List of Excipients in Branded Drug IOPAMIDOL

Generic Drugs Containing IOPAMIDOL

Company	Ingredient	NDC	Excipient
Slate Run Pharmaceuticals	iopamidol	70436-124	EDETATE CALCIUM DISODIUM
Slate Run Pharmaceuticals	iopamidol	70436-124	HYDROCHLORIC ACID
Slate Run Pharmaceuticals	iopamidol	70436-124	TROMETHAMINE
Slate Run Pharmaceuticals LLC	iopamidol	70436-126	EDETATE CALCIUM DISODIUM
Slate Run Pharmaceuticals LLC	iopamidol	70436-126	HYDROCHLORIC ACID
Slate Run Pharmaceuticals LLC	iopamidol	70436-126	TROMETHAMINE
Slate Run Pharmaceuticals LLC	iopamidol	70436-211	EDETATE CALCIUM DISODIUM

What are the Most Frequently-Used Excipients in IOPAMIDOL?

# Of NDCs	Excipient
3	EDETATE CALCIUM DISODIUM
3	HYDROCHLORIC ACID
3	TROMETHAMINE

Iopamidol Excipient Strategy and Commercial Opportunities

Last updated: October 26, 2026

Iopamidol is a mature, off-patent, nonionic low-osmolar iodinated contrast medium used for intra-arterial and intravenous imaging. The commercial opportunity is concentrated in sterile manufacturing, supply reliability, high-concentration presentations, hospital contracting, packaging, and regional generic launches rather than new-molecule exclusivity. The core formulation uses a limited excipient system centered on water for injection, a pH-adjusting agent, and a chelating stabilizer. Product differentiation depends on stability, container closure, injectability, regulatory execution, and cost.

What is iopamidol and how is it commercialized?

Iopamidol is a triiodinated benzene contrast agent marketed in the United States primarily as Isovue by Bracco Diagnostics. U.S. products include concentrations of 200, 250, 300, and 370 mg iodine/mL. The presentations support computed tomography, angiography, urography, and other radiographic procedures depending on concentration and route of administration (Bracco Diagnostics Inc., 2023).

Attribute	Iopamidol profile
Active ingredient	Iopamidol
Drug class	Nonionic, low-osmolar iodinated contrast medium
Primary U.S. brand	Isovue
Major U.S. manufacturer	Bracco Diagnostics
Common concentrations	200, 250, 300, and 370 mg iodine/mL
Dosage form	Sterile injectable solution
Administration	Intravenous and intra-arterial, depending on product and indication
Regulatory category	Prescription drug
Biosimilar pathway	Not applicable
Principal commercial competitors	Iohexol, iopromide, ioversol, iodixanol, ioxilan
Core patent position	Mature and off-patent
Main barriers	Sterile fill-finish, quality control, supply continuity, regulatory compliance, and hospital contracts

Iopamidol does not benefit from the commercial characteristics of a biologic, specialty tablet, or long-acting injectable. The product is purchased through hospital systems, radiology departments, group purchasing organizations, distributors, and imaging providers. Availability, price, compatibility with injector systems, and dependable supply can determine purchasing decisions.

What excipients are used in iopamidol formulations?

The marketed Isovue formulation uses a relatively short excipient list. The U.S. prescribing information identifies water for injection as the vehicle and includes tromethamine and edetate calcium disodium as formulation components. Exact quantities can vary by product concentration and should be controlled against the applicable approved label and chemistry, manufacturing, and controls documentation (Bracco Diagnostics Inc., 2023).

Formulation component	Primary function	Commercial relevance
Water for injection	Sterile vehicle	Requires pharmaceutical-grade water system and validated aseptic processing
Tromethamine	Buffer and pH-control agent	Supports formulation pH and chemical stability
Edetate calcium disodium	Chelating agent	Binds trace metals that can promote degradation or discoloration
Iopamidol	Active contrast agent	Determines iodine concentration, radiopacity, viscosity, and osmotic properties
Container closure system	Maintains sterility and stability	Includes vial, bottle, syringe, elastomer, seal, and overwrap components

The formulation is generally preservative-free and intended for single-use administration. A preservative strategy would offer limited commercial value because it could introduce compatibility, toxicity, labeling, and regulatory issues into a product routinely supplied as a sterile single-dose injection.

Why are tromethamine and edetate calcium disodium important?

Tromethamine is used to control pH. Iopamidol products require a controlled pH range because pH affects chemical stability, material compatibility, and patient tolerability. Buffer selection also influences the formulation’s regulatory comparability.

Edetate calcium disodium functions as a trace-metal chelator. Metal contamination from raw materials, manufacturing equipment, water systems, or container components can accelerate degradation pathways. The chelator therefore has value as a stability-control excipient, even at a low concentration.

The practical development issue is not whether these excipients are novel. It is whether the finished product demonstrates equivalent quality, stability, sterility, particulate control, extractables and leachables performance, and container compatibility.

What excipient strategy is most attractive for iopamidol?

The strongest strategy is a minimal, label-aligned excipient platform rather than a novel-excipient formulation.

1. Maintain the established excipient system

A generic or follow-on manufacturer should generally preserve the established buffer and chelator architecture where possible. This reduces formulation-development risk and supports an abbreviated regulatory argument based on pharmaceutical equivalence.

Changing tromethamine concentration, replacing the chelator, or introducing a different buffer may affect:

• pH and pH drift over shelf life
• degradation impurity profile
• osmolality
• viscosity
• container compatibility
• injection performance
• toxicological assessment
• comparability requirements

A changed-excipient product may be commercially defensible, but the change must create a measurable benefit. Examples include longer shelf life, improved compatibility with a particular container, reduced particulate formation, or simplified global manufacturing.

2. Optimize high-concentration presentations

The 300 and 370 mg iodine/mL presentations have the greatest commercial relevance in CT and angiographic procedures. Higher iodine concentration can support imaging protocols that require a high iodine delivery rate while limiting injection volume.

The development target is not simply a high concentration of iopamidol. It is a stable, injectable product with acceptable viscosity, controlled osmolality, reliable transfer through injectors, and consistent performance across temperature conditions.

Excipient changes that reduce viscosity or improve cold-temperature handling may have commercial value. They also create regulatory risk because viscosity, injectability, and administration-device interaction are product attributes that must remain controlled.

3. Develop packaging as part of the formulation strategy

Packaging is a material opportunity in a mature contrast-media market. Relevant formats include:

• single-dose plastic bottles
• glass vials
• polymer containers
• prefilled syringes
• bulk imaging containers
• injector-compatible presentations
• tamper-evident secondary packaging

A packaging platform can create value through lower breakage rates, reduced weight, improved workflow, or compatibility with automated contrast injectors. Any claim of improved safety or performance requires container-closure, sterility, extractables, leachables, and stability data.

4. Use a supplier-controlled excipient platform

Tromethamine and edetate calcium disodium are established pharmaceutical excipients, but supply qualification remains important. A manufacturer should qualify multiple sources where possible and maintain tight controls for:

• elemental impurities
• bioburden and endotoxin
• assay and identity
• residual solvents
• particle burden
• microbial contamination
• lot-to-lot variability

For iopamidol, excipient supplier changes can affect the impurity profile even when the nominal formulation remains unchanged. The regulatory impact depends on the change, the product filing, and the extent of comparability data.

What formulations are protected by iopamidol patents?

The original composition, use, and manufacturing protection for iopamidol are mature and no longer provide meaningful new-product exclusivity in the United States. Iopamidol was commercialized decades ago, and the core small-molecule patent estate has expired.

The commercially relevant IP questions now concern narrower rights:

IP category	Current commercial significance
Core iopamidol composition	Low; original protection has expired
Basic injectable formulation	Low; mature formulation technology
Manufacturing process	Potentially relevant if a process is non-public or operationally superior
Container and injector compatibility	Potentially relevant, usually narrow
Method of use	Limited because contrast-agent uses are established and competitive
Device integration	Potential opportunity for injector or workflow patents
Trade secrets	Important for yields, impurity control, filling, inspection, and supply operations
Trademark rights	Relevant to Isovue branding, not generic market entry

The strongest remaining defensible positions are likely to be process know-how, quality systems, manufacturing scale, packaging, device integration, and customer contracts rather than broad composition claims.

What is the Orange Book status of iopamidol?

Iopamidol is a small-molecule injectable drug and may be associated with an approved reference product and related FDA listings, but Orange Book data should be assessed at the specific product and NDA level. Orange Book inclusion does not itself establish that a listed patent remains enforceable or commercially significant. FDA identifies listed patents and exclusivity information, while patent term and enforceability require separate legal analysis (U.S. Food and Drug Administration, 2024a).

For a potential ANDA applicant, the relevant questions are:

1. Which Isovue product is the reference listed drug?
2. Are any patents currently listed against that reference product?
3. Are the patents expired, delisted, disclaimed, or subject to pediatric or regulatory exclusivity?
4. Does the proposed label create a method-of-use certification issue?
5. Does the formulation match the reference product closely enough for an ANDA?

Because iopamidol is an old product, the expected regulatory route for a conventional generic is an ANDA under section 505(j), assuming pharmaceutical equivalence and bioequivalence requirements can be addressed. A 505(b)(2) application may be more appropriate for a materially different concentration, excipient system, dosage form, packaging configuration, or indication.

When does iopamidol lose exclusivity?

Iopamidol has already lost core market exclusivity. The relevant commercial question is generic and follow-on entry, not future loss of originator exclusivity.

Exclusivity type	Iopamidol position
New chemical entity exclusivity	Expired
Core composition patent	Expired
Standard injectable generic entry	Legally available, subject to FDA approval
Biosimilar exclusivity	Not applicable
Pediatric exclusivity	No central commercial significance for current entry planning
Formulation or process protection	Potentially narrow and product-specific
Brand protection	Continues through trademark and commercial presence

The lack of active molecule-level exclusivity does not eliminate barriers. Sterile injectable manufacturing has higher failure costs than oral solid-dose manufacturing. A supplier must establish aseptic processing, container-closure integrity, particulate control, stability, and reliable commercial-scale production.

What Paragraph IV challenges and litigation affect iopamidol?

A Paragraph IV certification is relevant only when an ANDA applicant challenges a patent listed for the reference product. For a mature iopamidol product, the primary risk is not a broad composition patent but a possible listed patent directed to a formulation, use, packaging system, or other narrow claim.

The litigation profile is therefore likely to be less significant than for recently approved oncology, immunology, or metabolic drugs. The expected disputes are more likely to involve:

• listed formulation patents
• method-of-use labeling
• infringement allegations based on manufacturing processes
• declaratory judgments concerning patent listings
• contractual or supply disputes
• regulatory disputes concerning reference-product selection

A generic launch plan should separate patent risk from manufacturing risk. Even where Paragraph IV litigation is absent, FDA review deficiencies, facility inspections, sterile-processing failures, or supply interruptions can delay launch.

How strong is the iopamidol patent estate?

The patent estate is weak for broad molecule-level exclusion and stronger only in narrow operational areas.

Strength dimension	Assessment
Active ingredient protection	Weak or expired
Broad formulation protection	Weak
Method-of-use protection	Limited
Manufacturing know-how	Moderate, depending on process complexity
Container and device integration	Potentially moderate
Regulatory barriers	Moderate for sterile injectable approval
Commercial barriers	Moderate to high because hospital supply is operationally sensitive
Litigation deterrence	Low for the core molecule

The strongest competitive advantages belong to companies with validated sterile facilities, established iodine and iopamidol supply chains, global registrations, injector compatibility, and hospital contracts.

What generic entry risks exist for iopamidol?

Generic entry can occur through several scenarios.

Scenario 1: Conventional ANDA entry

A manufacturer matches the reference product in active ingredient, strength, dosage form, route, and key quality attributes. This is the most direct route and creates price pressure on Isovue.

Scenario 2: Regional sterile supply

A manufacturer launches in selected markets where hospital procurement is fragmented or where the originator has experienced supply constraints. This approach limits initial commercial investment.

Scenario 3: Private-label or contract-manufactured product

An established injectable manufacturer supplies a distributor or hospital network under a private label. The commercial value comes from manufacturing utilization and procurement access.

Scenario 4: 505(b)(2) differentiated product

A company uses a changed concentration, packaging system, or formulation to pursue a regulatory pathway other than a conventional ANDA. The opportunity is larger if the change solves a recognized workflow or stability problem, but development costs and regulatory requirements also increase.

Scenario 5: Device-integrated product

An iopamidol presentation designed for automated injectors, prefilled systems, or radiology workflow may command value through reduced preparation time and lower handling burden. Device-related claims must be separated from drug approval requirements.

How does iopamidol compare with competing iodinated contrast agents?

Product	Active ingredient	Typical positioning	Excipient and commercial implications
Isovue	Iopamidol	Low-osmolar, nonionic contrast	Mature formulation; opportunity in supply, packaging, and cost
Omnipaque	Iohexol	Broad CT and angiography use	Major branded competitor with strong hospital presence
Optiray	Ioversol	Low-osmolar contrast	Competes on concentration, availability, and contracting
Visipaque	Iodixanol	Iso-osmolar contrast	Differentiated osmolarity profile; generally higher-value positioning
Iopromide products	Iopromide	Low-osmolar contrast	Competes across CT and angiography channels
Ioxilan	Ioxilan	Low-osmolar contrast	Smaller competitive position in many markets

Iopamidol’s principal commercial weakness is substitutability. Hospitals can often use more than one iodinated contrast agent if protocols, injector systems, formularies, and supply agreements permit. Its principal advantage is established clinical use and available concentration breadth.

What FDA regulatory strategy applies to iopamidol?

A standard generic product would generally pursue an ANDA where the proposed product is pharmaceutically equivalent to the reference listed drug. FDA review will focus on the active ingredient, concentration, dosage form, route, inactive ingredients, sterility, stability, particulate matter, container closure, and manufacturing controls (U.S. Food and Drug Administration, 2024b).

A 505(b)(2) approach may be appropriate when the product differs materially in:

• excipient composition
• iodine concentration
• container or delivery system
• dosing configuration
• indication or administration method
• stability profile

The regulatory strategy should avoid unnecessary excipient novelty. Established excipients reduce toxicological and formulation risk, while novel excipient use can expand the data package and create a less predictable review.

What commercial opportunities exist in iopamidol excipients and manufacturing?

The highest-value opportunities are operational.

Excipient supply

Qualified supply of pharmaceutical-grade tromethamine and edetate calcium disodium can support multiple contrast-media manufacturers. Suppliers can differentiate through global regulatory files, dual sourcing, low-metal specifications, and documented change control.

Contract development and manufacturing

Sterile contract manufacturers can offer:

• formulation matching
• aseptic fill-finish
• terminal sterilization assessment
• container-closure qualification
• stability programs
• injectable inspection and packaging
• global registration support

Packaging and delivery systems

Prefilled syringes, lightweight polymer containers, and injector-compatible formats can reduce preparation steps and product waste. The commercial case is strongest where the package integrates with existing radiology equipment.

Regional generic launches

Smaller companies can target markets with limited competition, public procurement tenders, or supply shortages. Regulatory filings must account for country-specific requirements for contrast agents, sterile products, packaging, and pharmacovigilance.

Manufacturing IP barriers

The principal barriers are likely to involve process capability rather than patent exclusion. Important know-how includes impurity control, iodine concentration consistency, dissolved-gas management, particulate reduction, filling accuracy, container compatibility, and shelf-life validation.

What revenue exposure does iopamidol create for originators and entrants?

Bracco does not generally disclose Isovue revenue as a separate public line item. Revenue exposure is embedded in the broader imaging portfolio. The product remains commercially relevant because contrast media are recurring-use hospital products with substantial procedure volume.

For a generic entrant, revenue depends on:

• awarded hospital contracts
• formulary placement
• supply reliability
• manufacturing yield
• distributor discounts
• tender pricing
• ability to supply multiple concentrations
• injector and packaging compatibility

A single-concentration launch may limit purchasing access. A portfolio covering 300 and 370 mg iodine/mL generally has greater contracting value than a narrowly selected presentation, although it also increases manufacturing and inventory requirements.

Key Takeaways

• Iopamidol is a mature, off-patent iodinated contrast medium marketed primarily as Isovue.
• The established excipient system is simple and centers on water for injection, tromethamine, and edetate calcium disodium.
• A minimal, label-aligned formulation is generally the lowest-risk development strategy.
• The strongest commercial opportunities are sterile generic supply, high-concentration products, packaging, injector compatibility, and regional contracting.
• Core molecule and composition protection do not represent the main entry barrier.
• Manufacturing reliability, container closure, particulate control, stability, and hospital procurement access are more important than new patent claims.
• Biosimilar risk is irrelevant because iopamidol is a synthetic small molecule.
• Conventional products may qualify for an ANDA, while materially differentiated products may require a 505(b)(2) strategy.
• Excipient changes should be made only when they create a measurable stability, packaging, workflow, or supply benefit.

FAQs

Is iopamidol a generic drug?

Iopamidol is an active pharmaceutical ingredient used in both branded and generic injectable contrast products. Isovue is the leading U.S. reference brand associated with iopamidol.

Can tromethamine be replaced in an iopamidol formulation?

Replacement is technically possible but may change pH, stability, impurity formation, compatibility, and regulatory requirements. The commercial benefit must justify the comparability and approval burden.

Does iopamidol require a preservative?

Commercial iopamidol injections are generally supplied as sterile, preservative-free products intended for single use. Adding a preservative would require a clear clinical and regulatory rationale.

What is the most valuable iopamidol concentration?

The 300 and 370 mg iodine/mL concentrations are generally the most commercially important for CT and angiographic applications. Product value varies by market, procedure mix, procurement contracts, and injector compatibility.

Can a company patent a new iopamidol excipient combination?

A new combination may be patentable if it meets novelty, non-obviousness, and utility requirements. Patent value depends on whether the combination produces a measurable technical advantage and whether competitors can design around it.

References

1. Bracco Diagnostics Inc. (2023). Isovue (iopamidol injection) prescribing information. Princeton, NJ: Bracco Diagnostics Inc.

2. U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. Silver Spring, MD: U.S. Department of Health and Human Services.

3. U.S. Food and Drug Administration. (2024b). Abbreviated new drug application submissions: Stability, bioequivalence, and pharmaceutical equivalence requirements. Silver Spring, MD: U.S. Department of Health and Human Services.

4. United States Pharmacopeia. (2024). United States Pharmacopeia and National Formulary. Rockville, MD: U.S. Pharmacopeial Convention.

5. International Council for Harmonisation. (2023). ICH Q3D(R2): Guideline for elemental impurities. Geneva, Switzerland: International Council for Harmonisation.