List of Excipients in Branded Drug FERAHEME

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
AMAG Pharmaceuticals Inc	FERAHEME	ferumoxytol	59338-775	MANNITOL

Feraheme Excipient Strategy and Commercial Opportunities

Last updated: August 19, 2026

Feraheme, the branded ferumoxytol injection, uses a low-complexity parenteral formulation built around a carbohydrate-coated iron oxide nanoparticle. Its excipient system is limited to mannitol, sodium chloride, and water for injection. The commercial value of this design is its high iron concentration, two-dose administration schedule, preservative-free presentation, and compatibility with intravenous use in adults with iron-deficiency anemia who have failed or cannot tolerate oral iron therapy.[1]

The strongest commercial opportunities are in generic or 505(b)(2) injectable iron products, alternative vial and infusion presentations, manufacturing improvements, hospital contracting, and differentiated formulations that reduce hypersensitivity-management costs. The main barriers are complex nanomedicine characterization, clinical equivalence requirements, intravenous safety, manufacturing controls, and competition from ferric carboxymaltose and ferric derisomaltose.

What excipients are used in Feraheme?

Feraheme contains ferumoxytol, mannitol, sodium chloride, and water for injection. The product is supplied as a 30 mg elemental iron/mL intravenous injection in a 17 mL single-dose vial containing 510 mg of elemental iron.[1]

Component	Function in product	Commercial relevance
Ferumoxytol	Iron oxide-carbohydrate therapeutic complex	Determines clinical activity, particle behavior, pharmacokinetics, and product-specific equivalence
Mannitol	Stabilizing and formulation-support excipient	May support dispersion and physical stability of the nanoparticle suspension
Sodium chloride	Tonicity and ionic-strength adjustment	Supports intravenous tolerability and formulation consistency
Water for injection	Vehicle	Enables sterile intravenous administration

The formulation does not use a preservative. That is commercially relevant because the product is a single-dose injectable and is administered under healthcare-provider supervision.

Ferumoxytol is not a conventional dissolved iron salt. It is a superparamagnetic iron oxide complex surrounded by a carbohydrate coating, identified in the label as a nonstoichiometric magnetite core with a carbohydrate shell.[1] The carbohydrate-coated particle is central to product identity. Mannitol and sodium chloride support the formulation but do not define the active pharmaceutical ingredient.

How does the Feraheme excipient strategy affect product performance?

The formulation supports delivery of 510 mg of elemental iron per dose, with a second dose administered three to eight days after the first. This allows a total 1,020 mg treatment course using two administrations.[1]

The excipient strategy has four practical consequences:

1. It supports a concentrated intravenous suspension rather than a dilute iron solution.
2. It limits the number of formulation variables that must be controlled during manufacturing.
3. It avoids preservatives in a single-dose presentation.
4. It leaves the nanoparticle structure, surface carbohydrate, particle-size distribution, and iron-release behavior as the principal technical control points.

For a complex iron oxide product, the excipient list alone does not determine equivalence. Regulators and purchasers will focus on particle morphology, hydrodynamic diameter, surface chemistry, iron oxidation state, carbohydrate coating, free iron, aggregation, osmolality, pH, sterility, endotoxin, and release of iron under physiologic conditions.

What formulation characteristics are commercially protected?

The highest-value formulation characteristics are likely tied to the ferumoxytol complex and its manufacturing process rather than to mannitol or sodium chloride individually.

Potentially defensible technical features include:

• Iron oxide core composition and oxidation state.
• Carbohydrate coating composition and substitution pattern.
• Particle-size distribution.
• Surface charge and colloidal stability.
• Iron loading and iron-release profile.
• Control of unbound or labile iron.
• Sterile filtration or aseptic processing strategy.
• Concentration of elemental iron per vial.
• Stability during storage and transport.
• Reconstitution or dilution behavior, if an alternative presentation is developed.

Simple excipient substitution is unlikely to create a strong commercial product unless it produces a measurable advantage in stability, infusion tolerability, particle integrity, shelf life, or manufacturing yield. A formulation using the same ferumoxytol complex with a different tonicity agent or stabilizer may face a limited differentiation pathway.

When did Feraheme receive FDA approval and exclusivity?

The FDA approved Feraheme under NDA 022180 on June 30, 2009, for treatment of iron-deficiency anemia in adults with chronic kidney disease.[2] The approved indication was expanded in 2020 to adults with iron-deficiency anemia who have intolerance to oral iron, have had an unsatisfactory response to oral iron, or have chronic kidney disease.[3]

Milestone	Date	Commercial implication
Original FDA approval	June 30, 2009	Established ferumoxytol as an approved intravenous iron product
Original indication	2009	Chronic kidney disease-associated iron-deficiency anemia
Broader adult IDA indication	2020	Expanded addressable market beyond CKD
Five-year new chemical entity period	Ended in 2014	NCE exclusivity is no longer the primary barrier to competition
Current competition analysis	Patent- and regulatory-dependent	Generic or hybrid entry depends on FDA requirements and enforceable rights

The original five-year new chemical entity exclusivity period has expired. Feraheme does not have biosimilar exclusivity because ferumoxytol is a chemically defined, non-biologic nanoparticle drug rather than a biologic licensed under the Public Health Service Act.

What patents protect Feraheme?

Feraheme protection has historically centered on ferumoxytol, iron oxide-carbohydrate complexes, composition parameters, and manufacturing methods. The most commercially important rights are not expected to be claims directed only to sodium chloride or mannitol. They are more likely to involve the nanoparticle complex and the process used to produce a clinically consistent product.

A practical patent review should separate four categories:

Patent category	Relevance to Feraheme competition
Composition patents	May claim the iron oxide core, carbohydrate coating, or particle architecture
Process patents	May cover synthesis, coating, purification, sterilization, or control of particle attributes
Formulation patents	May cover concentration, excipient ratios, pH, osmolality, or storage stability
Method-of-use patents	May cover treatment of specific anemia populations or dosing regimens

The FDA Orange Book is the controlling source for listed patents and regulatory-use codes associated with the approved product.[4] Patent expiration analysis should also account for patent-term adjustment, patent-term extension, pediatric exclusivity, terminal disclaimers, and the scope of any listed method-of-use claims.

What generic entry risks exist for Feraheme?

Feraheme presents a higher regulatory barrier than a conventional small-molecule injectable. A prospective competitor may need to establish pharmaceutical equivalence and demonstrate that its product has sufficiently comparable physicochemical and structural properties.

The likely regulatory pathways are:

ANDA pathway

An ANDA applicant would need to address FDA requirements for a generic version of a complex iron oxide product. The application could face detailed comparative characterization and may require additional evidence because particle attributes can affect distribution, iron release, safety, and clinical performance.

505(b)(2) pathway

A 505(b)(2) application could support a product that relies partly on Feraheme’s FDA findings but differs in formulation, presentation, concentration, administration method, or manufacturing process. This pathway may offer more flexibility than an ANDA but can require clinical studies and may remain subject to patent certifications.

New NDA pathway

A fully independent ferumoxytol or iron oxide nanoparticle product could require a conventional NDA if the sponsor cannot rely sufficiently on the Feraheme reference product.

The main generic-entry risks are:

• Difficulty proving sameness of a nanoparticle product.
• Differences in carbohydrate coating or particle-size distribution.
• Clinical concerns involving hypersensitivity and hypotension.
• Inability to match the branded product’s high-concentration presentation.
• Patent claims covering composition or manufacturing.
• Hospital reluctance to switch products without a clear acquisition-cost advantage.

What manufacturing and intellectual-property barriers affect Feraheme competition?

Manufacturing is a central barrier. The product requires control over nanoparticle nucleation, iron oxide formation, carbohydrate coating, purification, concentration, and sterile filling. Small changes in process conditions can alter particle size, surface properties, free iron, and pharmacokinetics.

A competitor may therefore obtain more value from process intellectual property than from a new excipient combination. Commercially useful process claims could cover:

• Narrow particle-size distributions.
• Reduced batch-to-batch variability.
• Higher iron concentration.
• Lower free-iron content.
• Improved storage stability.
• More efficient coating or purification.
• Lower-cost sterile manufacturing.
• Reduced reliance on specialized equipment.

Supply-chain control also matters. A sponsor that can secure consistent pharmaceutical-grade mannitol, sodium chloride, carbohydrate coating materials, and sterile injectable manufacturing capacity may achieve a cost advantage. The excipients themselves are generally commodity inputs; the manufacturing process and quality system are harder to replicate.

What commercial opportunities exist for Feraheme excipients?

The excipient opportunity is strongest when tied to a measurable product benefit. The following approaches have commercial potential:

Alternative stabilizer systems

A new stabilizer could target reduced aggregation, improved freeze-thaw resistance, or longer shelf life. The opportunity is limited if the change does not improve a critical quality attribute or reduce manufacturing cost.

Ready-to-use high-concentration presentations

A prefilled syringe, smaller-volume vial, or delivery system designed for hospital workflow could reduce preparation time and medication errors. Any presentation change would need to preserve sterility, dose accuracy, particle integrity, and intravenous safety.

Low-cost generic formulations

A competitor could use the same active nanoparticle architecture with an optimized excipient package and lower-cost manufacturing. The commercial case would depend on achieving regulatory acceptance without expensive clinical development.

Infusion-center logistics

Feraheme’s two-dose regimen is commercially attractive relative to iron products requiring multiple administrations. A product that preserves the two-dose course while improving storage stability or administration convenience could compete in nephrology, hematology, oncology-supportive care, and hospital outpatient settings.

Combination and co-packaging opportunities

The product is unlikely to support a conventional fixed-dose combination because intravenous iron is administered according to laboratory values and clinical need. Co-packaging with administration supplies, dilution components, or standardized infusion accessories may produce workflow value but would not necessarily create strong intellectual-property protection.

How does Feraheme compare with competing intravenous iron products?

Product	Active iron complex	Typical course structure	Main competitive issue
Feraheme	Ferumoxytol	Two 510 mg doses	High iron dose per administration; boxed warning for serious hypersensitivity
Injectafer	Ferric carboxymaltose	Often one or two administrations	Strong competition in broad adult IDA
Monoferric	Ferric derisomaltose	Often one high-dose administration	Convenience and total-dose replacement
Venofer	Iron sucrose	Multiple smaller doses	Established use, especially in CKD
Infed	Iron dextran	Variable dosing	Longstanding product with dextran-related safety considerations

Feraheme’s excipient simplicity does not by itself create market leadership. Its commercial position depends on dose convenience, reimbursement, provider familiarity, safety management, and acquisition cost. Ferric carboxymaltose and ferric derisomaltose compete directly on high-dose administration and may have stronger positioning in some outpatient settings.

What is the regulatory and litigation outlook for Feraheme?

The FDA label contains a boxed warning for serious hypersensitivity reactions, including anaphylaxis, and requires monitoring during and after administration.[1] This safety profile raises the value of formulation work that reduces labile iron, improves particle stability, or supports more predictable infusion behavior.

Patent litigation risk is concentrated in three areas:

• ANDA Paragraph IV challenges to listed composition or method-of-use patents.
• Disputes over whether a competing nanoparticle is the same product or a distinct complex.
• Process patent claims involving coating, purification, or particle-size control.

Method-of-use patents may have narrower practical value than composition or process patents because physicians can prescribe intravenous iron across overlapping anemia populations. A litigation strategy based on formulation and manufacturing claims may therefore provide broader commercial protection than a narrow dosing claim.

What is the revenue exposure and market opportunity?

Historical Feraheme sales established a substantial commercial base for a specialty intravenous iron product. AMAG Pharmaceuticals reported Feraheme net product sales of approximately $239 million in 2019.[5] The later expansion of the label increased the potential market beyond chronic kidney disease, although actual revenue depends on reimbursement, competitive pricing, and prescribing patterns.

The principal revenue pools are:

• Non-dialysis chronic kidney disease.
• Dialysis-associated anemia management.
• Gastrointestinal blood loss.
• Heavy menstrual bleeding.
• Inflammatory and chronic disease-associated iron deficiency.
• Patients unable to tolerate or absorb oral iron.
• Hospital outpatient and infusion-center treatment.

For a generic or 505(b)(2) entrant, the best commercial strategy is likely a combination of lower acquisition cost, reliable supply, equivalent two-dose convenience, and evidence supporting interchangeability or operational substitution. A differentiated excipient system alone is unlikely to justify premium pricing.

Key Takeaways

• Feraheme uses a minimalist excipient system: mannitol, sodium chloride, and water for injection.
• The active product identity is driven by the ferumoxytol iron oxide-carbohydrate nanoparticle, not by the conventional excipients.
• The formulation delivers 510 mg of elemental iron per vial and supports a two-dose 1,020 mg treatment course.
• NCE exclusivity expired in 2014; current entry risk depends on patents, FDA requirements, and manufacturing complexity.
• Biosimilar competition is not the relevant pathway because Feraheme is not a biologic.
• The strongest intellectual-property opportunities involve nanoparticle composition, coating, process control, particle-size distribution, stability, and sterile manufacturing.
• Commercial opportunities exist in ANDA products, 505(b)(2) formulations, high-concentration presentations, workflow improvements, and lower-cost manufacturing.
• Safety, especially hypersensitivity risk, remains a central regulatory and commercial issue.
• Ferric carboxymaltose and ferric derisomaltose are the principal high-dose intravenous iron competitors.

FAQs

Can mannitol be replaced in a Feraheme generic?

Potentially, but replacement would require evidence that the alternative excipient preserves particle stability, sterility, osmolality, iron release, shelf life, and clinical performance. A substitution may also affect the regulatory pathway.

Is Feraheme a biologic drug?

No. Feraheme is an intravenously administered iron oxide-carbohydrate nanoparticle product regulated as a drug. It is not a biosimilar reference product under the biologics framework.

Does Feraheme require a preservative?

The marketed single-dose vial formulation does not use a preservative. This simplifies preservative-toxicity concerns but places greater emphasis on aseptic manufacturing and single-use handling.

Can an excipient supplier obtain patent protection around Feraheme?

A supplier would generally need claims directed to a novel excipient composition, particle-stabilization system, manufacturing process, or measurable product-performance improvement. Commodity mannitol or sodium chloride alone would not ordinarily provide meaningful product differentiation.

Which Feraheme competitor has the strongest formulation opportunity?

High-dose ferric carboxymaltose and ferric derisomaltose products have the closest commercial positioning. A competitor that combines high-dose administration with lower hypersensitivity risk, lower hypophosphatemia risk, improved stability, or lower acquisition cost would have the clearest differentiation path.

References

1. U.S. Food and Drug Administration. (2023). Feraheme (ferumoxytol injection) prescribing information.
2. U.S. Food and Drug Administration. (2009). FDA approves Feraheme for anemia in chronic kidney disease.
3. U.S. Food and Drug Administration. (2020). Feraheme supplemental approval for adults with iron-deficiency anemia.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
5. AMAG Pharmaceuticals, Inc. (2020). 2019 annual report.