Generic CONIVAPTAN HYDROCHLORIDE INN entry, pharmaceutical patent expiry and freedom to operate

Sponsor	Phase
Canadian Dermatology Foundation	Phase 3
Vanderbilt University Medical Center	Phase 3
University of Toronto	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
Apotex	VAPRISOL IN 5% DEXTROSE IN PLASTIC CONTAINER	conivaptan hydrochloride	INJECTABLE;INTRAVENOUS	021697-002	Oct 8, 2008		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				⤷ Start Trial
Apotex	VAPRISOL	conivaptan hydrochloride	INJECTABLE;INTRAVENOUS	021697-001	Dec 29, 2005		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

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Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Apotex	VAPRISOL	conivaptan hydrochloride	INJECTABLE;INTRAVENOUS	021697-001	Dec 29, 2005	⤷ Start Trial	⤷ Start Trial
Apotex	VAPRISOL IN 5% DEXTROSE IN PLASTIC CONTAINER	conivaptan hydrochloride	INJECTABLE;INTRAVENOUS	021697-002	Oct 8, 2008	⤷ Start Trial	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>Patent No.	>Patent Expiration

Last updated: September 9, 2026

Conivaptan hydrochloride is a mature, hospital-only vasopressin V1A/V2 receptor antagonist marketed in the United States as Vaprisol. The product has limited commercial scale because it is intravenous, indicated for a narrow inpatient population, requires close sodium monitoring, and competes with oral tolvaptan and lower-cost fluid-management protocols. Its core composition-of-matter patent and regulatory exclusivity have expired. No biosimilar pathway applies, and the primary remaining commercial barriers are manufacturing, hospital contracting, clinical familiarity, and limited generic competition rather than enforceable patent rights.

Product-specific revenue is not separately disclosed by Cumberland Pharmaceuticals, the U.S. rights holder. The financial profile is therefore best assessed through product lifecycle, hospital utilization, competitive substitution, and Cumberland’s broader specialty-pharmaceutical portfolio.

What is conivaptan hydrochloride approved to treat?

Conivaptan hydrochloride injection is approved for the treatment of euvolemic and hypervolemic hyponatremia in hospitalized adults. The FDA-approved regimen begins with a 20 mg intravenous loading dose administered over 30 minutes, followed by continuous infusion of 20 mg per day. The dose may be increased to 40 mg per day. Treatment is limited to four days under the U.S. label.[1]

Conivaptan inhibits both V1A and V2 vasopressin receptors. V2 antagonism increases free-water excretion, while V1A activity affects vascular tone. The product is used in a controlled inpatient setting because excessive correction of serum sodium can cause serious neurologic injury.

Attribute	Conivaptan hydrochloride
Brand	Vaprisol
Active ingredient	Conivaptan hydrochloride
Drug class	Vasopressin receptor antagonist
Receptor activity	V1A and V2 antagonist
Dosage form	Intravenous injection
FDA approval	December 2005
Approved setting	Hospitalized adults
Approved indication	Euvolemic and hypervolemic hyponatremia
Maximum labeled treatment	Four days
Original sponsor	Astellas Pharma US
Current U.S. commercial rights	Cumberland Pharmaceuticals
Biosimilar relevance	None; conivaptan is a small molecule

The product is not approved for routine outpatient treatment, chronic heart-failure management, cirrhosis-related hyponatremia, or general fluid overload outside the labeled hospital setting.

How large is the conivaptan hydrochloride market?

The addressable market is structurally small and specialized. Demand is limited to hospitalized patients with clinically significant hyponatremia who require rapid, monitored correction and for whom an intravenous vasopressin antagonist is appropriate.

Four factors constrain utilization:

Intravenous administration requires hospital pharmacy and nursing resources.
Treatment is limited to four days.
Serum sodium must be monitored closely.
Oral tolvaptan and non-pharmacologic fluid restriction can address overlapping clinical needs.

Conivaptan may be selected when rapid inpatient aquaresis is needed or when oral treatment is unsuitable. It is less attractive when a hospital favors oral therapy, lower-cost fluid management, or a standardized hyponatremia protocol based on hypertonic saline and fluid restriction.

The market is also affected by the relatively small number of patients who meet the labeled criteria and by treatment heterogeneity. Hyponatremia is common in hospitals, but not every case requires a vasopressin antagonist. Many patients are managed by treating the underlying cause, restricting fluids, discontinuing causative medicines, or administering saline.

When does conivaptan hydrochloride lose exclusivity?

Conivaptan’s principal regulatory and patent exclusivities expired years ago.

Exclusivity or protection	Approximate status
FDA approval	December 1, 2005
New chemical entity exclusivity	Expired
Core composition-of-matter patent	Expired
Marketed product exclusivity	Expired
Current patent-driven barrier to generic entry	No material barrier identified
Biosimilar exclusivity	Not applicable

The FDA approved Vaprisol in 2005. Any five-year new chemical entity exclusivity associated with the original approval would have expired by the end of 2010. The core conivaptan patent portfolio also reached the end of its statutory term during the 2010s.

Patent term for a U.S. patent generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and applicable transitional rules. The original conivaptan patent family was filed well before the product’s 2005 approval, leaving no meaningful patent runway today.[2]

What patents protect conivaptan hydrochloride?

The early conivaptan portfolio included patents covering vasopressin receptor antagonists and related chemical compounds. U.S. Patent No. 5,723,457 is associated with the conivaptan chemical class and was issued in 1998. Its ordinary term expired before or around the middle of the 2010s, depending on the applicable priority date and patent-term adjustment.[2]

The patent estate does not provide a current composition-of-matter moat. Any remaining protection would have to arise from later patents covering a specific formulation, manufacturing process, crystalline form, dosing method, or other narrow claim set. Such patents would not restore broad protection over conivaptan hydrochloride as an active ingredient.

What formulations are protected by conivaptan patents?

The commercial product is an injectable formulation supplied for hospital use. Formulation protection is less commercially significant than it would be for an extended-release oral product because the labeled treatment period is short and the formulation is relatively conventional for hospital administration.

A later formulation patent could potentially affect a particular injectable composition or manufacturing method without blocking all conivaptan products. No publicly prominent, unexpired U.S. formulation patent has emerged as a recognized barrier to generic conivaptan injection in the major public patent and FDA databases reviewed for this analysis.[2][3]

What is the Orange Book status of Vaprisol?

Vaprisol was approved under NDA 021697. The FDA Orange Book is the relevant source for determining whether a drug product has listed patents, pediatric exclusivity, or other patent-related information that can support a Paragraph IV filing.[3]

The commercial implications are straightforward:

Original product exclusivity has expired.
A generic applicant would not face an active NCE exclusivity block.
Any Paragraph IV certification would depend on the patents listed for the relevant NDA at the time of filing.
Expired composition patents cannot delay approval.
A later-listed method-of-use patent would have narrower commercial reach and would not necessarily prevent approval for non-infringing use.

Orange Book listing status can change as FDA records are updated. The historical patent position does not indicate an active broad patent barrier to conivaptan hydrochloride injection.

Which companies are challenging conivaptan hydrochloride?

No major, publicly visible Paragraph IV litigation campaign has shaped the current U.S. conivaptan market. The product has not generated the type of high-value patent challenge seen with blockbuster oral medicines or biologic products.

The likely generic-entry pattern is different:

A manufacturer may file an ANDA after confirming the reference product and injectable presentation.
The applicant could use a Paragraph III certification for any unexpired listed patent or a Paragraph IV certification if it contests patent validity or enforceability.
If no relevant listed patent remains, the applicant could file without a meaningful patent litigation risk.
Limited market size may discourage the development of a generic despite the absence of patent protection.

This distinction matters. Patent expiry removes legal exclusivity, but it does not guarantee generic entry. Injectable products require specialized manufacturing, sterility controls, stability data, hospital distribution, and sufficient expected volume to justify development costs.

What is the FDA regulatory status of conivaptan hydrochloride?

The FDA-approved product remains an injectable hospital therapy under NDA 021697. The label contains clinically important restrictions:

Treatment is limited to hospitalized patients.
Serum sodium and volume status require monitoring.
Rapid correction of hyponatremia can cause osmotic demyelination.
Conivaptan is a CYP3A4 inhibitor and is affected by CYP3A4-mediated interactions.
It should not be administered with strong CYP3A4 inhibitors.
The product can cause infusion-site reactions, including phlebitis.
The recommended treatment duration is no more than four days.[1]

These requirements increase the operational cost of use and reduce the ability of the product to compete on price alone.

How does conivaptan compare with tolvaptan?

Tolvaptan is the closest pharmacologic competitor, but the products have materially different commercial profiles.

Factor	Conivaptan	Tolvaptan
Administration	Intravenous	Oral
Vasopressin targets	V1A and V2	Primarily V2
Typical use	Short-term inpatient correction	Inpatient and selected longer-term use, depending on indication
Treatment duration	Maximum four days under U.S. label	Varies by indication and label
Major operational burden	IV access, infusion monitoring, phlebitis	Oral administration, hepatic and sodium monitoring depending on use
Commercial advantage	Rapid controlled inpatient aquaresis	Convenience and broader oral applicability
Generic competition	Limited or unclear commercial participation	Established generic competition in some markets
Patent position	Mature and expired	More complex historical product and method-of-use landscape

Tolvaptan generally has greater commercial flexibility because it is orally administered. Conivaptan retains a niche where intravenous treatment is clinically preferred, but the IV route limits market expansion.

What factors determine conivaptan’s financial trajectory?

Cumberland acquired U.S. rights to Vaprisol from Astellas in 2012. The transaction gave Cumberland a marketed hospital product without requiring original development of the compound.[4]

The financial trajectory is likely characterized by mature, low-growth revenue rather than expansion. Key drivers include:

Hospital demand

Sales depend on formulary placement, hospital protocols, and the number of patients requiring monitored inpatient aquaresis. A product used for a short course in a narrow population has low repeat volume compared with chronic outpatient medicines.

Net pricing

Hospital purchasing organizations and group purchasing organizations can pressure pricing. A niche injectable may maintain a premium over generic oral therapies if it offers a clinically useful route of administration, but price increases are constrained by therapeutic substitution.

Supply reliability

Conivaptan’s commercial value depends on uninterrupted sterile manufacturing and distribution. A shortage of an injectable competitor can temporarily increase demand, but shortages can also expose the product to procurement substitution and encourage hospitals to revise protocols.

Portfolio contribution

Cumberland does not generally report Vaprisol revenue as a standalone public segment. Its financial statements report consolidated product revenue, while the company commercializes multiple specialty products. This prevents a precise public calculation of Vaprisol’s revenue, gross margin, or share of company sales.[4]

The product is therefore best viewed as a niche contributor to a diversified specialty-pharmaceutical portfolio. Its value is based on recurring hospital demand, existing regulatory approval, and commercial infrastructure, not on exclusivity-driven pricing power.

What generic entry risks exist for conivaptan hydrochloride?

Generic entry risk is legally high but commercially uncertain.

Legal risk

The core patent estate has expired, and FDA exclusivity has expired. A new applicant would not face the type of active patent wall that protects a recently approved small molecule.

Technical risk

Sterile injectable products require validated aseptic processing, container-closure integrity, stability testing, and reliable API supply. These requirements can discourage smaller generic companies.

Commercial risk

The market may be too small to support multiple entrants. A generic manufacturer must account for:

Limited annual unit volume
Hospital contracting costs
Inventory requirements
Sterile manufacturing expenses
Competitive pricing
Potential substitution by tolvaptan and saline-based protocols

A single generic entrant could materially reduce the branded product’s price and volume. Several entrants would increase the probability of rapid price erosion.

What patent litigation affects conivaptan hydrochloride?

No major active patent litigation is publicly associated with Vaprisol that currently changes the product’s market outlook. The absence of litigation is consistent with an old product whose core patents have expired and whose commercial opportunity is modest.

Any future dispute would more likely concern:

A newly filed ANDA
A narrow formulation patent
A manufacturing process
Trade-secret or supply issues
Product labeling and method-of-use claims

A broad infringement action based on the original conivaptan compound patents would not be commercially viable after expiration.

How strong is the conivaptan hydrochloride patent estate?

The patent estate is weak for lifecycle protection and moderate only as a historical development asset.

Patent-estate factor	Assessment
Composition-of-matter protection	Expired
NCE exclusivity	Expired
Formulation protection	No material broad barrier identified
Method-of-use protection	Limited practical relevance
Manufacturing protection	Potentially relevant to process execution, not broad market exclusivity
Orange Book leverage	Low
Generic litigation leverage	Low
Commercial differentiation	Primarily clinical and operational

The product has no realistic patent-based route to restore exclusivity. Future value depends on supply, clinical positioning, and hospital economics.

What are the likely generic launch scenarios?

Scenario 1: No generic launch

This is plausible if market volume is insufficient to justify sterile injectable development. Cumberland would retain the branded market, although revenue would remain limited.

Scenario 2: Single generic entrant

A single approved generic could pressure price and hospital contracts while leaving the originator with some supply and brand-recognition value. This is the most commercially balanced risk scenario.

Scenario 3: Multiple generic entrants

Multiple entrants could produce rapid price erosion and reduce the branded product to a residual or shortage-driven role. The probability depends on actual market volume and the number of manufacturers with suitable sterile capacity.

Scenario 4: Hospital protocol displacement

Even without generic entry, hospitals may substitute tolvaptan, hypertonic saline, fluid restriction, or treatment of the underlying condition. This scenario creates gradual volume erosion rather than a sharp patent cliff.

What is the revenue exposure for Cumberland Pharmaceuticals?

Cumberland’s public reporting does not separately identify Vaprisol revenue. The company reports at the consolidated level across its portfolio, which has included products such as Acetadote, Caldolor, Kristalose, Biorphen, and Vaprisol.[4]

As a result, Vaprisol’s revenue exposure cannot be calculated from reported financial statements with precision. The commercial indicators point to a limited contribution:

The product addresses a narrow inpatient indication.
It is not a chronic outpatient therapy.
It has no remaining core patent exclusivity.
It competes with an oral branded and generic class.
Product-specific revenue is not highlighted as a major public company growth driver.

The financial trajectory is therefore likely stable-to-declining absent a supply disruption affecting competitors, expanded clinical adoption, or a strategic transaction. The main downside event is generic or protocol-driven substitution. The main upside event is temporary demand growth caused by competitor shortages or increased use of intravenous therapy in high-acuity hospitals.

Key Takeaways

Conivaptan hydrochloride, marketed as Vaprisol, is an FDA-approved IV treatment for hospitalized adults with euvolemic or hypervolemic hyponatremia.
FDA exclusivity and the core conivaptan patent estate have expired.
No biosimilar risk applies because conivaptan is a small molecule.
The product has limited market scale because treatment is short-term, hospital-based, and operationally intensive.
Tolvaptan is the principal pharmacologic competitor, with a commercial advantage from oral administration.
No major current patent litigation or Paragraph IV campaign publicly defines the market.
Generic entry is legally feasible but commercially uncertain because sterile injectable development may not be economical.
Cumberland does not disclose Vaprisol revenue separately, preventing a precise product-level financial forecast.
The product’s residual value comes from regulatory approval, hospital access, manufacturing capability, and supply reliability rather than patent protection.

FAQs

Is conivaptan hydrochloride still sold in the United States?

Vaprisol is associated with FDA-approved NDA 021697 and U.S. commercialization by Cumberland Pharmaceuticals. Current product availability depends on commercial distribution and supply status.

Is there a generic version of conivaptan injection?

The absence of active core patent protection permits generic development, but generic availability depends on FDA approval and commercial launch. Patent expiry alone does not establish that a marketed generic is available.

Can conivaptan be used outside the hospital?

The FDA label limits use to hospitalized adults because sodium correction, fluid status, infusion reactions, and drug interactions require monitoring.[1]

Does conivaptan have orphan-drug protection?

Conivaptan’s commercial position is not based on an active orphan-drug exclusivity period. Any historical regulatory exclusivity associated with its original approval has expired.

What would most reduce Vaprisol sales?

The largest risks are a reliable generic injectable launch, hospital protocol substitution with tolvaptan or saline-based treatment, and reduced use of IV therapy for hyponatremia.

References

U.S. Food and Drug Administration. (2005). Vaprisol (conivaptan hydrochloride) injection prescribing information. FDA.
United States Patent and Trademark Office. (1998). U.S. Patent No. 5,723,457: Vasopressin receptor antagonists. USPTO.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book; Drugs@FDA, NDA 021697. FDA.
Cumberland Pharmaceuticals, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.

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What excipients (inactive ingredients) are in conivaptan hydrochloride?	conivaptan hydrochloride excipients list
DailyMed Link:	conivaptan hydrochloride at DailyMed

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