List of Excipients in Branded Drug IMIPENEM AND CILASTATIN

Generic Drugs Containing IMIPENEM AND CILASTATIN

Company	Ingredient	NDC	Excipient
WG Critical Care LLC	imipenem and cilastatin	44567-705	SODIUM BICARBONATE
Fresenius Kabi USA LLC	imipenem and cilastatin sodium	63323-349	SODIUM BICARBONATE

What are the Most Frequently-Used Excipients in IMIPENEM AND CILASTATIN?

# Of NDCs	Excipient
2	SODIUM BICARBONATE

Imipenem and Cilastatin Excipient Strategy, Patent Position, and Commercial Opportunities

Last updated: September 4, 2026

Imipenem/cilastatin is a mature injectable antibiotic combination with no meaningful biosimilar barrier and limited composition-of-matter protection. Commercial opportunity is concentrated in supply reliability, ready-to-use presentations, stability improvement, regional registration, hospital procurement, and differentiated formulations rather than in basic generic powder-for-injection products.

The principal formulation challenge is chemical stability. Imipenem is susceptible to degradation in aqueous solution, while cilastatin is co-formulated to inhibit renal metabolism of imipenem. Excipients must support pH control, reconstitution, container compatibility, sodium-load management, and short in-use storage periods without creating new safety or regulatory liabilities.

What is imipenem/cilastatin and how is it supplied?

Imipenem/cilastatin is a carbapenem antibacterial administered by intravenous infusion. Imipenem provides antibacterial activity, while cilastatin inhibits renal dehydropeptidase-I, which would otherwise metabolize imipenem and reduce urinary recovery.

The reference product in the United States is Primaxin, originally developed by Merck. Current products are generally supplied as sterile powders for reconstitution in single-dose vials. Strengths commonly include:

Product presentation	Typical labeled strength	Route	Primary commercial use
Imipenem/cilastatin vial	250 mg/250 mg	IV infusion	Hospital and institutional use
Imipenem/cilastatin vial	500 mg/500 mg	IV infusion	Adult inpatient therapy
Fixed-dose generic equivalents	250/250 mg or 500/500 mg	IV infusion	Generic hospital supply
Imipenem/cilastatin/relebactam	250/250/125 mg or 500/500/250 mg	IV infusion	Resistant Gram-negative infections

The imipenem/cilastatin combination is not interchangeable with imipenem/cilastatin/relebactam. Relebactam adds a beta-lactamase inhibitor and creates a separate regulatory, clinical, and patent framework.

Which excipients are used in imipenem/cilastatin injections?

Commercial imipenem/cilastatin powders generally use a restrained excipient system. Sodium bicarbonate is the most commercially important listed excipient in many products because it supports formulation pH and powder stability.

Representative product labeling identifies the formulation as containing imipenem, cilastatin, and sodium bicarbonate. Products are generally free of antimicrobial preservatives and are reconstituted before administration with compatible intravenous diluents such as sodium chloride injection or dextrose injection, subject to the individual label.[1-4]

Excipient or formulation element	Function	Commercial relevance
Sodium bicarbonate	Buffering and pH control	Core formulation element in many products
Water for injection	Manufacturing and reconstitution medium	Required for parenteral processing
Sodium chloride injection	Common infusion diluent	Supports hospital compatibility
Dextrose injection	Alternative infusion diluent	Useful where saline restriction matters
Nitrogen or controlled atmosphere	Oxygen-management strategy during manufacture	May reduce oxidative degradation
Low-extractables vial and stopper system	Container closure compatibility	Important for stability and hospital handling

The exact excipient profile varies by manufacturer and jurisdiction. A generic manufacturer cannot assume that the reference product's qualitative formulation is the only acceptable approach. FDA approval depends on pharmaceutical equivalence, bioequivalence where applicable, sterility, stability, manufacturing controls, and labeling conformity.

Why sodium bicarbonate is important

Imipenem has limited aqueous stability. The formulation must balance chemical stability against tolerability, compatibility, and the risk that a high-pH environment accelerates other degradation pathways. Sodium bicarbonate can help maintain the desired formulation environment, but it also increases the product's sodium burden.

The sodium contribution is relevant for patients with heart failure, renal impairment, sodium-restricted diets, or high cumulative intravenous fluid exposure. A low-sodium formulation could have clinical and procurement value, but it would require robust stability data and a clear regulatory rationale.

Which excipients should be avoided?

Imipenem/cilastatin products are generally not formulated with antimicrobial preservatives. Preservatives can create toxicity, compatibility, and labeling issues in a product intended for intravenous administration.

Potentially problematic formulation choices include:

• Excipients that promote imipenem hydrolysis.
• Reactive reducing or oxidizing agents.
• Chelators that alter active ingredient stability or container compatibility.
• High levels of organic cosolvents.
• Latex-containing or extractable-prone container components.
• Buffers that increase degradation at elevated temperatures.
• Excipients that complicate compatibility with common infusion solutions.

A commercially viable formulation should minimize excipient count. Each added excipient creates additional extractables, impurity, toxicology, supply-chain, and regulatory work.

What formulation strategies offer the strongest commercial opportunity?

The strongest opportunities are differentiated hospital-use products rather than simple powder copies.

Ready-to-use liquid infusion

A ready-to-use solution could reduce pharmacy compounding steps and shorten preparation time. The commercial barrier is chemical stability. The product must maintain potency, impurity limits, sterility, and container integrity over the claimed shelf life and in-use period.

Potential formats include:

• Ready-to-use bags.
• Dual-chamber bags.
• Pharmacy bulk packages.
• Premixed flexible containers.
• Small-volume sterile infusion containers.

A ready-to-use product would compete on labor reduction, medication-error prevention, and emergency availability. It would also carry higher manufacturing and cold-chain risk than a conventional vial.

Extended-stability presentation

A vial or dual-chamber system with longer post-reconstitution stability could reduce pharmacy waste. This is valuable because conventional imipenem solutions have relatively short labeled storage periods compared with many other hospital antibiotics.

Potential differentiation includes:

• Longer room-temperature stability.
• Longer refrigerated stability.
• Reduced sensitivity to light or oxygen.
• Validated compatibility with multiple diluents.
• Broader temperature excursion tolerance.

Any claim must be supported by real-time and accelerated stability data, impurity profiling, sterility studies, and container-closure integrity testing.

Low-sodium formulation

A lower-sodium product could target intensive-care, renal, cardiac, and pediatric settings. The opportunity is clinically credible, but the product would need to demonstrate that sodium reduction does not reduce powder stability or create reconstitution problems.

Commercial value would be highest where hospitals impose sodium restrictions or where total parenteral sodium exposure affects treatment selection.

Pediatric and weight-based presentations

Pediatric hospitals may value smaller vial sizes, reduced overfill, and dosing formats that reduce waste. A 250 mg/250 mg vial can be commercially useful even where the 500 mg/500 mg strength has higher volume sales.

Opportunity areas include:

• Smaller fill sizes.
• Clear dose-conversion labeling.
• Reduced reconstitution volume.
• Pediatric-compatible administration devices.
• Preservative-free, latex-free packaging.
• Low-dead-space transfer systems.

Premixed combination with relebactam

Imipenem/cilastatin/relebactam is a higher-value product category for selected resistant infections. It is not simply an excipient extension of imipenem/cilastatin. A manufacturer would need to address the stability and regulatory requirements of all three active ingredients.

Relebactam creates a stronger commercial position, but it also increases intellectual-property exposure, clinical differentiation requirements, and procurement complexity.

What patents protect imipenem/cilastatin products?

The original imipenem and cilastatin composition patents are old and do not provide current market exclusivity in the United States. The principal regulatory barrier is therefore generic approval and manufacturing quality, not active ingredient patent protection.

Protection category	Current commercial assessment
Imipenem composition patents	Expired
Cilastatin composition patents	Expired
Original imipenem/cilastatin combination claims	Expired or commercially nonblocking
Basic powder-for-injection formulation	Generally weak as a new-entry barrier
Method-of-use claims for established indications	Limited value against approved generic substitution
Device or premix claims	Potentially meaningful if narrowly drafted and enforceable
Imipenem/cilastatin/relebactam patents	Separate and potentially active estate
Manufacturing-process patents	Can protect process know-how, but often difficult to enforce against unobserved manufacturing

The Orange Book status must be assessed product by product because listed patents, reference products, and exclusivity entries can change. The original imipenem/cilastatin market is generally characterized by generic competition rather than by a blocking Orange Book patent estate.[5]

Are formulation patents commercially meaningful?

Formulation patents can have value when they claim a specific stability solution, container system, premixed presentation, or reconstitution method. Their strength depends on whether competitors can design around the claim while preserving the same clinical and commercial profile.

Potentially defensible claim areas include:

• A defined pH range combined with a specific excipient ratio.
• A low-sodium imipenem/cilastatin formulation.
• A lyophilized or non-lyophilized composition with defined impurity limits.
• A dual-chamber container separating incompatible components.
• A ready-to-use product with a defined shelf life.
• A specific oxygen-control or packaging configuration.
• A reconstitution system that reduces preparation errors.

A patent claiming only "imipenem, cilastatin, and sodium bicarbonate" would face substantial validity and obviousness risk because the combination is historically established and widely disclosed. Commercially stronger claims would connect composition parameters to unexpected stability, reduced degradation, improved usability, or a specific container technology.

When did imipenem/cilastatin lose exclusivity?

The original product lost practical exclusivity decades ago. FDA approved Primaxin in 1985, and generic imipenem/cilastatin products have been marketed for many years.[1,5]

Milestone	Timing
Original FDA approval of Primaxin	1985
Core small-molecule patent protection	Expired
Generic injectable competition	Established
Current market structure	Multi-source generic hospital market
Recarbrio approval	2019
Current strategic focus	Supply, formulation, access, and differentiated delivery

The product does not have biologic exclusivity. It is a small-molecule injectable administered through the ANDA pathway when the generic product meets applicable requirements.

What is the FDA regulatory status of imipenem/cilastatin?

FDA-approved imipenem/cilastatin products are prescription injectable antibacterial drugs. Generic applicants typically pursue an ANDA demonstrating pharmaceutical equivalence and bioequivalence or other applicable equivalence requirements. For an injectable solution or powder for reconstitution, the regulatory review emphasizes:

• Active ingredient identity and strength.
• Sterility and endotoxin control.
• Particulate matter.
• Reconstitution performance.
• Stability and degradation products.
• Container-closure integrity.
• Extractables and leachables.
• Compatibility with labeled diluents.
• Manufacturing-process validation.
• Labeling consistency.

The injectable route makes facility quality and supply reliability central to approval and commercialization. A technically acceptable formulation can still fail commercially if the manufacturer cannot maintain uninterrupted sterile production.

Which companies are challenging the imipenem/cilastatin market?

The market is generally challenged by generic injectable manufacturers, contract manufacturers, and regional hospital suppliers rather than by a single high-profile Paragraph IV campaign.

Potential competitors include:

• Large multinational generic companies.
• Specialized sterile-injectable manufacturers.
• Indian and European antibiotic manufacturers.
• Regional suppliers in public-procurement markets.
• Contract development and manufacturing organizations.
• Companies offering imipenem/cilastatin/relebactam or other reserve antibiotics.

Specific active ANDA holders and litigation positions must be checked against the current FDA Orange Book, FDA ANDA records, and court dockets. A Paragraph IV certification is less commercially significant for a mature product with broad existing generic supply than it is for a newly launched branded product.

What is the Paragraph IV risk?

For the base imipenem/cilastatin product, Paragraph IV risk is generally low as a strategic barrier because the principal market already has generic competition. A new applicant may still encounter:

• Residual listed patents for a particular reference product.
• Patent claims covering a newer dosage form.
• Litigation involving a branded combination product.
• Manufacturing or process patents outside the Orange Book.
• State or hospital-contract barriers unrelated to patent law.

A new entrant should assume price competition, potential shortages, and procurement qualification are more important than Paragraph IV litigation.

What generic launch scenarios exist?

Standard vial launch

This is the lowest-risk route. The product can compete through price, supply reliability, quality history, and hospital contracting. The downside is low differentiation and substantial price pressure.

Shortage-driven launch

Injectable antibiotics periodically experience shortages because sterile manufacturing capacity is concentrated and production economics are difficult. A supplier with validated capacity can gain share quickly during shortages. FDA Drug Shortages data should be monitored before launch planning.[6]

Regional registration strategy

Some markets rely heavily on public tenders and local manufacturing requirements. A company can prioritize countries where:

• Carbapenem demand is high.
• Local competitors have inconsistent supply.
• Hospital procurement rewards multiple approved suppliers.
• Imported products face less severe price erosion.
• National antibiotic-reserve policies support reliable supply.

Premium differentiated launch

A ready-to-use or extended-stability product could command a premium if it reduces pharmacy labor, decreases waste, and improves emergency availability. The commercial case must quantify avoided compounding costs rather than rely solely on a higher unit price.

How does imipenem/cilastatin compare with competing carbapenems?

Product	Main differentiation	Excipient and commercial implication
Imipenem/cilastatin	Broad-spectrum carbapenem with renal enzyme protection	Mature generic market; stability and supply are central
Meropenem	Broad-spectrum carbapenem with strong hospital use	Competes on formulary preference and dosing convenience
Ertapenem	Once-daily dosing	Greater outpatient and step-down utility
Doripenem	Carbapenem with narrower commercial footprint	Limited competitive pressure in many markets
Imipenem/cilastatin/relebactam	Adds beta-lactamase inhibition	Higher value in selected resistant infections; separate IP estate

Imipenem/cilastatin remains commercially relevant where hospital protocols, local resistance patterns, and procurement arrangements support its use. Meropenem often competes strongly because of dosing and formulary familiarity. Ertapenem has a different value proposition because of once-daily administration.

How strong is the patent estate for imipenem/cilastatin?

The base product's patent estate is weak for blocking purposes and moderate for targeted formulation protection.

Estate component	Strength	Reason
Active ingredients	Low	Long-expired core protection
Basic combination	Low	Mature, widely disclosed technology
Conventional vial	Low	Limited differentiation
Low-sodium composition	Moderate	Potential clinical and formulation differentiation
Ready-to-use presentation	Moderate to strong	May support distinct device and stability claims
Manufacturing process	Moderate	Valuable as know-how; enforcement may be difficult
Relebactam combination	Potentially stronger	Newer product and separate development history

The best investment thesis is a formulation and supply platform, not a conventional patent-arbitrage strategy based on the base molecule.

What licensing and partnering opportunities exist?

Licensing opportunities are most credible in four areas:

1. Sterile injectable manufacturing capacity in regions with limited supply.
2. Ready-to-use or dual-chamber delivery technology.
3. Improved stability and packaging technology.
4. Rights to imipenem/cilastatin/relebactam in jurisdictions where hospital resistance patterns support premium pricing.

A partner should evaluate freedom to operate across composition, container, manufacturing, and regulatory filings. A license limited to an old imipenem/cilastatin formulation is unlikely to command substantial value unless paired with manufacturing capacity, market access, or a differentiated presentation.

What revenue exposure and commercial risks should investors assess?

Public revenue figures for imipenem/cilastatin are difficult to isolate because products are sold under multiple generic names, strengths, countries, tenders, and hospital contracts. Revenue exposure depends on:

• Hospital tender awards.
• Generic price erosion.
• Sterile-facility utilization.
• Regional antibiotic demand.
• Shortage conditions.
• Government procurement concentration.
• Reimbursement and formulary placement.
• Product recalls or manufacturing interruptions.

The principal downside risks are commoditization, low gross margins, sterile manufacturing failures, and limited ability to pass through higher excipient or packaging costs. The principal upside is a differentiated product that reduces hospital preparation burden or improves supply continuity.

Key Takeaways

• Imipenem/cilastatin is a mature generic injectable antibiotic with expired core exclusivity.
• Sodium bicarbonate is a common and commercially important formulation excipient.
• The main technical problem is imipenem stability after reconstitution.
• Ready-to-use, extended-stability, low-sodium, and pediatric presentations offer the strongest formulation opportunities.
• Basic powder-for-injection products face weak patent protection and intense price competition.
• The product has no biosimilar pathway; generic ANDA competition is the relevant model.
• Paragraph IV litigation is generally less important than sterile manufacturing capacity and hospital procurement.
• The strongest potential IP lies in stability-enhancing compositions, container systems, delivery devices, and defined reconstitution methods.
• Imipenem/cilastatin/relebactam should be analyzed as a separate, newer commercial and patent opportunity.
• Regional supply reliability can create more value than a conventional composition patent.

FAQs

Is sodium bicarbonate required in every imipenem/cilastatin product?

No. It is used in many commercial formulations, but excipient composition varies by manufacturer and jurisdiction. Each product's approved label controls.

Can imipenem/cilastatin be formulated as a premixed infusion bag?

Yes, but the product must overcome imipenem's aqueous stability limitations and demonstrate sterility, potency, impurity control, container compatibility, and labeled shelf life.

Does imipenem/cilastatin qualify for biosimilar approval?

No. Imipenem and cilastatin are small molecules. Follow-on products generally use generic drug pathways rather than the biosimilar pathway.

Is a low-sodium imipenem/cilastatin product commercially attractive?

Potentially. It could address renal, cardiac, pediatric, and sodium-restricted hospital populations, but its value depends on demonstrated stability, meaningful sodium reduction, and procurement recognition.

Can a company patent a new imipenem/cilastatin formulation?

Yes. Patentability may exist for a non-obvious composition, stability profile, container system, or administration technology. A basic combination of known actives and conventional sodium bicarbonate would face a weak patent position.

References

1. U.S. Food and Drug Administration. (1985). Primaxin intravenous: Original approval and prescribing information. FDA Drugs@FDA database.

2. Merck & Co., Inc. (2023). PRIMAXIN IV (imipenem and cilastatin) prescribing information. U.S. Food and Drug Administration labeling database.

3. DailyMed. (2024). Imipenem and cilastatin for injection prescribing information. National Library of Medicine.

4. U.S. Food and Drug Administration. (2024). Generic drug products and injectable drug product quality requirements. FDA.

5. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. 44th ed. Orange Book.

6. U.S. Food and Drug Administration. (2024). Drug shortages database. FDA.