 42-fold in male and female rats, respectively. Mutagenesis Macitentan was not genotoxic in a standard battery of in vitro and in vivo assays that included a bacterial reverse mutation assay, an assay for gene mutations in mouse lymphoma cells, a chromosome aberration test in human lymphocytes, and an in vivo micronucleus test in rats.

Impairment of Fertility Reversible testicular tubular dilatation was observed in chronic toxicity studies at exposures greater than 7-fold and 23-fold the human exposure in rats and dogs, respectively. After 2 years of treatment, tubular atrophy was seen in rats at 4-fold the human exposure. Macitentan did not affect male or female fertility at exposures ranging from 19- to 44-fold the human exposure, respectively, and had no effect on sperm count, motility, and morphology in male rats.

No testicular findings were noted in mice after treatment up to 2 years.

📄 Recent Major Changes 23 words ▾

Boxed Warning 4/2025 Dosage and Administration ( 2.2 ) 4/2025 Warnings and Precautions ( 5.1 ) 4/2025 Warnings and Precautions (5.2) Removal 4/2025

📄 Package Label / Principal Display Panel 40 words ▾

PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Carton NDC 66215-501-30 Opsumit ® (macitentan) tablets 10 mg Dispense the accompanying Medication Guide to each patient Rx only 30 film-coated tablets janssen PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
17.7K
Units reimbursed last 4 qtrs
531.8K
Gross reimbursed last 4 qtrs
$226.71M
Avg / prescription
$12,804.40
Avg / unit
$426.28
Latest quarter Q1 2026
4.1KRx
Fee-for-service vs managed care ⓘ
47% FFS 53% MCO
Fee-for-service · 8,355 Rx Managed care · 9,351 Rx
State Medicaid map
Alaska: 720 units · 98.2 per 100k residents AK Maine: 3,210 units · 230 per 100k residents ME Washington: 10,704 units · 137 per 100k residents WA Idaho: 2,880 units · 147 per 100k residents ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 13,274 units · 231 per 100k residents MN Wisconsin: 8,910 units · 151 per 100k residents WI Michigan: 9,817 units · 97.8 per 100k residents MI New York: 30,464 units · 156 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 11,700 units · 276 per 100k residents OR Nevada: 10,664 units · 334 per 100k residents NV Wyoming: no data reported WY South Dakota: 720 units · 78.3 per 100k residents SD Iowa: 8,530 units · 266 per 100k residents IA Illinois: 18,066 units · 144 per 100k residents IL Indiana: 15,240 units · 222 per 100k residents IN Ohio: 19,530 units · 166 per 100k residents OH Pennsylvania: 11,820 units · 91.2 per 100k residents PA New Jersey: 4,627 units · 49.8 per 100k residents NJ Massachusetts: 9,301 units · 133 per 100k residents MA California: 150,612 units · 387 per 100k residents CA Utah: 4,500 units · 132 per 100k residents UT Colorado: 10,290 units · 175 per 100k residents CO Nebraska: 4,440 units · 224 per 100k residents NE Missouri: 6,953 units · 112 per 100k residents MO Kentucky: 10,760 units · 238 per 100k residents KY West Virginia: 1,680 units · 94.9 per 100k residents WV Virginia: 4,080 units · 46.8 per 100k residents VA Maryland: 4,223 units · 68.3 per 100k residents MD Connecticut: 2,910 units · 80.5 per 100k residents CT Rhode Island: 1,290 units · 118 per 100k residents RI Arizona: 19,801 units · 266 per 100k residents AZ New Mexico: 8,580 units · 406 per 100k residents NM Kansas: 1,740 units · 59.2 per 100k residents KS Arkansas: 2,789 units · 90.9 per 100k residents AR Tennessee: 5,130 units · 72.0 per 100k residents TN North Carolina: 8,563 units · 79.0 per 100k residents NC South Carolina: 1,980 units · 36.9 per 100k residents SC Delaware: 660 units · 64.0 per 100k residents DE Oklahoma: 8,940 units · 221 per 100k residents OK Louisiana: 15,162 units · 331 per 100k residents LA Mississippi: 2,836 units · 96.5 per 100k residents MS Alabama: 4,358 units · 85.3 per 100k residents AL Georgia: 6,210 units · 56.3 per 100k residents GA D.C.: no data reported DC Hawaii: 750 units · 52.3 per 100k residents HI Texas: 29,814 units · 97.7 per 100k residents TX Florida: 20,125 units · 89.0 per 100k residents FL
Units reimbursed · per 100k residents
36.9406
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 New Mexico 406 /100k
2 California 387 /100k
3 Nevada 334 /100k
4 Louisiana 331 /100k
5 Oregon 276 /100k
6 Arizona 266 /100k
7 Iowa 266 /100k
8 Kentucky 238 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
30 tablets this page66215-0501-30 17,706 Rx · $226,714,680
15 tablets66215-0501-15 No Medicaid data
Drug total (last 4 qtrs): 17,706 Rx · 531,843 units · $226,714,680 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Opsumit — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Opsumit. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$307.88M
Claims incl. refills
22.8K
Beneficiaries
8.8K
Spend / beneficiary
$34,820.11
Spend / claim
$13,485.15
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for OPSUMIT (this brand).

Top reported reactions

Dyspnoea11,956
Headache8,323
Death7,367
Diarrhoea6,581
Nausea5,972
Fatigue5,041
Pneumonia4,550

Reporter sex

68,840 reports
Male · 25%
Female · 75%
Unknown · 0%

Serious outcomes

Hospitalization34,017
Death12,527
Life-threatening1,098
Disabling658
Reports over time (by year) — tap or hover for the count & year
2022 2023 2024 2026 6,937 1,913
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Actelion Pharmaceuticals US, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 15 tablets (66215-0501-15). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Actelion Pharmaceuticals US, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 66215-0403-01 · Actelion 66215-0602-06 · Actelion →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.