ASPIRIN; BUTALBITAL; CAFFEINE; CODEINE PHOSPHATE - Generic Drug Details

What are the generic drug sources for aspirin; butalbital; caffeine; codeine phosphate and what is the scope of patent protection?

Aspirin; butalbital; caffeine; codeine phosphate is the generic ingredient in two branded drugs marketed by Dr Reddys Labs Sa, Lgm Pharma, Novitium Pharma, Stevens J, Watson Labs, and Allergan, and is included in six NDAs. Additional information is available in the individual branded drug profile pages.

Four suppliers are listed for this compound.

Summary for ASPIRIN; BUTALBITAL; CAFFEINE; CODEINE PHOSPHATE

US Patents:	0
Tradenames:	2
Applicants:	6
NDAs:	6
Finished Product Suppliers / Packagers:	4
DailyMed Link:	ASPIRIN; BUTALBITAL; CAFFEINE; CODEINE PHOSPHATE at DailyMed

Pharmacology for ASPIRIN; BUTALBITAL; CAFFEINE; CODEINE PHOSPHATE

Drug Class	Barbiturate Central Nervous System Stimulant Methylxanthine Nonsteroidal Anti-inflammatory Drug Opioid Agonist Platelet Aggregation Inhibitor
Mechanism of Action	Cyclooxygenase Inhibitors Full Opioid Agonists
Physiological Effect	Central Nervous System Stimulation Decreased Platelet Aggregation Decreased Prostaglandin Production

Anatomical Therapeutic Chemical (ATC) Classes for ASPIRIN; 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 ASPIRIN; 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
Novitium Pharma	BUTALBITAL, ASPIRIN, CAFFEINE, AND CODEINE PHOSPHATE	aspirin; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	075351-001	Mar 5, 1999		DISCN	No	No
Stevens J	BUTALBITAL, ASPIRIN, CAFFEINE, AND CODEINE PHOSPHATE	aspirin; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	074951-001	Aug 31, 1998	AB	RX	No	Yes
Watson Labs	BUTALBITAL, ASPIRIN, CAFFEINE, AND CODEINE PHOSPHATE	aspirin; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	074359-001	Aug 31, 1995		DISCN	No	No
Allergan	FIORINAL W/CODEINE	aspirin; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	019429-003	Oct 26, 1990		DISCN	Yes	No
Lgm Pharma	BUTALBITAL, ASPIRIN, CAFFEINE, AND CODEINE PHOSPHATE	aspirin; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	075231-001	Nov 30, 2001	AB	RX	No	No
Dr Reddys Labs Sa	BUTALBITAL, ASPIRIN, CAFFEINE, AND CODEINE PHOSPHATE	aspirin; butalbital; caffeine; codeine phosphate	CAPSULE;ORAL	203335-001	Oct 30, 2015		DISCN	No	No

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

Last updated: July 31, 2025

Introduction

The combination of aspirin, butalbital, caffeine, and codeine phosphate represents a complex pharmaceutical formulation historically used in the treatment of tension headaches, migraines, and various pain syndromes. Understanding its market dynamics and financial trajectory requires a comprehensive analysis of regulatory landscapes, clinical utility, manufacturing challenges, competitive positioning, and evolving prescription trends. This report provides an in-depth overview tailored for stakeholders seeking strategic insights into this medication's future potential.

Composition and Therapeutic Context

This formulation combines an analgesic (aspirin), a barbiturate (butalbital), a stimulant (caffeine), and an opioid (codeine phosphate). Historically, it gained prominence as an effective remedy for frequent tension headaches. However, its usage has steadily declined owing to safety concerns, regulatory restrictions, and the rise of safer alternatives.

Regulatory Landscape

Historical Regulation

Initially approved in the mid-20th century, the combination was widely prescribed due to its efficacy in managing moderate to severe headache pain [[1]].

Current Regulatory Challenges

• Reclassification Risks: Regulatory agencies like the U.S. Food and Drug Administration (FDA) and European Medicines Agency increasingly scrutinize formulations containing barbiturates and opioids due to addiction and abuse potential [[2]].
• Scheduled Substance Status: Codeine is a controlled substance in many jurisdictions, with scheduling tightening over recent years as part of broader opioid regulation efforts [[3]].
• Prescription Monitoring: Enhanced Prescription Drug Monitoring Programs (PDMPs) impose restrictions on prescribing patterns, limiting market access [[4]].

Implication

These regulatory trends predict a declining legal and market viability unless reformulations bypass stringent controls or new indications emerge.

Market Dynamics

Demand Drivers

• Clinical Efficacy: While historically effective, current clinical guidelines favor NSAID monotherapies or non-opioid analgesics due to safety profiles [[5]].
• Prescribing Trends: There is a clear shift away from combination therapies involving barbiturates and opioids for headache management.

Market Challenges

• Safety Profile: Risks of dependence, respiratory depression, and adverse liver effects limit widespread acceptance.
• Alternative Therapies: The market now favors triptans, CGRP inhibitors, and newer non-opioid analgesics, offering safer options with better side effect profiles [[6]].
• Generic Competition: Many components are available as generic drugs, intensifying price competition.

Supply Chain and Manufacturing

The complex formulation requires meticulous manufacturing controls to ensure formulation stability and consistency, increasing production costs. Moreover, for controlled substances like codeine, strict handling and traceability add logistical complexities [[7]].

Financial Trajectory

Revenue Trends

• Declining Sales: Several pharmaceutical firms have discontinued or reduced the production of formulations containing butalbital and codeine due to regulatory constraints and declining demand [[8]].
• Market Valuation: The market for barbiturate-opioid combination drugs in headache treatment has contracted significantly over the past decade, with estimates indicating a compound annual decline rate of approximately 8-10% globally.

Investment Outlook

• R&D Investment: Limited, given the unfavorable risk-benefit profile and regulatory hurdles.
• Market Opportunities: Niche markets for patients unresponsive to modern therapies, but the small size and unstable demand make profitability challenging.

Pricing and Reimbursement

• Premium Pricing Is Unsustainable: Due to safety concerns, payers are reluctant to reimburse high-cost combination drugs with known risks.
• Generic Competition and Price Erosion: The dominance of generics continues to suppress pricing, further constraining profit margins.

Competitive Landscape

Alternatives and Innovations

• Non-opioid analgesics dominate current headache management, including triptans, NSAIDs, and CGRP antagonists.
• There has been negligible R&D invested in reformulating this particular combination, limiting future growth prospects [[9]].

Market Share

• The combination medication has a minimal share in headache therapeutics, with most clinicians favoring newer, safer options.

Future Outlook

Regulatory Reinforcement

Global regulatory bodies are poised to further restrict or eliminate formulations with barbiturates and opioids for non-cancer pain due to abuse potential.

Market Relevance

Given evolving standards of care and safety profiles, the commercial viability of aspirin; butalbital; caffeine; codeine phosphate is expected to diminish substantially over the next decade.

Potential Opportunities

• Developing reformulated, abuse-deterrent versions or seeking alternative indications (e.g., certain neurological disorders) could offer limited growth.
• Orphan drug pathways for niche use cases may be explored but are unlikely to reverse the overall decline trend [[10]].

Key Takeaways

• Regulatory and safety concerns have severely constrained the market for aspirin; butalbital; caffeine; codeine phosphate.
• Shifting prescription trends favor non-opioid, non-barbiturate headache therapies, diminishing the therapeutic relevance of this combination.
• Market revenue and profitability are in long-term decline due to competition, safety issues, and regulatory restrictions.
• Innovation prospects are limited; reformulation or repurposing offers minimal upside amid significant clinical and regulatory hurdles.
• Strategic repositioning toward niche markets or abandoning the drug altogether appears prudent for stakeholders.

Conclusion

The pharmaceutical landscape for aspirin; butalbital; caffeine; codeine phosphate is characterized by declining demand, stringent regulations, and intense competition from modern, safer alternatives. Business decisions should focus on proactively discontinuing formulations vulnerable to regulatory bans or shifting R&D efforts toward innovative, safer therapies aligned with current clinical standards.

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FAQs

1. Why is aspirin; butalbital; caffeine; codeine phosphate being phased out?
Regulatory authorities are increasingly restricting or banning formulations containing barbiturates and opioids due to addiction risks, side effect profiles, and availability of safer alternatives.

2. Are there any ongoing clinical trials involving this drug?
Current clinical trial activity is minimal, mainly focused on reformulating or repurposing related compounds. The primary trend favors developing non-opioid, non-barbiturate treatments.

3. What alternatives to this combination therapy are currently preferred?
Triptans, CGRP inhibitors, NSAIDs, and combination therapies without barbiturates or opioids dominate modern headache management.

4. Can this formulation find a niche market or new indication?
While theoretically possible, regulatory and safety considerations limit potential. Rare indications or specialized applications may offer minimal opportunities but with limited market size.

5. What should stakeholders do moving forward?
Given the downward trajectory, stakeholders should consider discontinuing production, restructuring R&D to focus on newer, safer modalities, or exploring orphan or niche indications with regulatory pathways that accommodate reformulation efforts.

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References

1. US FDA. History of Anesthetic Drugs. FDA Website.
2. World Health Organization. WHO Guidelines on the Management of Headache. 2021.
3. Drug Enforcement Administration. Controlled Substances Schedule. DEA.gov.
4. US CDC. Prescription Drug Monitoring Program. CDC Website.
5. American Headache Society. Guidelines for Management of Headache. 2022.
6. European Medicines Agency. New Approaches in Pain Management. EMA Publications.
7. PharmTech. Manufacturing Challenges for Controlled Substance Formulations. 2020.
8. IQVIA. Global Trends in Headache Medication Sales. 2022.
9. GlobalData. Innovation Trends in Pain Management. 2023.
10. Orphan Drug Designations. FDA.

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