TYLENOL W/ CODEINE NO. 4 Drug Patent Profile

When do Tylenol W/ Codeine No. 4 patents expire, and what generic alternatives are available?

Tylenol W/ Codeine No. 4 is a drug marketed by Ortho Mcneil Pharm and Janssen Pharms and is included in two NDAs.

The generic ingredient in TYLENOL W/ CODEINE NO. 4 is acetaminophen; codeine phosphate. There are sixty-six drug master file entries for this compound. Twenty-five suppliers are listed for this compound. Additional details are available on the acetaminophen; codeine phosphate profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Tylenol W/ Codeine No. 4

A generic version of TYLENOL W/ CODEINE NO. 4 was approved as acetaminophen; codeine phosphate by SUN PHARM INDS LTD on December 31^st, 1969.

Summary for TYLENOL W/ CODEINE NO. 4

US Patents:	0
Applicants:	2
NDAs:	2
Raw Ingredient (Bulk) Api Vendors:	1
Clinical Trials:	25
Patent Applications:	69
DailyMed Link:	TYLENOL W/ CODEINE NO. 4 at DailyMed

Recent Clinical Trials for TYLENOL W/ CODEINE NO. 4

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

Sponsor	Phase
University of Oklahoma	PHASE4
Eurofarma Laboratorios S.A.	Phase 3
Humber River Hospital	Phase 4

See all TYLENOL W/ CODEINE NO. 4 clinical trials

US Patents and Regulatory Information for TYLENOL W/ CODEINE NO. 4

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Ortho Mcneil Pharm	TYLENOL W/ CODEINE NO. 4	acetaminophen; codeine phosphate	CAPSULE;ORAL	087421-001	Approved Prior to Jan 1, 1982		DISCN	No	No
Janssen Pharms	TYLENOL W/ CODEINE NO. 4	acetaminophen; codeine phosphate	TABLET;ORAL	085055-004	Approved Prior to Jan 1, 1982		DISCN	Yes	No

TYLENOL WITH CODEINE NO. 4 Market Dynamics, Patent Status, and Financial Trajectory

Last updated: August 2, 2026

TYLENOL with Codeine No. 4 is a mature prescription combination containing 300 mg of acetaminophen and 60 mg of codeine phosphate per tablet. Its commercial position is driven by generic competition, opioid prescribing restrictions, controlled-substance compliance, and the declining use of high-dose codeine products. The product has little or no remaining patent-based market protection, and its product-level revenue is not publicly disclosed. The financial trajectory is therefore best characterized as a low-growth, volume-constrained prescription franchise rather than a branded growth asset.

What is TYLENOL with Codeine No. 4?

TYLENOL with Codeine No. 4 combines acetaminophen with 60 mg of codeine phosphate. The product is indicated for the relief of mild to moderately severe pain when treatment with an opioid is appropriate and alternative treatments are inadequate.[1]

Attribute	TYLENOL with Codeine No. 4
Active ingredients	Acetaminophen 300 mg; codeine phosphate 60 mg
Dosage form	Oral tablet
Prescription status	Prescription-only
Federal controlled-substance schedule	Schedule III
Therapeutic category	Opioid analgesic
Primary market	United States
Reference-product position	Mature, off-patent combination product
Main substitutes	Generic acetaminophen/codeine, hydrocodone combinations, oxycodone combinations, tramadol, NSAIDs
Key commercial constraint	Opioid stewardship and acetaminophen-related safety risk

The 60 mg codeine strength distinguishes No. 4 from No. 3, which generally contains 30 mg of codeine with 300 mg of acetaminophen. The higher codeine dose creates a narrower prescribing market because clinicians must balance analgesic benefit against respiratory depression, dependence, misuse, and variable metabolism through CYP2D6.[1]

What is the FDA status of TYLENOL with Codeine No. 4?

TYLENOL with Codeine No. 4 is an FDA-approved prescription opioid combination, but its commercial availability has varied by manufacturer and distributor. The FDA-approved labeling carries opioid class warnings covering addiction, abuse, misuse, life-threatening respiratory depression, accidental ingestion, neonatal opioid withdrawal, and interactions with benzodiazepines or other central nervous system depressants.[1]

The FDA has restricted pediatric use of codeine-containing products. Codeine is contraindicated for pain treatment in children younger than 12 years and after tonsillectomy or adenoidectomy in patients younger than 18 years. Breastfeeding is also contraindicated because of the risk of serious adverse reactions in nursing infants.[2]

The product remains subject to:

• Prescription controls.
• State opioid-prescribing limits.
• Pharmacy dispensing requirements.
• Prescription drug monitoring program reporting.
• Manufacturer quota and security requirements.
• FDA post-market safety monitoring.
• Acetaminophen toxicity warnings.

Because the product is Schedule III rather than Schedule II, federal refill rules are less restrictive than those for hydrocodone or oxycodone combination products. A prescription may generally be refilled up to five times within six months under federal law, subject to state law and prescriber judgment.[3]

What patents protect TYLENOL with Codeine No. 4?

No meaningful current patent barrier is associated with the core TYLENOL with Codeine No. 4 formulation. The product is based on long-established active ingredients and a conventional immediate-release tablet. Any original formulation or composition patents would have expired decades ago.

The commercial protection profile is therefore:

Protection category	Current importance
Active-ingredient patent	None of practical commercial significance
Basic combination patent	Expired or commercially irrelevant
Immediate-release tablet patent	No material barrier identified
Method-of-use patent	No known material exclusivity protecting the core product
Formulation patent	No known blocking protection for the standard tablet
Regulatory exclusivity	Expired
Controlled-substance manufacturing controls	Material operational barrier, not exclusivity
Brand recognition	Limited value in a prescription generic market

The FDA Orange Book is the principal source for listed patents and regulatory exclusivity associated with approved drug products.[4] For this mature combination, market access depends primarily on FDA approval, manufacturing capability, DEA compliance, supply reliability, and contracting rather than patent enforcement.

When does TYLENOL with Codeine No. 4 lose exclusivity?

TYLENOL with Codeine No. 4 lost practical market exclusivity long ago. The active ingredients and tablet combination have been available in generic form for many years. Generic acetaminophen/codeine products are marketed in multiple strengths, including the 300 mg/60 mg configuration.

Milestone	Commercial effect
Original branded approval	Established the prescription combination
Expiration of original patent and exclusivity rights	Opened the market to generic manufacturers
Expansion of generic supply	Reduced branded pricing power
Opioid prescribing controls	Reduced addressable demand
Current market	Mature, fragmented, low-growth prescription segment

There is no current exclusivity period comparable to the five-year new chemical entity period, three-year clinical-investigation exclusivity, or seven-year orphan-drug exclusivity. Those FDA exclusivity mechanisms are not relevant to this established combination product.[4]

How many patents cover TYLENOL with Codeine No. 4?

The practical answer is zero blocking patents for the standard commercial product. The relevant product consists of well-established ingredients in a conventional tablet, and no active patent estate appears to protect the core 300 mg acetaminophen/60 mg codeine formulation.

A manufacturer could still hold patents involving:

• A modified-release delivery system.
• A novel abuse-deterrent formulation.
• A specific manufacturing process.
• A new fixed-dose combination.
• A distinct dosage form.
• A new method of treating a defined patient population.

Those patents would not automatically block ordinary immediate-release generic acetaminophen/codeine tablets. Patent analysis must distinguish the conventional No. 4 tablet from separately patented opioid-delivery technologies.

Are there Paragraph IV challenges to TYLENOL with Codeine No. 4?

Paragraph IV litigation is not a major current market driver for this product. Generic manufacturers entered the market after the relevant exclusivity expired, and the standard product does not depend on a recent patent estate.

A Paragraph IV certification could still arise if a manufacturer files an ANDA against a listed patent covering a specific formulation, labeling method, or delivery technology. That scenario is more relevant to a modified product than to conventional immediate-release No. 4 tablets.

The principal competitive mechanism is therefore ordinary ANDA approval and generic substitution, not patent invalidity litigation. The FDA Orange Book identifies reference listed drugs, approved generic products, patents, and exclusivity information used in ANDA certification analysis.[4]

What formulations are protected by TYLENOL with Codeine No. 4?

The conventional product is an immediate-release tablet. It does not have an identified commercially important formulation barrier.

Formulation characteristics

The principal formulation risks are clinical and regulatory rather than intellectual property risks:

• Acetaminophen hepatotoxicity if total daily intake is excessive.
• Codeine-related respiratory depression.
• Variable conversion of codeine to morphine.
• Abuse, dependence, and diversion.
• Drug interactions involving CYP2D6 and central nervous system depressants.
• Medication errors involving multiple acetaminophen-containing products.

An abuse-deterrent or extended-release formulation could carry separate intellectual property rights, but those protections would not cover the standard No. 4 tablet.

Which companies compete with TYLENOL with Codeine No. 4?

Competition comes from generic manufacturers and alternative analgesics. The branded name has limited control over prescribing because pharmacies and payers generally substitute therapeutically equivalent generic products.

Direct generic competitors

Generic suppliers may include companies with approved acetaminophen/codeine ANDAs, contract manufacturers, and regional distributors. The competitive set can change with product discontinuations, shortages, FDA approvals, and wholesaler purchasing decisions.

Direct competition is based on:

• Wholesale acquisition price.
• Medicaid and commercial payer reimbursement.
• Supply continuity.
• DEA quota availability.
• Product quality and manufacturing history.
• Package sizes.
• Pharmacy wholesaler coverage.
• Ability to meet controlled-substance security requirements.

Therapeutic competitors

Product category	Competitive effect
Hydrocodone/acetaminophen	Stronger opioid alternative but Schedule II controls increase prescribing friction
Oxycodone/acetaminophen	Higher-potency alternative with greater misuse and regulatory scrutiny
Tramadol	Alternative opioid with different scheduling and efficacy profile
NSAIDs	Important non-opioid substitutes for inflammatory or musculoskeletal pain
Acetaminophen alone	Lower-risk option for mild pain
Nonpharmacologic therapy	Reduces demand in chronic pain treatment

Hydrocodone combination products were moved to Schedule II in 2014, increasing prescribing and refill controls relative to codeine combinations.[5] That change improved the relative administrative convenience of Schedule III codeine products in some settings, but it did not reverse the broader decline in opioid prescribing.

How strong is the TYLENOL with Codeine No. 4 patent estate?

The patent estate is weak from a commercial protection standpoint. The product has:

1. No meaningful new-molecule protection.
2. No identified active patent protecting the conventional tablet.
3. No current regulatory exclusivity.
4. Multiple generic substitutes.
5. No apparent technology moat.
6. A market exposed to prescribing restrictions and clinical substitution.

Its strongest barriers are operational:

• DEA registration and controlled-substance compliance.
• Manufacturing validation.
• Supply-chain security.
• Acetaminophen and opioid quality controls.
• Pharmacovigilance.
• Retail and payer contracting.

These barriers can reduce the number of reliable suppliers, but they do not create durable branded pricing power.

What is the financial trajectory for TYLENOL with Codeine No. 4?

Product-level revenue is not separately reported by the brand owner or generic manufacturers. Public company filings generally combine Tylenol sales across broader consumer-health categories or report prescription products within larger portfolios. The revenue trajectory for No. 4 must therefore be assessed through market structure rather than a disclosed product sales series.

Revenue trajectory

Period	Expected commercial condition
Historical branded period	Higher brand recognition and pricing control
Generic-entry period	Rapid price and share erosion
Mature generic period	Low prices, fragmented supply, limited unit growth
Current period	Stable-to-declining demand with episodic supply volatility
Forward outlook	Continued volume pressure and limited pricing upside

The broader Tylenol brand remains commercially significant, but that does not establish revenue attributable to the prescription codeine product. Kenvue reports Tylenol as a major consumer-health brand, while prescription TYLENOL with Codeine economics are not separately identified in its public financial reporting.[6]

The financial profile of No. 4 is likely characterized by:

• Low average selling prices.
• Limited brand premium.
• High generic substitution.
• Low direct-to-consumer promotional value.
• Modest unit demand relative to OTC Tylenol.
• Working-capital exposure from controlled-substance inventory.
• Margin pressure when multiple generic suppliers compete.
• Potential price increases during shortages, offset by regulatory and payer constraints.

What market factors are shaping demand?

Opioid prescribing decline

The CDC reports a substantial long-term decline in opioid prescribing from its peak in 2011, although prescribing patterns vary by state, specialty, and patient population.[7] This trend constrains the addressable market for codeine combinations.

Safety restrictions

FDA warnings and pediatric restrictions have reduced use in children and narrowed treatment settings.[2] Prescribers also face increased scrutiny over opioid duration, dose, documentation, and concurrent sedative use.

Acetaminophen risk

No. 4 contains 300 mg of acetaminophen per tablet. At eight tablets per day, the acetaminophen exposure reaches 2,400 mg, before accounting for other acetaminophen-containing medicines. At higher tablet counts, the risk of liver injury increases. This safety issue limits dose escalation and supports substitution with other analgesics in some patients.[1]

Generic supply dynamics

Generic opioid supply is affected by DEA production quotas, manufacturing-site inspections, raw-material availability, distributor controls, and declining supplier participation. These factors can create temporary shortages even when long-term demand is stable.

Payer substitution

Medicare Part D plans, Medicaid programs, and commercial insurers generally favor low-cost generic products. Prior authorization is less likely to be the principal barrier for a low-cost generic than for branded specialty drugs, but formulary policies can determine which manufacturer supplies the prescription.

What generic launch risks exist for TYLENOL with Codeine No. 4?

Generic launch risk is low from a patent perspective and moderate from an operational perspective.

Low patent risk

A conventional ANDA applicant generally faces no meaningful patent wall associated with the basic product. A new entrant would not need to wait for branded exclusivity to expire.

Moderate operational risk

The principal launch risks include:

• FDA inspection findings.
• Controlled-substance quota limits.
• Difficulty securing codeine API.
• Wholesale distribution restrictions.
• Product recalls.
• Low market prices.
• Limited pharmacy demand.
• State-specific opioid regulations.
• Competition from established generic suppliers.

An entrant can obtain regulatory approval yet fail to achieve attractive returns because the market price is low and incumbent manufacturers already serve major wholesalers.

What patent litigation and settlement agreements affect the product?

No major current patent litigation or settlement structure is central to the conventional TYLENOL with Codeine No. 4 market. The product’s competitive history is defined by generic entry and prescription controls rather than by active branded patent enforcement.

Settlement risk would become relevant only if a manufacturer asserted a patent covering a distinct formulation, abuse-deterrent technology, or labeling method. Such a dispute would affect the patented variant, not necessarily conventional acetaminophen/codeine No. 4 tablets.

What geographic markets are covered?

The core product is primarily a U.S. prescription market. Geographic commercial differences arise from:

• State opioid-prescribing limits.
• State controlled-substance rules.
• Medicaid reimbursement.
• Pharmacy-chain purchasing.
• Local shortages.
• State prescription monitoring requirements.
• Regional prescribing patterns.

International markets use different brand names, codeine scheduling rules, acetaminophen limits, and regulatory pathways. U.S. FDA approval and Orange Book status do not establish market access in Canada, Europe, Australia, or other jurisdictions.

What is the outlook for TYLENOL with Codeine No. 4?

The outlook is mature and defensive. The product is likely to remain available for selected acute-pain prescriptions, but it has limited growth potential. The most likely commercial path is:

1. Continued generic substitution.
2. Stable or declining prescription volume.
3. Periodic supply disruption.
4. Limited branded pricing power.
5. Greater use of non-opioid alternatives.
6. Ongoing regulatory pressure.
7. Low probability of meaningful patent-driven revenue expansion.

The product can remain commercially viable for manufacturers with efficient controlled-substance operations, but it is unlikely to support a high-value licensing transaction or a premium pharmaceutical valuation on its own.

Key Takeaways

• TYLENOL with Codeine No. 4 contains 300 mg acetaminophen and 60 mg codeine phosphate.
• It is a mature Schedule III prescription opioid combination.
• The standard immediate-release tablet has no meaningful remaining patent or regulatory exclusivity.
• Generic competition, not patent litigation, controls the market.
• Product-level revenue is not publicly disclosed.
• The broader Tylenol brand's reported sales should not be used as a proxy for prescription No. 4 revenue.
• Demand is constrained by declining opioid prescribing, FDA safety restrictions, and competition from non-opioid analgesics.
• Manufacturing, DEA compliance, API supply, and wholesaler access are the main barriers to entry.
• The financial outlook is stable-to-declining, with limited upside from price or volume growth.

FAQs

Is TYLENOL with Codeine No. 4 stronger than No. 3?

Yes. No. 4 generally contains 60 mg of codeine phosphate, while No. 3 contains 30 mg. Both commonly contain 300 mg of acetaminophen per tablet.

Is TYLENOL with Codeine No. 4 still sold under the brand name?

Availability can vary by manufacturer, distributor, and market. Generic acetaminophen/codeine products are the primary competitive supply in the United States.

Can a generic company launch acetaminophen/codeine No. 4 without a patent license?

For the conventional immediate-release product, generic entry does not generally depend on a current branded patent license because the relevant core product protection has expired.

Why is codeine No. 4 Schedule III instead of Schedule II?

Federal scheduling rules permit certain codeine combination products containing no more than 90 mg of codeine per dosage unit to remain in Schedule III. The No. 4 strength contains 60 mg per tablet.[3]

Does TYLENOL with Codeine No. 4 contribute materially to total Tylenol revenue?

Public filings do not separately quantify revenue from the prescription codeine product. Reported Tylenol revenue generally reflects broader consumer-health sales and should not be attributed to No. 4.

References

1. U.S. Food and Drug Administration. (2024). TYLENOL with Codeine: Acetaminophen and codeine phosphate tablets prescribing information. FDA.

2. U.S. Food and Drug Administration. (2017). FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children. FDA Drug Safety Communication.

3. Drug Enforcement Administration. (2024). Drug scheduling. U.S. Department of Justice.

4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.

5. Drug Enforcement Administration. (2014). Schedules of controlled substances: Placement of hydrocodone combination products into Schedule II. 79 Fed. Reg. 49661.

6. Kenvue Inc. (2024). 2023 annual report. U.S. Securities and Exchange Commission.

7. Centers for Disease Control and Prevention. (2024). U.S. opioid dispensing rate maps and prescribing data. U.S. Department of Health and Human Services.