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Indomethacin 1 mg/mL Injection, Powder, Lyophilized, For Solution, 1 vial — NDC 63323-0659-09 package photo

Indomethacin 1 mg/mL Injection, Powder, Lyophilized, For Solution, 1 vial

by Fresenius Kabi USA, LLC · 1 VIAL in 1 CARTON (63323-659-09) / 1 mL in 1 VIAL
NDC 63323-0659-09
🏷️ FDA NDC (as labeled) 63323-659-09 billing pads the product segment with a zero
This package
Contains1 vial Pack sizes3 compare ↓
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →
⚠️
Other active recalls for Indomethacin (different manufacturers) — 5 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · May 15, 2025 — cGMP deviations (Amerisource Health Services LLC) · FDA recall D-0454-2025
Class II · May 9, 2025 — cGMP deviations (KVK Tech, Inc.) · FDA recall D-0445-2025
Class II · Mar 13, 2025 — CGMP Deviations (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-0329-2025
Class II · Jul 31, 2024 — Failed Dissolution Specifications: below specification results (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-0643-2024
Class II · Nov 7, 2023 — Labeling: Label Mix-Up-Indomethacin bottles may be labeled as Naproxen (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-0123-2024
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 63323-659-09
Product NDC 63323-659
11-digit billing NDC 63323065909
NCPDP billing unit EA — each (per item)
RxCUI 346508
UNII XXE1CET956
UPC 0363323659035
Application # NDA022536
SPL Set ID 30e38747-c553-4e2d-bc23-634e1dd90b8d
Established class (EPC) Nonsteroidal Anti-inflammatory Drug
Mechanism of action Cyclooxygenase Inhibitors
Chemical class Anti-Inflammatory Agents, Non-Steroidal
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2010-03-19
Route INTRAVENOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance INDOMETHACIN
GPI-14 66100030102105
GPI class Indomethacin Sodium
GCN Seq No 008335
GCN 34690
HICL code 003718
Ingredient (HICL) Indomethacin Sodium
HIC1 code A
Therapeutic class — broad (HIC1) Cardiovascular System
HIC2 code A5
Therapeutic class — intermediate (HIC2) Cardiac Treatment Agents, Other
HIC3 code A5A
Therapeutic class — specific (HIC3) Patent Ductus Arteriosus Treat. Agents, Nsaid-Type
AHFS code 28:08.04.04
AHFS class Reversible Cox-1/Cox-2 Inhibitors
FDB label name INDOMETHACIN 1 MG VIAL
FDB brand name Indomethacin
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 63323-659-09 — 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 → 63323-0659-09. 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 Nonsteroidal Anti-inflammatory Drug class.

Pharmacologic class Nonsteroidal Anti-inflammatory Drug
Drug family (ATC) Other cardiac preparations, Acetic acid derivatives and related substances, Antiinflammatory preparations, non-steroids for topical use
How it works Cyclooxygenase Inhibitors
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.

🏭 Manufacturer & labeler

LabelerFresenius Kabi USA, LLC
Application holderFRESENIUS KABI USA LLC
FDA applicationNDA022536 (NDA)
Labeler code63323
First marketedMar 2010
Product typeHuman Prescription Drug
Portfolio554 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.

🩺 Clinical

Label name INDOMETHACIN 1 MG VIAL Ingredient Indomethacin Sodium
📗 Our plain-language guide HelloPharmacist
  • Indomethacin is a strong anti-inflammatory medication used mainly for moderate to severe arthritis — including rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis — as...
  • Yes — and this is important. Always take indomethacin with food, right after a meal, or with antacids. This helps protect your stomach lining and reduces the chance of stomach upse...
  • Common side effects like headache, mild nausea, dizziness, or indigestion are typical and often improve as your body adjusts — taking it with food can help. But call your doctor im...
  • What side effects should I just watch for versus call my doctor about right away?
📖 Read our full Indomethacin guide →
1
Nutrient depletion considerations

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

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.

🧪 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 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • 0.41 mg / 1 mL UNII GR686LBA74
    Sodium phosphate, dibasic is a salt derived from phosphoric acid. It acts as a buffer to help maintain the medicine's pH balance and may serve as a binder or filler in tablets and capsules.
  • 0.29 mg / 1 mL UNII 3980JIH2SW
    A salt form of phosphoric acid that acts as a buffer and pH adjuster in medicines. It helps keep the product at the correct acidity level for stability and effectiveness.

3 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 DailyMedingredient 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.

💲 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.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 1 mL 1 mL
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Indomethacin 1 mg/mLthis 63323-0659-09 Fresenius 1 vial FDA listed
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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

🏛️
2010
On the market since
Mar 2010
📍
2026
Currently FDA-listed
16 years listed
🔒
·
No generic listed yet
brand only
ℹ️No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route.

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.

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

Medicare Part D (outpatient prescription) spending for Indomethacin — 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 Indomethacin. 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
$870.6K
Claims incl. refills
60.5K
Beneficiaries
46K
Spend / beneficiary
$18.94
Spend / claim
$14.38
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Indomethacin — the ingredient across all brands.

Top reported reactions

Fatigue1,141
Headache1,047
Arthralgia1,032
Pain939
Nausea938
Diarrhoea897
Dizziness889

Age at onset

Neonate231
Infant48
Child25
Adolescent29
Adult1,041
Elderly650

Reporter sex

13,179 reports
Male · 47%
Female · 53%
Unknown · 1%

Serious outcomes

Hospitalization4,454
Life-threatening806
Disabling511
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 1,011 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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
63323-0659-09 You're viewing this 1 VIAL in 1 CARTON (63323-659-09) / 1 mL in 1 VIAL 2010-03-19 Active
63323-0659-03 1 VIAL in 1 CARTON (63323-659-03) / 1 mL in 1 VIAL 2010-03-19 Active
63323-0659-94 1 VIAL in 1 CARTON (63323-659-94) / 1 mL in 1 VIAL 2010-03-19 Active

Pack size FAQ

What quantity is in NDC 63323-0659-09?
NDC 63323-0659-09 contains 1 vial — 1 vial in 1 carton / 1 ml in 1 vial.
What is the difference between NDC 63323-0659-09 and NDC 63323-0659-03?
Both are Indomethacin 1 mg/mL Injection, Powder, Lyophilized, For Solution — the drug itself is identical. NDC 63323-0659-09 is the 1 vial package, while NDC 63323-0659-03 is the 1 vial package.
What NDC number is used to bill for this package of Indomethacin 1 mg/mL Injection, Powder, Lyophilized, For Solution?
Bill NDC 63323-0659-09 — the 11-digit billing format is 63323065909. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“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 FDA registers it as 63323-659-09, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 63323-0659-09, written without dashes as 63323065909. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 63323-0659-09, the first segment (63323) is the labeler code FDA assigned to Fresenius Kabi USA, LLC; the middle segment (0659) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (09) identifies this exact package size and type. Together they name one specific package of one specific product.
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 Fresenius Kabi USA, LLC. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 1 vial (63323-0659-03), 1 vial (63323-0659-94). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Fresenius Kabi USA, LLC 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage 100 words

1 INDICATIONS AND USAGE Indomethacin for Injection is indicated to close a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1,750 g when 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective. Clear-cut clinical evidence of a hemodynamically significant patent ductus arteriosus should be present, such as respiratory distress, a continuous murmur, a hyperactive precordium, cardiomegaly, or pulmonary plethora on chest x-ray.

Indomethacin for Injection is a cardiovascular drug indicated: To close a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1,750 g. ( 1 )

⏱️ Dosage and Administration ~3 min read

2 DOSAGE AND ADMINISTRATION For intravenous administration only . Dosage recommendations for closure of the ductus arteriosus depend on the age of the infant at the time of therapy. A course of therapy is defined as three intravenous doses of Indomethacin for Injection given at 12 to 24 hour intervals, with careful attention to urinary output.

If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of Indomethacin for Injection, do not give additional doses until laboratory studies indicate that renal function has returned to normal [see Warnings and Precautions ( 5.7 )] . Dosage according to age is as follows: AGE at 1st dose DOSAGE (mg/kg) Less than 48 hours 1st 0.2 2nd 0.1 3rd 0.1 2 to 7 days 0.2 0.2

0.2Over 7 days 0.2 0.25

0.25If the ductus arteriosus closes or is significantly reduced in size after an interval of 48 hours or more from completion of the first course of Indomethacin for Injection, no further doses are necessary. If the ductus arteriosus re-opens, a second course of 1 to 3 doses may be given, each dose separated by a 12 to 24 hour interval as described above. If the neonate remains unresponsive to therapy with Indomethacin for Injection after 2 courses, surgery may be necessary for closure of the ductus arteriosus.

Dosage is dependent on the age of the infant at time of therapy. A course of therapy requires intravenous doses of Indomethacin for Injection given at 12 to 24 hour intervals. AGE at 1st dose DOSAGE (mg/kg) Less than 48 hours 1st 0.2 2nd 0.1 3rd 0.1 2 to 7 days 0.2 0.2

0.2Over 7 days 0.2 0.25

0.25If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of Indomethacin for Injection, do not give additional doses until laboratory studies indicate that renal function has returned to normal If the ductus arteriosus closes or is significantly reduced in size after an interval of 48 hours or more from completion of the first course of Indomethacin for Injection, no further doses are necessary If the neonate remains unresponsive to therapy with Indomethacin for Injection after 2 courses, surgery may be necessary for closure of the ductus arteriosus.

( 2.1 )

2.1Directions for Use Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The reconstituted solution, pH 6.0 to 7.5, is clear, slightly yellow and essentially free from visible particles. Prepare the solution with 1 to 2 mL of preservative-free Sterile Sodium Chloride Injection, 0.9 percent or preservative-free Sterile Water for Injection.

Benzyl alcohol as a preservative has been associated with toxicity in neonates. Therefore, do not use diluents that contain preservatives. If 1 mL of diluent is used, the concentration of indomethacin in the solution will equal approximately 0.1 mg/0.1 mL; if 2 mL of diluent are used, the concentration of the solution will equal approximately 0.05 mg/0.1 mL.

Discard any unused portion of the solution as it does not contain a preservative. Prepare a fresh solution just prior to each administration. Once reconstituted, the indomethacin solution may be injected intravenously.

While the optimal rate of injection has not been established, published literature suggests an infusion rate over 20 to 30 minutes. Further dilution with intravenous infusion solutions is not recommended.

💊 Dosage Forms and Strengths 47 words

3 DOSAGE FORMS AND STRENGTHS Indomethacin for Injection is supplied in single dose vials containing 1 mg of indomethacin as a sterile lyophilized powder or plug for reconstitution. Single dose vials of 1 mg indomethacin as a sterile, lyophilized powder or plug for reconstitution. ( 3 )

Contraindications 147 words

4 CONTRAINDICATIONS Indomethacin for Injection is contraindicated in neonates: With proven or suspected infection that is untreated Who are bleeding, especially those with active intracranial hemorrhage or gastrointestinal bleeding With thrombocytopenia or coagulation defects With or who are suspected of having necrotizing enterocolitis With significant impairment of renal function With congenital heart disease in whom patency of the ductus arteriosus is necessary for satisfactory pulmonary or systemic blood flow (e.g., pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta).

Indomethacin for Injection is contraindicated in neonates: With proven or suspected infection that is untreated Who are bleeding, especially those with active intracranial hemorrhage or gastrointestinal bleeding With thrombocytopenia or coagulation defects Suspected of having necrotizing enterocolitis With significant impairment of renal function With congenital heart disease in whom patency of the ductus arteriosus is necessary for satisfactory pulmonary or systemic blood flow. ( 4 )

⚠️ Warnings and Cautions ~2 min read

5 WARNINGS AND PRECAUTIONS Indomethacin may mask the usual signs of infection. ( 5.1 ) Monitor for signs of hepatic reactions. Indomethacin for Injection may need to be discontinued.

( 5.2 ) Indomethacin for Injection may inhibit platelet aggregation. ( 5.3 ) Gastrointestinal Effects: Monitor neonates for blood in stool. ( 5.4 ) Central Nervous System Effects: Monitor neonates for intraventricular hemorrhage.

( 5.5 ) Renal Effects: Monitor renal function and serum electrolytes. ( 5.6 )

5.1Infection Indomethacin may mask the usual signs and symptoms of infection. Therefore, the physician must be continually on the alert for this and should use the drug with extra care in the presence of existing controlled infection.

5.2Hepatic Reactions Severe hepatic reactions have been reported in adults treated chronically with oral indomethacin for arthritic disorders. [For further information, see package insert for oral indomethacin]. If clinical signs and symptoms consistent with liver disease develop in the neonate, or if systemic manifestations occur, discontinue Indomethacin for Injection.

5.3Platelet Aggregation Indomethacin for Injection may inhibit platelet aggregation. In one small study, platelet aggregation was grossly abnormal after indomethacin therapy (given orally to premature infants to close the ductus arteriosus). Platelet aggregation returned to normal by the tenth day. Observe premature infants for signs of bleeding.

5.4Gastrointestinal Effects In the collaborative study, major gastrointestinal bleeding was no more common in neonates receiving indomethacin than in neonates on placebo. However, minor gastrointestinal bleeding (i.e., chemical detection of blood in the stool) was more commonly noted in neonates treated with indomethacin. Severe gastrointestinal effects have been reported in adults with various arthritic disorders treated chronically with oral indomethacin. [For further information, see package insert for oral indomethacin].

5.5Central Nervous System Effects Prematurity per se is associated with an increased incidence of spontaneous intraventricular hemorrhage. Because indomethacin may inhibit platelet aggregation, the potential for intraventricular bleeding may be increased. However, in the large multicenter study of Indomethacin for Injection, the incidence of intraventricular hemorrhage in neonates treated with Indomethacin for Injection was not significantly higher than in the control neonates.

5.6Renal Effects Indomethacin for Injection may cause significant reduction in urine output (50 percent or more) with concomitant elevations of blood urea nitrogen and creatinine, and reductions in glomerular filtration rate and creatinine clearance. These effects in most neonates are transient, disappearing with cessation of therapy with Indomethacin for Injection. However, because adequate renal function can depend upon renal prostaglandin synthesis, Indomethacin for Injection may precipitate renal insufficiency, including acute renal failure, especially in neonates with other conditions that may adversely affect renal function (e.g., extracellular volume depletion from any cause, congestive heart failure, sepsis, concomitant use of any nephrotoxic drug, hepatic dysfunction).

When significant suppression of urine volume occurs after a dose of Indomethacin for Injection, do not give additional doses until urine output returns to normal levels. Indomethacin for Injection in pre-term infants may suppress water excretion to a greater extent than sodium excretion. When this occurs, a significant reduction in serum sodium values (i.e., hyponatremia) may result.

Monitor renal function and serum electrolyte levels during therapy with Indomethacin for Injection [see Dosage and Administration ( 2 )] .

5.7Administration Administer Indomethacin for Injection carefully to avoid extravascular injection or leakage as the solution may be irritating to tissue.

🤒 Adverse Reactions ~2 min read

6 ADVERSE REACTIONS Most common adverse reactions are bleeding problems, higher incidence of transient oliguria and elevations of serum creatinine. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience In a double-blind, placebo-controlled trial of 405 premature infants weighing less than or equal to 1,750 g with evidence of large ductal shunting, in those neonates treated with indomethacin (n=206), there was a statistically significantly greater incidence of bleeding problems, including gross or microscopic bleeding into the gastrointestinal tract, oozing from the skin after needle stick, pulmonary hemorrhage, and disseminated intravascular coagulopathy. There was no statistically significant difference between treatment groups in intracranial hemorrhage.

The neonates treated with Indomethacin for Injection had a significantly higher incidence of transient oliguria and elevations of serum creatinine (greater than or equal to 1.8 mg/dL) than did the neonates treated with placebo. The incidences of retrolental fibroplasia (grades III and IV) and pneumothorax in neonates treated with Indomethacin for Injection were no greater than in placebo controls and were statistically significantly lower than in surgically-treated neonates. The following additional adverse reactions in neonates have been reported from the collaborative study, anecdotal case reports, from other studies using rectal, oral, or intravenous indomethacin for treatment of patent ductus arteriosus or in marketed use.

The rates are calculated from a database that contains experience of 849 indomethacin-treated neonates reported in the medical literature, regardless of the route of administration. One year follow-up is available on 175 neonates and shows no long-term sequelae that could be attributed to indomethacin. In controlled clinical studies, only electrolyte imbalance and renal dysfunction (of the reactions listed below) occurred statistically significantly more frequently after Indomethacin for Injection than after placebo.

Reactions marked with a single asterisk (*) occurred in 3 to 9 percent of indomethacin-treated neonates; those marked with a double asterisk (**) occurred in 3 to 9 percent of both indomethacin- and placebo-treated neonates. Unmarked reactions occurred in less than 3 percent of neonates. Renal: renal failure, renal dysfunction in 41 percent of neonates, including one or more of the following: reduced urinary output; reduced urine sodium, chloride, or potassium, urine osmolality, free water clearance, or glomerular filtration rate; elevated serum creatinine or BUN; uremia.

Cardiovascular: intracranial bleeding**, pulmonary hypertension. Gastrointestinal: gastrointestinal bleeding*, vomiting, abdominal distention, transient ileus, gastric perforation, localized perforation(s) of the small and/or large intestine, necrotizing enterocolitis. Metabolic: hyponatremia*, elevated serum potassium*, reduction in blood sugar, including hypoglycemia, increased weight gain (fluid retention).

Coagulation: decreased platelet aggregation [see Warnings and Precautions ( 5.3 )] . The following adverse reactions have also been reported in neonates treated with indomethacin, however, a causal relationship to therapy with Indomethacin for Injection has not been established: Cardiovascular: bradycardia. Respiratory: apnea, exacerbation of pre-existing pulmonary infection.

Metabolic: acidosis/alkalosis. Hematologic: disseminated intravascular coagulation, thrombocytopenia. Ophthalmic: retrolental fibroplasia.** Dermatologic: drug reaction with eosinophilia and systemic symptoms (DRESS) A variety of additional adverse experiences have been reported in adults treated with oral indomethacin for moderate to severe rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute painful shoulder and acute gouty arthritis (see package insert f…

🔄 Drug Interactions ~2 min read

7 DRUG INTERACTIONS As renal function may be reduced by Indomethacin for Injection, consider reducing the dosage of those medications that rely on adequate renal function for their elimination. When used concomitantly with digoxin, monitor neonates for the development of digoxin toxicity. ( 7.1 ) Monitor prothrombin time when indomethacin is added to anticoagulants. ( 7.2 )

7.1Digoxin Because the half-life of digoxin (given frequently to pre-term infants with patent ductus arteriosus and associated cardiac failure) may be prolonged when given concomitantly with indomethacin, observe neonates receiving concomitant digoxin closely; frequent ECGs and serum digoxin levels may be required to prevent or detect digoxin toxicity early.

7.2Anticoagulants Indomethacin usually does not influence the hypoprothrombinemia produced by anticoagulants. When indomethacin is added to anticoagulants, monitor prothrombin time closely. In post-marketing experience, bleeding has been reported in patients on concomitant treatment with anticoagulants and Indomethacin for Injection.

7.3Furosemide Therapy with indomethacin may blunt the natriuretic effect of furosemide. This response has been attributed to inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs. In a study of 19 premature infants with patent ductus arteriosus treated with either Indomethacin for Injection alone or a combination of Indomethacin for Injection and furosemide, results showed that neonates receiving both Indomethacin for Injection and furosemide had significantly higher urinary output, higher levels of sodium and chloride excretion, and higher glomerular filtration rates than did those receiving Indomethacin for Injection alone.

In this study, therapy with furosemide helped to maintain renal function in the premature infant when Indomethacin for Injection was added.

7.4Aminoglycosides In one study of premature infants treated with Indomethacin for Injection and also receiving either gentamicin or amikacin, both peak and trough levels of these aminoglycosides were significantly elevated.

7.5Drugs that Act on the Renin-Angiotensin System In some patients with compromised renal function, the co-administration of an NSAID and an ACE inhibitor or angiotensin II antagonist may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.

🧬 Clinical Pharmacology ~2 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Although the exact mechanism of action through which indomethacin causes closure of a patent ductus arteriosus is not known, it is believed to be through inhibition of prostaglandin synthesis.

12.2Pharmacodynamics Indomethacin has been shown to be a potent inhibitor of prostaglandin synthesis, both in vitro and in vivo . In human newborns with certain congenital heart malformations, PGE 1 dilates the ductus arteriosus. In fetal and newborn lambs, E type prostaglandins have also been shown to maintain the patency of the ductus, and as in human newborns, indomethacin causes its constriction.

Studies in healthy young animals and in premature infants with patent ductus arteriosus indicated that, after the first dose of intravenous indomethacin, there was a transient reduction in cerebral blood flow velocity and cerebral blood flow. Similar decreases in mesenteric blood flow and velocity have been observed. The clinical significance of these effects has not been established.

In double-blind, placebo-controlled studies of Indomethacin for Injection in 460 small pre-term infants, weighing 1,750 g or less, the neonates treated with placebo had a ductus closure rate after 48 hours of 25 to 30 percent, whereas those treated with Indomethacin for Injection had a 75 to 80 percent closure rate. In one of these studies, a multicenter study, involving 405 pre-term infants, later reopening of the ductus arteriosus occurred in 26 percent of neonates treated with Indomethacin for Injection however, 70 percent of these closed subsequently without the need for surgery or additional indomethacin.

12.3Pharmacokinetics The disposition of indomethacin following intravenous administration (0.2 mg/kg) in pre-term neonates with patent ductus arteriosus has not been extensively evaluated. Even though the plasma half-life of indomethacin was variable among premature infants, it was shown to vary inversely with postnatal age and weight. In one study, of 28 neonates who could be evaluated, the plasma half-life in those less than 7 days old averaged 20 hours (range: 3 to 60 hours, n=18).

In neonates older than 7 days, the mean plasma half-life of indomethacin was 12 hours (range: 4 to 38 hours, n=10). Grouping the neonates by weight, mean plasma half-life in those weighing less than 1,000 g was 21 hours (range: 9 to 60 hours, n=10); in those neonates weighing more than 1,000 g, the mean plasma half-life was 15 hours (range: 3 to 52 hours, n=18). Following intravenous administration in adults, indomethacin is eliminated via renal excretion, metabolism, and biliary excretion.

Indomethacin undergoes appreciable enterohepatic circulation. The mean plasma half-life of indomethacin is 4.5 hours. In the absence of enterohepatic circulation, it is 90 minutes.

Indomethacin has been found to cross the blood-brain barrier and the placenta. In adults, about 99 percent of indomethacin is bound to protein in plasma over the expected range of therapeutic plasma concentrations. The percent bound in neonates has not been studied.

In controlled trials in premature infants, however, no evidence of bilirubin displacement has been observed as evidenced by increased incidence of bilirubin encephalopathy (kernicterus).

🧬 Mechanism of Action 33 words

12.1Mechanism of Action Although the exact mechanism of action through which indomethacin causes closure of a patent ductus arteriosus is not known, it is believed to be through inhibition of prostaglandin synthesis.

📦 How Supplied / Storage and Handling 145 words

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Sterile Indomethacin for Injection is a lyophilized white to yellow powder or plug supplied as single dose vials containing indomethacin for injection, equivalent to 1 mg indomethacin. Product No. NDC No. NP605903 63323-659-09 1 mg per vial, Packaged individually. The container closure is not made with natural rubber latex.

16.2Storage Store at 25°C (77°F) with excursions permitted to 15° to 30°C (59° to 86°F). Protect from light. Store container in carton until contents have been used. Novaplus is a registered trademark of Vizient, Inc.

16.1How Supplied Sterile Indomethacin for Injection is a lyophilized white to yellow powder or plug supplied as single dose vials containing indomethacin for injection, equivalent to 1 mg indomethacin. Product No. NDC No. NP605903 63323-659-09 1 mg per vial, Packaged individually. The container closure is not made with natural rubber latex.

📦 Storage and Handling 36 words

16.2Storage Store at 25°C (77°F) with excursions permitted to 15° to 30°C (59° to 86°F). Protect from light. Store container in carton until contents have been used. Novaplus is a registered trademark of Vizient, Inc.

📋 Description 151 words

11 DESCRIPTION Sterile Indomethacin for Injection for intravenous administration is lyophilized indomethacin for injection. Each vial of indomethacin for injection contains 1 mg indomethacin; 0.29 mg monobasic sodium phosphate, 0.41 mg dibasic sodium phosphate and not more than 0.24 mg of sodium hydroxide (used for converting indomethacin base to the sodium salt) as a white to yellow lyophilized powder or plug. Variations in the size of the lyophilized plug and the intensity of color have no relationship to the quality or amount of indomethacin present in the vial.

If necessary, hydrochloric acid (q.s.) and sodium hydroxide (q.s.) are added as pH adjusters. The reconstituted solution, pH 6.0 to 7.5, is clear, slightly yellow and essentially free from visible particles. The pH of the product does not meet the USP monograph [FD&C Act Chapter V, SEC.

501. [21USC §351](b)]. Indomethacin is designated chemically as 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid. The structural formula is: Structural Formula

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