Sponsor	Phase
ZonMw: The Netherlands Organisation for Health Research and Development	Phase 3
Saltro	Phase 3
MJM Bonten	Phase 3

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Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Watson Labs	NITROFURANTOIN MACROCRYSTALLINE	nitrofurantoin, macrocrystalline	CAPSULE;ORAL	070248-001	Jun 24, 1988		DISCN	No	No	⤷ Start Trial	⤷ Start Trial				⤷ Start Trial
Watson Labs	NITROFURANTOIN MACROCRYSTALLINE	nitrofurantoin, macrocrystalline	CAPSULE;ORAL	070249-001	Jun 24, 1988		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: October 26, 2026

Executive summary: Nitrofurantoin macrocrystalline is a mature, low-cost oral antibacterial with stable clinical demand in uncomplicated urinary tract infection. Its commercial profile is defined by generic competition, limited patent protection, low pricing, and modest manufacturing economics rather than exclusivity. Demand remains supported by guideline preference for uncomplicated cystitis and continued resistance to older antibiotics. Growth is constrained by the drug’s narrow indication, renal-function restrictions, adverse-event monitoring, and substitution by nitrofurantoin monohydrate/macrocrystals, trimethoprim-sulfamethoxazole, fosfomycin, and beta-lactams.

Nitrofurantoin Macrocrystalline Market Dynamics, Patent Status, and Financial Trajectory

What is nitrofurantoin macrocrystalline and how is it used?

Nitrofurantoin macrocrystalline is an oral formulation of nitrofurantoin used primarily for the treatment and suppression of susceptible urinary-tract infections. It is sold in capsule strengths of 25 mg, 50 mg, and 100 mg under the Macrodantin brand and through generic equivalents. The drug is rapidly eliminated into urine, producing antibacterial activity in the urinary tract while limiting systemic exposure.

The macrocrystalline formulation differs from nitrofurantoin monohydrate/macrocrystals, marketed historically as Macrobid. Macrodantin is generally dosed four times daily, while Macrobid is typically dosed twice daily because the monohydrate component changes dissolution and release characteristics.

Product	Active formulation	Typical adult treatment regimen	Commercial position
Macrodantin	Nitrofurantoin macrocrystals	50-100 mg four times daily	Mature brand and generic product
Generic nitrofurantoin macrocrystals	Nitrofurantoin macrocrystals	50-100 mg four times daily	Main market supply
Macrobid	Nitrofurantoin monohydrate/macrocrystals	100 mg twice daily	Competing branded/generic formulation
Other UTI antibiotics	Various active ingredients	Product-specific	Substitutable alternatives

The FDA labeling limits use to susceptible infections and states that nitrofurantoin is not indicated for pyelonephritis or other systemic infections because it does not achieve adequate tissue concentrations outside the urinary tract (FDA, 2023).

What is the FDA regulatory status of nitrofurantoin macrocrystalline?

Nitrofurantoin macrocrystalline is an approved small-molecule prescription drug. The Macrodantin reference product is associated with FDA New Drug Application 016791. Multiple abbreviated new drug applications support generic competition.

The product is not a new chemical entity and does not have current FDA regulatory exclusivity. Its market access depends on ANDA approval, bioequivalence, manufacturing compliance, and continuing supply rather than clinical exclusivity.

What are the key FDA labeling restrictions?

The principal regulatory restrictions are:

Use for lower urinary-tract infection caused by susceptible organisms.
No use for pyelonephritis or suspected systemic infection.
Contraindication in patients with significant renal impairment, with contemporary labeling commonly using a creatinine-clearance threshold below 30 mL/min.
Caution in elderly patients and in patients with pulmonary, hepatic, neurologic, or hematologic risk factors.
Risk of acute or chronic pulmonary reactions, hepatotoxicity, peripheral neuropathy, and hemolytic anemia in susceptible patients, including some patients with glucose-6-phosphate dehydrogenase deficiency.

FDA labeling has evolved with renal-function evidence. Older labeling used a creatinine-clearance threshold below 60 mL/min, while more recent practice and labeling generally use a lower threshold. Prescribers and payers therefore assess the current product label and patient-specific renal function rather than relying on historical restrictions.

When does nitrofurantoin macrocrystalline lose exclusivity?

Nitrofurantoin macrocrystalline lost meaningful market exclusivity decades ago. No active composition-of-matter exclusivity, pediatric exclusivity, or modern regulatory exclusivity drives the current market.

Exclusivity category	Current status
New chemical entity exclusivity	Expired
Composition-of-matter patent	Expired or not commercially relevant
Formulation exclusivity	No material current barrier identified
Method-of-use exclusivity	No material current barrier identified
Orphan exclusivity	None
Pediatric exclusivity	None
Reference-product exclusivity	Expired
Generic substitution	Established

The Orange Book is the relevant FDA source for listed patents and exclusivity tied to approved products. Nitrofurantoin macrocrystalline has no commercially significant active Orange Book patent estate comparable to newer branded antibiotics (FDA, 2024a).

What patents protect nitrofurantoin macrocrystalline?

No active patent estate appears to provide meaningful market protection for the basic nitrofurantoin macrocrystalline capsule.

The original chemical and early formulation rights are historical. Any current patent activity would more likely concern:

A specific modified-release formulation.
A manufacturing process.
A capsule composition or excipient system.
A combination product.
A separate delivery technology.

Those rights would not automatically block conventional generic nitrofurantoin macrocrystalline capsules. Generic applicants generally rely on the expired reference-product pathway and must demonstrate pharmaceutical equivalence and bioequivalence.

How strong is the patent estate?

The patent estate is weak from a commercial-exclusivity perspective.

Patent-strength factor	Assessment
Basic active ingredient	Very weak; legacy compound
Standard macrocrystalline capsule	Very weak
Brand formulation differentiation	Limited
Manufacturing complexity	Low to moderate
Regulatory substitution barrier	Low
Litigation leverage	Low
Generic entry barrier	Low

Manufacturing know-how can still affect supply continuity, impurity control, particle-size specifications, and cost. Those factors are operational barriers, not durable exclusionary rights.

What is the Orange Book status of nitrofurantoin macrocrystalline?

The Macrodantin reference product is listed in FDA drug databases, but the product does not have an Orange Book profile that supports durable patent-based exclusivity. Generic versions are approved through ANDAs and compete on price, wholesaler availability, formulary status, and supply reliability.

No active patent listing is known to create a material barrier to ANDA approval for conventional nitrofurantoin macrocrystalline capsules. The absence of an active listed patent reduces the strategic value of Paragraph IV litigation.

FDA’s Orange Book records should be used for product-specific confirmation because listed patents, marketing status, and applicant information can change over time (FDA, 2024a).

Which companies are challenging nitrofurantoin macrocrystalline?

The market has already undergone generic entry. The relevant competitive set consists primarily of generic pharmaceutical manufacturers rather than current Paragraph IV challengers.

Companies that have marketed nitrofurantoin products in the U.S. generic market have included large and mid-sized ANDA suppliers such as Actavis/Teva, Amneal, Hikma, Mylan/Viatris, Rising Pharmaceuticals, and other approved applicants. The exact active supplier group varies by dosage strength, package configuration, and time period.

A current Paragraph IV dispute is not a central market issue for standard nitrofurantoin macrocrystalline. Any litigation involving a particular manufacturer would more likely concern ANDA certification, manufacturing quality, supply contracts, or a differentiated formulation rather than protection of the basic active ingredient.

What formulation patents protect nitrofurantoin macrocrystalline?

Conventional macrocrystalline capsules have limited formulation differentiation. The principal technical variables are particle size, dissolution, excipients, capsule fill, stability, and manufacturing controls.

The more commercially differentiated formulation is nitrofurantoin monohydrate/macrocrystals, historically associated with Macrobid. That product uses a different physical form and dosing schedule. Its historical formulation and product-specific rights do not restore exclusivity to conventional macrocrystalline capsules.

Formulation issue	Effect on competition
Particle-size distribution	Can affect dissolution and bioequivalence
Capsule excipients	Usually reproducible through ANDA development
Four-times-daily dosing	Commercial disadvantage versus twice-daily products
Monohydrate component	Supports differentiated Macrobid formulation
Modified release	Could support separate claims if valid and enforceable
Packaging and stability	Relevant to quality, not usually exclusivity

What method-of-use patents cover nitrofurantoin macrocrystalline?

No current method-of-use patent is known to create material exclusivity for standard treatment of uncomplicated cystitis. The core use is longstanding and described in FDA labeling and clinical guidelines.

The Infectious Diseases Society of America identifies nitrofurantoin as a first-line option for acute uncomplicated cystitis, generally administered for five days in the formulation and regimen evaluated in contemporary practice (Gupta et al., 2011). Macrocrystalline nitrofurantoin remains clinically relevant, but its four-times-daily regimen can make it less attractive than twice-daily formulations.

Preventive use in recurrent urinary-tract infection is clinically recognized in selected patients, but it does not create meaningful commercial exclusivity. Long-term use raises monitoring concerns, particularly pulmonary and hepatic toxicity.

How large is the nitrofurantoin macrocrystalline market?

Public financial reporting generally does not separate nitrofurantoin macrocrystalline revenue from other nitrofurantoin products. Manufacturers typically report generic portfolios in aggregate, and government utilization data may combine strengths, formulations, and suppliers.

The addressable market is supported by the high incidence of urinary-tract infection. U.S. outpatient antibiotic-prescribing data consistently identify urinary-tract infections as a major antibiotic-use category, while nitrofurantoin is favored when the infection is limited to the bladder and susceptibility is appropriate (CDC, 2022).

The commercial market is constrained by:

Generic price compression.
Substitution by Macrobid-equivalent products.
Availability of fosfomycin and trimethoprim-sulfamethoxazole.
Renal-function limitations.
Restricted use in pyelonephritis and complicated systemic infection.
Low opportunity for premium pricing.

The product is therefore a volume-driven market with low revenue per prescription.

What is the financial trajectory for nitrofurantoin macrocrystalline?

The financial trajectory is mature and largely stable, with limited pricing power.

Financial driver	Directional effect
UTI prescription volume	Supports demand
Guideline preference for uncomplicated cystitis	Supports demand
Generic competition	Reduces price
Macrobid substitution	Limits macrocrystalline growth
Antibiotic resistance to alternatives	Can support use
Renal impairment restrictions	Limits eligible patients
Supply interruptions	Can temporarily improve pricing
Manufacturing concentration	Can create short-term volatility
New product innovation	Limited

Revenue is likely to remain low and fragmented at the manufacturer level. A supplier with an approved product can generate recurring revenue, but the product is unlikely to become a major growth asset without a differentiated formulation, combination product, new delivery system, or supply advantage.

The most plausible commercial trajectory is:

Stable underlying prescription demand.
Continued unit-volume resilience.
Gradual or episodic price erosion.
Occasional price increases during shortages or supplier exits.
No durable expansion from patent protection.
Increasing competition from twice-daily nitrofurantoin products.

What generic entry risks exist?

Generic-entry risk is already realized for conventional nitrofurantoin macrocrystalline capsules. The remaining risks concern individual products and suppliers.

Price risk

Multiple ANDA holders can reduce reimbursement and wholesaler pricing. Pharmacy benefit managers and hospital systems generally treat the product as substitutable.

Supply risk

Low-margin antibiotics are vulnerable to manufacturer exits, raw-material disruptions, contract-manufacturing failures, and quality-related recalls. A concentrated supplier base can produce temporary shortages even when the product has no patent barrier.

Regulatory risk

FDA inspections, manufacturing deviations, dissolution failures, impurity findings, and labeling noncompliance can interrupt sales. Because the product is mature, quality and supply execution often matter more than intellectual-property strategy.

Clinical-positioning risk

Use is limited when renal function is poor, infection is suspected above the bladder, or the pathogen is resistant. These limitations protect appropriate prescribing but cap market expansion.

How does nitrofurantoin macrocrystalline compare with Macrobid?

Macrobid-equivalent products generally have the stronger commercial position because the twice-daily regimen improves convenience. Macrocrystalline capsules retain a role where prescribers, pharmacies, formularies, or patients favor the lower-cost formulation.

Attribute	Nitrofurantoin macrocrystalline	Nitrofurantoin monohydrate/macrocrystals
Common brand association	Macrodantin	Macrobid
Dosing frequency	Usually four times daily	Usually twice daily
Generic availability	Broad	Broad
Patient convenience	Lower	Higher
Patent leverage	Minimal	Historical formulation differentiation
Primary use	Lower UTI	Lower UTI
Systemic infection utility	Inadequate	Inadequate
Commercial outlook	Mature, low-price	Larger practical market position

The two products compete clinically but are not interchangeable on a simple milligram-for-milligram basis. FDA-approved labeling and pharmacy substitution rules govern interchangeability.

What licensing deals affect nitrofurantoin macrocrystalline?

No major current licensing transaction is central to the standard nitrofurantoin macrocrystalline market. The product is generally supplied through direct generic manufacturing, contract manufacturing, distribution agreements, or portfolio acquisitions.

Commercial transactions involving nitrofurantoin are more likely to transfer:

An ANDA.
A legacy brand.
A generic product portfolio.
Manufacturing rights.
Distribution rights.
A supply contract.

These arrangements can change market share without changing patent ownership. For investors, the key diligence points are approved strengths, active marketing status, manufacturing site, supplier concentration, back orders, and net price by channel.

What patent litigation and settlement agreements affect the product?

No major current patent litigation or reverse-payment settlement is central to standard nitrofurantoin macrocrystalline capsules. The absence of meaningful Orange Book patents reduces the basis for Hatch-Waxman litigation.

If a future modified-release or combination nitrofurantoin product were introduced, litigation could focus on formulation claims, dissolution profiles, bioequivalence, or manufacturing methods. That would be a separate product-specific issue and would not materially alter the economics of established macrocrystalline capsules.

What generic launch scenarios are most likely?

The base case is continued generic supply with low pricing and modest volume growth tied to UTI incidence.

Scenario	Probability profile	Market effect
Base case	Continued multi-source generic supply	Stable volume, low pricing
Supplier exit	One or more manufacturers discontinue	Temporary shortage and price volatility
New low-cost entrant	Additional ANDA supplier launches	Greater price compression
Quality disruption	Recall or FDA action	Short-term share transfer
Formulation innovation	New dosing or delivery technology	Possible premium segment
Guideline shift	Reduced use in selected renal patients	Moderate demand pressure

A generic launch can gain share rapidly if it has reliable supply, competitive acquisition cost, and broad wholesaler access. The product’s low differentiation means commercial execution matters more than branding.

What is the geographic coverage of nitrofurantoin macrocrystalline?

The product is widely available in the United States and has international equivalents. Regulatory names, capsule strengths, approved indications, and dosing schedules vary by jurisdiction.

The commercial opportunity is strongest in markets with:

High outpatient UTI treatment volume.
Established generic substitution.
Reliable access to nitrofurantoin active pharmaceutical ingredient.
Guideline support for nitrofurantoin.
Routine susceptibility testing.
Reimbursement for low-cost oral antibiotics.

International demand can be affected by local antibiotic stewardship policies, renal-function guidance, procurement tenders, and availability of alternative formulations.

What manufacturing and intellectual-property barriers remain?

The remaining barriers are operational rather than patent-based. Manufacturers must control nitrofurantoin particle size, blend uniformity, capsule content, dissolution, stability, and impurity profiles. Bioequivalence can be sensitive to formulation and manufacturing variables.

The active pharmaceutical ingredient is established and generally available from multiple sources, but supplier qualification and regulatory compliance still affect continuity. A company with a reliable API source and compliant manufacturing network can outperform competitors despite having no patent advantage.

Key takeaways

Nitrofurantoin macrocrystalline is a mature generic antibacterial for lower urinary-tract infection.
Basic composition, formulation, and method-of-use exclusivity have expired or are commercially irrelevant.
No active Orange Book patent estate is known to create a material barrier to conventional generic entry.
Paragraph IV litigation and settlement activity are not central to the product’s current market.
Demand is supported by guideline preference for uncomplicated cystitis and resistance to some alternative antibiotics.
Revenue is constrained by low generic pricing, broad substitution, and competition from Macrobid-equivalent products.
The principal commercial risks are price compression, supplier exits, FDA manufacturing actions, and shortages.
The product’s strongest competitive advantages are low cost, established clinical use, and familiar regulatory status.
The product’s main weaknesses are four-times-daily dosing, renal restrictions, limited indication, and lack of patent differentiation.
Future upside would require a differentiated formulation, improved dosing convenience, supply consolidation, or a strategic portfolio transaction.

FAQs about nitrofurantoin macrocrystalline

Is nitrofurantoin macrocrystalline still commercially relevant?

Yes. It remains a low-cost treatment option for susceptible uncomplicated lower urinary-tract infections, although twice-daily monohydrate/macrocrystals products have stronger convenience positioning.

Does nitrofurantoin macrocrystalline have active patents?

No commercially significant active patent protection is associated with the conventional macrocrystalline capsule. Product-specific patents could apply to a distinct delivery system or modified formulation.

Can generic manufacturers launch nitrofurantoin macrocrystalline without Paragraph IV litigation?

Generally, yes, when no active Orange Book patent blocks the reference product. ANDA applicants still must satisfy FDA requirements for pharmaceutical equivalence, bioequivalence, manufacturing quality, and labeling.

Why can an old generic antibiotic experience price increases?

Manufacturers may exit low-margin markets, API supply may be disrupted, or an FDA quality action may remove a supplier. Reduced competition can produce temporary price increases even without patent protection.

Is nitrofurantoin macrocrystalline interchangeable with Macrobid?

The products contain related nitrofurantoin formulations but have different dosage designs. Substitution depends on FDA-approved product equivalence, state pharmacy law, and the applicable prescription and labeling.

References

Centers for Disease Control and Prevention. (2022). Outpatient antibiotic prescriptions: Urinary tract infections and antibiotic use. U.S. Department of Health and Human Services.

Gupta, K., Hooton, T. M., Naber, K. G., Wullt, B., Colgan, R., Miller, L. G., Moran, G. J., Nicolle, L. E., Raz, R., Schaeffer, A. J., & Soper, D. E. (2011). International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women. Clinical Infectious Diseases, 52(5), e103-e120. https://doi.org/10.1093/cid/ciq257

U.S. Food and Drug Administration. (2023). Macrodantin: Nitrofurantoin macrocrystals capsule prescribing information. FDA-approved labeling.

U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

U.S. Food and Drug Administration. (2024b). Drugs@FDA: FDA-approved drugs database. Center for Drug Evaluation and Research.

US Patents:	0
Applicants:	1
NDAs:	2
Raw Ingredient (Bulk) Api Vendors:	94
Clinical Trials:	3
Patent Applications:	5,623
Drug Prices:	Drug price information for NITROFURANTOIN MACROCRYSTALLINE
DailyMed Link:	NITROFURANTOIN MACROCRYSTALLINE at DailyMed

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