Generic CLIOQUINOL; NYSTATIN INN entry, drug patent expiry and freedom to operate

Subscribe to access the full database, or Start Trial
Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Bayer Pharms	NYSTAFORM	clioquinol; nystatin	OINTMENT;TOPICAL	050235-001	Approved Prior to Jan 1, 1982		DISCN	No	No	⤷ Start Trial	⤷ Start Trial				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Exclusivity Expiration

Last updated: September 9, 2026

Clioquinol and nystatin are mature, low-cost anti-infective ingredients with limited patent protection and fragmented commercial markets. Nystatin has the stronger regulatory and commercial base because it remains widely used in FDA-approved oral, topical, and vaginal products. Clioquinol has a narrower and more geographically variable market, concentrated in topical combination products and selected non-U.S. markets.

Neither ingredient has a credible path to premium pricing based on composition-of-matter exclusivity. Financial performance depends on manufacturing cost, distributor access, formulation differentiation, regional registration, and product availability rather than patent exclusivity.

What are clioquinol and nystatin used for?

Nystatin is a polyene antifungal used against Candida infections. Common dosage forms include oral suspension, topical cream and ointment, powder, vaginal tablets, and vaginal cream. Because nystatin is poorly absorbed from the gastrointestinal tract, oral suspension is used primarily for local treatment of oral candidiasis rather than systemic fungal disease. FDA labeling identifies nystatin products for candidiasis of the oral cavity, skin, and vagina, depending on the dosage form.[1]

Clioquinol is a halogenated hydroxyquinoline with antibacterial and antifungal activity. Its commercial use is predominantly topical, often in combination with a corticosteroid or another anti-infective. It has been used for superficial skin infections, infected eczema, dermatitis, and other localized conditions. Historical oral use was associated with subacute myelo-optic neuropathy, or SMON, in Japan and elsewhere, which materially constrained systemic development and left topical treatment as the principal commercial application.[2]

Attribute	Clioquinol	Nystatin
Primary pharmacology	Topical antibacterial and antifungal	Polyene antifungal
Main target organisms	Selected fungi and bacteria	Candida species and other susceptible fungi
Dominant dosage forms	Cream, ointment, lotion, combination products	Oral suspension, cream, ointment, powder, vaginal products
U.S. regulatory position	Product-specific and limited; no major current standalone FDA market	Established FDA-approved generic product category
Systemic use	Commercially constrained by historical safety concerns	Limited oral absorption; not a systemic oral treatment
Patent position	Legacy compound; meaningful composition patents expired	Legacy compound; meaningful composition patents expired
Competitive structure	Fragmented regional and combination-product market	Broad generic market with multiple suppliers
Commercial outlook	Stable niche or declining	Stable, low-growth, volume-driven

What is the FDA regulatory status of clioquinol and nystatin?

Nystatin has an established U.S. regulatory pathway. FDA-approved products include oral suspensions, topical preparations, and vaginal dosage forms marketed by multiple generic manufacturers. Product availability varies by manufacturer and supply conditions, but the active ingredient remains clinically established and commercially relevant.[1,3]

Clioquinol does not have the same U.S. regulatory footprint. Current U.S. availability is product-specific, and a standalone FDA-approved clioquinol product is not a major current market category in Drugs@FDA. Clioquinol-containing products may be marketed in other jurisdictions under national regulatory frameworks, particularly as topical combination products.

The regulatory distinction has direct financial consequences:

Nystatin can be commercialized through established abbreviated new drug application pathways for qualifying products.
Clioquinol products face greater country-by-country registration and market-access requirements.
Combination products containing clioquinol may require separate evaluation of each active ingredient, indication, safety profile, and formulation.
Historical safety concerns reduce the probability of regulatory expansion into systemic or broad consumer applications.

What is the Orange Book status of clioquinol and nystatin?

The Orange Book is relevant primarily to approved U.S. drug products and their listed patents and exclusivity. Nystatin's core active-ingredient patents and early product patents expired long ago. Current nystatin products are generally exposed to generic competition and do not depend on a live composition-of-matter patent.

No meaningful current Orange Book patent barrier is expected to protect the nystatin molecule itself. Any remaining protection would more likely relate to a specific formulation, delivery system, manufacturing process, or combination product. Those rights would have to be assessed at the individual product level.

Clioquinol has an even smaller U.S. Orange Book footprint. There is no commercially significant current U.S. exclusivity position associated with the clioquinol molecule. Any enforceable rights would more likely involve:

A specific topical formulation
A fixed-dose combination
A controlled-release or enhanced-penetration system
A manufacturing process
A method-of-use claim in a particular jurisdiction

Exclusivity category	Clioquinol	Nystatin
Composition-of-matter protection	Expired	Expired
Current U.S. regulatory exclusivity	No material standalone position identified	No material ingredient-level position
Orange Book relevance	Limited and product-specific	Primarily product-specific
Generic substitution risk	High where approved products exist	High
Patent-based price protection	Minimal	Minimal

When do clioquinol and nystatin lose exclusivity?

Both ingredients lost meaningful molecule-level exclusivity decades ago. There is no commercially relevant future patent cliff comparable to the loss of exclusivity for a recent branded drug.

For nystatin, commercial exclusivity has already been replaced by a mature generic market. The principal risks are not patent expiration but:

Manufacturer discontinuation
Active pharmaceutical ingredient supply interruptions
Hospital and pharmacy purchasing pressure
Reimbursement compression
Product-specific shortages
Substitution by azoles or other antifungals

For clioquinol, market access is more dependent on local regulatory approval and brand or distributor relationships. A product can retain regional commercial value without patent protection if it has registration, physician familiarity, or supply continuity. That value is vulnerable to regulatory reassessment and substitution by topical azoles, corticosteroid-antifungal combinations, and newer dermatology products.

What patents protect clioquinol and nystatin formulations?

The commercial patent estate for both compounds is likely to be formulation-led rather than molecule-led.

Potentially protectable nystatin technologies include:

Taste-masked oral suspensions
Improved suspension stability
Mucoadhesive oral formulations
Vaginal delivery systems
Powder or aerosol delivery
Combination products
Manufacturing processes that improve fermentation yield or impurity control

Potentially protectable clioquinol technologies include:

Cream and ointment vehicles
Enhanced skin penetration
Reduced irritation
Combination products with corticosteroids or antibacterials
Controlled-release topical systems
Preservative and stability systems
Packaging designed to protect the formulation from light or oxidation

These claims are usually narrower than composition patents. Their commercial value depends on whether the formulation produces a measurable clinical, stability, or usability advantage and whether competing manufacturers can design around the claims.

A formulation patent covering one product does not normally prevent generic or regional competitors from selling a different dosage form or vehicle. The practical protection is therefore limited unless the patented delivery system is commercially necessary.

Are there Paragraph IV challenges for clioquinol or nystatin?

Paragraph IV litigation is unlikely to be a material market event for these ingredients.

A Paragraph IV certification applies when an ANDA applicant challenges a listed patent for an approved reference product. Because nystatin is an old generic active ingredient and most core patents have expired, there is limited scope for a commercially important patent challenge. Any litigation would likely concern a narrow formulation or combination patent rather than nystatin itself.

Clioquinol has limited relevance to the U.S. ANDA litigation system because its current U.S. approved-product presence is narrow. The more significant barriers are product approval, market access, and regional registration rather than patent disputes.

Litigation issue	Clioquinol	Nystatin
Expected core patent challenge	Low	Low
Formulation patent challenge	Possible but limited	Possible for specialized products
Typical entry dispute	Regulatory approval or product registration	Product supply, reimbursement, or formulation
Likely settlement value	Low	Low to moderate for a differentiated product
Probability of major litigation-driven delay	Low	Low

Which companies are competing in the clioquinol and nystatin markets?

The markets are fragmented, and manufacturer participation varies by country.

Nystatin competition includes generic pharmaceutical companies, contract manufacturers, hospital suppliers, and regional branded-generic companies. Historical and current market participants have included companies such as Bristol Myers Squibb through Mycostatin legacy products, Perrigo, Taro, Teva, ANI Pharmaceuticals, and other regional suppliers, subject to product-specific approvals and discontinuations.

Clioquinol competition is more geographically dispersed. Products may be sold by regional dermatology companies, branded-generic manufacturers, and licensees under local trade names. Combination products are often more commercially important than standalone clioquinol products.

The competitive landscape is not driven by molecule ownership. It is driven by:

Manufacturing cost and batch reliability
Regulatory registrations
Distributor and pharmacy relationships
Brand recognition in local markets
Ability to supply low-volume products profitably
Formulation and packaging quality

What is the financial trajectory for nystatin?

Nystatin is a mature, low-growth pharmaceutical category. Revenue is generally stable to declining on a per-unit price basis, while unit demand remains supported by the continued prevalence of mucocutaneous Candida infections and the low cost of treatment.

The financial profile has four characteristics:

Low average selling prices
High generic competition
Limited marketing expenditure
Modest product-level margins unless supply is constrained or the product has a differentiated dosage form

Nystatin oral suspension can retain commercial value because pediatric prescribing, oral candidiasis treatment, and institutional use support recurring demand. Vaginal and topical products face substitution from azole antifungals and other local treatments.

Nystatin's main financial risks are price erosion and portfolio rationalization. Manufacturers may discontinue low-volume presentations when procurement prices fall below an acceptable margin. Conversely, a supplier with reliable manufacturing capacity can benefit during shortages or competitor exits.

A branded nystatin product can command a premium only where it has a recognized trade name, superior packaging, a preferred dosage form, or dependable supply. The active ingredient alone does not support premium pricing.

What is the financial trajectory for clioquinol?

Clioquinol is a niche, regionally variable product with limited public revenue disclosure. The market is likely flat to declining in mature jurisdictions and more dependent on local demand in emerging markets.

Revenue potential is constrained by:

Narrow approved indications
Limited systemic use
Safety history
Competition from topical azoles
Availability of corticosteroid-antifungal combinations
Low unit prices
Product-specific registration requirements

Clioquinol may remain profitable for a manufacturer with an established regional brand, low-cost production, or a portfolio of combination dermatology products. It is less attractive as a standalone global development asset because clinical differentiation would be difficult and regulatory expansion would carry disproportionate cost.

The commercial opportunity is stronger in a portfolio strategy than as an individual molecule investment. A company may benefit by combining clioquinol with established topical products, dermatology distribution, or contract manufacturing capacity. The molecule is unlikely to support a large independent revenue platform.

How strong are the patent estates for clioquinol and nystatin?

The patent estates are weak at the active-ingredient level and potentially moderate for carefully designed formulations.

Patent-strength factor	Clioquinol	Nystatin
Molecule-level exclusivity	Very low	Very low
Formulation opportunity	Low to moderate	Moderate
Manufacturing know-how	Moderate	Moderate to high
Regulatory moat	Moderate regionally	Low to moderate
Brand and distribution value	Moderate in selected markets	Moderate
Generic entry barrier	Low	Low
Litigation protection	Low	Low

Nystatin manufacturing may create more meaningful operational know-how because the ingredient is produced through fermentation. Yield, purification, potency control, stability, and contamination management can affect cost and supply reliability.

Clioquinol manufacturing is less dependent on biological production but may still involve process controls, impurity specifications, and formulation stability. These factors can protect margins through know-how without creating enforceable market exclusivity.

What generic entry risks exist for clioquinol and nystatin?

Generic entry risk is already realized rather than pending.

For nystatin, additional entry can cause further price erosion, but the category has a practical floor determined by manufacturing economics. The largest risk is not a single competitor launching after patent expiration. It is the cumulative effect of multiple suppliers competing for a limited number of prescriptions and institutional contracts.

For clioquinol, entry risk depends on the jurisdiction. Where the product is approved, a competitor can generally enter after satisfying local regulatory requirements unless a formulation or combination patent remains enforceable. Where the product is not approved, the relevant risk is substitution rather than generic launch.

Substitution threats include:

Clotrimazole
Miconazole
Ketoconazole
Terbinafine
Hydrocortisone-antifungal combinations
Newer dermatology formulations
Nonprescription skin-care and antifungal products

How do clioquinol and nystatin compare commercially?

Nystatin is the stronger commercial asset because it has broader regulatory recognition, more dosage forms, and a larger installed prescribing base. It remains suitable for low-cost generic production and recurring demand.

Clioquinol is a smaller specialty or regional asset. Its value depends more heavily on product registration, formulation positioning, and local physician practice.

Commercial metric	Clioquinol	Nystatin
Global market breadth	Narrow and regional	Broad but mature
Growth profile	Flat or declining	Stable to low growth
Pricing power	Low	Low
Regulatory expansion potential	Limited	Limited but established
Portfolio value	Regional dermatology	Generic anti-infective portfolio
Supply-chain value	Moderate	Moderate to high
Investment attractiveness	Selective, asset-specific	Operational and scale-driven

What licensing and transaction opportunities exist?

Licensing opportunities are more likely to involve products than molecules.

Potential transaction structures include:

Regional rights to registered topical products
Distribution agreements for nystatin presentations
Acquisition of legacy dermatology brands
Contract manufacturing and supply agreements
Licensing of improved nystatin delivery systems
Co-development of clioquinol combination products
Transfer of regulatory dossiers in non-U.S. markets

A transaction based solely on rights to clioquinol or nystatin is unlikely to command substantial upfront consideration unless it includes registrations, manufacturing capacity, an established brand, or protected formulation technology.

For nystatin, the most valuable assets are dependable supply, a broad product portfolio, and access to institutional or retail channels. For clioquinol, value is concentrated in approved regional products and combination-product registrations.

What generic launch scenarios should investors expect?

The most probable nystatin scenario is continued low-price generic supply with periodic manufacturer exits and occasional shortage-driven pricing increases. No major patent-triggered launch event is expected.

The most probable clioquinol scenario is continued regional availability through selected topical products, with gradual substitution where physicians favor azoles or newer dermatology therapies. Market growth would require a differentiated formulation, a new indication, or expansion into a jurisdiction with limited current competition.

A high-value launch scenario for either ingredient would require one of four changes:

A clinically superior delivery system
A new indication with meaningful unmet need
A combination product with clear therapeutic advantage
Supply disruption among incumbent manufacturers

Key Takeaways

Nystatin is the larger and more durable commercial asset.
Clioquinol is a niche topical ingredient with fragmented geographic coverage.
Core composition patents for both ingredients are expired.
Neither ingredient has a meaningful future patent cliff.
Paragraph IV litigation is unlikely to materially affect either market.
Nystatin revenue is driven by generic volume, supply reliability, and dosage-form breadth.
Clioquinol revenue depends on regional registrations, combination products, and dermatology distribution.
Formulation patents may provide limited protection but are unlikely to create broad market exclusivity.
Manufacturing know-how is more commercially important than patent ownership.
Investment value is strongest in established portfolios, registered products, and supply-constrained channels.

FAQs about clioquinol and nystatin

Is clioquinol still approved in the United States?

U.S. availability is limited and product-specific. Clioquinol does not have the broad standalone FDA-approved market presence associated with nystatin, and its commercial status varies by formulation and jurisdiction.

Is nystatin a generic drug?

Yes. Nystatin is a long-established generic active ingredient with multiple approved dosage forms and manufacturers. Brand and generic products may coexist, but molecule-level exclusivity has expired.

Can nystatin patents block generic entry?

Core nystatin patents cannot ordinarily block entry because they expired long ago. A narrow formulation, combination, or delivery-system patent could create a product-specific barrier.

Are clioquinol and nystatin biologics?

No. Both are small-molecule or naturally derived anti-infective compounds regulated through drug pathways rather than biosimilar pathways. Biosimilar competition is not relevant.

Which ingredient has better investment potential?

Nystatin generally has better investment potential because of its broader approved-product base and established demand. Clioquinol may be attractive only as part of a regional dermatology portfolio, a registered combination product, or a differentiated topical formulation.

References

U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs, nystatin product labeling. https://www.accessdata.fda.gov/scripts/cder/daf/
World Health Organization. (1978). Subacute myelo-optic neuropathy and clioquinol. World Health Organization technical report and pharmacovigilance materials.
U.S. National Library of Medicine. (2024). DailyMed: Nystatin product labeling. https://dailymed.nlm.nih.gov/dailymed/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
U.S. National Library of Medicine. (2024). PubChem compound summaries: Clioquinol and nystatin. https://pubchem.ncbi.nlm.nih.gov/

US Patents:	0
Tradenames:	1
Applicants:	1
NDAs:	1
DailyMed Link:	CLIOQUINOL; NYSTATIN at DailyMed

CLIOQUINOL; NYSTATIN - Generic Drug Details

What are the generic drug sources for clioquinol; nystatin and what is the scope of freedom to operate?

Summary for CLIOQUINOL; NYSTATIN

Anatomical Therapeutic Chemical (ATC) Classes for CLIOQUINOL; NYSTATIN

US Patents and Regulatory Information for CLIOQUINOL; NYSTATIN

Clioquinol and Nystatin Market Dynamics, Patent Exposure, and Financial Trajectory