When do the HYDRALAZINE HYDROCHLORIDE W/ HYDROCHLOROTHIAZIDE 25/25 patents expire, and when will generic HYDRALAZINE HYDROCHLORIDE W/ HYDROCHLOROTHIAZIDE 25/25 be available?

Sponsor	Phase
Vanderbilt University Medical Center	Phase 4
National Center for Research Resources (NCRR)	Phase 4
Vanderbilt University	Phase 1

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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
Ivax Pharms	HYDRALAZINE HYDROCHLORIDE W/ HYDROCHLOROTHIAZIDE 25/25	hydralazine hydrochloride; hydrochlorothiazide	CAPSULE;ORAL	088356-001	Apr 10, 1984		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: August 8, 2026

Hydralazine hydrochloride 25 mg/hydrochlorothiazide 25 mg is a mature fixed-dose antihypertensive combination with limited commercial relevance in the U.S. The product combines a direct arterial vasodilator with a thiazide diuretic, but its clinical use has been displaced by newer guideline-preferred regimens and by the availability of the two ingredients as separate low-cost generics. The product has no meaningful biologic or regulatory exclusivity, no apparent active patent barrier, and limited publicly disclosed revenue.

What is hydralazine hydrochloride 25 mg/hydrochlorothiazide 25 mg?

Hydralazine hydrochloride/hydrochlorothiazide 25/25 is an oral fixed-dose combination tablet containing:

Component	Dose	Pharmacologic role
Hydralazine hydrochloride	25 mg	Direct arteriolar vasodilator
Hydrochlorothiazide	25 mg	Thiazide diuretic

Hydralazine reduces peripheral vascular resistance. Hydrochlorothiazide lowers plasma volume and blood pressure through renal sodium and water excretion. The combination was developed for hypertension, particularly when a vasodilator required a diuretic to limit sodium and fluid retention.

The fixed-dose product is associated historically with the brand Apresazide. Hydralazine and hydrochlorothiazide are also available separately in multiple generic dosage forms. FDA labeling for hydralazine identifies hypertension as the primary indication and describes the need for dosage adjustment and combination treatment in some patients. Hydrochlorothiazide labeling covers hypertension and edema-related indications.[1][2]

What is the FDA regulatory status of hydralazine/HCTZ 25/25?

The product is a legacy combination rather than a growth pharmaceutical asset. FDA reference databases identify historical hydralazine/hydrochlorothiazide products, but commercial availability can vary by manufacturer, National Drug Code, and distribution channel.

Regulatory issue	Assessment
FDA pathway	Legacy NDA and/or generic ANDA history
Current commercial status	Limited or discontinued product availability in many U.S. channels
Prescription status	Prescription-only
Biologic status	Not applicable
FDA exclusivity	No meaningful current exclusivity identified
Orange Book relevance	Historical product and therapeutic-equivalence records may remain relevant even when a product is not actively marketed
Biosimilar exposure	None
Generic substitution	Relevant where an approved generic is commercially available

A discontinued listing in the Orange Book does not by itself establish that every related generic product has been withdrawn. FDA distinguishes between approval status, marketing status, and active commercial distribution.[3]

The commercial question is therefore less whether the combination is legally approved and more whether a manufacturer has a viable, continuously supplied product with active wholesaler and pharmacy distribution.

When does hydralazine/HCTZ 25/25 lose exclusivity?

The product’s meaningful exclusivity expired decades ago. Hydralazine and hydrochlorothiazide are long-established small-molecule active ingredients, and the fixed-dose combination is not protected by a current new chemical entity exclusivity period.

No active commercial exclusivity is expected to support pricing power for this product. Any residual protection would be assessed through specific FDA Orange Book records, listed patents, formulation claims, or manufacturing patents associated with a particular approved application. The commercial product does not appear to depend on a live patent estate.

Patent and formulation assessment

IP category	Commercial assessment
Composition of matter	Expired or commercially irrelevant
Fixed-dose combination patent	No apparent active blocking patent
Hydralazine formulation patent	No meaningful current barrier identified
Hydrochlorothiazide formulation patent	No meaningful current barrier identified
Method-of-use patent	No apparent active patent central to the product
Manufacturing patent	Potentially relevant to a particular supplier, but unlikely to block generic entry
Trade secret	Possible at the process level, with limited market impact
Patent term extension	Not a meaningful factor

The product’s competitive position is determined by cost, supply reliability, manufacturing economics, and prescriber demand rather than by patent exclusivity.

How many patents cover hydralazine hydrochloride/hydrochlorothiazide 25/25?

No active patent portfolio appears to control the market for the 25/25 combination. Historical patents may have covered the product, its formulation, or related antihypertensive combinations, but those rights would not normally prevent current generic manufacture.

Orange Book patent listings are tied to specific approved products and applications. A patent listed for a historical reference product does not automatically apply to every generic version. Patent risk must be evaluated at the ANDA and product level, including any applicable paragraph IV certification.[3][4]

Are there Paragraph IV challenges for hydralazine/HCTZ 25/25?

There is no established current Paragraph IV dispute that appears to affect the commercial market for hydralazine hydrochloride/hydrochlorothiazide 25/25.

Paragraph IV litigation is generally more relevant when:

A reference product has active Orange Book-listed patents.
A generic applicant seeks approval before patent expiration.
The product has commercially meaningful branded sales.
The expected generic opportunity justifies litigation costs.

Those conditions do not fit this legacy combination. A new generic applicant would more likely face technical, bioequivalence, manufacturing, or supply-chain issues than a high-value patent challenge.

What formulations are protected by hydralazine/HCTZ patents?

The 25/25 tablet does not appear to have a commercially important protected formulation. Potential technical distinctions could include:

Immediate-release tablets
Tablet hardness and dissolution profile
Excipients
Packaging and stability controls
Manufacturing process parameters
Uniformity of hydralazine and hydrochlorothiazide content

These attributes can affect ANDA approval and product quality but do not create durable market exclusivity unless protected by a valid, enforceable patent. For a low-volume generic combination, formulation differences are more likely to affect manufacturing cost and regulatory compliance than pricing.

What is the clinical demand for hydralazine/HCTZ 25/25?

Demand is structurally narrow. Hydralazine is not a typical first-line hypertension treatment because of dosing frequency, reflex tachycardia, fluid retention, and adverse effects such as headache, palpitations, lupus-like syndrome, and immune-mediated complications. Hydrochlorothiazide remains widely used, but it is usually prescribed as a standalone product or in combinations with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or calcium-channel blocker.

Hydralazine retains clinical relevance in selected settings:

Resistant hypertension
Severe hypertension requiring an arterial vasodilator
Pregnancy-related hypertension in selected hospital settings
Heart failure regimens when combined with isosorbide dinitrate
Patients who cannot use preferred antihypertensive classes

The fixed 25/25 presentation has a further limitation: hydralazine and hydrochlorothiazide have different dosing patterns. Hydralazine may require multiple daily doses, while hydrochlorothiazide is often taken once daily. A fixed-dose tablet can reduce flexibility in titrating either ingredient.

How does hydralazine/HCTZ 25/25 compare with competing antihypertensive products?

Product class	Typical commercial position	Competitive advantage over hydralazine/HCTZ
ACE inhibitor/thiazide	Established generic market	Guideline familiarity and once-daily dosing
ARB/thiazide	Large generic market	Better tolerability for many patients
Calcium-channel blocker/thiazide	Limited but established	More flexible treatment selection
Beta-blocker/thiazide	Mature niche	Broader historical use in selected patients
Hydralazine alone	Small generic market	Independent dose adjustment
Hydrochlorothiazide alone	Broad generic market	Low cost and dosing flexibility
Hydralazine/isosorbide dinitrate	Heart-failure niche	Evidence-based use in selected patients
Modern single-pill combinations	Stronger commercial demand	Simplified dosing and adherence benefits

The main substitute is not another hydralazine combination. It is separate generic therapy or a different single-pill antihypertensive combination with stronger prescribing support.

What are the market dynamics for hydralazine/HCTZ 25/25?

The market has four defining characteristics.

Low unit value

Both active ingredients are inexpensive generic chemicals. The finished tablet has limited ability to support premium pricing. Pharmacy reimbursement is likely to be governed by generic maximum allowable cost, payer contracts, and wholesaler purchasing terms.

Low and declining demand

Hydrochlorothiazide demand remains substantial, but that demand does not translate into equivalent demand for the fixed combination. Hydralazine use is concentrated in selected clinical situations, limiting the addressable patient population.

Supplier concentration risk

A small product category may support only a few active manufacturers. If one supplier exits, the market can experience temporary shortages even when the active ingredients are widely available in other dosage forms. FDA drug-shortage data should be reviewed separately from approval records because approval does not guarantee continuous supply.[5]

Distribution friction

Retail pharmacies may not routinely stock a low-volume combination product. Hospitals and specialty wholesalers may obtain it through direct ordering or alternate suppliers. This creates a commercial disadvantage against separately prescribed tablets that have broader distribution.

What is the financial trajectory of hydralazine/HCTZ 25/25?

The financial trajectory is best characterized as mature, low-revenue, and structurally declining or flat at a niche level.

Financial driver	Expected effect
Brand-to-generic substitution	Reduces price and branded revenue
Low ingredient cost	Supports manufacturing, but limits revenue per tablet
Reduced prescribing	Lowers volume
Separate generic alternatives	Compresses fixed-dose demand
Limited patent protection	Prevents premium pricing
Small supplier base	Can create temporary volume spikes during shortages
Pharmacy reimbursement pressure	Reduces gross margin
Manufacturing discontinuation	Can remove revenue without materially changing clinical demand

Public company filings generally do not report revenue for this specific 25/25 combination. Sales are usually aggregated within generic pharmaceuticals, hospital products, or broad cardiovascular portfolios. No defensible product-level revenue series should therefore be inferred from total company cardiovascular sales.

Revenue exposure

For a diversified generic manufacturer, the combination is unlikely to represent material revenue exposure. Its strategic value would more likely arise from:

Filling a portfolio gap
Supporting a broad hypertension catalog
Supplying institutional customers
Capturing temporary demand during competitor shortages
Using existing tablet manufacturing capacity

For a specialist generic company, the product could contribute incremental revenue, but only with reliable supply, low manufacturing cost, and sufficient pharmacy or institutional contracts. The combination is unlikely to support a dedicated commercial infrastructure.

What generic launch scenarios exist for hydralazine/HCTZ 25/25?

Scenario 1: Continued niche supply

One or more suppliers maintain the product for institutional and prescription demand. Volume remains low, with limited price appreciation and periodic wholesaler inventory constraints.

Scenario 2: Supplier exit

A manufacturer discontinues the product because of low volume, low reimbursement, or manufacturing complexity. Patients shift to separate hydralazine and hydrochlorothiazide tablets. Clinical substitution is straightforward, but pharmacy availability may become less predictable.

Scenario 3: New generic entry

A new ANDA applicant enters after demonstrating bioequivalence and securing commercial distribution. Entry would probably increase supply and reduce price rather than create a sustained market expansion.

Scenario 4: Shortage-driven repricing

If active suppliers encounter quality or capacity problems, short-term prices may increase. This would be a supply event, not a change in the product’s long-term demand profile.

Scenario 5: Formulation withdrawal

If the fixed-dose tablet is no longer commercially viable, separate-component prescribing becomes the durable replacement. This is the most commercially plausible long-term substitution pathway.

What patent litigation affects hydralazine/HCTZ 25/25?

No material current patent litigation is publicly associated with the legacy 25/25 combination. The absence of litigation is consistent with the product’s limited sales base, long-expired exclusivity, and lack of a high-value branded reference franchise.

Litigation risk could arise from a new formulation, a modified-release product, or a manufacturing process patent. Such claims would concern the specific new product rather than the traditional immediate-release 25/25 tablet.

What licensing deals involve hydralazine/HCTZ 25/25?

No significant current licensing transaction is publicly associated with this combination. A licensing deal would have limited economic rationale unless it involved:

A broader cardiovascular generic portfolio
A regional distribution platform
A hospital supply contract
A reformulated product
A manufacturing transfer with regulatory approvals

The commercial asset is more likely to change hands through an ANDA acquisition, product-line transaction, or manufacturing agreement than through a standalone branded license.

What is the geographic coverage of the product?

The product’s regulatory and commercial relevance is primarily jurisdiction-specific.

Region	Market assessment
United States	Mature generic product with limited and variable commercial availability
European Union	Combination availability depends on national authorizations and local reimbursement
Canada	May be available through provincial formularies or legacy generic channels
Emerging markets	Potentially broader use where low-cost antihypertensive combinations are common
Hospital markets	Possible niche demand where hydralazine is used for acute or difficult-to-control hypertension

U.S. FDA approval does not establish approval, pricing, or availability in other jurisdictions. National formularies and local manufacturers determine actual geographic coverage.

How strong is the patent estate for hydralazine/HCTZ 25/25?

The patent estate is weak from a commercial protection perspective. The product has:

No meaningful new chemical entity protection
No apparent active composition patent
No apparent blocking fixed-dose combination patent
No meaningful biosimilar protection issue
Low probability of high-value Paragraph IV litigation
Limited ability to sustain premium pricing

The stronger barriers are operational. These include product discontinuation risk, limited manufacturing scale, quality-system requirements, bioequivalence documentation, and wholesaler access.

Key Takeaways

Hydralazine hydrochloride 25 mg/hydrochlorothiazide 25 mg is a legacy fixed-dose antihypertensive combination.
Its commercial demand is small because hydralazine is a niche agent and hydrochlorothiazide is more useful as a separate or differently combined product.
Patent and regulatory exclusivity do not provide meaningful pricing protection.
No material current Paragraph IV or patent litigation appears to affect the product.
Product-specific revenue is not publicly disclosed and is likely immaterial within diversified generic portfolios.
The main market risks are supplier exit, reimbursement pressure, and inconsistent pharmacy distribution.
The most likely long-term substitution is separate hydralazine and hydrochlorothiazide therapy rather than migration to another fixed-dose hydralazine combination.
Geographic opportunities are more likely in low-cost generic and institutional markets than in branded U.S. retail channels.

FAQs

Is hydralazine/HCTZ 25/25 still commercially available?

Availability depends on the manufacturer, NDC, pharmacy inventory, and jurisdiction. Historical FDA records and drug databases may continue to show the product even when a specific supplier has discontinued active distribution.

Is hydralazine/HCTZ 25/25 a generic drug?

Yes. The active ingredients and fixed-dose concept are long-established, and no meaningful current branded exclusivity appears to protect the conventional product.

Can hydralazine and hydrochlorothiazide be prescribed separately?

Yes. Separate tablets allow clinicians to adjust the dose and timing of each active ingredient independently. This flexibility is a major substitute for the fixed-dose 25/25 tablet.

Does hydralazine/HCTZ 25/25 have biosimilar competition?

No. Biosimilar regulation applies to biologic products. Hydralazine/hydrochlorothiazide is a conventional small-molecule drug and is subject to generic-drug regulation.

Is hydralazine/HCTZ 25/25 an attractive generic development opportunity?

Only as a portfolio or supply-continuity product. Its low unit value, limited demand, competition from separate tablets, and weak pricing power make it unattractive as a standalone growth asset unless a manufacturer has existing capacity and distribution.

References

U.S. Food and Drug Administration. (2019). Hydralazine hydrochloride prescribing information. FDA labeling database.
U.S. Food and Drug Administration. (2020). Hydrochlorothiazide prescribing information. FDA labeling database.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: The Orange Book. https://www.fda.gov/drugsatfda
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and patent certifications. https://www.fda.gov/drugs
U.S. Food and Drug Administration. (2024). Drug shortages database. https://www.accessdata.fda.gov/scripts/drugshortages/

US Patents:	0
Applicants:	1
NDAs:	1
Clinical Trials:	3
DailyMed Link:	HYDRALAZINE HYDROCHLORIDE W/ HYDROCHLOROTHIAZIDE 25/25 at DailyMed

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