Acetaminophen; butalbital; caffeine; codeine phosphate - Generic Drug Details

What are the generic drug sources for acetaminophen; butalbital; caffeine; codeine phosphate and what is the scope of freedom to operate?

Acetaminophen; butalbital; caffeine; codeine phosphate is the generic ingredient in three branded drugs marketed by Able, Hikma, Hikma Intl Pharms, Lgm Pharma, Pharmobedient, Strides Pharma, Actavis Labs Ut Inc, and Valeant, and is included in eight NDAs. Additional information is available in the individual branded drug profile pages.

Five suppliers are listed for this compound.

Summary for acetaminophen; butalbital; caffeine; codeine phosphate

US Patents:	0
Tradenames:	3
Applicants:	8
NDAs:	8
Finished Product Suppliers / Packagers:	5
DailyMed Link:	acetaminophen; butalbital; caffeine; codeine phosphate at DailyMed

Pharmacology for acetaminophen; butalbital; caffeine; codeine phosphate

Drug Class	Barbiturate Central Nervous System Stimulant Methylxanthine Opioid Agonist
Mechanism of Action	Full Opioid Agonists
Physiological Effect	Central Nervous System Stimulation

Anatomical Therapeutic Chemical (ATC) Classes for acetaminophen; butalbital; caffeine; codeine phosphate

D11AX	Other dermatologicals
D11A	OTHER DERMATOLOGICAL PREPARATIONS
D11	OTHER DERMATOLOGICAL PREPARATIONS
D	Dermatologicals

N06BC	Xanthine derivatives
N06B	PSYCHOSTIMULANTS, AGENTS USED FOR ADHD AND NOOTROPICS
N06	PSYCHOANALEPTICS
N	Nervous system

R05DA	Opium alkaloids and derivatives
R05D	COUGH SUPPRESSANTS, EXCL. COMBINATIONS WITH EXPECTORANTS
R05	COUGH AND COLD PREPARATIONS
R	Respiratory system

US Patents and Regulatory Information for acetaminophen; butalbital; caffeine; codeine phosphate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Lgm Pharma	BUTALBITAL, ACETAMINOPHEN, CAFFEINE AND CODEINE PHOSPHATE	acetaminophen; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	076560-001	Jun 10, 2004	AB	RX	No	No
Hikma	BUTALBITAL, ACETAMINOPHEN, CAFFEINE AND CODEINE PHOSPHATE	acetaminophen; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	215138-002	Jan 26, 2022	AB	RX	No	No
Actavis Labs Ut Inc	FIORICET W/ CODEINE	acetaminophen; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	020232-001	Jul 30, 1992	AB	RX	Yes	Yes
Hikma	BUTALBITAL, ACETAMINOPHEN, CAFFEINE AND CODEINE PHOSPHATE	acetaminophen; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	215138-001	Jan 26, 2022	AB	RX	No	No
Able	BUTALBITAL, ACETAMINOPHEN, CAFFEINE AND CODEINE PHOSPHATE	acetaminophen; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	076528-001	Aug 21, 2003		DISCN	No	No
Hikma Intl Pharms	BUTALBITAL, ACETAMINOPHEN, CAFFEINE AND CODEINE PHOSPHATE	acetaminophen; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	075618-001	Mar 23, 2001		DISCN	No	No
Strides Pharma	BUTALBITAL, ACETAMINOPHEN, CAFFEINE AND CODEINE PHOSPHATE	acetaminophen; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	204649-001	Jul 8, 2020	AB	RX	No	No

Market Dynamics and Financial Trajectory for the Pharmaceutical Drug: Acetaminophen; Butalbital; Caffeine; Codeine Phosphate

Last updated: July 30, 2025

Introduction

The combination of acetaminophen, butalbital, caffeine, and codeine phosphate represents a multidimensional pharmaceutical formulation primarily used for treating tension headaches, migraines, and specific pain conditions. This compound, often marketed under various trade names such as Fioricet with Codeine, blends analgesic, sedative, and vasoconstrictive properties. Its market dynamics and financial prospects are shaped by clinical efficacy, regulatory landscapes, competitive forces, prescription trends, and societal concerns such as opioid misuse.

Understanding the evolving landscape of this combination drug necessitates a comprehensive analysis of its therapeutic profile, regulatory challenges, patent and patent expirations, competitive products, and shifts driven by the opioid epidemic and new pain management guidelines. An in-depth exploration of these factors offers actionable insights into the drug's commercial trajectory and investment considerations.

Therapeutic and Market Overview

Pharmacological Profile

The formulation combines:

• Acetaminophen: A widely used analgesic and antipyretic, with extensive over-the-counter (OTC) availability.
• Butalbital: A barbiturate-class sedative, historically employed for tension headaches but associated with dependence liabilities.
• Caffeine: Acts as a vasoconstrictor, enhancing analgesic efficacy in headache relief.
• Codeine phosphate: An opioid analgesic providing additional pain control, but with high potential for dependence and misuse.

This synergy creates a potent prescription medication favored for episodic migraine management but subject to regulation due to its addictive constituents.

Market Size and Growth Trends

The global analgesics (including opioids and non-opioid analgesics) market was valued at approximately USD 20 billion in 2022, with expectations of continuous growth driven by aging populations and increasing prevalence of chronic pain. The subset comprising combination drugs with opioids like codeine is significant, although faced with regulatory and societal pressures reducing growth prospects.

In the United States, prescriptions for opioids peaked in the early 2010s but declined markedly post-2016 owing to epidemiological and regulatory efforts. Nevertheless, formulations like acetaminophen with butalbital and codeine retain a niche segment for tension headaches, primarily in states with more permissive prescribing norms.

Regional Market Variations

• United States: Dominant for prescription opioids, but facing tightening restrictions due to opioid misuse concerns.
• Europe: Greater restrictions on barbiturates, leading to reduced use of butalbital-containing formulations.
• Emerging Markets: Growing demand for pain management solutions, with less stringent controls, presenting opportunities for niche drug segments.

Regulatory Landscape and Impact on Market Dynamics

Regulatory Challenges and Reforms

The primary regulatory issues impacting this drug formulation are:

• Opioid Resurgence and Restriction: Heightened opioid regulations, including prescription monitoring programs, restrict access to codeine-containing combinations.
• Barbiturate Schedules: Butalbital's scheduling varies by jurisdiction, with many countries reclassifying it to control misuse.
• Acetaminophen Limits: Concerns over hepatotoxicity at high doses restrict maximum daily doses, influencing formulation development.
• FDA and EMA Regulations: Regulatory agencies increasingly scrutinize combination drugs containing opioids or barbiturates, often demanding rigorous safety profiles.

Patent Protection and Generic Entry

Most formulations of this combination faced patent expirations in the late 2000s and early 2010s, leading to an influx of generics. The loss of exclusivity eroded profitability for branded products, pressing manufacturers to innovate or reformulate. For example, branded drugs like Fioricet with Codeine faced significant generic competition, impacting revenue streams.

Market Forces and Competitive Landscape

Key Competitors

• Other Migraine and Headache Medications: Triptans (e.g., sumatriptan), NSAIDs, and newer combination therapies that avoid opioids.
• Non-Opioid Combination Analgesics: Acetaminophen with NSAIDs or NSAID-free formulations gaining favor.
• Brand vs. Generic: The preponderance of generics has diminished the valuation of branded products but increased accessibility.

Innovation and Reformulation Strategies

• Non-Opioid Alternatives: Companies investing in non-opioid, non-barbiturate formulations to address societal health concerns and market restrictions.
• New Delivery Mechanisms: Transdermal patches or novel oral delivery systems aimed at improving compliance and reducing abuse potential.
• Combination Drugs with Abuse-deterrent Features: Incorporating abuse-deterrent formulations to mitigate misuse.

Societal and Ethical Considerations

The opioid epidemic has significantly altered prescribing behaviors, with many countries implementing strict guidelines, thus impacting market size. These societal shifts favor development of safer alternatives, leading to a potential decline in demand for combination drugs containing codeine.

Financial Trajectory and Future Outlook

Revenue Trends and Profitability

• Historical Data: Revenue peaks correlated with patent protections and widespread prescription practices.
• Current Trends: Declining due to regulatory restrictions, societal concerns about opioids, and availability of safer alternatives.
• Forecasts: Market analysts project continued contraction for formulations containing codeine and butalbital in countries with strict opioid policies. However, niche markets persist driven by specific indications and patient preferences.

Growth Drivers

• Expansion into Emerging Markets: Less regulated markets could sustain or grow demand for these formulations.
• Reformulation and Innovation: Developing abuse-deterrent, non-addictive formulations could unlock new revenue streams.
• Pain Management Paradigm Shift: Emphasis on multimodal and non-opioid pain therapies may re-center market focus.

Risks and Challenges

• Regulatory Stringency: Rapid policy changes can abruptly diminish market size.
• Market Saturation: Generics dominate, limiting profit margins.
• Public Perception and Litigation: Litigation related to opioid misuse damages brand reputation and financial stability.

Conclusion: Strategic Perspectives

The financial trajectory for acetaminophen; butalbital; caffeine; codeine phosphate hinges upon regulatory shifts, societal attitudes, and innovation. While current trends favor decline in high-opioid formulations, emerging opportunities in less regulated markets and reformulated, abuse-deterrent versions maintain potential for growth. Companies aligning R&D with evolving regulatory and societal demands will better position to capitalize on these dynamics.

---

Key Takeaways

• Regulatory landscape exerts a decisive influence, with increasing restrictions on opioids and barbiturates constricting market expansion but encouraging innovation.
• Patent expirations have transitioned the market towards generics, compressing margins but expanding accessibility.
• Societal concerns about misuse and addiction challenge ongoing demand; reformulation with abuse-deterrent features can mitigate impact.
• Emerging markets offer growth avenues amid declining mature market demand.
• Innovation is critical, with focus on non-addictive, safer alternatives aligning with global pain management trends.

---

FAQs

1. What are the primary factors influencing demand for acetaminophen-based combination drugs?
   Demand is driven by clinical efficacy in migraine and tension headache treatment, prescribing practices, regulatory restrictions on opioids, societal concerns about dependence, and the availability of alternative therapies.

2. How has the opioid epidemic affected the market for codeine-containing formulations?
   The epidemic prompted stricter regulatory controls and reduced prescribing of opioids, leading to declines in demand for such combination drugs, especially in North America and Europe.

3. Are there ongoing innovation efforts to replace codeine in these formulations?
   Yes. Pharmaceutical development focuses on non-opioid alternatives, abuse-deterrent formulations, and novel delivery systems to improve safety and compliance.

4. What are key regional differences affecting market prospects?
   The U.S. and Europe have tighter regulatory controls limiting use, whereas emerging markets have less restrictive policies, offering growth potential for these drugs.

5. What is the outlook for branded versus generic versions of this drug combination?
   Patents have expired, leading to dominance by generics. Branded products face revenue decline but may differentiate through abuse-deterrent features or novel formulations.

---

Sources
[1] MarketResearch.com: Global Pain Management Market Insights, 2022
[2] FDA Drug Approvals and Regulations Database, 2022
[3] IQVIA Prescription Data, 2022
[4] World Health Organization: Managing Pain with Opioids, 2021
[5] Deloitte Insights: Trends in Pharmaceutical Innovation, 2022