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Veletri epoprostenol .5 mg/10mL Injection, Powder, Lyophilized, For Solution — NDC 66215-403-01 (Billing 66215-0403-01)

by Actelion Pharmaceuticals US, Inc. · 1 VIAL in 1 CARTON / 10 mL in 1 VIAL

This is a package of Veletri epoprostenol .5 mg/10mL Injection, Powder, Lyophilized, For Solution from Actelion Pharmaceuticals US, Inc., marketed since Apr 2010 and currently FDA-listed. It is this product's only package size.

NDC 66215-0403-01
🏷️ FDA NDC (as labeled) 66215-403-01 billing pads the product segment with a zero
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 66215-403-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
66215 labeler · 403 product · 01 package
Package marketed since
Apr 22, 2010
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 6621540301 3
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 66215-403-01
Product NDC 66215-403
11-digit billing NDC 66215040301
NCPDP billing unit EA — each (per item)
RxCUI 562501, 562502, 1009216, 1302755
UNII DCR9Z582X0
Application # NDA022260
SPL Set ID df502787-46ec-4dd1-a2c0-be90f6d95a5d
Established class (EPC) Prostacycline Vasodilator
Physiologic effect Vasodilation
Chemical class Prostaglandins I
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2010-04-22
Route INTRAVENOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance EPOPROSTENOL
TE code (Orange Book) AP2 · RLD · RS

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

GPI-14 40170040102110
GPI class Veletri
GCN Seq No 069964
GCN 33243
HICL code 007323
Ingredient (HICL) Epoprostenol Sodium
HIC1 code B
Therapeutic class — broad (HIC1) Respiratory System
HIC2 code B1
Therapeutic class — intermediate (HIC2) Affect Primarily Lungs
HIC3 code B1C
Therapeutic class — specific (HIC3) Pulmonary Antihypertensives, Prostacyclin-Type
AHFS code 24:12.92.00
AHFS class Vasodilating Agents, Miscellaneous
FDB label name VELETRI 0.5 MG VIAL
FDB brand name Veletri
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 069964
  • GCN: 33243
  • GPI-14 (Medi-Span): 40170040102110
  • HICL (First Databank): 007323
  • AHFS class code: 24:12.92.00
  • RxCUI (RxNorm): 562501
Why two NDCs? The FDA registers this code as 66215-403-01 — 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 → 66215-0403-01. 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 Prostacycline Vasodilator class.

Pharmacologic class Prostacycline Vasodilator
Drug family (ATC) Platelet aggregation inhibitors excl. heparin
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 VELETRI 0.5 MG VIAL Ingredient Epoprostenol Sodium
📗 Our plain-language guide HelloPharmacist
  • It treats pulmonary arterial hypertension (PAH), which is high blood pressure in the arteries of your lungs. It helps you be more active and improves exercise capacity. Veletri and...
  • It runs continuously into a vein, usually through a central catheter and a small portable pump. Your care team prepares it and sets the rate. Don't mix it with anything else or cha...
  • Because the drug clears in just minutes, even a short break can bring back shortness of breath, dizziness, and weakness. This can be dangerous. Call your care team immediately if y...
  • Flushing, headache, nausea, diarrhea, and jaw pain are common. Many ease as your dose is adjusted. Call your doctor for fever, chills, or redness at the catheter site, fainting, un...
📖 Read our full Epoprostenol guide →
1
Nutrient depletion considerations

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

🧪 Full Epoprostenol 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 No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J1325 $16.918 / J1325 unit —
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.

Billing & reimbursement

FDA NDC (as labeled)66215-403-01
11-digit billing NDC66215-0403-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ1325
DescriptorINJECTION, EPOPROSTENOL, 0.5 MG
Billing units / pkg1 units
How the units are derivedThis package is 1 EA; the HCPCS unit is 0.5 MG, so one package = 1 billing unit.
Medicare Part B spend (2026 (Q1))$1,498,822 · 622 claims · $2,409.68 per claim (all NDCs under J1325)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
66215-0403-01 You're viewing this Main listing 1 VIAL in 1 CARTON / 10 mL in 1 VIAL 2010-04-22 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
epoprostenol .5 mg/10mL 62756-0059-40 Sun 1 vial — AP2 FDA listed —
Veletri .5 mg/10mLthis 66215-0403-01 Actelion 1 vial — AP2 FDA listed —
Epoprostenol .5 mg/10mL 67457-0587-10 Mylan 1 vial — AP2 FDA listed —
Epoprostenol .5 mg/10mL 68083-0707-01 Gland 1 vial — AP2 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

🏛️
2008
First FDA approval
Jun 2008
📍
2026
Currently FDA-listed
18 years listed
🛡️
2027
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 Mar 2027. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jun 27, 2008 AP2 TE-rated RLD RS ⏳ ~0.4 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 8598227 — drug product
US 8318802 — drug product
US 8318802 — drug product
US 8598227 — drug product
2008 2010 2012 2014 2016 2018 2020 2022 2024 2026
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 (4)
PatentTypeUse codeExpires
US 8598227 ↗ Drug product — Feb 2, 2027
US 8318802 ↗ Drug product — Mar 15, 2027
US 8318802 ↗ Drug product — Mar 15, 2027
US 8598227 ↗ Drug product — Feb 2, 2027
Common questions
Is there a generic version of VELETRI 0.5 MG VIAL?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for VELETRI 0.5 MG VIAL. 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 Epoprostenol 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 applicationNDA022260 (NDA)
Labeler code66215
First marketedApr 2010
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.
🎯 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 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 98 words ▾

1 INDICATIONS AND USAGE VELETRI is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III–IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases. VELETRI is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity.

Studies establishing effectiveness included predominantly patients with NYHA Functional Class III–IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Important Note: Reconstitute VELETRI only as directed with Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Do not dilute reconstituted solutions of VELETRI or administer it with other parenteral solutions or medications [see Dosage and Administration (2.4) ] . Dosage - Infusion of VELETRI should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established.

( 2.1 ) - If symptoms of pulmonary hypertension persist or recur after improving - the infusion should be increased by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be at least 15 minutes. ( 2.2 ) Administration - VELETRI is administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump. ( 2.3 ) - Do not mix with any other parenteral medications or solutions prior to or during administration.

( 2.4 ) Reconstitution - Reconstituted in vial with only 5 mL of either Sterile Water for Injection or Sodium Chloride 0.9% Injection. - VELETRI solution reconstituted and immediately diluted to the final concentration in the drug delivery reservoir can be administered per the conditions of use as outlined in Table 1. ( 2.4 ) - Solution for chronic delivery should be prepared in a drug delivery reservoir appropriate for the infusion pump. ( 2.4 )

2.1Dosage Prepare continuous chronic infusion of VELETRI as directed, and administer through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Initiate chronic infusion of VELETRI at 2 ng/kg/min and increase in increments of 2 ng/kg/min every 15 minutes or longer until a tolerance limit to the drug is established or further increases in the infusion rate are not clinically warranted.

If dose-limiting pharmacologic effects occur, then decrease the infusion rate until VELETRI is tolerated. In clinical trials, the most common dose-limiting adverse events were nausea, vomiting, hypotension, sepsis, headache, abdominal pain, or respiratory disorder (most treatment-limiting adverse events were not serious). If the initial infusion rate of 2 ng/kg/min is not tolerated, use a lower dose.

In the controlled 12-week trial in PAH/SSD, for example, the dose increased from a mean starting dose of 2.2 ng/kg/min. During the first 7 days of treatment, the dose was increased daily to a mean dose of 4.1 ng/kg/min on day 7 of treatment. At the end of week 12, the mean dose was 11.2 ng/kg/min.

The mean incremental increase was 2 to 3 ng/kg/min every 3 weeks.

2.2Dosage Adjustments Base changes in the chronic infusion rate on persistence, recurrence, or worsening of the patient's symptoms of pulmonary hypertension and the occurrence of adverse events due to excessive doses of VELETRI. In general, expect increases in dose from the initial chronic dose. Consider increments in dose if symptoms of pulmonary hypertension persist or recur.

Adjust the infusion by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be at least 15 minutes. In clinical trials, incremental increases in dose occurred at intervals of 24 to 48 hours or longer. Following establishment of new chronic infusion rate, observe the patient, and monitor standing and supine blood pressure and heart rate for several hours to ensure that the new dose is tolerated.

During chronic infusion, the occurrence of dose-limiting pharmacological events may necessitate a decrease in infusion rate, but the adverse event may occasionally resolve without dosage adjustment. Make dosage decreases gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve [see Adverse Reactions (6.1 and 6.2) ] . Avoid abrupt withdrawal of VELETRI or… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 54 words ▾

3 DOSAGE FORMS AND STRENGTHS VELETRI contains epoprostenol sodium equivalent to 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol and is supplied as a sterile lyophilized material in a 10 mL vial. Injection : 10 mL single-dose vial with 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) VELETRI. ( 3 )

⛔ Contraindications 160 words ▾

4 CONTRAINDICATIONS A large study evaluating the effect of epoprostenol on survival in NYHA Class III and IV patients with congestive heart failure due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving epoprostenol plus conventional therapy than in those receiving conventional therapy alone. The chronic use of VELETRI in patients with congestive heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated.

Some patients with pulmonary hypertension have developed pulmonary edema during dose initiation, which may be associated with pulmonary veno-occlusive disease. VELETRI should not be used chronically in patients who develop pulmonary edema during dose initiation. VELETRI is also contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds.

Congestive heart failure due to severe left ventricular systolic dysfunction ( 4 ) Pulmonary edema ( 4 ) Hypersensitivity to the drug or to structurally related compounds ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Do not abruptly lower the dose or withdraw dosing. All dosing initiation and changes should be closely monitored. ( 5.2 , 5.3 )

5.1Dose Initiation VELETRI is a potent pulmonary and systemic vasodilator. Initiate VELETRI in a setting with adequate personnel and equipment for physiologic monitoring and emergency care. Dose initiation has been performed during right heart catheterization and without cardiac catheterization.

During dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output occurred rarely. In such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated.

5.2Chronic Use and Dose Adjustment During chronic use, deliver VELETRI continuously on an ambulatory basis through a permanent indwelling central venous catheter. Unless contraindicated, administer anticoagulant therapy to patients receiving VELETRI to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale. To reduce the risk of infection, use aseptic technique in the reconstitution and administration of VELETRI and in routine catheter care.

Because epoprostenol is metabolized rapidly, even brief interruptions in the delivery of VELETRI may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia. Intravenous therapy with VELETRI will likely be needed for prolonged periods, possibly years, so consider the patient's capacity to accept and care for a permanent intravenous catheter and infusion pump. Based on clinical trials, the acute hemodynamic response (reduction in pulmonary artery resistance) to epoprostenol did not correlate well with improvement in exercise tolerance or survival during chronic use of epoprostenol.

Adjust dosage of VELETRI during chronic use at the first sign of recurrence or worsening of symptoms attributable to pulmonary hypertension or the occurrence of adverse events associated with epoprostenol [see Dosage and Administration (2.2) ] . Following dosage adjustments, monitor standing and supine blood pressure and heart rate closely for several hours.

5.3Withdrawal Effects Abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage of VELETRI may result in symptoms associated with rebound pulmonary hypertension, including dyspnea, dizziness, and asthenia. In clinical trials, one Class III primary pulmonary hypertension patient's death was judged attributable to the interruption of epoprostenol. Avoid abrupt withdrawal.

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Most common adverse reactions during: - Dose Initiation and Escalation: Nausea, vomiting, headache, hypotension, flushing, chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, and tachycardia ( 6.1 ) - Chronic Dosing: Headache, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms, and anxiety/nervousness ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, please contact: JANSSEN at 1-800-526-7736 (1-800 JANSSEN) 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. During clinical trials, adverse events were classified as follows: (1) adverse events during dose initiation and escalation, (2) adverse events during chronic dosing, and (3) adverse events associated with the drug delivery system.

Adverse Events during Dose Initiation and Escalation During early clinical trials, epoprostenol was increased in 2-ng/kg/min increments until the patients developed symptomatic intolerance. The most common adverse events and the adverse events that limited further increases in dose were generally related to vasodilation, the major pharmacologic effect of epoprostenol. The most common dose-limiting adverse events (occurring in ≥1% of patients) were nausea, vomiting, headache, hypotension, and flushing, but also include chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, and tachycardia.

Table 8 lists the adverse events reported during dose initiation and escalation in decreasing order of frequency. Table 8: Adverse Events during Dose Initiation and Escalation Adverse Events Occurring in ≥1% of Patients Epoprostenol (n=391) Flushing 58% Headache 49% Nausea/vomiting 32% Hypotension 16% Anxiety, nervousness, agitation 11% Chest pain 11% Dizziness 8% Bradycardia 5% Abdominal pain 5% Musculoskeletal pain 3% Dyspnea 2% Back pain 2% Sweating 1% Dyspepsia 1% Hypesthesia/paresthesia 1% Tachycardia 1% Adverse Events during Chronic Administration: Interpretation of adverse events is complicated by the clinical features of PAH, which are similar to some of the pharmacologic effects of epoprostenol (e.g., dizziness, syncope).

Adverse events which may be related to the underlying disease include dyspnea, fatigue, chest pain, edema, hypoxia, right ventricular failure, and pallor. Several adverse events, on the other hand, can clearly be attributed to epoprostenol. These include hypotension, bradycardia, tachycardia, pulmonary edema, bleeding at various sites, thrombocytopenia, headache, abdominal pain, pain (unspecified), sweating, rash, arthralgia, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms, anxiety/nervousness, and agitation.

In addition, chest pain, fatigue, and pallor have been reported during epoprostenol therapy, and a role for the drug in these events cannot be excluded. Adverse Events during Chronic Administration for Idiopathic or Heritable PAH In an effort to separate the adverse effects of the drug from the adverse effects of the underlying disease, Table 9 lists adverse events that occurred at a rate at least 10% greater on epoprostenol than on conventional therapy in controlled trials for idiopathic or heritable PAH. Table 9: Adverse Events Regardless of Attribution Occurring in Patients with Idiopathic or Heritable PAH with ≥10% Difference between Epoprostenol and Conventional Therapy Alone Adverse Event Epoprostenol (n=52) Conventional Therapy (n=54) Occurrence More Common With Epoprostenol General Chills/fever/sepsis/flu-like symptoms 25% 11% Cardiovascular Tachycardia 35% 24% Flushing 42% 2% Gastrointestinal Diarrhea 37% 6% Nausea/vomiting 67% 48% Musculoskeletal Jaw pain 54% 0% Myalgia 44% 31% Nonspecific musculoskel… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 214 words ▾

7 DRUG INTERACTIONS Additional reductions in blood pressure may occur when VELETRI is administered with diuretics, antihypertensive agents, or other vasodilators. When other antiplatelet agents or anticoagulants are used concomitantly, there is the potential for VELETRI to increase the risk of bleeding. However, patients receiving infusions of epoprostenol in clinical trials were maintained on anticoagulants without evidence of increased bleeding.

In clinical trials, epoprostenol was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen. In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide or digoxin in whom therapy with epoprostenol was initiated, apparent oral clearance values for furosemide (n=23) and digoxin (n=30) were decreased by 13% and 15%, respectively, on the second day of therapy and had returned to baseline values by day 87. The change in furosemide clearance value is not likely to be clinically significant.

However, patients on digoxin may show elevations of digoxin concentrations after initiation of therapy with epoprostenol, which may be clinically significant in patients prone to digoxin toxicity. Diuretics, antihypertensive agents, or other vasodilators : reduction in blood pressure ( 7 ) Antiplatelet agents or anticoagulants : increase the risk of bleeding ( 7 ) Patients on digoxin : elevations of digoxin concentrations clinically significant in patients prone to digoxin toxicity ( 7 )

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Limited published data from case series and case reports with VELETRI have not established a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes when used during pregnancy. There are risks to the mother and fetus from untreated pulmonary arterial hypertension ( see Clinical Considerations ). In animal reproduction studies, pregnant rats and rabbits received epoprostenol sodium during organogenesis at exposures of 2.5 and 4.8 times the maximum recommended human dose (MRHD), respectively, and there was no effect on the fetus ( see Data ).

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% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. Data Animal Data Embryo-fetal development studies have been performed in rats and rabbits during organogenesis. Epoprostenol sodium doses up to 100 mcg/kg/day, a dose that was maternally toxic in rabbits but not in rats, (600 mcg/m 2 /day in rats, 2.5 times the MRHD, and 1,180 mcg/m 2 /day in rabbits, 4.8 times the MRHD based on body surface area), had no effect on the fetus.

In a postnatal development study, epoprostenol sodium was administered subcutaneously to female rats for 2 weeks prior to mating through weaning and to male rats for 60 days prior to and through mating at a male and female toxic dose of up to 100 mcg/kg/day (600 mcg/m 2 /day, 2.5 times the MRHD based on body surface area). There was no effect on growth and development of the offspring.

8.2Lactation Risk Summary There are no data on the presence of epoprostenol in either human or animal milk, the effects on the breastfed infant, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VELETRI and any potential adverse effects on the breastfed child from epoprostenol or from the underlying maternal condition.

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5Geriatric Use Clinical studies of epoprostenol in pulmonary hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Limited published data from case series and case reports with VELETRI have not established a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes when used during pregnancy. There are risks to the mother and fetus from untreated pulmonary arterial hypertension ( see Clinical Considerations ). In animal reproduction studies, pregnant rats and rabbits received epoprostenol sodium during organogenesis at exposures of 2.5 and 4.8 times the maximum recommended human dose (MRHD), respectively, and there was no effect on the fetus ( see Data ).

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% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. Data Animal Data Embryo-fetal development studies have been performed in rats and rabbits during organogenesis. Epoprostenol sodium doses up to 100 mcg/kg/day, a dose that was maternally toxic in rabbits but not in rats, (600 mcg/m 2 /day in rats, 2.5 times the MRHD, and 1,180 mcg/m 2 /day in rabbits, 4.8 times the MRHD based on body surface area), had no effect on the fetus.

In a postnatal development study, epoprostenol sodium was administered subcutaneously to female rats for 2 weeks prior to mating through weaning and to male rats for 60 days prior to and through mating at a male and female toxic dose of up to 100 mcg/kg/day (600 mcg/m 2 /day, 2.5 times the MRHD based on body surface area). There was no effect on growth and development of the offspring.

🧒 Pediatric Use 13 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 86 words ▾

8.5Geriatric Use Clinical studies of epoprostenol in pulmonary hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

🆘 Overdosage 142 words ▾

10 OVERDOSAGE Signs and symptoms of excessive doses of epoprostenol during clinical trials are the expected dose-limiting pharmacologic effects of epoprostenol, including flushing, headache, hypotension, tachycardia, nausea, vomiting, and diarrhea. Treatment will ordinarily require dose reduction of epoprostenol. One patient with secondary pulmonary hypertension accidentally received 50 mL of an unspecified concentration of epoprostenol.

The patient vomited and became unconscious with an initially unrecordable blood pressure. Epoprostenol was discontinued and the patient regained consciousness within seconds. In clinical practice, fatal occurrences of hypoxemia, hypotension, and respiratory arrest have been reported following overdosage of epoprostenol.

Single intravenous doses of epoprostenol at 10 and 50 mg/kg (2,703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Epoprostenol has 2 major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation.

12.2Pharmacodynamics In animals, the vasodilatory effects reduce right- and left-ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated bradycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension.

No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying.

12.3Pharmacokinetics Epoprostenol is rapidly hydrolyzed at neutral pH in blood and is also subject to enzymatic degradation. Animal studies using tritium-labeled epoprostenol have indicated a high clearance (93 mL/kg/min), small volume of distribution (357 mL/kg), and a short half-life (2.7 minutes). During infusions in animals, steady-state plasma concentrations of tritium-labeled epoprostenol were reached within 15 minutes and were proportional to infusion rates.

No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol. The in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; therefore, the in vivo half-life of epoprostenol in humans is expected to be no greater than 6 minutes. The in vitro pharmacologic half-life of epoprostenol in human plasma, based on inhibition of platelet aggregation, was similar for males (n=954) and females (n=1,024).

Tritium-labeled epoprostenol has been administered to humans in order to identify the metabolic products of epoprostenol. Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF 1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF 1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. The recovery of radioactivity in urine and feces over a 1-week period was 82% and 4% of the administered dose, respectively.

Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.

🧬 Mechanism of Action 26 words ▾

12.1Mechanism of Action Epoprostenol has 2 major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation.

📦 How Supplied / Storage and Handling 194 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied VELETRI is supplied as a sterile lyophilized material in 10 mL vials. 10 mL vial with a white flip-off seal containing epoprostenol sodium equivalent to 0.5 mg (500,000 ng) epoprostenol, is packaged in carton of 1 vial (NDC 66215-403-01). 10 mL vial with a red flip-off seal containing epoprostenol sodium equivalent to 1.5 mg (1,500,000 ng) epoprostenol, is packaged in carton of 1 vial (NDC 66215-402-01).

Store the vials of VELETRI at 68° to 77°F (20° to 25°C) [see USP Controlled Room Temperature] .

16.2Storage and Stability Unopened vials of VELETRI are stable until the date indicated on the package when stored at 68° to 77°F (20° to 25°C). The unopened vial should be kept in the carton and not exposed to direct sunlight. Use after reconstitution and immediate dilution to final concentration can be found in Dosage and Administration (2.4) Reconstitution, Table 1: Maximum duration of administration (hours) at room temperature (77°F/25°C) of fully diluted solutions in the drug delivery reservoir.

Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. If either occurs, do not administer.

📦 Storage and Handling 102 words ▾

16.2Storage and Stability Unopened vials of VELETRI are stable until the date indicated on the package when stored at 68° to 77°F (20° to 25°C). The unopened vial should be kept in the carton and not exposed to direct sunlight. Use after reconstitution and immediate dilution to final concentration can be found in Dosage and Administration (2.4) Reconstitution, Table 1: Maximum duration of administration (hours) at room temperature (77°F/25°C) of fully diluted solutions in the drug delivery reservoir.

Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. If either occurs, do not administer.

📋 Description 161 words ▾

11 DESCRIPTION Epoprostenol sodium is the sodium salt of epoprostenol, formulated as a sterile lyophilized powder for intravenous (IV) administration. Each vial of VELETRI contains epoprostenol sodium equivalent to either 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol, 50 mg arginine and 100 mg sucrose. Sodium hydroxide is added to adjust pH.

Epoprostenol (PGI 2 , PGX, prostacyclin), a metabolite of arachidonic acid, is a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation. Epoprostenol is (5 Z ,9a,11a,13 E ,15 S )-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid. Epoprostenol sodium has a molecular weight of 374.45 and a molecular formula of C 20 H 31 NaO 5 .

The structural formula is: VELETRI is a white to off-white lyophilized powder material. It is reconstituted with Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. The reconstituted solution of VELETRI has a pH ranging from 11 to 13 and is increasingly unstable at a lower pH.

Chemical Structure

💬 Information for Patients 152 words ▾

17 PATIENT COUNSELING INFORMATION Patients receiving VELETRI should receive the following information. VELETRI must be reconstituted as directed using only Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. VELETRI is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump.

Thus, therapy with VELETRI requires commitment by the patient to drug reconstitution, drug administration, and care of the permanent central venous catheter. Patients must adhere to sterile technique in preparing the drug and in the care of the catheter, and even brief interruptions in the delivery of VELETRI may result in rapid symptomatic deterioration. A patient's decision to receive VELETRI should be based upon the understanding that there is a high likelihood that therapy with VELETRI will be needed for prolonged periods, possibly years.

The patient's ability to accept and care for a permanent intravenous catheter and infusion pump should also be carefully considered.

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics Epoprostenol is rapidly hydrolyzed at neutral pH in blood and is also subject to enzymatic degradation. Animal studies using tritium-labeled epoprostenol have indicated a high clearance (93 mL/kg/min), small volume of distribution (357 mL/kg), and a short half-life (2.7 minutes). During infusions in animals, steady-state plasma concentrations of tritium-labeled epoprostenol were reached within 15 minutes and were proportional to infusion rates.

No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol. The in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; therefore, the in vivo half-life of epoprostenol in humans is expected to be no greater than 6 minutes. The in vitro pharmacologic half-life of epoprostenol in human plasma, based on inhibition of platelet aggregation, was similar for males (n=954) and females (n=1,024).

Tritium-labeled epoprostenol has been administered to humans in order to identify the metabolic products of epoprostenol. Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF 1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF 1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. The recovery of radioactivity in urine and feces over a 1-week period was 82% and 4% of the administered dose, respectively.

Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.

🧬 Pharmacodynamics 81 words ▾

12.2Pharmacodynamics In animals, the vasodilatory effects reduce right- and left-ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated bradycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension.

No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Clinical Trials in Pulmonary Arterial Hypertension (PAH) Acute Hemodynamic Effects Acute intravenous infusions of epoprostenol for up to 15 minutes in patients with idiopathic or heritable PAH or PAH associated with scleroderma spectrum of diseases (PAH/SSD) produce dose-related increases in cardiac index (CI) and stroke volume (SV) and dose-related decreases in pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and mean systemic arterial pressure (SAPm). The effects of epoprostenol on mean pulmonary arterial pressure (PAPm) were variable and minor.

Chronic Infusion in Idiopathic or Heritable PAH Hemodynamic Effects Chronic continuous infusions of epoprostenol in patients with idiopathic or heritable PAH were studied in 2 prospective, open, randomized trials of 8 and 12 weeks' duration comparing epoprostenol plus conventional therapy to conventional therapy alone. Dosage of epoprostenol was determined as described in Dosage and Administration (2) and averaged 9.2 ng/kg/min at study's end. Conventional therapy varied among patients and included some or all of the following: anticoagulants in essentially all patients; oral vasodilators, diuretics, and digoxin in one half to two thirds of patients; and supplemental oxygen in about half the patients.

Except for 2 New York Heart Association (NYHA) functional Class II patients, all patients were either functional Class III or Class IV. As results were similar in the 2 studies, the pooled results are described. Chronic hemodynamic effects were generally similar to acute effects.

Increases in CI, SV, and arterial oxygen saturation and decreases in PAPm, mean right atrial pressure (RAPm), TPR, and systemic vascular resistance (SVR) were observed in patients who received epoprostenol chronically compared to those who did not. Table 11 illustrates the treatment-related hemodynamic changes in these patients after 8 or 12 weeks of treatment. Table 11: Hemodynamics during Chronic Administration of Epoprostenol in Patients with Idiopathic or Heritable PAH Baseline Mean Change from Baseline at End of Treatment Period At 8 weeks: Epoprostenol N=10, conventional therapy N=11 (N is the number of patients with hemodynamic data).

At 12 weeks: Epoprostenol N=38, conventional therapy N=30 (N is the number of patients with hemodynamic data). Hemodynamic Parameter Epoprostenol (N=52) Standard Therapy (N=54) Epoprostenol (N=48) Standard Therapy (N=41) CI=cardiac index, PAPm=mean pulmonary arterial pressure, PVR=pulmonary vascular resistance, SAPm=mean systemic arterial pressure, SV=stroke volume, TPR=total pulmonary resistance. CI (L/min/m 2 ) 2.0 2.0

0.3Denotes statistically significant difference between Epoprostenol and conventional therapy groups. -0.1 PAPm (mmHg) 60 60 -5 1 PVR (Wood U) 16 17 -4 1 SAPm (mmHg) 89 91 -4 -3 SV (mL/beat) 44 43 6 -1 TPR (Wood U) 20 21 -5 1 These hemodynamic improvements appeared to persist when epoprostenol was administered for at least 36 months in an open, nonrandomized study. Clinical Effects Statistically significant improvement was observed in exercise capacity, as measured by the 6-minute walk test in patients receiving continuous intravenous epoprostenol plus conventional therapy (N=52) for 8 or 12 weeks compared to those receiving conventional therapy alone (N=54).

Improvements were apparent as early as the first week of therapy. Increases in exercise capacity were accompanied by statistically significant improvement in dyspnea and fatigue, as measured by the Chronic Heart Failure Questionnaire and the Dyspnea Fatigue Index. Survival was improved in NYHA functional Class III and Class IV patients with idiopathic or heritable PAH treated with epoprostenol for 12 weeks in a multicenter, open, randomized, parallel study.

At the end of the treatment period, 8 of 40 (20%) patients receiving conventional therapy alone died, whereas none of the 41 patients receiving epoprostenol died (p=0.003). Chronic Infusion in PAH/Scle… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 93 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic potential. A micronucleus test in rats revealed no evidence of mutagenicity. The Ames test and DNA elution tests were also negative, although the instability of epoprostenol makes the significance of these tests uncertain.

Fertility was not impaired in rats given epoprostenol by subcutaneous injection at doses up to 100 mcg/kg/day (600 mcg/m 2 /day, 2.5 times the recommended human dose [4.6 ng/kg/min or 245.1 mcg/m 2 /day, IV] based on body surface area).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 90 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic potential. A micronucleus test in rats revealed no evidence of mutagenicity. The Ames test and DNA elution tests were also negative, although the instability of epoprostenol makes the significance of these tests uncertain.

Fertility was not impaired in rats given epoprostenol by subcutaneous injection at doses up to 100 mcg/kg/day (600 mcg/m 2 /day, 2.5 times the recommended human dose [4.6 ng/kg/min or 245.1 mcg/m 2 /day, IV] based on body surface area).

📄 Package Label / Principal Display Panel 84 words ▾

PRINCIPAL DISPLAY PANEL - 0.5 mg Vial Carton NDC 66215-403-01 Single-dose Vial Discard unused portion. VELETRI ® (epoprostenol) for Injection 0.5 mg (500,000 ng)/vial Sterile, Lyophilized Product For Intravenous Infusion Only Rx only janssen Principal Display Panel - 0.5 mg Vial Carton

PRINCIPAL DISPLAY PANEL - 1.5 mg Vial Carton NDC 66215-402-01 Single-dose Vial Discard unused portion. VELETRI ® (epoprostenol) for Injection 1.5 mg (1,500,000 ng)/vial Sterile, Lyophilized Product For Intravenous Infusion Only Rx only janssen Principal Display Panel - 1.5 mg Vial Carton

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

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

Medicare Part D (outpatient prescription) spending for Veletri — 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 Veletri. 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
$126.9K
Claims incl. refills
38
Beneficiaries
12
Spend / beneficiary
$10,577.00
Spend / claim
$3,340.11
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.

About this NDC listing & data coverage

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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
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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.
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.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J1325 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
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.
← 66215-0402-01 · Actelion 66215-0501-15 · 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.