ISOFLUROPHATE - Generic Drug Details

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What are the generic sources for isoflurophate and what is the scope of freedom to operate?

Isoflurophate is the generic ingredient in one branded drug marketed by Merck and is included in one NDA. Additional information is available in the individual branded drug profile pages.

Summary for ISOFLUROPHATE

US Patents:	0
Tradenames:	1
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	40
DailyMed Link:	ISOFLUROPHATE at DailyMed

Medical Subject Heading (MeSH) Categories for ISOFLUROPHATE

Cholinesterase Inhibitors

Protease Inhibitors

US Patents and Regulatory Information for ISOFLUROPHATE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Merck	FLOROPRYL	isoflurophate	OINTMENT;OPHTHALMIC	010656-001	Approved Prior to Jan 1, 1982		DISCN	No	No

Isoflurophate Market Dynamics and Financial Trajectory

Last updated: September 3, 2026

Isoflurophate is an obsolete ophthalmic organophosphate used historically to reduce intraocular pressure in glaucoma and to treat selected accommodative disorders. Its commercial market has effectively disappeared. No major branded product, active U.S. generic market, current FDA-approved commercial sponsor, or publicly reported revenue stream is identifiable in the principal U.S. drug databases. Financial value is therefore concentrated in legacy clinical use, research relevance, and potential niche access rather than pharmaceutical sales.

What is isoflurophate and how is it used?

Isoflurophate, also known as diisopropyl fluorophosphate or DFP, is an irreversible acetylcholinesterase inhibitor. In ophthalmology, topical administration produces prolonged miosis and ciliary muscle contraction, which can reduce intraocular pressure and alter accommodation.

Historically reported uses included:

• Chronic open-angle glaucoma
• Selected cases of angle-closure glaucoma after control of acute symptoms
• Accommodative esotropia and related pediatric ophthalmic disorders
• Experimental investigation of cholinergic mechanisms

Isoflurophate is pharmacologically distinct from echothiophate iodide, another long-acting ophthalmic organophosphate historically marketed as Phospholine Iodide. The two compounds are sometimes grouped together in historical ophthalmic literature, but they are different active ingredients and should not be treated as interchangeable commercial products.

Attribute	Isoflurophate
Chemical class	Organophosphate acetylcholinesterase inhibitor
Common chemical name	Diisopropyl fluorophosphate
Primary historical dosage form	Ophthalmic preparation
Historical therapeutic area	Glaucoma and accommodation disorders
Pharmacologic effect	Prolonged cholinergic stimulation and miosis
Current commercial position	Legacy or discontinued product
Biosimilar relevance	None
Generic competition	No meaningful current U.S. market identified
Principal substitutes	Prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, alpha agonists, laser and surgical therapies

When did isoflurophate lose exclusivity?

Isoflurophate no longer has a commercially meaningful exclusivity position in the United States. Any composition-of-matter, formulation, or product patents associated with historical development would have expired decades ago under modern patent-term calculations.

The product’s market withdrawal appears to have resulted from commercial and clinical obsolescence rather than a recent patent event. Modern glaucoma treatment displaced long-acting organophosphate miotics because newer therapies generally offer easier administration, better tolerability, fewer systemic cholinergic effects, and more predictable dosing.

Key commercial constraints included:

• Prolonged miosis and impaired night vision
• Accommodation spasm and induced refractive effects
• Risk of systemic cholinergic toxicity
• Potential ocular inflammation and other local adverse effects
• Complex dosing and monitoring requirements
• Availability of better-tolerated alternatives

There is no current loss-of-exclusivity event comparable to the patent cliffs affecting major branded glaucoma medicines. Isoflurophate is already beyond the normal commercial life cycle for a prescription ophthalmic product.

What is the FDA regulatory status of isoflurophate?

Isoflurophate does not have a significant current FDA commercial presence. The FDA’s Drugs@FDA database and Orange Book are the primary sources for determining whether an approved product, active application, or listed patent remains relevant.[1][2]

The regulatory position can be summarized as follows:

Regulatory issue	Current commercial significance
Active branded U.S. product	No major product identified
Active generic U.S. product	No meaningful marketed product identified
Current Orange Book patent barrier	No commercially relevant barrier identified
FDA exclusivity	No current exclusivity identified
Biosimilar pathway	Not applicable
OTC substitution	Not applicable
Compounding opportunity	Possible only under applicable pharmacy and state-law requirements

Historical approval records and discontinued-product records should be separated from current marketing authorization. A product may remain visible in archival regulatory databases even when no sponsor actively markets it.

How large is the isoflurophate market?

The current market is effectively negligible at the global branded-drug level. Public company filings do not identify isoflurophate as a material revenue product, and standard commercial market reports generally do not assign it a standalone forecast category.

Current revenue exposure

No reliable public revenue series is available for isoflurophate. The absence of reported sales is consistent with:

• No active multinational commercial franchise
• No identifiable current branded launch
• No material presence in major glaucoma treatment guidelines
• Limited or absent pharmacy distribution
• Replacement by newer drug classes

Historical sales data also appear limited because isoflurophate was marketed before the widespread disclosure of product-level revenue in public filings. Any historical revenue estimate would require proprietary prescription, wholesaler, or archival company data.

Market size assessment

Market segment	Isoflurophate exposure
Global branded ophthalmology	Effectively zero
U.S. retail prescription market	De minimis or absent
Hospital ophthalmology	Highly limited
Compounded formulations	Niche and institution-specific
Research use	Limited, non-therapeutic
Patent licensing value	Minimal
Manufacturing asset value	Low without a reformulation or specialty indication

The economic value of a redevelopment program would depend on regulatory exclusivity, clinical differentiation, and a new delivery system rather than on the legacy molecule alone.

What drugs compete with isoflurophate?

Isoflurophate competes pharmacologically with other miotics but commercially competes with the entire modern glaucoma treatment ladder.

Direct pharmacologic substitutes

• Pilocarpine
• Carbachol
• Echothiophate iodide, historically
• Other cholinergic miotics

These products also have limited use relative to newer therapies.

Modern therapeutic substitutes

Drug class	Examples	Commercial position
Prostaglandin analogs	Latanoprost, bimatoprost, travoprost, tafluprost	Dominant first-line medical therapy in many markets
Beta blockers	Timolol, betaxolol	Mature generic market
Carbonic anhydrase inhibitors	Dorzolamide, brinzolamide, acetazolamide	Established generic and branded use
Alpha-2 agonists	Brimonidine	Established adjunctive therapy
Rho kinase inhibitors	Netarsudil	Newer branded specialty segment
Fixed combinations	Multiple combinations	Improve adherence and reduce administration burden
Laser therapy	Selective laser trabeculoplasty	Non-drug substitute
Surgery and implants	MIGS, trabeculectomy, drainage devices	Procedural alternatives for advanced disease

Isoflurophate’s long duration of action does not compensate for its tolerability and safety liabilities in a market where once-daily prostaglandin analogs and minimally invasive procedures are available.

What formulations are protected by isoflurophate patents?

No active, commercially relevant formulation patent estate has been identified for isoflurophate. Historical formulations would likely have involved aqueous ophthalmic solutions containing the active organophosphate, stabilizers, buffering agents, and sterile packaging.

Potential formulation-development issues include:

• Chemical stability of the organophosphate
• Sterility and preservative selection
• Container compatibility
• Controlled ocular exposure
• Reduction of systemic absorption
• Dose uniformity
• Shelf-life under pharmacy and distribution conditions

A modern reformulation could theoretically use a preservative-free multidose container, gel, implant, depot, or targeted delivery platform. Such a product would need to establish a clinical advantage over existing glaucoma therapies. A delivery patent alone would not solve the underlying tolerability problem.

Does isoflurophate have method-of-use patent protection?

No current method-of-use exclusivity is commercially material. Historical claims would likely have covered the use of the compound as a miotic, intraocular-pressure-lowering agent, or treatment for specific accommodation disorders. Those claims would not block present-day development.

A new method-of-use program would face a high evidentiary threshold. The sponsor would need to demonstrate a defined population in which the prolonged cholinergic effect provides a benefit unavailable from:

• Prostaglandin analogs
• Pilocarpine or other modern miotics
• Laser treatment
• Surgical intervention
• Combination therapy

Potentially differentiated populations could include rare ophthalmic disorders, but the addressable market would be small and clinical development costs would be difficult to recover without orphan-drug economics or premium specialty pricing.

Are there Paragraph IV challenges involving isoflurophate?

No material current Paragraph IV litigation has been identified. Paragraph IV activity requires an active abbreviated new drug application opportunity linked to a relevant approved reference product and Orange Book listing. Isoflurophate lacks the commercial conditions that typically generate generic patent challenges.

The absence of Paragraph IV activity indicates:

1. No meaningful active reference-product market.
2. No valuable listed patent blocking generic entry.
3. Limited expected return from developing a conventional generic.
4. No credible near-term generic launch cycle.

A company seeking to commercialize isoflurophate today would more likely evaluate a new drug application, a compounding route, or a reformulated specialty product than pursue a standard ANDA strategy.

What patent litigation affects isoflurophate?

No significant recent patent litigation involving isoflurophate has been identified in the major U.S. pharmaceutical litigation record. The molecule’s age, lack of active commercial sponsorship, and absence of an important Orange Book patent estate make patent litigation unlikely.

The more relevant legal risks would be:

• FDA compliance for any proposed marketed product
• Sterile ophthalmic manufacturing requirements
• Drug shortage and compounding rules
• Product liability exposure from systemic toxicity
• Labeling requirements for long-lasting cholinergic effects
• State-law restrictions on pharmacy compounding
• Ownership of any new formulation or delivery technology

How strong is the isoflurophate patent estate?

The legacy patent estate is commercially weak. Its remaining value is likely limited to historical technical disclosure rather than enforceable exclusivity.

Patent-estate factor	Assessment
Composition-of-matter protection	Expired
Basic ophthalmic-use claims	Expired or commercially irrelevant
Active formulation patents	None of material current significance identified
Method-of-use exclusivity	None of material current significance identified
Manufacturing know-how	Potentially relevant but not publicly established
Freedom-to-operate risk	Low for the old molecule; higher for new delivery systems
Redevelopment value	Dependent on new clinical and formulation IP

A redevelopment sponsor could create a new patent position around particle size, excipients, packaging, sustained release, combination therapy, or a defined patient population. Patentability would depend on novelty, non-obviousness, enablement, and credible clinical benefit.

Are there licensing deals for isoflurophate?

No major current licensing transaction involving isoflurophate has been publicly identified. The asset is unlikely to attract conventional pharmaceutical licensing interest because it lacks:

• Current prescription demand
• A protected commercial indication
• A recognized branded platform
• Near-term regulatory exclusivity
• A large reimbursed patient population

Potential counterparties would more likely include specialty ophthalmology companies, academic groups, hospital pharmacies, or drug-delivery developers. The likely deal structure would involve a low upfront payment, development milestones, and rights tied to a new formulation or indication rather than royalties on legacy sales.

What generic launch risks exist for isoflurophate?

A conventional generic launch would face limited patent risk but substantial commercial and regulatory risk.

Regulatory risk

The sponsor would need to establish the appropriate reference product, formulation equivalence, quality specifications, and sterile manufacturing controls. A product absent from the current market may also create practical difficulties in sourcing an acceptable reference standard.

Manufacturing risk

Organophosphate handling requires controlled production, validated containment, accurate assay methods, and robust impurity controls. Ophthalmic products carry additional requirements for sterility, particulate control, preservative performance, and container closure integrity.

Commercial risk

The principal risk is insufficient demand. Ophthalmologists have broad access to low-cost generic glaucoma medicines with stronger guideline support and better tolerability. Wholesalers and pharmacies have little incentive to stock a low-volume legacy miotic.

Clinical risk

Long-lasting cholinergic activity could produce adverse effects that limit use even if the product is inexpensive. A lower acquisition price would not necessarily overcome physician reluctance or patient discontinuation.

How does isoflurophate compare with pilocarpine and echothiophate iodide?

Factor	Isoflurophate	Pilocarpine	Echothiophate iodide
Pharmacology	Irreversible organophosphate inhibitor	Direct muscarinic agonist	Irreversible organophosphate inhibitor
Duration	Prolonged	Shorter and dose-dependent	Prolonged
Historical use	Glaucoma and accommodation disorders	Glaucoma, selected acute uses	Glaucoma
Current availability	Limited or absent	Generic availability in some markets	Limited or discontinued in many markets
Patent value	None of material current significance	Mature and largely generic	Legacy
Commercial outlook	Negligible	Niche but viable in selected indications	Negligible
Main limitation	Toxicity and prolonged ocular effects	Frequent dosing and visual side effects	Toxicity, availability, and monitoring burden

Pilocarpine has a stronger residual market because it remains available as a generic and has a clearer role in selected clinical settings. Isoflurophate lacks that same practical position.

What is the financial trajectory for isoflurophate?

The financial trajectory is best described as a completed decline from historical ophthalmic use to negligible current commercial activity.

Period	Financial and market trajectory
Early commercial era	Used as a long-acting ophthalmic cholinesterase inhibitor
Mature historical period	Faced competition from other miotics and expanding glaucoma therapies
Decline period	Lost share to prostaglandin analogs, beta blockers, and combination products
Current period	No material branded revenue or active global franchise identified
Redevelopment scenario	Value would depend on new formulation, indication, or delivery technology

No public evidence supports a near-term revenue recovery based on the legacy product. A commercial revival would require a new product thesis, not simple reintroduction of the historical ophthalmic preparation.

Key Takeaways

• Isoflurophate is an old organophosphate ophthalmic drug, also known as diisopropyl fluorophosphate.
• Its current commercial market is negligible or absent.
• No current FDA exclusivity, material Orange Book patent barrier, or active Paragraph IV dispute has been identified.
• The molecule has no biosimilar pathway because it is a small-molecule drug.
• Prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, laser therapy, and surgery have displaced its historical role.
• The legacy patent estate has little commercial strength.
• A viable redevelopment strategy would require a differentiated formulation, delivery system, or rare ophthalmic indication.
• Historical and current revenue cannot be reliably quantified from public company disclosures or standard FDA records.

FAQs

Is isoflurophate still sold in the United States?

No major currently marketed U.S. product has been identified. Historical regulatory records should not be interpreted as evidence of current commercial availability.

Is isoflurophate the same drug as echothiophate iodide?

No. Both are long-acting organophosphate cholinesterase inhibitors, but they are chemically distinct active ingredients.

Can a company launch a generic isoflurophate product?

Potentially, but the principal obstacles would be reference-product selection, sterile manufacturing, clinical demand, and commercial distribution rather than patent expiration.

Does isoflurophate have orphan-drug potential?

Only in a narrowly defined rare ophthalmic indication. The molecule itself would not receive orphan-drug value without a qualifying disease population and supporting clinical evidence.

What would make isoflurophate commercially valuable again?

A sustained-release or targeted ocular delivery system, a clinically differentiated rare-disease indication, or a combination product that materially improves efficacy or dosing could create value. The legacy molecule alone is unlikely to support a meaningful pharmaceutical franchise.

References

1. U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

3. National Library of Medicine. (n.d.). DailyMed: Current medication labeling. https://dailymed.nlm.nih.gov/dailymed/

4. National Library of Medicine. (n.d.). PubChem compound summary: Diisopropyl fluorophosphate. https://pubchem.ncbi.nlm.nih.gov/

5. American Academy of Ophthalmology. (2020). Primary open-angle glaucoma preferred practice pattern. Ophthalmology, 127(1), P71-P138.