List of Excipients in Branded Drug PYRIMETHAMINE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
OAKRUM PHARMA LLC	PYRIMETHAMINE	pyrimethamine	72647-330	LACTOSE
OAKRUM PHARMA LLC	PYRIMETHAMINE	pyrimethamine	72647-330	MAGNESIUM STEARATE
OAKRUM PHARMA LLC	PYRIMETHAMINE	pyrimethamine	72647-330	STARCH, CORN
OAKRUM PHARMA LLC	PYRIMETHAMINE	pyrimethamine	72647-330	STARCH, POTATO

Generic Drugs Containing PYRIMETHAMINE

Company	Ingredient	NDC	Excipient
Teva Pharmaceuticals Inc	pyrimethamine	0480-3720	MAGNESIUM STEARATE
Teva Pharmaceuticals Inc	pyrimethamine	0480-3720	MANNITOL
Teva Pharmaceuticals Inc	pyrimethamine	0480-3720	STARCH, CORN
DRREDDYS LABORATORIES INC	pyrimethamine	43598-672	LACTOSE MONOHYDRATE
DRREDDYS LABORATORIES INC	pyrimethamine	43598-672	MAGNESIUM STEARATE
DRREDDYS LABORATORIES INC	pyrimethamine	43598-672	STARCH, CORN

What are the Most Frequently-Used Excipients in PYRIMETHAMINE?

# Of NDCs	Excipient
5	LACTOSE MONOHYDRATE
6	MAGNESIUM STEARATE
1	MANNITOL
2	SILICON DIOXIDE
6	STARCH, CORN

Pyrimethamine Excipient Strategy and Commercial Opportunities

Last updated: August 7, 2026

Pyrimethamine is an old, small-molecule antiparasitic with limited patent protection and a narrow commercial market. The strongest opportunities are not new chemical-entity patents or biosimilar barriers. They are improved pediatric dosage forms, stable oral liquids, lower-cost generic supply, fixed-dose combinations, and formulations that reduce compounding requirements.

The active ingredient is available as a 25 mg immediate-release tablet, historically marketed in the United States as Daraprim. Its commercial value is shaped by supply reliability, pricing, clinical access, and formulation convenience rather than exclusivity. Pyrimethamine is poorly water-soluble and used in vulnerable patient populations, making excipient selection central to product performance, taste, stability, and dose accuracy.

What is the FDA regulatory status of pyrimethamine?

Pyrimethamine is an FDA-approved small-molecule drug used primarily with a sulfonamide and folinic acid for toxoplasmosis. The U.S. reference product is Daraprim, 25 mg tablets, associated with NDA 008578. The product was originally approved decades ago, and its regulatory exclusivity has expired [1].

Regulatory issue	Current commercial significance
Active ingredient	Pyrimethamine
U.S. reference product	Daraprim
Strength	25 mg tablet
FDA pathway	Original NDA and ANDA pathways
Drug type	Small molecule
Biosimilar pathway	Not applicable
New chemical exclusivity	Expired
Orphan-drug exclusivity	No current exclusivity identified for the legacy product
Primary approval risk	Bioequivalence, CMC, supply, and market access
Primary formulation opportunity	Pediatric oral liquid, dispersible tablet, and taste-masked dosage forms

The approved labeling identifies pyrimethamine tablets as an oral product containing conventional tablet excipients, including lactose, corn starch, magnesium stearate, and sodium starch glycolate [1]. The formulation is functional but not optimized for pediatric administration, swallowing impairment, or flexible weight-based dosing.

What excipients are used in pyrimethamine tablets?

The conventional Daraprim tablet uses a standard immediate-release excipient system:

Excipient function	Representative excipient	Formulation role
Diluent	Lactose	Provides tablet mass and improves manufacturability
Filler and disintegrant support	Corn starch	Supports compression and breakup
Superdisintegrant	Sodium starch glycolate	Promotes tablet disintegration
Lubricant	Magnesium stearate	Reduces sticking and ejection force
Active ingredient	Pyrimethamine	Antiparasitic drug substance

The existing formulation creates several development constraints. Lactose may require exclusion for selected patient groups, although lactose intolerance is generally distinct from milk-protein allergy. Magnesium stearate can affect wetting and dissolution if over-lubrication occurs. Sodium starch glycolate supports rapid breakup but can be sensitive to compression force and formulation moisture.

A generic developer could use the existing qualitative excipient profile to reduce development risk. A differentiated product would need a clear clinical or commercial advantage, such as improved dose flexibility, better palatability, reduced preparation error, or improved stability.

Why is pyrimethamine solubility important for excipient selection?

Pyrimethamine is practically insoluble in water. Its limited aqueous solubility complicates liquid formulation and can produce dose nonuniformity, sedimentation, slow dissolution, and variable absorption if the formulation is poorly controlled [1, 2].

For a liquid or dispersible product, the developer must decide whether to create:

1. A true solution using solubilization technology.
2. A suspension with controlled particle size and sedimentation behavior.
3. A dry powder that is reconstituted before administration.
4. A multiparticulate or granule system that can be sprinkled onto food or dispersed in liquid.

A suspension is likely to be more practical than a simple aqueous solution because pyrimethamine has low water solubility. The excipient system may include a wetting agent, suspending polymer, viscosity modifier, buffer, sweetener, flavor system, and preservative. Each component affects dose uniformity and regulatory risk.

Potential excipient classes include:

Development objective	Potential excipient approach
Improve wetting	Polysorbate, poloxamer, or other low-level surfactant
Maintain suspension	Xanthan gum, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, or similar polymer
Improve palatability	Sucrose, sorbitol, sucralose, flavoring agents
Control pH	Citrate, phosphate, or other suitable buffer
Protect against microbial growth	Preservative system compatible with pH and packaging
Improve dissolution	Cosolvent, surfactant, micronization, or amorphous dispersion
Reduce sediment compaction	Controlled particle size, structured vehicle, polymeric suspending system

A pediatric suspension must be evaluated for redispersibility after storage, not only initial dissolution. A compact sediment can create a subtherapeutic first dose followed by an excessive dose after vigorous shaking.

What formulations are protected by pyrimethamine patents?

No active U.S. composition-of-matter patent is commercially relevant to pyrimethamine. The molecule was discovered and approved many decades ago. Any meaningful protection for a new product would likely arise from a formulation, dosage form, manufacturing process, combination, or method-of-use claim.

Patent category	Commercial status
Pyrimethamine composition patent	Expired or no longer commercially blocking
Conventional 25 mg tablet	No meaningful current exclusivity identified
Pediatric suspension	Potentially patentable if technically differentiated
Orally disintegrating tablet	Potentially patentable, subject to novelty and non-obviousness
Taste-masked granule	Potentially patentable
Fixed-dose combination	Potentially patentable, but clinical and regulatory requirements remain
Manufacturing process	Potentially patentable if it provides a measurable advantage
Method of use	Potentially patentable only for qualifying new uses and subject to statutory limitations

A formulation patent would need more than a routine substitution of one binder, diluent, or sweetener. Stronger claims could cover a defined particle-size distribution, a specific suspension vehicle, a stability profile, a dose-uniformity result, a taste-masking architecture, or a multiparticulate system with controlled release or dispersibility.

Patent value would depend on whether the claim blocks a commercially practical alternative. A narrow claim to one polymer or flavor combination would be easier to design around than a claim covering the product's critical performance characteristics.

When does pyrimethamine lose exclusivity?

Pyrimethamine's original regulatory and patent exclusivity expired long ago. The commercial product does not depend on a live new-drug exclusivity period.

The relevant timeline is:

Period	Event
1950s	Pyrimethamine introduced as an antiparasitic drug
Legacy period	Daraprim marketed as a prescription tablet
2015	Daraprim acquired by Turing Pharmaceuticals and its price was sharply increased
2020s	Generic and compounded-access strategies developed amid continuing supply and affordability concerns
Current market	Competition depends on FDA approval, supply capability, payer access, and formulation differentiation

Turing's 2015 price increase from approximately $13.50 to $750 per tablet became the central commercial event associated with Daraprim [3]. The episode also increased interest in alternative suppliers and compounded formulations. In 2021, the Federal Trade Commission and New York Attorney General announced a settlement with Vyera Pharmaceuticals involving restrictions on distribution practices and financial penalties [4].

What is the Orange Book status of pyrimethamine?

The Orange Book identifies Daraprim as the reference listed drug for pyrimethamine tablets. The legacy product does not have a commercially significant active patent barrier comparable to newer branded medicines [5].

Orange Book issue	Assessment
Reference listed drug	Daraprim
Dosage form	Tablet
Strength	25 mg
ANDA opportunity	Legally available in principle
Paragraph IV exposure	Limited because no major active patent barrier is identified
Regulatory obstacle	Demonstrating pharmaceutical equivalence and bioequivalence
Market obstacle	Small demand, pricing pressure, distribution access, and supply economics

A Paragraph IV challenge is therefore not the primary entry mechanism for this product. An applicant can pursue an ANDA against the reference product without confronting the type of active patent thicket found with newer specialty drugs. The principal risk is economic: a small patient population may not support manufacturing, validation, pharmacovigilance, and distribution costs.

Which companies are challenging or competing with pyrimethamine?

The competitive field has included branded supply, generic manufacturers, and compounding pharmacies.

Branded and generic manufacturers

Daraprim has been associated with Turing Pharmaceuticals and later Vyera Pharmaceuticals. Generic pyrimethamine opportunities have attracted manufacturers because the product has no meaningful new chemical exclusivity. Actual commercial availability can vary by wholesaler, pharmacy, and period.

Compounding pharmacies

ImprimisRx and other compounding pharmacies have marketed customized pyrimethamine preparations or access alternatives. Compounded products do not automatically have the same regulatory status as an FDA-approved generic and are not substitutes for an ANDA-approved product in all institutional purchasing contexts.

Competitive substitutes

Clinical treatment generally uses pyrimethamine with sulfadiazine and folinic acid. In certain settings, trimethoprim-sulfamethoxazole or other regimens may be used, depending on patient factors and clinical guidance [6]. These alternatives compete with pyrimethamine at the regimen level even when they do not contain the same active ingredient.

What pediatric pyrimethamine formulations offer the strongest opportunity?

Pediatric toxoplasmosis is the clearest formulation opportunity. Infants and young children may need weight-based dosing, prolonged therapy, and administration of multiple drugs. A fixed 25 mg tablet can require tablet splitting, crushing, or extemporaneous suspension preparation.

The most commercially attractive options are:

Ready-to-use oral suspension

A ready-to-use suspension could reduce pharmacy compounding and improve dose flexibility. The product would need validated stability, reliable redispersion, preservative effectiveness, dose uniformity, and child-acceptable taste.

Reconstitutable powder

A dry powder may offer better shelf stability and lower shipping weight than a liquid. The development program would need to establish reconstitution instructions, in-use stability, microbial control, and consistent dosing throughout the bottle's use period.

Dispersible tablet

A dispersible tablet could be administered in a small volume of water. This format may simplify transport and improve dose flexibility, but the formulation must control disintegration, dispersion, taste, and dose recovery from the administration vessel.

Taste-masked granules

Granules or multiparticulates can be sprinkled onto soft food or dispersed in liquid. A polymer coating or lipid-based taste-masking layer may improve acceptability. The dosage form must prevent incomplete recovery of the active ingredient from food or drink.

Orally disintegrating tablet

An orally disintegrating tablet could address swallowing difficulty, although the 25 mg dose and bitter taste may make taste masking and tablet robustness difficult.

How strong is the patent estate for a new pyrimethamine product?

The underlying patent estate is weak because pyrimethamine is an old molecule. A new formulation could have moderate patent strength only if it produces a technically measurable benefit that competitors cannot easily reproduce.

A stronger formulation patent would typically include:

• Defined active-particle size or crystal form.
• A specific excipient ratio linked to dissolution or stability.
• A suspension with controlled sedimentation and redispersibility.
• A taste-masking coating that survives storage and administration.
• A dose-uniformity profile across the full dosing period.
• A defined preservative and buffer system.
• A manufacturing process that improves content uniformity or reduces degradation.

Patent claims based only on a broad list of common pharmaceutical excipients would face substantial obviousness and design-around risk. Regulatory exclusivity could be more important than patent exclusivity if a sponsor obtains approval for a genuinely new dosage form or indication.

What manufacturing and intellectual-property barriers exist?

The active ingredient is not the principal barrier. The barriers are operational:

1. Low and unpredictable demand.
2. Small batch sizes.
3. Need for validated content uniformity at a low dose.
4. Stability risks in liquid formulations.
5. Pediatric taste and administration requirements.
6. Distribution and pharmacy stocking costs.
7. Clinical documentation for new dosage forms.
8. Limited return on investment for a narrowly used medicine.

For tablets, low-dose uniformity is a central manufacturing issue. Pyrimethamine must be evenly distributed throughout the blend, and process controls must address segregation, lubrication, compression, and dissolution.

For suspensions, the critical controls shift to particle-size distribution, wetting, viscosity, sedimentation, redispersibility, microbial quality, and preservative effectiveness.

What licensing deals affect pyrimethamine?

The most visible commercial transaction was Turing Pharmaceuticals' acquisition of Daraprim rights from Impax Laboratories in 2015 [3]. Publicly reported commercial activity has focused on product ownership, distribution, and access rather than licensing of a valuable active patent estate.

A new formulation sponsor could pursue licensing or co-development with:

• A manufacturer with approved tablet capacity.
• A pediatric pharmaceutical company.
• A hospital or specialty-pharmacy network.
• A compounding or drug-delivery company with suspension technology.
• A nonprofit or public-health organization supporting toxoplasmosis treatment access.

The strongest deal structure would likely combine formulation know-how with guaranteed manufacturing and distribution. A pure patent license would have limited value unless the formulation delivered a clear clinical or operational advantage.

What generic entry risks exist for pyrimethamine?

Generic entry risk is high from a legal perspective and moderate from a commercial perspective.

Risk type	Assessment
Patent blocking	Low
Regulatory exclusivity	Low
Biosimilar competition	None
Tablet design-around risk	High
Pediatric formulation competition	Moderate
Supply-chain risk	High
Price erosion	High after reliable generic entry
Market-size risk	High
Litigation risk	More likely commercial or antitrust than patent-based

A generic tablet could enter without challenging a complex patent estate. A new suspension or dispersible tablet may receive more durable protection if it is supported by formulation patents, clinical data, or regulatory differentiation. The sponsor should expect competition from both approved generics and lower-cost compounded products.

How does pyrimethamine compare with other antiparasitic products?

Product	Primary differentiation	Patent position	Formulation opportunity
Pyrimethamine	Toxoplasmosis treatment and combination therapy	Legacy molecule; weak current exclusivity	Pediatric liquid, dispersible tablet, taste masking
Sulfadiazine	Partner drug in toxoplasmosis regimen	Generic market	Pediatric liquid and combination packaging
Folinic acid	Reduces pyrimethamine-associated folate toxicity	Generic market	Co-packaging and regimen simplification
Pyrimethamine-sulfadoxine	Antimalarial combination in some markets	Market-specific legacy rights	Fixed-dose combination and global-access products
Trimethoprim-sulfamethoxazole	Alternative regimen in selected uses	Generic market	Lower-cost oral liquids and pediatric dosing

Pyrimethamine's commercial position depends on the complete treatment regimen. A co-pack containing pyrimethamine, sulfadiazine, and folinic acid could improve adherence and reduce prescribing complexity, but combination packaging does not eliminate separate regulatory requirements for each component.

What revenue exposure and commercial opportunities exist?

Revenue exposure for a conventional pyrimethamine tablet is limited by the small treatment population and the availability of alternative regimens. The historical Daraprim price increase showed that unit price can rise sharply when supply is concentrated, but such pricing creates payer, political, and enforcement risk rather than durable product value [3, 4].

The most defensible opportunities are:

1. A reliable, reasonably priced generic tablet.
2. A ready-to-use pediatric suspension.
3. A reconstitutable powder with long shelf life.
4. A dispersible or taste-masked dosage form.
5. A regimen-based co-pack with folinic acid and the companion sulfonamide.
6. A global-health product for toxoplasmosis or malaria markets where pyrimethamine combinations remain clinically relevant.
7. Contract manufacturing for hospitals and specialty pharmacies.

The commercial case is strongest where the product replaces manual compounding and reduces medication errors. A tablet-only strategy may face low margins unless the sponsor has efficient manufacturing and established distribution.

Key Takeaways

• Pyrimethamine has no meaningful new chemical or regulatory exclusivity remaining.
• Daraprim is the U.S. reference product for 25 mg pyrimethamine tablets.
• The principal market barriers are supply economics, demand variability, and distribution, not patent litigation.
• Poor aqueous solubility makes suspension design, wetting, particle-size control, and redispersibility critical.
• Pediatric oral liquids, dispersible tablets, and taste-masked granules offer the clearest formulation opportunities.
• A new formulation patent must claim measurable technical performance, not merely a routine excipient substitution.
• Biosimilar risk is irrelevant because pyrimethamine is a small molecule.
• A co-pack or fixed-dose strategy involving sulfadiazine and folinic acid could improve regimen access, but it would require careful regulatory positioning.
• The highest-value commercial proposition is dependable access with a formulation that reduces compounding and dosing errors.

FAQs

Is pyrimethamine a good candidate for an orally disintegrating tablet?

Yes, but taste masking, dose recovery, mechanical strength, and low-dose content uniformity are critical. A conventional rapidly disintegrating tablet may not be commercially adequate if the bitter active ingredient is exposed in the mouth.

Can pyrimethamine be formulated as a stable oral solution?

A true solution is technically more difficult because pyrimethamine is poorly water-soluble. A suspension, reconstitutable powder, or solubilized system may be more practical, subject to stability and dose-uniformity testing.

Does pyrimethamine have biosimilar competition?

No. Pyrimethamine is a chemically synthesized small molecule. Competition occurs through generic drugs, branded products, and compounded preparations under small-molecule regulatory pathways.

Could a pyrimethamine suspension receive new patent protection?

Yes. Protection could cover a specific suspension system, particle-size profile, taste-masking structure, stability result, or manufacturing process. The claims must provide a non-obvious technical advantage over conventional formulations.

Is a pyrimethamine-sulfadiazine-folinic acid combination commercially viable?

It could be viable where it reduces dispensing complexity and improves pediatric access. The opportunity depends on clinical demand, regulatory requirements for the combination, manufacturing economics, and reimbursement.

References

1. U.S. Food and Drug Administration. (n.d.). Daraprim (pyrimethamine) tablets, prescribing information. FDA/DailyMed.

2. National Library of Medicine. (n.d.). Pyrimethamine drug information. PubChem.

3. U.S. Senate Committee on Aging. (2016). Sudden price spikes in off-patent drugs: Perspectives from the front lines. U.S. Government Publishing Office.

4. Federal Trade Commission. (2021). FTC, New York attorney general settle antitrust lawsuit against Vyera Pharmaceuticals and former executives. Federal Trade Commission.

5. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

6. Panel on Opportunistic Infections in Adults and Adolescents with HIV. (2023). Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: Toxoplasma gondii encephalitis. National Institutes of Health.