SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE Drug Patent Profile
When do Spironolactone And Hydrochlorothiazide patents expire, and what generic alternatives are available?
Spironolactone And Hydrochlorothiazide is a drug marketed by Ascot, Chartwell Rx, Mutual Pharm, Mylan, Purepac Pharm, Rubicon Research, Sun Pharm Industries, Superpharm, and Watson Labs. and is included in nine NDAs.
The generic ingredient in SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE is hydrochlorothiazide; spironolactone. There is one drug master file entry for this compound. Seven suppliers are listed for this compound. Additional details are available on the hydrochlorothiazide; spironolactone profile page.
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Summary for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
| US Patents: | 0 |
| Applicants: | 9 |
| NDAs: | 9 |
| Finished Product Suppliers / Packagers: | 6 |
| Raw Ingredient (Bulk) Api Vendors: | 1 |
| Clinical Trials: | 11 |
| Patent Applications: | 63 |
| What excipients (inactive ingredients) are in SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE? | SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE excipients list |
| DailyMed Link: | SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE at DailyMed |
Recent Clinical Trials for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Identify potential brand extensions & 505(b)(2) entrants
| Sponsor | Phase |
|---|---|
| Dutch Kidney Foundation | NA |
| Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | NA |
| Pfizer | PHASE1 |
See all SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE clinical trials
Pharmacology for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
| Drug Class | Aldosterone Antagonist Thiazide Diuretic |
| Mechanism of Action | Aldosterone Antagonists |
| Physiological Effect | Increased Diuresis |
US Patents and Regulatory Information for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Spironolactone and Hydrochlorothiazide Market Dynamics, Patent Status, and Financial Trajectory
Spironolactone and hydrochlorothiazide is a mature, low-cost fixed-dose generic combination marketed primarily for hypertension and edema. The product has no meaningful branded exclusivity, no biologic or biosimilar exposure, and limited patent-driven launch risk. Commercial performance depends on prescription volume, generic contracting, manufacturing reliability, and clinical substitution rather than on price increases or new indications.
The combination remains clinically relevant, but its market position is constrained by competition from single-agent spironolactone, thiazide and thiazide-like diuretics, mineralocorticoid receptor antagonists, and multidrug antihypertensive regimens. Public filings do not provide a reliable product-level revenue series for spironolactone/hydrochlorothiazide. Its financial profile is best characterized as a high-volume, low-margin generic product.
What is spironolactone and hydrochlorothiazide used for?
The combination pairs a potassium-sparing diuretic with a thiazide diuretic. Spironolactone blocks aldosterone-mediated sodium retention and potassium excretion. Hydrochlorothiazide increases urinary sodium and water excretion while increasing potassium loss.
The combination is used when diuresis is required and potassium depletion from hydrochlorothiazide needs to be reduced. FDA labeling identifies hypertension and edema associated with congestive heart failure, hepatic cirrhosis, and nephrotic syndrome as principal uses. It also has utility in patients with suspected or confirmed hyperaldosteronism, although treatment may involve spironolactone alone depending on clinical circumstances. [1]
Available strengths and dosage forms
The reference combination is an oral tablet. Common strengths include:
| Strength | Spironolactone | Hydrochlorothiazide |
|---|---|---|
| 25/25 mg | 25 mg | 25 mg |
| 25/50 mg | 25 mg | 50 mg |
| 50/50 mg | 50 mg | 50 mg |
Availability can vary by manufacturer, National Drug Code, and supply status. The product is generally dispensed as a prescription tablet rather than an extended-release, injectable, transdermal, or combination-device product.
What is the FDA regulatory status of spironolactone and hydrochlorothiazide?
The product is an FDA-approved prescription drug available through generic abbreviated new drug applications. The branded reference product is Aldactazide, historically associated with Searle and later Pfizer corporate ownership. FDA records identify the reference product under NDA 012151. [2]
The regulatory profile is mature:
| Regulatory element | Status |
|---|---|
| FDA pathway | Original NDA plus multiple generic ANDAs |
| Product type | Small-molecule oral tablet |
| Reference product | Aldactazide |
| Biologic status | Not applicable |
| Biosimilar exposure | None |
| Pediatric exclusivity | No current market significance |
| Orphan exclusivity | None identified as a commercial driver |
| OTC status | Prescription only |
| Approval basis for generics | Pharmaceutical equivalence and bioequivalence |
FDA-approved generic versions must generally demonstrate that they contain the same active ingredients, strength, dosage form, route of administration, and therapeutic equivalence characteristics as the reference product. [3]
What patents protect spironolactone and hydrochlorothiazide?
The original composition and use patents for spironolactone and hydrochlorothiazide expired many years ago. The combination does not have a meaningful active patent estate that would support branded exclusivity or delay ordinary generic competition.
The principal patent conclusions are:
- No commercially material primary patent barrier remains for the basic combination.
- No current patent protection is expected to prevent generic substitution.
- Any historical patents covering the active ingredients, composition, or methods of treatment are long expired.
- Manufacturing-process patents, if held by individual suppliers, would generally affect a specific process rather than block the entire market.
- Device, formulation, or delivery-system patents are not central to the conventional immediate-release tablet market.
How many patents cover the combination today?
The relevant commercial answer is that no active patent family appears to control the conventional spironolactone/hydrochlorothiazide tablet market. Patent databases may show expired historical records, continuation filings, or unrelated patents involving spironolactone, hydrochlorothiazide, or other formulations. Those records should not be treated as barriers to generic entry without confirming claim scope, expiration, and enforceability.
The Orange Book remains the controlling source for FDA-listed patents associated with approved products. [4]
What is the Orange Book status of spironolactone and hydrochlorothiazide?
The product is an established reference-listed drug with generic competition. Its Orange Book position is commercially mature rather than exclusivity-driven.
A standard Orange Book review should distinguish:
- The reference NDA for Aldactazide.
- Therapeutically equivalent ANDA products.
- Any current patent listings tied to the reference NDA.
- Whether a listed patent applies to all strengths or only a specific formulation.
- Whether the reference product is currently marketed, discontinued, or retained for regulatory reference purposes.
For this combination, the market does not depend on an active Orange Book patent dispute. Generic applicants entered after the core exclusivity period expired, and ordinary ANDA competition is established.
When did spironolactone and hydrochlorothiazide lose exclusivity?
The combination lost practical exclusivity decades ago. Both active ingredients are longstanding generic medicines, and the fixed-dose combination has been commercially available for many years.
| Exclusivity category | Commercial status |
|---|---|
| New chemical entity exclusivity | Expired |
| Original product patent protection | Expired |
| Fixed-combination exclusivity | Expired |
| Regulatory exclusivity | No current barrier |
| Generic entry | Established |
| Current protection | Brand, manufacturing, and contracting advantages only |
There is no credible basis for a future patent-cliff event comparable to a recently launched specialty drug. The commercial trajectory is therefore gradual and volume-driven.
Are there Paragraph IV challenges for spironolactone and hydrochlorothiazide?
Paragraph IV litigation is not a central market issue for this combination. A Paragraph IV certification challenges the validity, enforceability, or infringement of an Orange Book-listed patent. That mechanism is most relevant when an approved product still has listed patents that can delay ANDA approval or trigger patent litigation.
For spironolactone/hydrochlorothiazide:
- Generic entry is already established.
- The core patents are expired.
- The product has no commercially important pending patent cliff.
- Any isolated Paragraph IV filing would likely involve a particular formulation, manufacturer, or listed patent rather than the basic market.
No major, market-defining Paragraph IV settlement or litigation event is associated with the conventional combination product.
What formulations are protected by patents?
The conventional immediate-release tablet has little formulation-based differentiation. Commercially relevant formulation categories include:
Immediate-release tablets
These are the dominant products and are supplied by multiple generic manufacturers. Their formulation economics are based on manufacturing scale and procurement contracts, not patent protection.
Alternative spironolactone formulations
Standalone spironolactone products include tablets and, in some markets, compounded liquid preparations. These products compete directly with the fixed combination when clinicians want to adjust spironolactone without increasing hydrochlorothiazide exposure.
Hydrochlorothiazide combinations
Hydrochlorothiazide is available in numerous fixed-dose combinations with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, and other antihypertensive agents. These competing products reduce the need for spironolactone/hydrochlorothiazide when blood-pressure control is the primary objective.
No major extended-release or proprietary delivery platform defines the commercial market for the two-drug combination.
How strong is the patent estate for spironolactone and hydrochlorothiazide?
The patent estate is weak from a commercial defense perspective.
| Patent-strength factor | Assessment |
|---|---|
| Composition-of-matter protection | Expired |
| Fixed-combination protection | Expired |
| Formulation protection | Limited or nonmaterial for standard tablets |
| Method-of-use protection | No meaningful blocking position for core uses |
| Manufacturing protection | Potentially supplier-specific |
| Generic substitution barrier | Low |
| Litigation leverage | Low |
| Ability to support premium pricing | Minimal |
The strongest remaining intellectual-property opportunities would be outside the standard tablet: differentiated dosing systems, new indications, proprietary formulations, or combination products with clinically meaningful benefits. None is central to the existing market.
What is driving market demand for the combination?
Demand is supported by several durable clinical uses:
- Hypertension requiring diuretic therapy.
- Edema associated with heart failure.
- Cirrhotic ascites and other fluid-retention states.
- Nephrotic syndrome-related edema.
- Suspected or confirmed hyperaldosteronism.
- Patients requiring potassium-sparing treatment alongside a thiazide.
Spironolactone has gained clinical importance in resistant hypertension and heart failure. The 2018 American Heart Association scientific statement identifies mineralocorticoid receptor antagonists as effective options for resistant hypertension, particularly when primary aldosteronism or excess aldosterone activity is relevant. [5]
Demand is limited by safety and treatment flexibility. Clinicians may prefer separate tablets because they can:
- Adjust spironolactone independently.
- Stop hydrochlorothiazide while maintaining aldosterone blockade.
- Manage potassium and renal-function changes more precisely.
- Avoid unnecessary thiazide exposure.
- Select a thiazide-like agent such as chlorthalidone or indapamide.
The combination is therefore useful but less strategically important than standalone spironolactone and broader antihypertensive combination markets.
What safety issues affect commercial demand?
The principal safety concern is hyperkalemia caused by spironolactone, particularly in patients with renal impairment or in patients receiving angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or other potassium-elevating medicines. Hydrochlorothiazide can cause hyponatremia, hypokalemia, hypomagnesemia, hyperuricemia, and glucose or lipid abnormalities. [1]
Other commercial constraints include:
- Renal-function monitoring.
- Electrolyte monitoring.
- Gynecomastia and menstrual effects associated with spironolactone.
- Dehydration and hypotension.
- Photosensitivity and sulfonamide-related labeling considerations for hydrochlorothiazide.
- Reduced flexibility compared with separate-agent therapy.
These risks do not eliminate demand, but they discourage indiscriminate use and reduce the value of a fixed-dose product for patients requiring frequent dose adjustment.
How does spironolactone/hydrochlorothiazide compare with competing drugs?
| Product or class | Main competitive advantage | Effect on the combination |
|---|---|---|
| Spironolactone alone | Flexible dosing and strong aldosterone-focused use | Directly substitutes when HCTZ is unnecessary |
| Hydrochlorothiazide alone | Low price and broad familiarity | Substitutes when potassium-sparing therapy is not needed |
| Chlorthalidone | Longer duration and strong hypertension evidence | Takes share in blood-pressure-focused treatment |
| Indapamide | Thiazide-like efficacy with different dosing profile | Competes in hypertension |
| Eplerenone | More selective mineralocorticoid receptor antagonism | Competes where spironolactone adverse effects are problematic |
| ACE inhibitor/HCTZ combinations | Established hypertension use | Competes for fixed-dose adherence |
| ARB/HCTZ combinations | Broad use and generally favorable tolerability | Competes for fixed-dose hypertension prescriptions |
| Loop diuretics | Stronger fluid removal | Used in more advanced edema and heart failure |
| SGLT2 inhibitors | Cardiorenal benefits beyond diuresis | Can reduce reliance on traditional diuretic strategies in some patients |
The combination is most defensible where both potassium preservation and thiazide diuresis are clinically desirable. It is less competitive when the treatment objective is only blood-pressure reduction or when renal function makes the fixed dose difficult to manage.
What is the financial trajectory of spironolactone and hydrochlorothiazide?
The financial trajectory is stable to declining on a per-unit basis, with demand sustained by chronic use. The product is unlikely to generate material branded-drug revenue without a new formulation, new indication, or proprietary delivery system.
Revenue exposure
Public company filings generally report generic portfolios in aggregate rather than disclosing revenue for spironolactone/hydrochlorothiazide specifically. A precise product-level revenue figure cannot be derived from standard annual reports.
The commercial profile is nevertheless clear:
| Financial factor | Expected effect |
|---|---|
| Unit demand | Stable, supported by chronic cardiovascular use |
| Net price | Low and pressured by generic competition |
| Gross margin | Variable; often constrained by tendering and wholesaler purchasing |
| Revenue growth | Limited without volume gains or supply disruption |
| Market concentration | Potentially high at individual manufacturing sites |
| Brand premium | Minimal |
| Litigation value | Minimal |
| Licensing value | Low for the basic product |
| Supply-chain value | Material if competitors experience shortages |
The largest profit opportunity is not patent exclusivity. It is reliable supply, low-cost manufacturing, and participation in pharmacy-benefit and institutional contracts.
Generic pricing dynamics
Pricing is shaped by:
- Number of approved suppliers.
- Available dosage strengths.
- Wholesaler and pharmacy purchasing agreements.
- Government and institutional tenders.
- Active pharmaceutical ingredient costs.
- Manufacturing-site compliance.
- Temporary shortages or product discontinuations.
- Reimbursement rates and generic dispensing fees.
When several manufacturers compete, prices tend to compress. A supplier can improve economics if it maintains dependable availability while competitors face manufacturing interruptions. That advantage is usually temporary and operational rather than patent-based.
Which companies are challenging or supplying the market?
The market is supplied by multiple generic manufacturers and labelers. The exact supplier set changes by strength, National Drug Code, manufacturing status, and commercial contracting. FDA’s Drugs@FDA, Orange Book, and National Drug Code Directory are the appropriate sources for current product-level verification. [2][4][6]
Typical market participants in generic diuretics include large diversified generic companies, specialty generic manufacturers, contract manufacturers, and private-label distributors. No single company has a durable monopoly over the combination.
Commercial competition is more likely to occur through:
- Lowest-cost supply bids.
- Preferred wholesaler contracts.
- Hospital and long-term-care tenders.
- Service levels and fill rates.
- Manufacturing quality records.
- Ability to maintain multiple strengths.
What manufacturing and intellectual-property barriers exist?
Manufacturing barriers are moderate operationally and low legally.
The active ingredients are established small molecules with mature synthetic routes. The main barriers are:
- Consistent control of impurities and degradation products.
- Tablet uniformity and dissolution performance.
- Reliable supply of active pharmaceutical ingredients.
- FDA-compliant manufacturing sites.
- Validation of bioequivalence for each strength.
- Packaging and labeling compliance.
- Stability data across commercial shelf life.
A manufacturing problem at one supplier can cause temporary market tightness, but it does not create durable exclusivity. Competitors with approved ANDAs can generally increase supply if capacity is available.
What generic launch scenarios exist?
The basic generic-launch scenario has already occurred. Future market events are more likely to involve supplier entry, exit, or capacity changes.
Base case
Multiple generic suppliers remain active. Prices stay low, prescription volume remains broadly stable, and revenue declines gradually with reimbursement pressure.
Upside case
A competitor exits or experiences a manufacturing disruption. Remaining suppliers gain temporary volume and improve realized pricing.
Downside case
Use shifts toward standalone spironolactone, chlorthalidone, indapamide, or newer heart-failure therapies. Fixed-dose combination volume declines, while generic price erosion continues.
Strategic case
A manufacturer introduces a clinically differentiated formulation or obtains a new indication. This would be outside the economics of the current immediate-release tablet and would require new clinical, regulatory, and commercial investment.
What licensing deals affect the product?
No major current licensing transaction is necessary to commercialize the standard generic combination. The product is based on long-expired small-molecule rights and is generally supplied through internal generic portfolios, contract manufacturing, or private-label arrangements.
Any licensing value would likely arise from:
- A proprietary formulation.
- A regional commercialization agreement.
- Manufacturing rights for a regulated market.
- A differentiated combination product.
- A specialty indication supported by new clinical data.
For the conventional tablet, licensing economics are limited because multiple equivalent suppliers are available.
What patent litigation or settlement agreements affect the market?
No major active patent litigation or settlement agreement defines the conventional spironolactone/hydrochlorothiazide market. The absence of a meaningful patent dispute is consistent with the product’s age, generic penetration, and expired core exclusivity.
Litigation risk is more likely to involve:
- Product liability.
- Manufacturing-quality claims.
- Antitrust or pricing conduct.
- Contract disputes.
- Regulatory enforcement.
- Supply agreements.
Those issues may affect individual companies but do not create marketwide exclusivity.
Key Takeaways
- Spironolactone/hydrochlorothiazide is a mature generic fixed-dose tablet marketed for hypertension and edema.
- Aldactazide is the historical reference product; generic competition is established.
- Core composition, combination, and use patents are expired or commercially nonblocking.
- The product has no meaningful current Orange Book exclusivity advantage.
- Paragraph IV litigation is not a major market driver.
- Revenue is low-margin and generally undisclosed at the individual-product level.
- Demand is supported by chronic cardiovascular and edema indications.
- Standalone spironolactone, thiazide-like diuretics, and ACE inhibitor/ARB combinations are the main competitive pressures.
- Supply reliability, manufacturing quality, and contracting are more important than patent protection.
- Long-term financial performance is likely to be stable to declining unless shortages, supplier exits, or a differentiated formulation change the market.
FAQs
Is spironolactone and hydrochlorothiazide still under patent?
The basic fixed-dose combination is not protected by a commercially meaningful active patent estate. Generic competition has been established for many years.
Is Aldactazide still a branded product?
Aldactazide is the historical reference brand for the combination. Market demand is primarily served by generic equivalents, and brand-level pricing power is limited.
Can a generic manufacturer obtain exclusivity for this combination?
A manufacturer could obtain regulatory exclusivity only through a qualifying new regulatory or clinical program. The ordinary immediate-release generic tablet does not carry meaningful new exclusivity.
Why might physicians prescribe separate spironolactone and hydrochlorothiazide tablets?
Separate tablets allow independent adjustment of each drug, which is important when potassium, renal function, blood pressure, or fluid status changes.
Does the combination have biosimilar competition?
No. Spironolactone and hydrochlorothiazide are small-molecule drugs, not biologics. Their competition occurs through generic ANDAs rather than biosimilar applications.
References
-
U.S. Food and Drug Administration. (2015). Aldactazide: Spironolactone and hydrochlorothiazide prescribing information.
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U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/
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U.S. Food and Drug Administration. (n.d.). Generic drug facts. https://www.fda.gov/drugs/generic-drugs
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U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
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Carey, R. M., Calhoun, D. A., Bakris, G. L., Brook, R. D., Daugherty, S. L., Dennison-Himmelfarb, C. R., Egan, B. M., Flack, J. M., Gidding, S. S., Judd, E., Lackland, D. T., Laffer, C. L., Newton-Cheh, C., Smith, S. M., Taler, S. J., Textor, S. C., Turgeon, R. D., & White, W. B. (2018). Resistant hypertension: Detection, evaluation, and management. Hypertension, 72(5), e53-e90. https://doi.org/10.1161/HYP.0000000000000084
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U.S. Food and Drug Administration. (n.d.). National Drug Code Directory. https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory
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