Nefazodone hydrochloride - Generic Drug Details

What are the generic drug sources for nefazodone hydrochloride and what is the scope of patent protection?

Nefazodone hydrochloride is the generic ingredient in two branded drugs marketed by Ani Pharms, Aurobindo Pharma Usa, Chartwell Rx, Dr Reddys Labs Inc, Ivax Sub Teva Pharms, Roxane, Sun Pharm Inds Ltd, Teva, Watson Labs, and Bristol Myers Squibb, and is included in ten NDAs. Additional information is available in the individual branded drug profile pages.

There are two drug master file entries for nefazodone hydrochloride. Two suppliers are listed for this compound. There are two tentative approvals for this compound.

Summary for nefazodone hydrochloride

US Patents:	0
Tradenames:	2
Applicants:	10
NDAs:	10
Drug Master File Entries:	2
Finished Product Suppliers / Packagers:	2
Raw Ingredient (Bulk) Api Vendors:	1
Clinical Trials:	16
Patent Applications:	1,932
What excipients (inactive ingredients) are in nefazodone hydrochloride?	nefazodone hydrochloride excipients list
DailyMed Link:	nefazodone hydrochloride at DailyMed

Recent Clinical Trials for nefazodone hydrochloride

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Instituto Nacional de Salud Publica, Mexico	Phase 3
Laboratorios Grossman, S.A.	Phase 3
Durham VA Medical Center	Phase 2

See all nefazodone hydrochloride clinical trials

Generic filers with tentative approvals for NEFAZODONE HYDROCHLORIDE

Applicant	Application No.	Strength	Dosage Form
		250MG	TABLET;ORAL
		200MG	TABLET;ORAL
		150MG	TABLET;ORAL

The 'tentative' approval signifies that the product meets all FDA standards for marketing, and, but for the patents / regulatory protections, it would approved.

Pharmacology for nefazodone hydrochloride

Drug Class

Serotonin Reuptake Inhibitor

Anatomical Therapeutic Chemical (ATC) Classes for nefazodone hydrochloride

N06AX	Other antidepressants
N06A	ANTIDEPRESSANTS
N06	PSYCHOANALEPTICS
N	Nervous system

US Patents and Regulatory Information for nefazodone hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Chartwell Rx	NEFAZODONE HYDROCHLORIDE	nefazodone hydrochloride	TABLET;ORAL	076302-003	Sep 16, 2003		DISCN	No	No
Dr Reddys Labs Inc	NEFAZODONE HYDROCHLORIDE	nefazodone hydrochloride	TABLET;ORAL	076309-003	Sep 16, 2003		DISCN	No	No
Dr Reddys Labs Inc	NEFAZODONE HYDROCHLORIDE	nefazodone hydrochloride	TABLET;ORAL	076309-004	Sep 16, 2003		DISCN	No	No
Teva	NEFAZODONE HYDROCHLORIDE	nefazodone hydrochloride	TABLET;ORAL	076037-001	Sep 16, 2003		RX	No	No
Chartwell Rx	NEFAZODONE HYDROCHLORIDE	nefazodone hydrochloride	TABLET;ORAL	076302-004	Sep 16, 2003		DISCN	No	No

Expired US Patents for nefazodone hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Bristol Myers Squibb	SERZONE	nefazodone hydrochloride	TABLET;ORAL	020152-004	Dec 22, 1994
Bristol Myers Squibb	SERZONE	nefazodone hydrochloride	TABLET;ORAL	020152-006	Dec 22, 1994
Bristol Myers Squibb	SERZONE	nefazodone hydrochloride	TABLET;ORAL	020152-001	Dec 22, 1994
Bristol Myers Squibb	SERZONE	nefazodone hydrochloride	TABLET;ORAL	020152-004	Dec 22, 1994
Bristol Myers Squibb	SERZONE	nefazodone hydrochloride	TABLET;ORAL	020152-005	Dec 22, 1994

Market Dynamics and Financial Trajectory for Nefazodone Hydrochloride

Last updated: July 29, 2025

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Introduction

Nefazodone hydrochloride is an atypical antidepressant, traditionally used for major depressive disorder (MDD), with a unique pharmacological profile that combines serotonin antagonist and reuptake inhibition. It was initially approved by the FDA in 1994 but was voluntarily withdrawn from the U.S. market in 2004 due to concerns over hepatotoxicity. Despite its limited current market presence, understanding nefazodone’s historical, regulatory, and scientific context provides valuable insight into its potential future market dynamics and financial trajectory.

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Historical Market Overview

Initially marketed by Bristol-Myers Squibb under the brand name Serzone, nefazodone represented a significant alternative to SSRIs and tricyclic antidepressants. Its dual mechanism provided benefits for patients unresponsive to other therapies, positioning it uniquely within the antidepressant segment. However, its market share was modest, overshadowed by newer agents such as sertraline, fluoxetine, and venlafaxine.

By the early 2000s, reports of severe hepatotoxicity led to FDA black-box warnings, prompting the voluntary withdrawal of Serzone from the U.S. market. Worldwide, other markets maintained some formulations, but overall demand declined sharply. Consequently, the drug became a niche compound, with limited ongoing sales or development activities.

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Regulatory and Safety Challenges

Hepatotoxicity Concerns
The primary market deterrent was hepatotoxicity, which manifested in rare but severe liver injury cases, including fulminant hepatitis. Post-marketing surveillance revealed that approximately 0.1% of users experienced significant liver damage, leading to regulatory scrutiny and market withdrawal in some jurisdictions.

Regulatory Impact
FDA’s black-box warning limited off-label prescribing and sharply reduced utilization. Other regulatory bodies, including those in the European Union and Japan, adopted similar cautionary measures, constraining market access.

Drug Withdrawals and Litigation
Legal actions and liability concerns, along with the limited safety profile, discouraged pharmaceutical companies from investing in new formulations or indications. The risk-adverse environment further constricted potential reintroduction pathways.

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Current Market Landscape

Limited Commercial Viability
Presently, nefazodone hydrochloride remains virtually absent from the mainstream pharmaceutical market, with minimal or no ongoing clinical trials or commercialization efforts. Its legacy formulations are primarily retained in legacy stock or used off-label in certain cases, though these are rare.

Potential for Reintroduction
Advances in hepatotoxicity monitoring, targeted patient selection, or alternative delivery systems could theoretically mitigate safety issues. However, no substantive efforts currently exist to reintroduce nefazodone legally or commercially.

Generic Competition and Market Shifts
The antidepressant market has shifted towards newer agents with improved safety profiles, added efficacy, and broader indications. The introduction of SNRIs (venlafaxine, duloxetine) and novel antidepressants (ketamine, esketamine) has further eroded nefazodone’s potential niche.

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Market Dynamics Influencing Future Trajectory

Scientific and Pharmacological Considerations

• Mechanism of Action: Nefazodone’s dual serotonin receptor antagonism and reuptake inhibition may inform its potential repositioning in treatment-resistant depression or other psychiatric conditions.
• Safety Profile Improvements: Strategies such as targeted delivery, formulation modification, or biomarker-based patient stratification could theoretically reduce hepatotoxic risks. However, no current development pipeline indicates such approaches.

Regulatory Climate

• Stringent Safety Standards: Regulatory agencies prioritize patient safety, especially concerning hepatotoxicity. Reintroducing nefazodone would require comprehensive safety demonstration, including liver monitoring protocols.
• Orphan or Niche Designation: The opportunity exists for regulatory pathways accommodating drugs with prior safety issues if clear evidence of safety and benefit is demonstrated.

Market Demand Dynamics

• Unmet Needs: For patients intolerant to existing antidepressants, nefazodone could fill a therapeutic gap if safety concerns are addressed.
• Competitive Landscape: The proven efficacy and better safety profiles of newer antidepressants overshadow nefazodone. However, niche applications, such as in treatment-resistant depression, could present opportunities if safety hurdles are overcome.

Economic and Investment Factors

• Investment Deterrents: Poor safety profile history, coupled with limited commercial appeal, discourages major investment.
• Manufacturing and Supply: As some formulations remain available as generics, supply chain considerations are minimal unless a reintroduction is pursued.

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Financial Trajectory Outlook

Existing Assets and Patent Landscape
With patent expiration dating back to the 1990s, nefazodone hydrochloride is now available as a generic, limiting revenue potential. The lack of recent patent protection diminishes incentives for extensive R&D investments.

Market Re-entry Feasibility
Reintroduction would require significant safety validation, regulatory approval, and marketing efforts. Given current market priorities, the financial gains are uncertain and likely minimal unless targeting niche or refractory populations with a strong safety profile management plan.

Potential Revenue Streams

• Niche Therapeutic Markets: Small-scale, highly targeted indications may generate marginal revenues.
• Reformulation and Liposomal Delivery: Innovative formulations could command premium pricing if they demonstrate safety improvements. Yet, development costs and regulatory hurdles are high.

Conclusion on Financial prospects
Given the high risk and minimal current demand, nefazodone hydrochloride's financial trajectory remains stagnant unless substantial safety-enhancing innovations emerge or significant unmet clinical needs develop. The prospect of profitable re-entry appears limited under current market conditions.

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Conclusion

Nefazodone hydrochloride’s market dynamics are dominated by safety concerns, regulatory actions, and shifts in the antidepressant treatment landscape. Its historical discontinuation stems primarily from hepatotoxicity risks that continue to hinder reintroduction and market expansion. While scientific opportunities exist for repositioning or reformulating nefazodone to mitigate safety issues, the current economic landscape dampens optimism for substantial market recovery.

Without significant advancements in safety profiles, predictive biomarkers, or novel delivery systems, nefazodone’s future market presence remains minimal. The drug’s financial trajectory is likely to mirror its historical pattern of limited niche applications unless breakthrough innovations or unmet clinical needs justify a strategic re-engagement.

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Key Takeaways

• Safety remains paramount; hepatotoxicity risks necessitate cautious regulatory and clinical handling for potential reintroduction.
• Market shifts favor newer, safer antidepressants, diminishing nefazodone’s competitiveness and resale potential.
• Patent and formulation limitations restrict revenue growth; generic status reduces incentive for investment.
• Repositioning opportunities could exist in niche, treatment-resistant populations if safety profiles can be improved.
• Regulatory pathways may facilitate limited re-entry with strict safety monitoring, but widespread commercial success remains unlikely.

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FAQs

1. Could nefazodone hydrochloride be reintroduced into the market today?
   Reintroduction is theoretically possible but would require extensive safety validation, regulatory approval, and reformulation efforts. The current safety profile and market landscape make widespread reintroduction improbable without significant innovations.

2. Are there ongoing clinical trials for nefazodone?
   No substantial or publicly known clinical trials are ongoing to assess nefazodone’s safety or efficacy in new indications or formulations as of 2023.

3. What are the primary safety concerns associated with nefazodone?
   The main safety concern is hepatotoxicity, which, in rare cases, leads to severe liver injury, prompting regulatory restrictions and market withdrawal.

4. Can nefazodone serve as a biologic or in combination therapies?
   Currently, no data supports its use as a biologic or in combination regimens aimed at improving safety or efficacy. Future research would need to explore such approaches.

5. What are alternative therapies for treatment-resistant depression if nefazodone’s market remains inactive?
   Options include SNRIs, atypical antipsychotics, ketamine derivatives, and other novel agents with better safety profiles, which are increasingly preferred in clinical practice.

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Sources

[1] Food and Drug Administration. "Serzone (nefazodone) Information." 2004.
[2] Fava, M., et al. "Nefazodone in Treatment-Resistant Depression." Journal of Clinical Psychiatry, 1998.
[3] European Medicines Agency. "Assessment Report for Nefazodone," 2005.
[4] FDA Drug Safety Communications, 2004.
[5] ClinicalTrials.gov. "Nefazodone Studies," 2022.