Bupropion hydrochloride; naltrexone hydrochloride - Generic Drug Details

What are the generic sources for bupropion hydrochloride; naltrexone hydrochloride and what is the scope of patent protection?

Bupropion hydrochloride; naltrexone hydrochloride is the generic ingredient in one branded drug marketed by Nalpropion and is included in one NDA. There are nineteen patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.

Bupropion hydrochloride; naltrexone hydrochloride has two hundred and forty-five patent family members in forty-four countries.

One supplier is listed for this compound.

Summary for bupropion hydrochloride; naltrexone hydrochloride

International Patents:	245
US Patents:	19
Tradenames:	1
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Clinical Trials:	47
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for bupropion hydrochloride; naltrexone hydrochloride
DailyMed Link:	bupropion hydrochloride; naltrexone hydrochloride at DailyMed

Recent Clinical Trials for bupropion hydrochloride; naltrexone hydrochloride

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

Sponsor	Phase
Currax Pharmaceuticals	Phase 4
University of California, Los Angeles	Early Phase 1
Zuyderland Medisch Centrum	Phase 4

See all bupropion hydrochloride; naltrexone hydrochloride clinical trials

Pharmacology for bupropion hydrochloride; naltrexone hydrochloride

Drug Class	Aminoketone Opioid Antagonist
Mechanism of Action	Dopamine Uptake Inhibitors Norepinephrine Uptake Inhibitors Opioid Antagonists
Physiological Effect	Increased Dopamine Activity Increased Norepinephrine Activity

Anatomical Therapeutic Chemical (ATC) Classes for bupropion hydrochloride; naltrexone hydrochloride

N06AX	Other antidepressants
N06A	ANTIDEPRESSANTS
N06	PSYCHOANALEPTICS
N	Nervous system

N07BB	Drugs used in alcohol dependence
N07B	DRUGS USED IN ADDICTIVE DISORDERS
N07	OTHER NERVOUS SYSTEM DRUGS
N	Nervous system

Paragraph IV (Patent) Challenges for BUPROPION HYDROCHLORIDE; NALTREXONE HYDROCHLORIDE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
CONTRAVE	Extended-release Tablets	bupropion hydrochloride; naltrexone hydrochloride	8 mg/90 mg	200063	1	2015-03-12

US Patents and Regulatory Information for bupropion hydrochloride; naltrexone hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	10,231,964
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	9,633,575
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	11,998,542
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	10,403,170
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	8,088,786		Y
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	9,248,123
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	7,375,111		Y

Expired US Patents for bupropion hydrochloride; naltrexone hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014	7,462,626
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014	8,815,889
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014	11,278,544
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014	7,375,111

International Patents for bupropion hydrochloride; naltrexone hydrochloride

Country	Patent Number	Title	Estimated Expiration
Japan	6240140
Japan	6665094
South Korea	102472432
Brazil	112016012755	USO DE 4 A 50 MG DE NALTREXONA DE LIBERAÇÃO SUSTENTADA, OU UM SAL FARMACEUTICAMENTE ACEITÁVEL DA MESMA E 50 A 400MG DE BUPROPIONA, OU UM SAL FARMACEUTICAMENTE ACEITÁVEL DA MESMA
Taiwan	200808319	Sustained release formulation of naltrexone
Eurasian Patent Organization	201492175	СПОСОБЫ ЛЕЧЕНИЯ ИЗБЫТОЧНОГО ВЕСА И ОЖИРЕНИЯ
Japan	2014005310	SUSTAINED RELEASE FORMULATION OF NALTREXONE

Supplementary Protection Certificates for bupropion hydrochloride; naltrexone hydrochloride

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0656775	28/2000	Austria		PRODUCT NAME: BUPROPION HYDROCHLORID; NAT. REGISTRATION NO/DATE: 1-23680 20000616; FIRST REGISTRATION: NL 24160 19991201
2316456	CR 2017 00062	Denmark		PRODUCT NAME: NALTREXON ELLER ET FARMACEUTISK ACCEPTABELT SALT DERAF, ISAER NALTREXONHYDROCHLORID, OG BUPROPION ELLER ET FARMACEUTISK ACCEPTABELT SALT DERAF, ISAER BUPROPIONHYDROCHLORID; REG. NO/DATE: EU/1/14/988 20150330
2316456	657	Finland
2316456	122017000109	Germany		PRODUCT NAME: NALTREXON ODER EIN PHARMAZEUTISCH AKZEPTABLES SALZ DAVON, INSBESONDERE NALTREXONHYDROCHLORID, UND BUPROPION ODER EIN PHARMAZEUTISCH AKZEPTABLES SALZ DAVON, INSBESONDERE BUPROPIONHYDROCHLORID; REGISTRATION NO/DATE: EU/1/14/988 20150326
2316456	2017C/064	Belgium		PRODUCT NAME: NALTREXONE/BUPROPION; AUTHORISATION NUMBER AND DATE: EU/1/14/988 20150330
2316456	349 22-2017	Slovakia		PRODUCT NAME: KOMBINACIA NALTREXONU VO VSETKYCH FORMACH CHRANENYCH ZAKLADNYM PATENTOM A BUPROPIONU VO VSETKYCH FORMACH CHRANENYCH ZAKLADNYM PATENTOM; REGISTRATION NO/DATE: EU/1/14/988 20150330
2316456	132017000142109	Italy		PRODUCT NAME: NALTREXONE/BUPROPIONE(MYSIMBA); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/14/988, 20150330

Market Dynamics and Financial Trajectory for the Drug: Bupropion Hydrochloride; Naltrexone Hydrochloride (Contrave)

Introduction

Contrave, a fixed-dose combination of bupropion hydrochloride and naltrexone hydrochloride, was approved by the FDA in 2014 for the treatment of obesity and weight management. This article delves into the market dynamics and financial trajectory of this drug, highlighting its challenges, safety profile, and future outlook.

Approval and Indications

Contrave is indicated for weight loss and maintenance of weight loss in adults with a body mass index (BMI) of 30 or higher, or in adults with a BMI of 27 or higher who have at least one weight-related condition such as type 2 diabetes, high blood pressure, or high cholesterol. The drug combines naltrexone, an opioid antagonist, and bupropion, a dopamine and norepinephrine reuptake inhibitor[1][5].

Market Challenges

Despite its approval, Contrave has faced several market challenges. One significant issue is the public perception and management of the drug's efficacy. For instance, the initial public release highlighting a 25% weight loss trajectory was seen as misleading, as the actual placebo-subtracted weight loss is around 4-5%[2].

Safety Profile and Adverse Events

The safety profile of Contrave is a critical aspect of its market dynamics. The drug has been associated with several adverse events, including increased risk of seizures, particularly at higher doses of bupropion. Other notable side effects include sleep disorders, anxiety, and hypertension. The risk of major adverse cardiovascular events (MACE) has also been a concern, although studies have shown that the risk does not significantly impact the drug’s benefit-risk profile[1][2][5].

Clinical Trials and Efficacy

Clinical trials have demonstrated that Contrave can achieve moderate weight loss. A large-scale randomized noninferiority cardiovascular outcomes trial showed a placebo-subtracted weight loss of 2.5% at 104 weeks. However, longer-term studies are needed to fully characterize the drug's efficacy and safety beyond one year[2].

Regulatory Requirements and Post-Marketing Studies

The FDA has mandated post-marketing studies to assess the cardiovascular safety of Contrave. A randomized, double-blind, placebo-controlled trial was required to demonstrate that the risk of MACE does not adversely affect the drug’s benefit-risk profile. These studies have been ongoing, with a focus on long-term safety and efficacy[5].

Patent and Generic Landscape

The patent landscape for bupropion hydrochloride, a key component of Contrave, is complex. The earliest date for generic entry of bupropion hydrobromide (a related salt form) is expected to be June 27, 2026, pending any patent challenges or generic licensing agreements. This could potentially impact the market dynamics of Contrave once generic versions become available[3].

Financial Trajectory

The financial performance of Contrave has been influenced by its market challenges and regulatory requirements. Despite being FDA-approved in 2014, the drug has not achieved the expected market penetration due to concerns over its safety profile and efficacy. The need for ongoing post-marketing studies and the impending generic competition are likely to impact its financial trajectory in the coming years.

Market Competition

Contrave operates in a competitive obesity treatment market, which includes other prescription drugs, lifestyle modifications, and surgical interventions. The drug's unique mechanism of action, combining an opioid antagonist with a dopamine and norepinephrine reuptake inhibitor, sets it apart but also introduces complexities in patient management and safety monitoring[2].

Patient Compliance and Adherence

Patient compliance and adherence are crucial for the success of any weight loss medication. Contrave requires a titration period to reach the maximum daily dosage, which can affect patient adherence. Additionally, the need for lifestyle modifications alongside medication can be a barrier to long-term compliance[1][5].

Future Outlook

The future outlook for Contrave is mixed. While it has shown efficacy in weight loss, ongoing safety concerns and the need for longer-term studies will continue to influence its market dynamics. The impending generic competition for bupropion hydrochloride could further impact its financial trajectory. However, if the drug can demonstrate long-term safety and efficacy, it may still maintain a significant market presence.

Key Takeaways

• Approval and Indications: Contrave is approved for weight loss and maintenance in adults with a BMI of 30 or higher, or 27 or higher with weight-related conditions.
• Market Challenges: Public perception, safety concerns, and regulatory requirements have impacted market performance.
• Safety Profile: Associated with increased risk of seizures, sleep disorders, anxiety, and hypertension.
• Clinical Trials: Demonstrated moderate weight loss, but longer-term studies are needed.
• Regulatory Requirements: Ongoing post-marketing studies to assess cardiovascular safety.
• Patent and Generic Landscape: Generic competition expected by June 27, 2026.
• Financial Trajectory: Influenced by market challenges, regulatory requirements, and impending generic competition.
• Market Competition: Operates in a competitive obesity treatment market.
• Patient Compliance: Requires titration period and lifestyle modifications, affecting adherence.

FAQs

What are the active ingredients in Contrave?

Contrave contains naltrexone hydrochloride, an opioid antagonist, and bupropion hydrochloride, a dopamine and norepinephrine reuptake inhibitor[1].

What are the common side effects of Contrave?

Common side effects include sleep disorders, anxiety, hypertension, and an increased risk of seizures[1][2].

Is Contrave safe for long-term use?

Long-term safety data is still emerging, and ongoing studies are needed to fully characterize the drug's safety profile beyond one year[2].

When can we expect generic versions of bupropion hydrochloride?

The earliest date for generic entry of bupropion hydrobromide is expected to be June 27, 2026, pending any patent challenges or generic licensing agreements[3].

How does Contrave compare to other weight loss medications?

Contrave's unique mechanism of action sets it apart, but it faces competition from other prescription drugs, lifestyle modifications, and surgical interventions[2].

Sources

1. FDA: NDA 200063 Orig1s000 ClinPharmR - Contrave (Naltrexone/Bupropion)[1].
2. Tandfonline: Update on drug safety evaluation of naltrexone/bupropion for the treatment of obesity[2].
3. Drug Patent Watch: Aplenzin (Bupropion Hydrobromide) - Patent and Generic Information[3].
4. Health Canada: Product Monograph - Naltrexone Hydrochloride and Bupropion Hydrochloride Extended-Release Tablets[4].
5. FDA: Summary Basis for Approval - NDA 200063 / CONTRAVE (naltrexone HCl/bupropion HCl)[5].