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Bosentan 32 mg Tablet, For Suspension — NDC 68180-0340-13 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Bosentan 32 mg Tablet, For Suspension — NDC 68180-340-13 (Billing 68180-0340-13)

by Lupin Pharmaceuticals, Inc. · 4 BLISTER PACK in 1 CARTON / 14 TABLET, FOR SUSPENSION in 1 BLISTER PACK

This is a package of Bosentan 32 mg Tablet, For Suspension from Lupin Pharmaceuticals, Inc., marketed since Aug 2025 and currently FDA-listed. It is this product's only package size.

NDC 68180-0340-13
🏷️ FDA NDC (as labeled) 68180-340-13 billing pads the product segment with a zero
Rx only Generic On market Non-controlled 🛡 REMS ⇄ 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

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68180-340-13
Product NDC 68180-340
11-digit billing NDC 68180034013
NCPDP billing unit EA — each (per item)
RxCUI 1989081
UNII Q326023R30
Application # ANDA213154
SPL Set ID 540b6f6a-79f3-4681-8c2a-268cf7cecbc9
Established class (EPC) Endothelin Receptor Antagonist
Mechanism of action Cytochrome P450 2C9 Inducers; Cytochrome P450 3A Inducers; Endothelin Receptor Antagonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-08-18
Route ORAL
Dosage form TABLET, FOR SUSPENSION
Substance BOSENTAN
TE code (Orange Book) AB · RLD · RS

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

GPI-14 40160015007320
GCN Seq No 077706
GCN 43819
HICL code 022990
Ingredient (HICL) Bosentan
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 BOSENTAN 32 MG TABLET FOR SUSP
FDB brand name Bosentan
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 077706
  • GCN: 43819
  • GPI-14 (Medi-Span): 40160015007320
  • HICL (First Databank): 022990
  • AHFS class code: 24:12.92.00
  • RxCUI (RxNorm): 1989081
Why two NDCs? The FDA registers this code as 68180-340-13 — 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 → 68180-0340-13. 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, Cytochrome P450 2C9 Inducers, Cytochrome P450 3A Inducers
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 BOSENTAN 32 MG TABLET FOR SUSP Ingredient Bosentan
📖 What it is MedlinePlus · NLM

Bosentan is used to treat pulmonary arterial hypertension (PAH, high blood pressure in the vessels that carry blood to the lungs).  Bosentan is in a class of medications called endothelin receptor antagonists. It works by stopping the action of endothelin, a natural substance that causes blood vessels to narrow and prevents normal blood flow in people who have PAH.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats pulmonary arterial hypertension, or high blood pressure in the lung arteries. In adults it helps you exercise better and slows worsening. It is also used in children 3 ye...
  • You take it by mouth twice a day, with or without food. Dispersible tablets get mixed in a little water right before you take them. Your dose depends on your age and weight, so fol...
  • Bosentan can raise liver enzymes and, rarely, cause serious liver damage. Monthly tests catch problems early, often before you feel anything. Call us right away if you get nausea,...
  • Only with strict precautions. Bosentan is likely to cause major birth defects, so you need a negative pregnancy test first and monthly tests. You must use two reliable birth contro...
📖 Read our full Bosentan guide →
1
Nutrient depletion considerations

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

🧪 Full Bosentan 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 mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $157.29 —
Medicare drug plans payPart D · Q2 2026 $169.02 —
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
68180-0340-13 You're viewing this Main listing 4 BLISTER PACK in 1 CARTON / 14 TABLET, FOR SUSPENSION in 1 BLISTER PACK 2025-08-18 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Tracleer 32 mg 66215-0232-56 Actelion 14 tablets — AB FDA listed —
Bosentan 32 mgthis 68180-0340-13 Lupin 14 tablets — AB FDA listed —
bosentan 32 mg 70710-1508-08 Zydus 14 tablets — AB FDA listed —
bosentan 32 mg 70771-1908-08 Zydus 14 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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

🏛️
2025
First FDA approval
Feb 2025
📍
2026
Currently FDA-listed
1 year listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

🛡️ Latest patent/protection date listed: The latest listed FDA patent/protection lapsed Feb 2026 — those protections no longer apply, though a generic still needs FDA approval and a manufacturer to market it.
📅 FDA approved Feb 5, 2025 AB TE-rated RLD RS

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
Exclusivity PC
2025
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.

FDA exclusivity
CodeWhat it grantsExpires
PCPediatric Exclusivity (+6 months)Feb 14, 2026
Common questions
Is there a generic version of BOSENTAN 32 MG TABLET FOR SUSP?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for BOSENTAN 32 MG TABLET FOR SUSP. 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.

What it looks like

Color White
ShapeClover
Imprint32
Size1 mm
ScoringScored — splits in 4
FlavorTutti Frutti
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 23OV73Q5G9
    Acesulfame potassium is an artificial sweetener that tastes about 200 times sweeter than sugar. It's added to medicines to improve taste without adding calories or affecting blood sugar.
  • UNII L11K75P92J
    A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
  • UNII Z0H242BBR1
    Aspartame is an artificial sweetener made from amino acids. It's added to medicines to improve taste, making bitter or unpleasant-tasting drugs easier to take.
  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.

7 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

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

LabelerLupin Pharmaceuticals, Inc.
Application holderNATCO PHARMA LTD
FDA applicationANDA213154 (ANDA)
Labeler code68180
First marketedAug 2025
Product typeHuman Prescription Drug
Portfolio404 products on file
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 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~3 min read ▾

WARNING: RISKS OF HEPATOTOXICITY and EMBRYO-FETALTOXICITY Because of the risks of hepatotoxicity and birth defects, bosentan tablets for oral suspension is available only through a restricted program called the Bosentan REMS Program. Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions (5.3) ] . Hepatotoxicity In clinical studies, bosentan caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases.

Because these changes are a marker for potential serious hepatotoxicity, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) ] . In the post marketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (> 12 months) therapy with bosentan in patients with multiple comorbidities and drug therapies. There have also been reports of liver failure.

The contribution of bosentan in these cases could not be excluded. In at least one case, the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of bosentan. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping bosentan with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction [see Dosage and Administration (2.4) ] .

Elevations in aminotransferases require close attention [see Dosage and Administration (2.4) ] . Bosentan should generally be avoided in patients with elevated aminotransferases (>3xULN) at baseline because monitoring for hepatotoxicity may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥2xULN, treatment with bosentan should be stopped.

There is no experience with the reintroduction of bosentan in these circumstances. Embryo-Fetal Toxicity Bosentan is likely to cause major birth defects if used by pregnant females based on animal data [see Warnings and Precautions (5.2) , Use in Specific Populations (8.1) ] . Therefore, pregnancy must be excluded before the start of treatment with bosentan.

Throughout treatment and for one month after stopping bosentan, females of reproductive potential must use two reliable methods of contraception unless the patient has an intrauterine device (IUD) or tubal sterilization, in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective in patients receiving bosentan [see Drug Interactions (7.2) ] . Obtain monthly pregnancy tests.

WARNING: RISKS OF HEPATOTOXICITY and EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Bosentan tablets for oral suspension are available only through a restricted distribution program called the Bosentan REMS Program because of these risks ( 5.3 ): Elevations of liver aminotransferases (ALT, AST) and liver failure have been reported with bosentan ( 5.1 ). Measure liver aminotransferases prior to initiation of treatment and then monthly ( 2.1 , 5.1 ).

Discontinue bosentan if aminotransferase elevations are accompanied by signs or symptoms of liver dysfunction or injury or increases in bilirubin ≥2xULN ( 2.4 , 5.1 ). Based on animal data, bosentan is likely to cause major birth defects if used during pregnancy ( 4.1 , 5.2 , 8.1 ). Must exclude pregnancy be… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage 206 words ▾

1. INDICATIONS AND USAGE Bosentan is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): in adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) [see Clinical Studies (14.1) ] . in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability.

Bosentan is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): in adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) ( 1 ). in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability ( 1 ).

⏱️ Dosage and Administration ~3 min read ▾

2. DOSAGE AND ADMINISTRATION • Patients older than 12 years of age: initiate at 62.5 mg orally twice daily; for patients weighing greater than 40 kg, increase to 125 mg orally twice daily after 4 weeks ( 2.2 ). • Patients 12 years of age and younger: dosage is based on weight, see Table 1 ( 2.2 ). • Reduce the dose and closely monitor patients developing aminotransferase elevations more than 3 x Upper Limit of Normal (ULN) ( 2.1 ).

2.1Required Monitoring Healthcare professionals who prescribe bosentan tablets for oral suspension must enroll in the Bosentan REMS Program and must comply with the required monitoring to minimize the risks associated with bosentan [see Warnings and Precautions (5.3) ] . Obtain a pregnancy test in females of reproductive potential prior to bosentan treatment, monthly during treatment and one month after stopping bosentan. Initiate treatment with bosentan in females of reproductive potential only after a negative pregnancy test [see Boxed Warning , Contraindications (4.1) , Warnings and Precautions (5.3) , Use in Specific Populations (8.1 , 8.3) ] .

Measure liver aminotransferase levels prior to initiation of treatment and then monthly [see Warnings and Precautions (5.1) ] .

2.2Recommended Dosage Administer bosentan orally following the dosing recommendations in Table 1. Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of hepatotoxicity. Table 1: Dosing Recommendations Initial 4 weeks Maintenance (after 4 weeks) Patients >12 years of age and >40 kg 62.5 mg twice daily 125 mg twice daily Patients >12 years of age and <40 kg 62.5 mg twice daily 62.5 mg twice daily Patients ≤12 years of age ≥4-8 kg ˃8-16 kg ˃16-24 kg ˃24-40 kg 16 mg twice daily 32 mg twice daily 48 mg twice daily 64 mg twice daily 16 mg twice daily 32 mg twice daily 48 mg twice daily 64 mg twice daily

2.3Administration Bosentan tablets for oral suspension (dispersible tablets) should be administered orally twice daily. Disperse tablets for oral suspension, or dispersible tablet half, in a minimal amount of water immediately before administration. Store divided dispersible tablet pieces at 20 ºC to 25 ºC (68 ºF to 77 ºF) in the opened blister for up to 7 days.

2.4Dosage Adjustments for Aminotransferase Elevations If aminotransferase levels increase, adjust monitoring and treatment plan according to Table 2. Discontinue bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or bilirubin ≥2xUpper Limit of Normal (ULN). There is no experience with the reintroduction of bosentan in these circumstances.

Table 2: Dosage Adjustment and Monitoring in Patients Developing Aminotransferase Elevations >3xULN ALT/AST levels Treatment and monitoring recommendations > 3 and ≤ 5xULN Confirm by another aminotransferase test; if confirmed, - in adults and pediatric patients >12 years and >40 kg , reduce the daily dose to 62.5 mg twice daily or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks. If the aminotransferase levels return to pretreatment values, treatment may continue or be reintroduced at 62.5 mg twice daily, with reassessment of aminotransferase levels within 3 days. - in all other pediatric patients, interrupt treatment with no prior dose reduction.

If the aminotransferase levels return to pretreatment values, reintroduce at the dose used prior to treatment interruption, with reassessment of aminotransferase levels within 3 days. > 5 and ≤ 8xULN Confirm by another aminotransferase test; if confirmed, stop treatment and monitor aminotransferase levels at least every 2 weeks. Once the aminotransferase levels return to pretreatment values, - in adults and pediatric patients >12 years and >40 kg , consider reintroduction of treatment at 62.5 mg twice daily, with reassessment of aminotransferase levels within 3 day… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 40 words ▾

3. DOSAGE FORMS AND STRENGTHS 32 mg tablets for oral suspension: off-white to pale yellow colored, clover shaped, uncoated tablets, debossed with “32” on the side opposite the quadrisection lines. • Tablet for oral suspension: 32 mg ( 3 )

⛔ Contraindications 200 words ▾

4. CONTRAINDICATIONS • Pregnancy ( 4.1 ) • Use with Cyclosporine A ( 4.2 ) • Use with Glyburide ( 4.3 ) • Hypersensitivity ( 4.4 )

4.1Pregnancy Use of bosentan is contraindicated in females who are or may become pregnant. To prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan [see Boxed Warning , Warnings and Precautions (5.2) , Drug Interactions (7.2) , Use in Specific Populations (8.1) ] .

4.2Use with Cyclosporine A Co-administration of cyclosporine A and bosentan resulted in markedly increased plasma concentrations of bosentan. Therefore, concomitant use of bosentan and cyclosporine A is contraindicated [see Cytochrome P450 Drug Interactions (7.1) ] .

4.3Use with Glyburide An increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. Therefore co-administration of glyburide and bosentan is contraindicated [see Cytochrome P450 Drug Interactions (7.1) ] .

4.4Hypersensitivity Bosentan is contraindicated in patients who are hypersensitive to bosentan or any component of the product. Observed reactions include Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), anaphylaxis, rash, and angioedema [see Adverse Reactions (6.2) , Description (11) ] .

⚠️ Warnings and Cautions ~3 min read ▾

5. WARNINGS AND PRECAUTIONS • Fluid retention: May require intervention ( 5.4 ). • Pulmonary veno-occlusive disease (PVOD): If signs of pulmonary edema occur, consider the diagnosis of associated PVOD and consider discontinuing bosentan ( 5.5 ). • Decreased sperm counts ( 5.6 ). • Decreases in hemoglobin and hematocrit: Monitor hemoglobin levels after 1 and 3 months of treatment, then every 3 months thereafter ( 5.7 ).

5.1Hepatotoxicity ALT or AST > 3xULN were observed in 11% of bosentan-treated patients (n = 658) compared to 2% of placebo-treated patients (n = 280). Three-fold increases were seen in 12% of 95 pulmonary arterial hypertension (PAH) patients on 125 mg twice daily and 14% of 70 PAH patients on 250 mg twice daily. Eight-fold increases were seen in 2% of PAH patients on 125 mg twice daily and 7% of PAH patients on 250 mg twice daily.

Bilirubin increases to ≥3xULN were associated with aminotransferase increases in 2 of 658 (0.3%) of patients treated with bosentan. In a pooled analysis of four pediatric studies conducted in PAH (n =100), elevations in liver aminotransferases ≥3×ULN were observed in 2% of patients. The combination of hepatocellular injury (increases in aminotransferases of > 3xULN) and increases in total bilirubin (≥2xULN) is a marker for potential serious hepatotoxicity.

Elevations of AST or ALT associated with bosentan are dose-dependent, occur both early and late in treatment, usually progress slowly, are typically asymptomatic, and usually have been reversible after treatment interruption or cessation. Aminotransferase elevations also may reverse spontaneously while continuing treatment with bosentan. Liver aminotransferase levels must be measured prior to initiation of treatment and then monthly and therapy adjusted accordingly [see Dosage and Administration (2.1 , 2.4 )] .

Discontinue bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥2xULN. Avoid initiation of bosentan in patients with elevated aminotransferases (>3xULN) prior to drug initiation because monitoring hepatotoxicity in these patients may be more difficult [see Boxed Warning , Dosage and Administration (2.6) , Use in Specific Populations (8.6) ] . In WHO Functional Class II patients, consider whether the benefits of bosentan are sufficient to offset the risk of hepatotoxicity, which may preclude future use as their disease progresses.

5.2Embryo-fetal Toxicity Based on data from animal reproduction studies, bosentan may cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test prior to bosentan treatment, monthly during treatment and for one month after stopping treatment.

Advise females of reproductive potential to use two reliable forms of contraception during treatment with bosentan and for at least one month after the last dose [see Dosage and Administration (2) , Use in Specific Populations (8.1 , 8.3) ] . Bosentan tablets for oral suspension is only available for females through a restricted program under REMS [see Warnings and Precautions (5.3) ] .

5.3Prescribing and Distribution Program for Bosentan Because of the risks of hepatotoxicity and birth defects, bosentan tablets for oral suspension is available only through a restricted program called the Bosentan REMS Program. As a component of the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program [see Boxed Warning , Warnings and Precautions (5.1 , 5.2) , Contraindications (4.1) ] . Required components of the bosentan tablets for oral suspension REMS are: Healthcare professionals who prescribe bosentan tablets for oral suspension must review the prescriber educational materials, enroll in the Bosentan REMS Program and comply with its r… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6. ADVERSE REACTIONS The following important adverse reactions are described elsewhere in the labeling: • Hepatotoxicity [see Boxed Warning , Warnings and Precautions (5.1) ] • Embryo-fetal Toxicity [see Boxed Warning , Warnings and Precautions (5.2) ] • Fluid Retention [see Warnings and Precautions (5.4) ] Common adverse reactions (≥15%) for the dispersible tablet are upper respiratory tract infections and pyrexia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. Safety data on bosentan were obtained from 13 clinical studies (9 placebo-controlled and 4 open-label) in 870 adult patients with PAH and other diseases. Doses up to 8 times the currently recommended clinical dose (125 mg twice daily) were administered for a variety of durations.

The exposure to bosentan in these trials ranged from 1 day to 4.1 years (n=94 for 1 year; n=61 for 1.5 years; and n=39 for more than 2 years). Exposure of PAH patients (n=328) to bosentan ranged from 1 day to 1.7 years (n=174 more than 6 months and n=28 more than 12 months). Treatment discontinuations due to adverse events other than those related to pulmonary hypertension during the clinical trials in adult patients with PAH were more frequent on bosentan (6%; 15/258 patients) than on placebo (3%; 5/172 patients).

In this database the only cause of discontinuations > 1% and occurring more often on bosentan was abnormal liver function. The adverse drug events that occurred in ≥ 3% of the bosentan-treated patients and were more common on bosentan in placebo-controlled trials in PAH at doses of 125 or 250 mg twice daily are shown in Table 3: Table 3. Adverse Events* Occurring in ≥3% of Patients Treated with Bosentan 125-250 mg Twice Daily and More Common on Bosentan in Placebo-Controlled Studies in Pulmonary Arterial Hypertension Adverse Event Bosentan n = 258 Placebo n = 172 No. % No. % Respiratory Tract Infection** 56 22% 30 17% Headache 39 15% 25 14% Edema 28 11% 16 9% Chest Pain 13 5% 8 5% Syncope 12 5% 7 4% Flushing 10 4% 5 3% Hypotension 10 4% 3 2% Sinusitis 9 4% 4 2% Arthralgia 9 4% 3 2% Serum Aminotransferases, abnormal 9 4% 3 2% Palpitations 9 4% 3 2% Anemia 8 3% - - *Note: only AEs with onset from start of treatment to 1 calendar day after end of treatment are included.

All reported events (at least 3%) are included except those too general to be informative, and those not reasonably associated with the use of the drug because they were associated with the condition being treated or are very common in the treated population. **Respiratory Tract Infection combines the terms "Nasopharyngitis", "Upper Respiratory Tract Infection" and "Respiratory Tract Infection". Combined data from Study 351, BREATHE-1 and EARLY Bosentan was evaluated for safety in 119 pediatric patients in uncontrolled studies.

The safety profile was similar to that observed in adult patients with PAH. Decreased Sperm Counts An open-label, single-arm, multicenter, safety study evaluated the effect on testicular function of bosentan 62.5 mg twice daily for 4 weeks, followed by 125 mg twice daily for 5 months. Twenty-five male patients with WHO functional class III and IV PAH and normal baseline sperm count were enrolled.

Twenty-three completed the study and 2 discontinued due to adverse events not related to testicular function. There was a decline in sperm count of at least 50% in 25% of the patients after 3 or 6 months of treatment with bosentan. Sperm count remained within the normal range in all 22 patients with data after 6 months and no changes in sperm morphology, sperm motility, or hormone levels were observed.

One patien… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7. DRUG INTERACTIONS • Cytochrome P450: Coadministration of bosentan with drugs metabolized by CYP2C9 and CYP3A can increase exposure to bosentan and/or the coadministered drug ( 4.2 , 4.3 , 7.1 ). • Hormonal contraceptives: Bosentan use decreases contraceptive exposure and reduces effectiveness ( 7.2 ).

7.1Cytochrome P450 Drug Interactions Bosentan is metabolized by CYP2C9 and CYP3A. Inhibition of these enzymes may increase the plasma concentration of bosentan [see Pharmacokinetics (12.3) ] . Concomitant administration of both a CYP2C9 inhibitor (such as fluconazole or amiodarone) and a strong CYP3A inhibitor (e.g., ketoconazole, itraconazole) or a moderate CYP3A inhibitor (e.g., amprenavir, erythromycin, fluconazole, diltiazem) with bosentan will likely lead to large increases in plasma concentrations of bosentan.

Co-administration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with bosentan is not recommended. Bosentan is an inducer of CYP3A and CYP2C9. Consequently plasma concentrations of drugs metabolized by these two isozymes will be decreased when bosentan is co-administered.

Bosentan had no relevant inhibitory effect on any CYP isozyme in vitro (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A). Consequently, bosentan is not expected to increase the plasma concentrations of drugs metabolized by these enzymes. Figure 1.

CYP3A induction-mediated effect of bosentan on other drugs Figure 2. Effect of other drugs on bosentan figure 1 figure 2

7.2Hormonal Contraceptives Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when bosentan is co-administered. Females should practice additional methods of contraception and not rely on hormonal contraception alone when taking bosentan [see Use in Specific Populations (8.3) ] . An interaction study demonstrated that co-administration of bosentan and a combination oral hormonal contraceptive produced average decreases of norethindrone and ethinyl estradiol levels of 14% and 31%, respectively.

However, decreases in exposure were as much as 56% and 66%, respectively, in individual subjects.

👥 Use in Specific Populations ~3 min read ▾

8. USE IN SPECIFIC POPULATIONS • Nursing mothers: Choose breastfeeding or bosentan ( 8.2 ).

8.1Pregnancy Risk Summary Based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see Contraindications (4.1) ] . There are limited data on bosentan use in pregnant women. In animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (MRHD) on a mg/m 2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [ see Animal Data ].

Advise pregnant women of the potential risk to a fetus. 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. Data Animal Data Bosentan was teratogenic in rats given oral doses two times the MRHD (on a mg/m 2 basis). In an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels.

Bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the MRHD (on a mg/m 2 basis). Although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat. The similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs.

8.2Lactation Risk Summary Data from a case report describe the presence of bosentan in human milk. There is insufficient information about the effects of bosentan on the breastfed infant and no information on the effects of bosentan on milk production. Because of the potential for serious adverse reactions, such as fluid retention and hepatotoxicity, in breastfed infants from bosentan, advise women not to breastfeed during treatment with bosentan.

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating bosentan, monthly during treatment and one month after stopping treatment with bosentan. The patient should contact her 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 must discuss the risks to her, the pregnancy, and the fetus.

Contraception Drug interaction studies show that bosentan reduces serum levels of the estrogen and progestin in oral contraceptives. Based on these findings, hormonal contraceptives (including oral, injectable, transdermal, and implantable contraceptives) may be less effective for preventing pregnancy in patients using bosentan and should not be used as a patient’s only contraceptive method [see Drug Interactions (7.2) ] . Females of reproductive potential using bosentan must use two acceptable methods of contraception during treatment and for 1 month after treatment with bosentan.

Patients may choose one highly effective form of contraception (intrauterine devices (IUD) or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. Counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive couns… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see Contraindications (4.1) ] . There are limited data on bosentan use in pregnant women. In animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (MRHD) on a mg/m 2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [ see Animal Data ].

Advise pregnant women of the potential risk to a fetus. 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. Data Animal Data Bosentan was teratogenic in rats given oral doses two times the MRHD (on a mg/m 2 basis). In an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels.

Bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the MRHD (on a mg/m 2 basis). Although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat. The similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs.

🧒 Pediatric Use 188 words ▾

8.4Pediatric Use The efficacy of bosentan in patients <18 years is supported by data from an uncontrolled trial in which 19 pediatric patients were treated with bosentan. In this study, cardiopulmonary hemodynamic improvements were similar to those seen in adults treated with bosentan [see Pulmonary Arterial Hypertension (14.1) ] . Safety in pediatric patients is supported by data from 100 pediatric patients treated with bosentan for a median of 17 months [see Clinical Studies Experience (6.1) , Pulmonary Arterial Hypertension (14.1) ] .

Juvenile Animal Toxicity Data In a juvenile rat toxicity study, rats were treated from Day 4 postpartum to adulthood (Day 69 postpartum). Decreased body weights, absolute weights of testes and epididymides, and reduced number of sperm in epididymides were observed after weaning. No effect on testis histology or sperm morphology and function was seen.

The NOAEL was 4 times (at Day 4 postpartum) and 2 times (Day 69 postpartum) the human therapeutic exposure, respectively. No effects on general development, sensory, cognitive function and reproductive performance were detected at the highest dose tested in juvenile rats, 7 times the therapeutic exposure in children with PAH.

🧓 Geriatric Use 27 words ▾

8.5Geriatric Use Clinical studies of bosentan did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

🆘 Overdosage 161 words ▾

10. OVERDOSAGE Bosentan has been given as a single dose of up to 2400 mg in normal volunteers, or up to 2000 mg/day for 2 months in patients, without any major clinical consequences. The most common side effect was headache of mild to moderate intensity.

In the cyclosporine A interaction study, in which doses of 500 and 1000 mg twice daily of bosentan were given concomitantly with cyclosporine A, trough plasma concentrations of bosentan increased 30-fold, resulting in severe headache, nausea, and vomiting, but no serious adverse events. Mild decreases in blood pressure and increases in heart rate were observed. In the postmarketing period, there was one reported overdose of 10,000 mg of bosentan taken by an adolescent male patient.

He had symptoms of nausea, vomiting, hypotension, dizziness, sweating, and blurred vision. He recovered within 24 hours with blood pressure support. Bosentan is unlikely to be effectively removed by dialysis due to the high molecular weight and extensive plasma protein binding.

🧬 Clinical Pharmacology ~3 min read ▾

12. CLINICAL PHARMACOLOGY

12.1Mechanism of Action Bosentan is a specific and competitive antagonist at endothelin receptor types ET A and ET B . Bosentan has a slightly higher affinity for ET A receptors than for ET B receptors. The clinical impact of dual endothelin blockage is unknown.

Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET A and ET B receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with PAH, suggesting a pathogenic role for ET-1 in this disease.

12.3Pharmacokinetics General After oral administration, maximum plasma concentrations of bosentan are attained within 3–5 hours and the terminal elimination half-life is about 5 hours in healthy adult subjects. The exposure to bosentan after intravenous and oral administration is about twice as high in adult patients with PAH as it is in healthy adult subjects. In a relative bioavailability study in healthy adults, the peak plasma concentration and area under the plasma concentration-time curve for bosentan are on an average 14% and 11%, respectively, lower following administration of the oral dispersible tablet compared to the film-coated tablet.

Absorption The absolute bioavailability of bosentan in normal volunteers is about 50% and is unaffected by food. Bosentan is highly bound (> 98%) to plasma proteins, mainly albumin. Bosentan does not penetrate into erythrocytes.

The volume of distribution is about 18 L. Elimination Metabolism Bosentan has three metabolites, one of which is pharmacologically active and may contribute 10%–20% of the effect of bosentan. Bosentan is an inducer of CYP2C9 and CYP3A and possibly also of CYP2C19.

Upon multiple oral dosing, plasma concentrations in healthy adults decrease gradually to 50-65% of those seen after single dose administration, probably the effect of auto-induction of the metabolizing liver enzymes. Steady-state is reached within 3-5 days. Excretion Bosentan is eliminated by biliary excretion following metabolism in the liver.

Less than 3% of an administered oral dose is recovered in urine. Total clearance after a single intravenous dose is about 4 L/h in patients with PAH. Specific Populations Pediatrics The average plasma exposure to bosentan at steady state (AUC ss ) in pediatric patients with PAH aged 3 to 15 years treated with 31.25, 62.5 or 125 mg (approximately 2 mg/kg) film-coated tablet twice daily is 37% lower than that observed in adult patients with PAH receiving 125 mg film-coated tablet twice daily.

Following administration of 4 mg/kg twice daily doses of dispersible tablet in patients with PAH aged 2 to 11 years, the average systemic exposure to bosentan at steady state is similar to that observed with 2 mg/kg. The average exposure to bosentan in these pediatric patients was approximately half the exposure in adult patients treated with 125 mg film-coated tablets twice daily. The exposure to bosentan at 2 mg/kg three times daily dosing of dispersible tablet is similar to that of 2 mg/kg twice daily dosing in patients with PAH aged 3 months to 12 years.

Based on these findings, exposure to bosentan reaches a plateau at lower doses in pediatric patients than in adults, and doses higher than 2 mg/kg twice daily do not increase the exposure to bosentan in pediatric patients. Hepatic Impairment In vitro and in vivo evidence showing extensive hepatic metabolism of bosentan suggests that liver impairment could significantly increase exposure to bosentan. In a study comparing 8 patients with mild liver impairment (Child-Pugh Class A) to 8 controls, the single- and multiple-dose pharmacokinetics of bosentan were not altered in patients with mild hepatic impairment.

In another small (N=8) pharmacokinetic study, the steady-state AUC of bosentan was on average 4.7 times higher and the active metabolite Ro 48-5033 was 12.4 times higher in 5 patients with moderately impaired liver function (Child-Pugh Class… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 94 words ▾

12.1Mechanism of Action Bosentan is a specific and competitive antagonist at endothelin receptor types ET A and ET B . Bosentan has a slightly higher affinity for ET A receptors than for ET B receptors. The clinical impact of dual endothelin blockage is unknown.

Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET A and ET B receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with PAH, suggesting a pathogenic role for ET-1 in this disease.

📦 How Supplied / Storage and Handling 127 words ▾

16. HOW SUPPLIED/STORAGE AND HANDLING 32 mg tablets for oral suspension, off white to pale yellow colored, clover shaped, uncoated tablets debossed with "32" on one side and ‘quadrisected’ on other side. NDC 68180-340-13: Carton of 56 tablets for oral suspension in 4 blister-strips of 14 tablets.

NDC 68180-340-11: Blister strip of 14 tablets for oral suspension. 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]. Divided dispersible tablets should be stored under the same conditions and used within 7 days.

Tablet pieces may be returned to the opened blister and stored there out of reach of children for up to 7 days. Keep out of reach of children.

📋 Description 182 words ▾

11. DESCRIPTION Bosentan, an endothelin receptor antagonist that belongs to a class of highly substituted pyrimidine derivatives, with no chiral centers. It is designated chemically as 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2´]bipyrimidin-4-yl]- benzenesulfonamide monohydrate and has the following structural formula: Bosentan has a molecular weight of 569.63 and a molecular formula of C 27 H 29 N 5 O 6 S•H 2 O.

Bosentan is a white to yellowish powder. It is poorly soluble in water (1.0 mg/100 mL) and in aqueous solutions at low pH (0.1 mg/100 mL at pH 1.1 and 4.0; 0.2 mg/100 mL at pH 5.0). Solubility increases at higher pH values (43 mg/100 mL at pH 7.5).

In the solid state, bosentan is very stable, is not hygroscopic and is not light sensitive. Bosentan is available as a 32 mg tablet for oral suspension and contains the following excipients: microcrystalline cellulose, dibasic calcium phosphate, croscarmellose sodium, colloidal silicon dioxide, tutti fruitti flavor, aspartame, acesulfame potassium and magnesium stearate. Each dispersible tablet contains 1.85 mg of phenylalanine.

Each dispersible tablet contains 33.045 mg of bosentan monohydrate, equivalent to 32 mg anhydrous bosentan. chemical-structure

💬 Information for Patients ~2 min read ▾

17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) Restricted access Advise the patient that bosentan tablets for oral suspension is only available through a restricted access program called the Bosentan REMS Program. As a component of the Bosentan REMS, prescribers must review the contents of the bosentan tablets for oral suspension Medication Guide with the patient before initiating bosentan tablets for oral suspension.

Instruct patients that the risks associated with bosentan include: • Hepatotoxicity Discuss with the patient the requirement to measure serum aminotransferases monthly. • Embryo-fetal toxicity Educate and counsel female patients of reproductive potential about the need to use reliable methods of contraception during treatment with bosentan and for one month after treatment discontinuation. Females of reproductive potential must have monthly pregnancy tests and must use two different forms of contraception while taking bosentan and for one month after discontinuing bosentan [see Use in Specific Populations (8.1) ] .

Females who have intrauterine devices (IUD) or tubal sterilization can use these contraceptive methods alone. Patients should be instructed to immediately 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. Advise patients to contact their gynecologist or healthcare provider if they want to change the form of birth control which is used to ensure that another acceptable form of birth control is selected.

Advise the patient that bosentan tablets for oral suspension is available only from certified pharmacies that are enrolled in the Bosentan REMS Program. Patients must sign the Bosentan REMS Program Patient Enrollment Form to confirm that they understand the risks of bosentan. • Lactation Advise women not to breastfeed during treatment with bosentan [see Use in Specific Populations (8.2) ] . • Infertility Advise males of reproductive potential that bosentan may impair fertility [see Warnings and Precautions (5.6) , Adverse Reactions (6.1) , Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1) ] . • Phenylketonurics Bosentan tablets for oral suspension dispersible tablets contain phenylalanine, a component of aspartame.

Each dispersible tablet contains 1.87 mg of phenylalanine. Other Risks Associated with Bosentan Instruct patients that the risks associated with bosentan also include the following: Decreases in hemoglobin and hematocrit – advise patients of the importance of hemoglobin testing, Decreases in sperm count, Fluid retention Administration Considerations Advise patients that bosentan tablets for oral suspension dispersible tablets should not be split into quarters. Manufactured by: Natco Pharma Limited Parawada – 531 019, India.

Distributed by: Lupin Pharmaceuticals, Inc. Naples FL 34108 United States Revised: 11/2025

💬 Medication Guide ~3 min read ▾

SPL MEDGUIDE SECTION Medication Guide Bosentan (boe sen’ tan) Tablets for Oral Suspension 32 mg Read the Medication Guide that comes with bosentan tablets for oral suspension before you start taking it 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 bosentan tablets for oral suspension? Bosentan tablets for oral suspension are only available through the Bosentan REMS Program. Before you begin taking bosentan tablets for oral suspension, you must read and agree to all of the instructions in the Bosentan REMS Program.

Bosentan tablets for oral suspension can cause serious side effects including: Liver damage. Liver damage may not cause symptoms at first. Only a blood test can show if you have early liver damage.

You must have your blood tested to check your liver function before you start bosentan and each month after that. Your healthcare provider will order these tests. Regular blood tests are important because they will help your healthcare provider adjust or stop your treatment before there is permanent damage.

Tell your healthcare provider if you have had liver problems, including liver problems while taking other medicines. Call your healthcare provider right away if you have any of these symptoms of liver problems while taking bosentan: nausea vomiting fever unusual tiredness stomach area (abdominal) pain yellowing of the skin or the whites of your eyes (jaundice) Serious birth defects. Bosentan can cause serious birth defects if taken during pregnancy.

You must not be pregnant when you start taking bosentan or during bosentan treatment. Serious birth defects from bosentan can happen early in pregnancy. Females who are able to get pregnant must have a negative pregnancy test before starting treatment with bosentan, each month during treatment with bosentan, and 1 month after stopping treatment with bosentan.

Talk to your healthcare provider about your menstrual cycle. Your healthcare provider will decide when to do a 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 must use two acceptable forms of birth control during treatment with bosentan, and for one month after stopping bosentan because the medicine may still be in the body. If you have had a tubal sterilization or have an IUD (intrauterine device), these methods can be used alone and no other form of birth control is needed. 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 bosentan.

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. See the chart below for Acceptable Birth Control Options during treatment with bosentan. 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 f… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics General After oral administration, maximum plasma concentrations of bosentan are attained within 3–5 hours and the terminal elimination half-life is about 5 hours in healthy adult subjects. The exposure to bosentan after intravenous and oral administration is about twice as high in adult patients with PAH as it is in healthy adult subjects. In a relative bioavailability study in healthy adults, the peak plasma concentration and area under the plasma concentration-time curve for bosentan are on an average 14% and 11%, respectively, lower following administration of the oral dispersible tablet compared to the film-coated tablet.

Absorption The absolute bioavailability of bosentan in normal volunteers is about 50% and is unaffected by food. Bosentan is highly bound (> 98%) to plasma proteins, mainly albumin. Bosentan does not penetrate into erythrocytes.

The volume of distribution is about 18 L. Elimination Metabolism Bosentan has three metabolites, one of which is pharmacologically active and may contribute 10%–20% of the effect of bosentan. Bosentan is an inducer of CYP2C9 and CYP3A and possibly also of CYP2C19.

Upon multiple oral dosing, plasma concentrations in healthy adults decrease gradually to 50-65% of those seen after single dose administration, probably the effect of auto-induction of the metabolizing liver enzymes. Steady-state is reached within 3-5 days. Excretion Bosentan is eliminated by biliary excretion following metabolism in the liver.

Less than 3% of an administered oral dose is recovered in urine. Total clearance after a single intravenous dose is about 4 L/h in patients with PAH. Specific Populations Pediatrics The average plasma exposure to bosentan at steady state (AUC ss ) in pediatric patients with PAH aged 3 to 15 years treated with 31.25, 62.5 or 125 mg (approximately 2 mg/kg) film-coated tablet twice daily is 37% lower than that observed in adult patients with PAH receiving 125 mg film-coated tablet twice daily.

Following administration of 4 mg/kg twice daily doses of dispersible tablet in patients with PAH aged 2 to 11 years, the average systemic exposure to bosentan at steady state is similar to that observed with 2 mg/kg. The average exposure to bosentan in these pediatric patients was approximately half the exposure in adult patients treated with 125 mg film-coated tablets twice daily. The exposure to bosentan at 2 mg/kg three times daily dosing of dispersible tablet is similar to that of 2 mg/kg twice daily dosing in patients with PAH aged 3 months to 12 years.

Based on these findings, exposure to bosentan reaches a plateau at lower doses in pediatric patients than in adults, and doses higher than 2 mg/kg twice daily do not increase the exposure to bosentan in pediatric patients. Hepatic Impairment In vitro and in vivo evidence showing extensive hepatic metabolism of bosentan suggests that liver impairment could significantly increase exposure to bosentan. In a study comparing 8 patients with mild liver impairment (Child-Pugh Class A) to 8 controls, the single- and multiple-dose pharmacokinetics of bosentan were not altered in patients with mild hepatic impairment.

In another small (N=8) pharmacokinetic study, the steady-state AUC of bosentan was on average 4.7 times higher and the active metabolite Ro 48-5033 was 12.4 times higher in 5 patients with moderately impaired liver function (Child-Pugh Class B) and PAH associated with portal hypertension than in 3 patients with normal liver function and PAH of other etiologies. The pharmacokinetics of bosentan have not been evaluated in patients with severe liver impairment (Child-Pugh Class C) [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) , Use in Specific Populations (8.6) ] .

Renal Impairment In patients with severe renal impairment (creatinine clearance 15–30 mL/min), plasma concentrations of bosentan were essentially unchanged and plasma concentrations of the three metabolites were increased about 2-fo… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14. CLINICAL STUDIES

14.1Pulmonary Arterial Hypertension WHO Functional Class III-IV Two randomized, double-blind, multi-center, placebo-controlled trials were conducted in 32 and 213 patients. The larger study (BREATHE-1) compared 2 doses (125 mg twice daily and 250 mg twice daily) of bosentan with placebo. The smaller study (Study 351) compared 125 mg twice daily with placebo.

Patients had severe (WHO functional Class III–IV) PAH: idiopathic or heritable PAH (72%) or PAH associated with scleroderma or other connective tissue diseases (21%), or to autoimmune diseases (7%). There were no patients with PAH associated with other conditions such as HIV disease or recurrent pulmonary emboli. In both studies, bosentan or placebo was added to patients' current therapy, which could have included a combination of digoxin, anticoagulants, diuretics, and vasodilators (e.g., calcium channel blockers, ACE inhibitors), but not epoprostenol.

Bosentan was given at a dose of 62.5 mg twice daily for 4 weeks and then at 125 mg twice daily or 250 mg twice daily for either 12 (BREATHE-1) or 8 (Study 351) additional weeks. The primary study endpoint was 6-minute walk distance. In addition, symptoms and functional status were assessed.

Hemodynamic measurements were made at 12 weeks in Study 351. The mean age was about 49 years. About 80% of patients were female, and about 80% were Caucasian.

Patients had been diagnosed with pulmonary hypertension for a mean of 2.4 years. Submaximal Exercise Ability Results of the 6-minute walk distance at 3 months (Study 351) or 4 months (BREATHE-1) are shown in Table 4. Table 4.

Effects of bosentan on 6-minute walk distance BREATHE-1 Study 351 Bosentan 125 mg twice daily (n = 74) Bosentan 250 mg twice daily (n = 70) Placebo (n = 69) Bosentan 125 mg twice daily (n = 21) Placebo (n = 11) Baseline 326 ± 73 333 ± 75 344 ± 76 360 ± 86 355 ± 82 End point 353 ± 115 379 ± 101 336 ± 129 431 ± 66 350 ± 147 Change from baseline 27 ± 75 46 ± 62 -8 ± 96 70 ± 56 -6 ± 121 Placebo – subtracted 35 (a) 54 (b) 76 (c) Distance in meters: mean ± standard deviation. Changes are to week 16 for BREATHE-1 and to week 12 for Study 351.

(a) p=0.01; by Wilcoxon; (b) p=0.0001; by Wilcoxon; (c) p=0.02; by Student’s t-test. In both trials, treatment with bosentan resulted in a significant increase in exercise ability. The improvement in walk distance was apparent after 1 month of treatment (with 62.5 mg twice daily) and fully developed by about 2 months of treatment (Figure 5).

It was maintained for up to 7 months of double-blind treatment. Walking distance was somewhat greater with 250 mg twice daily, but the potential for increased hepatotoxicity causes this dose not to be recommended [see Dosage and Administration (2.1) ] . There were no apparent differences in treatment effects on walk distance among subgroups analyzed by demographic factors, baseline disease severity, or disease etiology, but the studies had little power to detect such differences.

Figure 5. Mean Change in 6-min Walk Distance (BREATHE-1) Change from baseline in 6-minute walking distance from start of therapy to week 16 in the placebo and combined bosentan (125 mg twice daily and 250 mg twice daily) groups. Values are expressed as mean ± standard error of the mean.

Hemodynamic Changes Invasive hemodynamic parameters were assessed in Study 351. Treatment with bosentan led to a significant increase in cardiac index (CI) associated with a significant reduction in pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP) (Table 5). The relationship between hemodynamic effects and improvements in 6-minute walk distance is unknown.

Table 5: Change from Baseline to Week 12: Hemodynamic Parameters Bosentan 125 mg twice daily Placebo CI (L/min/m 2 ) n=20 n=10 Baseline 2.35±0.73 2.48±1.03 Absolute Change 0.50±0.46 -0.52±0.48 Treatment Effect 1.02 (a) Mean PAP (mmHg) n=20 n=10 Baseline 53.7±13.4 55.7±10.5 Absolute Change -1.6±5.1 5.1±8… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~2 min read ▾

13. NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis and Mutagenesis Two years of dietary administration of bosentan to mice produced an increased incidence of hepatocellular adenomas and carcinomas in males at doses as low as 450 mg/kg/day (about 8 times the maximum recommended human dose [MRHD] of 125 mg twice daily, on a mg/m2 basis). In the same study, doses greater than 2000 mg/kg/day (about 32 times the MRHD) were associated with an increased incidence of colon adenomas in both males and females.

In rats, dietary administration of bosentan for two years was associated with an increased incidence of brain astrocytomas in males at doses as low as 500 mg/kg/day (about 16 times the MRHD). In a comprehensive battery of in vitro tests (the microbial mutagenesis assay, the unscheduled DNA synthesis assay, the V-79 mammalian cell mutagenesis assay, and human lymphocyte assay) and an in vivo mouse micronucleus assay, there was no evidence for any mutagenic or clastogenic activity of bosentan. Impairment of Fertility/Testicular Function The development of testicular tubular atrophy and impaired fertility has been linked with the chronic administration of certain endothelin receptor antagonists in rodents.

Treatment with bosentan at oral doses of up to 1500 mg/kg/day (50 times the MRHD on a mg/m 2 basis) or intravenous doses up to 40 mg/kg/day had no effects on sperm count, sperm motility, mating performance or fertility in male and female rats. An increased incidence of testicular tubular atrophy was observed in rats given bosentan orally at doses as low as 125 mg/kg/ day (about 4 times the MRHD and the lowest doses tested) for two years but not at doses as high as 1500 mg/kg/day (about 50 times the MRHD) for 6 months.

Effects on sperm count and motility were evaluated only in the much shorter duration fertility studies in which males had been exposed to the drug for 4-6 weeks. An increased incidence of tubular atrophy was not observed in mice treated for 2 years at doses up to 4500 mg/kg/day (about 75 times the MRHD) or in dogs treated up to 12 months at doses up to 500 mg/kg/day (about 50 times the MRHD).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis and Mutagenesis Two years of dietary administration of bosentan to mice produced an increased incidence of hepatocellular adenomas and carcinomas in males at doses as low as 450 mg/kg/day (about 8 times the maximum recommended human dose [MRHD] of 125 mg twice daily, on a mg/m2 basis). In the same study, doses greater than 2000 mg/kg/day (about 32 times the MRHD) were associated with an increased incidence of colon adenomas in both males and females.

In rats, dietary administration of bosentan for two years was associated with an increased incidence of brain astrocytomas in males at doses as low as 500 mg/kg/day (about 16 times the MRHD). In a comprehensive battery of in vitro tests (the microbial mutagenesis assay, the unscheduled DNA synthesis assay, the V-79 mammalian cell mutagenesis assay, and human lymphocyte assay) and an in vivo mouse micronucleus assay, there was no evidence for any mutagenic or clastogenic activity of bosentan. Impairment of Fertility/Testicular Function The development of testicular tubular atrophy and impaired fertility has been linked with the chronic administration of certain endothelin receptor antagonists in rodents.

Treatment with bosentan at oral doses of up to 1500 mg/kg/day (50 times the MRHD on a mg/m 2 basis) or intravenous doses up to 40 mg/kg/day had no effects on sperm count, sperm motility, mating performance or fertility in male and female rats. An increased incidence of testicular tubular atrophy was observed in rats given bosentan orally at doses as low as 125 mg/kg/ day (about 4 times the MRHD and the lowest doses tested) for two years but not at doses as high as 1500 mg/kg/day (about 50 times the MRHD) for 6 months.

Effects on sperm count and motility were evaluated only in the much shorter duration fertility studies in which males had been exposed to the drug for 4-6 weeks. An increased incidence of tubular atrophy was not observed in mice treated for 2 years at doses up to 4500 mg/kg/day (about 75 times the MRHD) or in dogs treated up to 12 months at doses up to 500 mg/kg/day (about 50 times the MRHD).

📄 Package Label / Principal Display Panel 33 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Blister Carton: NDC-68180-340-13 Bosentan Tablets for Oral Suspension 32 mg Rx only 56 tablets for oral suspension per carton. Each carton contains 4 blister-strips of 14 tablets each. bosentan-final-carton-label

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.
📅 Q3 2025 – Q1 2026 · 3 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
62
Units reimbursed last 4 qtrs
2.5K
Gross reimbursed last 4 qtrs
$392.7K
Avg / prescription
$6,334.62
Avg / unit
$157.29
Latest quarter Q1 2026
36Rx
Fee-for-service vs managed care ⓘ
100% FFS
Fee-for-service · 62 Rx Managed care · 0 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 502 units · 2.6 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 735 units · 1.9 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: 1,260 units · 23.5 per 100k residents SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.923.5
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 South Carolina 23.5 /100k
2 New York 2.6 /100k
3 California 1.9 /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.

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

Medicare Part D (outpatient prescription) spending for Bosentan — the program that covers self-administered drugs. 3 manufacturers.
⚠️ 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 Bosentan. 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
$3.14M
Claims incl. refills
1.1K
Beneficiaries
422
Spend / beneficiary
$7,438.38
Spend / claim
$2,797.68
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.
🛡
This drug has a REMS — Bosentan REMS. A Risk Evaluation & Mitigation Strategy is an FDA-required safety program. It is available only through a restricted program (certified prescribers/pharmacies, enrollment, or required monitoring). See the boxed warning & full label below, and REMS@FDA ↗.

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 Bosentan — the ingredient across all brands.

Top reported reactions

Death9,317
Dyspnoea6,001
Pneumonia2,698
Pulmonary Arterial Hypertension2,293
Fatigue2,258
Headache2,227
Nausea2,067

Age at onset

Neonate52
Infant619
Child686
Adolescent268
Adult5,284
Elderly5,819

Reporter sex

50,110 reports
Male · 27%
Female · 73%
Unknown · 0%

Serious outcomes

Hospitalization25,004
Death15,947
Life-threatening1,400
Disabling643
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 2,592 0
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 ✓ Available
Inactive ingredients (structured) ✓ 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 Lupin Pharmaceuticals, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Lupin Pharmaceuticals, 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.
← 68180-0339-01 · Lupin 68180-0345-07 · Lupin →
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.