When will the patents on OXYCODONE 5/APAP 500 expire, and when will generic OXYCODONE 5/APAP 500 be available?

Sponsor	Phase
Christopher D. Verrico	PHASE1
Baylor College of Medicine	PHASE1
Greta and Johan Kock Foundation	PHASE4

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Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Bristol Myers Squibb	OXYCODONE 5/APAP 500	acetaminophen; oxycodone hydrochloride	TABLET;ORAL	085911-001	Approved Prior to Jan 1, 1982		DISCN	No	No	⤷ Start Trial	⤷ Start Trial				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Exclusivity Expiration

Last updated: September 24, 2026

Oxycodone 5 mg/acetaminophen 500 mg, commonly called oxycodone/APAP 5/500 or oxycodone-paracetamol 5/500, is a legacy immediate-release opioid combination. In the United States, the product has largely been replaced by oxycodone/APAP 5/325 after the FDA required manufacturers to reduce acetaminophen content in prescription combination products. The 5/500 presentation has no meaningful branded exclusivity protection, faces extensive generic competition, and has limited standalone financial visibility because sales are reported within broader generic portfolios.

What is oxycodone 5/APAP 500?

Oxycodone/APAP 5/500 contains 5 mg of oxycodone hydrochloride and 500 mg of acetaminophen per tablet. Oxycodone provides opioid analgesia, while acetaminophen adds non-opioid analgesic activity.

Attribute	Product profile
Active ingredients	Oxycodone hydrochloride and acetaminophen
Strength	5 mg oxycodone / 500 mg acetaminophen
Dosage form	Immediate-release oral tablet
Drug class	Opioid analgesic combination
U.S. controlled-substance status	Schedule II
Primary historic brand	Percocet
Current U.S. market position	Legacy or discontinued 5/500 presentation; 5/325 is the principal replacement strength
Main competitors	Generic oxycodone/APAP 5/325, oxycodone immediate-release tablets, hydrocodone/APAP, tramadol and non-opioid analgesics
Primary commercial channel	Retail pharmacy, hospital and institutional procurement

The 5/500 formulation is commercially distinct from oxycodone/APAP 5/325. The lower-acetaminophen formulation became the standard U.S. replacement after FDA action on prescription combination products.

What is the FDA regulatory status of oxycodone/APAP 5/500?

The FDA required manufacturers of prescription combination products containing acetaminophen to limit the amount of acetaminophen to no more than 325 mg per dosage unit. The agency cited the risk of severe liver injury, particularly when patients exceed the recommended daily acetaminophen dose or combine multiple acetaminophen-containing medicines.[1]

The regulatory change materially weakened the U.S. commercial position of the 5/500 presentation:

Manufacturers had to reformulate affected products.
Oxycodone/APAP 5/500 lost practical relevance in the U.S. prescription market.
Oxycodone/APAP 5/325 became the dominant successor strength.
Prescribers and pharmacies shifted toward lower-acetaminophen products.
The change reduced the value of legacy 5/500 inventory, manufacturing lines and product-specific marketing.

The FDA-approved U.S. product commonly associated with the category is Percocet, originally marketed by Endo Pharmaceuticals and its predecessors. Current U.S. labeling and product availability should be assessed by specific NDC and application number because generic manufacturers have different approval and marketing statuses.

When did oxycodone/APAP 5/500 lose exclusivity?

The 5/500 product lost practical exclusivity many years ago through generic competition and the expiration of legacy branded protections. Its current commercial constraint is regulatory and competitive rather than patent-based.

Exclusivity category	Assessment
New chemical entity exclusivity	Not applicable to this long-established combination
Orphan exclusivity	Not applicable
Pediatric exclusivity	No material current protection identified
Branded formulation exclusivity	Expired or commercially obsolete
Generic entry	Established for many years
Current patent barrier	No material Orange Book patent barrier indicated for the legacy 5/500 strength
Regulatory exclusivity for 5/500	None identified as commercially relevant

Because oxycodone and acetaminophen are established active ingredients, the product does not have the exclusivity profile of a recently approved branded medicine. Any remaining patents would need to be evaluated by application, formulation, jurisdiction and claim scope. They would not generally restore market exclusivity to the legacy 5/500 tablet.

What patents protect oxycodone 5/APAP 500?

No active patent estate appears to provide meaningful market protection for the legacy U.S. oxycodone/APAP 5/500 tablet. The relevant intellectual-property categories are:

Active-ingredient patents

The underlying active ingredients are old and widely genericized. Composition-of-matter patent protection is not commercially relevant to this product.

Combination-product patents

A combination patent could theoretically claim a specific ratio, release profile or manufacturing process. Such claims would need to distinguish the product from decades of prior art involving oxycodone and acetaminophen. No current combination patent is known to block ordinary generic manufacture of the immediate-release 5/500 tablet.

Formulation patents

Immediate-release tablets generally have limited formulation differentiation. Excipients, compression methods and coating systems may be protected in isolated cases, but these patents do not typically prevent approval of non-infringing generic formulations.

Method-of-use patents

Pain-treatment use claims may exist in historical patent records, but broad treatment of acute or chronic pain with oxycodone/APAP is unlikely to create a meaningful modern barrier. Method-of-use patents also have limited value where generic products are approved for the same established indication through an abbreviated pathway.

How many patents cover oxycodone/APAP 5/500?

The commercially relevant answer is none that presently block ordinary U.S. generic entry into the legacy immediate-release product. The FDA Orange Book remains the principal source for patents listed against approved reference products, but Orange Book listings must be checked against the precise NDA, strength and dosage form.[2]

Patent counts can be misleading in this category because:

Historical patents may have expired.
Patents may cover a different strength, such as 5/325.
Extended-release oxycodone patents do not apply to immediate-release tablets.
Manufacturing patents may not cover all generic processes.
A listed patent does not establish infringement or enforceability.
A patent against a branded reference product may not cover every generic formulation.

The practical patent risk for a generic manufacturer is therefore low relative to regulatory, supply-chain and controlled-substance compliance risk.

What is the Orange Book status of oxycodone/APAP 5/500?

The Orange Book status must be analyzed at the product-application level. The historic Percocet reference product and successor oxycodone/APAP products may have different application records, marketing statuses and listed patents.

For commercial diligence, the relevant checks are:

Orange Book issue	Commercial significance
Reference listed drug	Establishes the product used for abbreviated generic applications
Therapeutic equivalence code	Determines whether a generic is rated substitutable
Marketing status	Shows whether the reference or generic is currently marketed
Patent listing	Identifies patents submitted by the NDA holder
Exclusivity	Shows any remaining regulatory protection
Discontinued status	Helps distinguish discontinued products from active market products

A discontinued 5/500 reference presentation does not necessarily eliminate generic availability. Generic manufacturers may have historical approvals, but commercial supply depends on active marketing, manufacturing capacity, DEA quotas and pharmacy demand.

Which companies manufacture or compete with oxycodone/APAP?

The U.S. market has historically included branded and generic manufacturers such as Endo, Mallinckrodt, Hikma, Amneal, Rhodes Pharmaceuticals, Par Pharmaceutical, Solco Healthcare and other approved ANDA holders. The competitive set changes as companies enter or exit the market.

The principal substitutes are:

Product	Competitive relationship
Oxycodone/APAP 5/325	Direct reformulated successor
Oxycodone immediate-release 5 mg	Removes acetaminophen exposure
Hydrocodone/APAP	Major opioid combination substitute
Tramadol	Lower-potency prescription alternative
Ibuprofen or naproxen	Non-opioid alternatives
Acetaminophen alone	Lower-risk non-opioid substitute for selected pain
Extended-release opioids	Different indication and abuse-risk profile

The shift from 5/500 to 5/325 was not a conventional loss of market share to a rival brand. It was a forced product migration within the same therapeutic category, followed by broader opioid-volume contraction.

What generic entry risks exist for oxycodone/APAP 5/500?

Generic-entry risk is high because the product has:

Long-established active ingredients.
A simple immediate-release tablet.
No meaningful new-drug exclusivity.
No apparent current patent barrier.
Multiple historical ANDA pathways.
A large base of manufacturing know-how.

The principal risks for a generic entrant are operational rather than intellectual property-related.

Regulatory and compliance risks

Oxycodone is a Schedule II controlled substance. Manufacturers and distributors must comply with DEA registration, quota controls, suspicious-order monitoring, recordkeeping and secure handling requirements.[3]

Manufacturing risks

Manufacturers must manage:

Controlled-substance API sourcing.
DEA production quotas.
Tablet-content uniformity.
Acetaminophen dose accuracy.
Cross-contamination controls.
Serialization and supply-chain traceability.
Quality-system compliance.

Commercial risks

A new entrant would compete in a mature, price-sensitive market with limited differentiation. Pharmacy buyers and wholesalers generally favor reliable supply, competitive pricing and established compliance records. A product that is technically approved may still be commercially unattractive if the 5/500 strength has limited demand.

What happened to the 5/500 market after the acetaminophen reduction?

The FDA action changed the product mix. Before reformulation, a patient receiving multiple tablets per day could accumulate substantial acetaminophen exposure. The 5/325 formulation reduced acetaminophen per tablet while preserving the same 5 mg oxycodone dose.

This produced several market effects:

Existing 5/500 products were discontinued, reformulated or deprioritized.
Pharmacies substituted 5/325 where clinically appropriate.
Prescribers became more attentive to total daily acetaminophen exposure.
Manufacturers concentrated on the 5/325 strength.
The 5/500 product became a low-priority or residual SKU.

The change also reinforced demand for oxycodone-only products in cases where acetaminophen exposure was undesirable.

How strong is the patent estate for oxycodone/APAP 5/500?

The patent estate is weak from a market-exclusivity perspective. The product has no evident protection comparable to a modern branded drug with active composition, formulation and method-of-use patents.

Patent-strength factor	Assessment
Composition-of-matter protection	None of practical relevance
Combination-product protection	Weak or expired for the legacy tablet
Formulation differentiation	Limited
Method-of-use protection	Low commercial value
Generic design-around difficulty	Low
Litigation leverage	Low
Regulatory dependence	High
Supply-chain dependence	High

The more important barriers are controlled-substance regulation, product discontinuation, manufacturing economics and demand erosion.

What patent litigation and Paragraph IV challenges affect the product?

No major current Paragraph IV controversy is commercially central to the legacy 5/500 presentation. Paragraph IV litigation historically has been more relevant to newer oxycodone formulations, abuse-deterrent products and extended-release products than to an old immediate-release combination tablet.

For the 5/500 product, generic approval risk is more likely to involve:

FDA completeness or bioequivalence questions.
Manufacturing-site compliance.
Controlled-substance quota availability.
Product discontinuation.
Commercial launch economics.

A Paragraph IV filing would have limited strategic value unless it targeted an active reference product with enforceable patents. The 5/500 strength does not present that profile.

Are there biosimilar risks for oxycodone/APAP 5/500?

No. Biosimilar competition is not relevant because oxycodone/APAP is a chemically synthesized small-molecule drug, not a biologic. Competition occurs through generic-drug pathways, principally ANDAs and therapeutic-equivalence determinations under the Federal Food, Drug, and Cosmetic Act.

What licensing deals involve oxycodone/APAP 5/500?

No material current licensing transaction is central to the 5/500 product. The product has historically been sold through branded ownership changes, generic supply agreements, contract manufacturing and distributor arrangements rather than through high-value innovation licenses.

Any transaction analysis should separate:

Brand acquisition of opioid portfolios.
Generic product commercialization agreements.
API supply contracts.
Contract manufacturing arrangements.
Distribution agreements.
Abuse-deterrent technology licenses.

Those transactions may involve oxycodone products broadly without covering the legacy 5/500 tablet specifically.

What is the financial trajectory of oxycodone/APAP 5/500?

Standalone revenue is generally not disclosed because the product is generic, sold across multiple manufacturers and reported within broader portfolios. The financial trajectory is best characterized as structural decline.

Period	Financial direction	Primary driver
Pre-2011	Mature, high-volume combination-opioid market	Broad prescribing and established brand demand
2011-2014	Decline in 5/500 sales	FDA acetaminophen reduction and reformulation
Mid-2010s	Continued contraction	Opioid prescribing controls and scrutiny
Late 2010s	Low-margin mature generic category	Price competition and reduced utilization
2020s	Residual or discontinued commercial position	Shift to 5/325, oxycodone-only and non-opioid therapy

The 5/500 product has several negative financial characteristics:

Low unit differentiation.
Weak pricing power.
Limited brand loyalty.
High compliance costs relative to product value.
Declining clinical preference.
Potentially narrow manufacturing runs.
Low return on regulatory maintenance.

The 5/325 product is commercially more relevant, but it also operates in a mature generic market with pricing pressure and opioid-demand constraints.

What is the geographic coverage of the product?

The product has had broad historical international availability, but strength, brand name and regulatory status vary by country. Outside the United States, oxycodone/APAP combinations may be marketed under different names or may face tighter restrictions.

Geographic factors include:

National controlled-substance scheduling.
Prescription and reimbursement rules.
Acetaminophen dose limits.
Opioid stewardship policies.
Local generic-substitution rules.
Import and API controls.
National tendering and hospital procurement.

U.S. commercial analysis should not be extrapolated directly to Canada, Europe, Australia or emerging markets. In many jurisdictions, oxycodone combinations face strict prescribing controls and limited reimbursement.

What generic launch scenarios exist?

A new 5/500 generic launch would have three likely scenarios:

Full commercial launch

This is unlikely in the current U.S. market unless a manufacturer identifies durable demand from institutional buyers, shortage conditions or a niche distribution channel.

Limited or opportunistic launch

A manufacturer could maintain approval but market the product only when customer demand, supply constraints or contract opportunities justify production.

No active launch

The manufacturer could hold an approved application without meaningful commercial distribution because the 5/500 strength has been superseded by 5/325.

The highest-value opportunity is generally not the legacy 5/500 product. It is reliable supply of currently demanded oxycodone/APAP 5/325 or oxycodone immediate-release products, subject to DEA quota and compliance capacity.

Key Takeaways

Oxycodone 5 mg/acetaminophen 500 mg is a legacy immediate-release combination product.
The FDA’s acetaminophen reduction initiative drove the U.S. market toward oxycodone/APAP 5/325.[1]
The 5/500 product has no meaningful current exclusivity or patent barrier.
Generic-entry risk is high, but commercial demand for the specific 5/500 strength is limited.
Controlled-substance compliance, DEA quotas and manufacturing economics are more important than patent litigation.
Biosimilar risk does not apply.
Standalone product revenue is not generally reported; the financial trajectory is one of long-term decline.
The commercially relevant successor is oxycodone/APAP 5/325, not the legacy 5/500 formulation.
A new launch would likely require a niche supply, institutional or shortage-related rationale.

FAQs

Is oxycodone/APAP 5/500 still available in the United States?

The 5/500 strength has largely been discontinued or replaced by 5/325. Availability depends on the specific manufacturer, NDC and pharmacy inventory.

Why was oxycodone/APAP changed from 5/500 to 5/325?

The FDA required manufacturers to reduce acetaminophen in prescription combination products because of the risk of severe liver injury from excessive acetaminophen exposure.[1]

Is oxycodone/APAP 5/500 stronger than 5/325?

Both products contain 5 mg of oxycodone. The 5/500 product contains 175 mg more acetaminophen per tablet.

Can a generic manufacturer still launch oxycodone/APAP 5/500?

A manufacturer may pursue approval or maintain an existing approval if regulatory requirements are met, but commercial demand and controlled-substance supply constraints make the product less attractive than 5/325.

Does oxycodone/APAP 5/500 have a patent that blocks generic competition?

No meaningful current patent barrier is commercially apparent for the legacy immediate-release 5/500 tablet. Orange Book status must be reviewed for the specific reference application and product listing.[2]

References

U.S. Food and Drug Administration. (2011). FDA drug safety communication: Prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure. https://www.fda.gov/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Drug Enforcement Administration. (2024). Drug scheduling. https://www.dea.gov/drug-information/drug-scheduling

US Patents:	0
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	1
Clinical Trials:	632
Patent Applications:	109
DailyMed Link:	OXYCODONE 5/APAP 500 at DailyMed

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