PROPOXYPHENE NAPSYLATE AND ACETAMINOPHEN Drug Patent Profile
When do Propoxyphene Napsylate And Acetaminophen patents expire, and what generic alternatives are available?
Propoxyphene Napsylate And Acetaminophen is a drug marketed by Able, Actavis Elizabeth, Cornerstone, Halsey, Ivax Sub Teva Pharms, Mallinckrodt, Mirror Pharms, Mutual Pharm, Mylan, Mylan Pharms Inc, Sandoz, Superpharm, Teva, Vintage Pharms, Watson Labs, Watson Labs Florida, and Wockhardt Ltd. and is included in twenty-six NDAs.
The generic ingredient in PROPOXYPHENE NAPSYLATE AND ACETAMINOPHEN is acetaminophen; propoxyphene napsylate. There is one drug master file entry for this compound. Additional details are available on the acetaminophen; propoxyphene napsylate profile page.
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Summary for PROPOXYPHENE NAPSYLATE AND ACETAMINOPHEN
| US Patents: | 0 |
| Applicants: | 17 |
| NDAs: | 26 |
| Raw Ingredient (Bulk) Api Vendors: | 2 |
| Patent Applications: | 38 |
| DailyMed Link: | PROPOXYPHENE NAPSYLATE AND ACETAMINOPHEN at DailyMed |
US Patents and Regulatory Information for PROPOXYPHENE NAPSYLATE AND ACETAMINOPHEN
Propoxyphene Napsylate and Acetaminophen Market Dynamics, FDA Withdrawal, and Financial Trajectory
Propoxyphene napsylate and acetaminophen, marketed primarily as Darvocet-N 50 and Darvocet-N 100, has no active U.S. pharmaceutical market. The FDA requested withdrawal of propoxyphene-containing products in November 2010 after safety data showed dose-dependent cardiac toxicity, including potentially fatal arrhythmias. Xanodyne Pharmaceuticals withdrew Darvocet and Darvon from the U.S. market, and generic manufacturers discontinued their products. The product’s commercial value collapsed from an established opioid analgesic franchise to a discontinued-product asset with no meaningful current revenue opportunity.[1]
What is propoxyphene napsylate and acetaminophen?
Propoxyphene napsylate and acetaminophen is an oral combination analgesic containing the opioid propoxyphene napsylate and nonopioid acetaminophen.
| Product | Propoxyphene napsylate strength | Acetaminophen strength | Historical dosage form |
|---|---|---|---|
| Darvocet-N 50 | 50 mg | 325 mg | Oral tablet |
| Darvocet-N 100 | 100 mg | 650 mg | Oral tablet |
Propoxyphene was approved in combination products for the treatment of mild to moderate pain. Darvocet-N 100 contained twice the propoxyphene dose of Darvocet-N 50 and a higher acetaminophen dose. The combination was commercially important because it occupied the lower-potency prescription analgesic segment before the expansion of newer nonopioid and opioid alternatives.
The product was distinct from Darvon, which contained propoxyphene without acetaminophen. Both products shared the same central safety problem: propoxyphene and its metabolite, norpropoxyphene, could affect cardiac conduction and cause serious arrhythmias.
What is the FDA status of propoxyphene napsylate and acetaminophen?
The FDA requested withdrawal of all propoxyphene-containing products from the U.S. market on November 19, 2010. The agency acted after reviewing new electrocardiographic data showing that propoxyphene could produce clinically significant changes in cardiac electrical activity at therapeutic doses.[1]
The withdrawal covered:
- Darvocet-N 50
- Darvocet-N 100
- Darvon
- Generic propoxyphene and acetaminophen tablets
- Other U.S. propoxyphene-containing products
The FDA stated that the risks of propoxyphene outweighed its benefits for pain treatment. The agency advised patients to contact health-care professionals about alternative treatments and instructed pharmacies to stop dispensing the products.[1]
FDA regulatory timeline
| Date | Regulatory event |
|---|---|
| 1950s | Propoxyphene introduced in the United States as an analgesic |
| 1970s-2000s | Propoxyphene products marketed broadly, including combination products with acetaminophen |
| July 2009 | FDA required strengthened warnings and a boxed warning regarding overdose and cardiac toxicity |
| November 19, 2010 | FDA requested withdrawal of propoxyphene products |
| November 2010 | Xanodyne announced withdrawal of Darvon and Darvocet from the U.S. market |
| 2010-2011 | Generic propoxyphene products were withdrawn or discontinued |
| 2011 onward | No lawful U.S. commercial market for the product |
The FDA action followed earlier regulatory restrictions in Europe. The European Medicines Agency recommended withdrawal of propoxyphene-containing products from the European Union in 2009 because the risks outweighed the benefits.[2]
When did propoxyphene napsylate and acetaminophen lose exclusivity?
Propoxyphene napsylate and acetaminophen lost practical market exclusivity long before the 2010 withdrawal. The combination was available from multiple manufacturers, and generic competition had materially reduced pricing by the time of the FDA action.
The primary commercial protection was not a contemporary patent monopoly. The product had been marketed for decades, and any early composition or formulation patents would have expired before the final U.S. withdrawal. The relevant commercial timeline was therefore:
- Original branded development and launch.
- Entry of generic propoxyphene and acetaminophen products.
- Declining clinical use because of safety concerns.
- FDA withdrawal and elimination of the U.S. market.
No current U.S. exclusivity period protects propoxyphene napsylate and acetaminophen. There is no active new chemical entity exclusivity, pediatric exclusivity, orphan exclusivity, or market exclusivity associated with the withdrawn combination.
What patents protect propoxyphene napsylate and acetaminophen?
No commercially material, unexpired U.S. patent estate is associated with the withdrawn combination.
Historical protection would have covered the active pharmaceutical ingredient, salt form, combination formulation, tablet composition, or manufacturing process. Those rights would have been filed decades before the product’s 2010 withdrawal. Their useful commercial life ended before the FDA safety action.
Patent-estate assessment
| Patent category | Historical relevance | Current commercial position |
|---|---|---|
| Propoxyphene compound patents | Covered early active ingredient rights | Expired |
| Propoxyphene napsylate salt patents | Could cover the salt form or preparation | Expired or commercially immaterial |
| Acetaminophen combination patents | Could cover fixed-dose compositions | Expired |
| Tablet formulation patents | Could cover excipients, release characteristics, or manufacturing | Expired or commercially immaterial |
| Method-of-use patents | Could cover treatment of pain | Expired or unavailable as a commercial barrier |
| Manufacturing patents | Could cover synthesis or purification | Expired or non-blocking |
| Current Orange Book patents | No meaningful active estate expected | No practical protection |
The central barrier is regulatory withdrawal, not patent infringement. A party cannot create a viable generic-entry opportunity merely by avoiding expired patents because the underlying drug product is no longer supported for U.S. marketing.
What is the Orange Book status of Darvocet-N?
Darvocet-N is a discontinued product in the U.S. regulatory market. The FDA’s Orange Book distinguishes between discontinued products and products that have been withdrawn for safety or effectiveness reasons. Propoxyphene-containing products were withdrawn after the FDA determined that the risk-benefit profile was unfavorable.
The Orange Book status is commercially significant because a withdrawn product is different from a routine discontinued product. A routine discontinuation may leave room for an ANDA holder or another sponsor to return a product to market. A safety-based withdrawal creates a much higher regulatory barrier because the applicant must address the agency’s underlying safety conclusion.
No current generic substitution market exists for propoxyphene napsylate and acetaminophen in the United States.
What generic entry risks exist for propoxyphene napsylate and acetaminophen?
The conventional Paragraph IV patent challenge is no longer the relevant risk. The patent barriers are old or expired, but the FDA safety determination prevents a normal generic launch.
A hypothetical applicant would face several issues:
- The reference product was withdrawn from the U.S. market.
- The withdrawal was tied to cardiac safety, not a commercial decision.
- Propoxyphene products require a regulatory basis that addresses the known arrhythmia risk.
- An ANDA pathway would not eliminate the need to satisfy FDA requirements for a withdrawn reference product.
- Any relaunch would face substantial medical, pharmacovigilance, labeling, and liability exposure.
The likely outcome is no U.S. generic re-entry absent a major change in the FDA’s benefit-risk assessment. The economic case is weak because established alternatives are available and the historic product’s safety profile would impose significant development and compliance costs.
What formulation patents protected Darvocet-N?
Darvocet-N used an immediate-release oral tablet combining propoxyphene napsylate with acetaminophen. Formulation protection, if any, would have focused on:
- The fixed-dose combination.
- Tablet composition.
- Excipient selection.
- Manufacturing and compression processes.
- Stability and dissolution characteristics.
Those technical features do not create a meaningful present-day barrier. Immediate-release tablets containing established active ingredients are generally vulnerable to generic replication once relevant patents and regulatory exclusivities expire. In this case, the FDA withdrawal removed the commercial incentive to pursue formulation differentiation.
No active long-acting, abuse-deterrent, transdermal, injectable, or modified-release formulation of this combination has created a current U.S. market.
What method-of-use patents covered the product?
Historical method-of-use rights could have covered treatment of mild to moderate pain using propoxyphene, with or without acetaminophen. Those rights have no current commercial value because:
- The product’s original therapeutic indication is old.
- Method-of-use patent terms would have expired.
- The FDA no longer supports the U.S. risk-benefit profile.
- Physicians and payers have access to alternative pain treatments.
No current method-of-use patent is known to preserve market exclusivity for the withdrawn combination.
Which companies marketed or challenged propoxyphene products?
The principal branded U.S. marketer at the time of withdrawal was Xanodyne Pharmaceuticals. Generic versions were sold by multiple manufacturers, including large generic-drug companies and labelers supplying pharmacies and wholesalers.
The relevant commercial parties included:
| Company type | Role |
|---|---|
| Xanodyne Pharmaceuticals | U.S. marketer of Darvon and Darvocet at withdrawal |
| Generic manufacturers | Supplied propoxyphene and acetaminophen tablets |
| Pharmacies and wholesalers | Distributed the product before withdrawal |
| FDA | Regulated approval, labeling, safety restrictions, and withdrawal |
| DEA | Controlled distribution under the federal controlled-substance framework |
The major competitive event was not a Paragraph IV litigation campaign. It was the loss of the entire market following the FDA’s safety action.
What patent litigation and settlement agreements affected Darvocet?
No current patent litigation materially affects propoxyphene napsylate and acetaminophen. The principal legal event was the FDA withdrawal and the associated discontinuation of sales.
There is no commercially relevant current settlement landscape involving:
- Paragraph IV challenges to Darvocet-N.
- Patent-term extensions.
- Authorized generic arrangements.
- Biosimilar-style litigation.
- Active formulation patent disputes.
- Current licensing transactions for U.S. propoxyphene products.
Any historical patent disputes would have lost commercial significance when the relevant patent terms expired and the product was withdrawn.
How strong is the patent estate for propoxyphene napsylate and acetaminophen?
The current patent estate is effectively nonblocking.
| Factor | Assessment |
|---|---|
| Composition-of-matter protection | Expired |
| Salt-form protection | Expired or noncommercial |
| Fixed-dose combination protection | Expired |
| Formulation protection | Expired or nonblocking |
| Method-of-use protection | Expired |
| Manufacturing protection | Expired or avoidable |
| Regulatory exclusivity | None |
| Freedom-to-operate risk | Low on patent grounds |
| Regulatory re-entry risk | Very high |
| Product-liability risk | Very high |
| Commercial attractiveness | Very low |
The distinction between patent strength and product viability is important. Patent freedom to operate is not equivalent to launch feasibility. A company could face little patent risk while still lacking a viable regulatory path or commercial rationale.
What was the financial trajectory of propoxyphene napsylate and acetaminophen?
Public filings do not provide a reliable, standalone revenue series for the combination. Darvocet revenue was generally embedded within broader company portfolios, and generic sales were distributed among multiple manufacturers. A precise historical revenue curve therefore cannot be established from public disclosures.
The financial trajectory is clear at a directional level:
Growth phase
Propoxyphene products benefited from a broad outpatient pain market and long-standing physician familiarity. The fixed-dose combination with acetaminophen supported recurring prescription volume.
Maturity phase
Generic competition reduced pricing and transferred value from the branded product to manufacturers with lower-cost supply. Clinical concerns also limited demand. The product’s commercial position weakened as safer or more effective analgesic options became available.
Decline phase
Regulatory warnings, including stronger labeling in 2009, increased prescriber and payer pressure. The FDA’s cardiac-risk findings accelerated the decline.
Terminal phase
The November 2010 withdrawal eliminated lawful U.S. sales. Revenue exposure for the product fell toward zero after inventory depletion and pharmacy removal.
| Period | Market condition | Financial implication |
|---|---|---|
| Pre-generic era | Branded analgesic with broad use | Higher product-level value |
| Generic era | Multiple suppliers and price competition | Lower branded and unit economics |
| 2009 safety-warning period | Demand erosion and higher regulatory risk | Accelerating revenue decline |
| Post-November 2010 | U.S. withdrawal | No ongoing U.S. product revenue |
The product’s value at withdrawal was therefore primarily residual inventory, working-capital recovery, and potential liability exposure rather than an ongoing intellectual-property stream.
How did propoxyphene compare with competing pain medicines?
Propoxyphene competed in a lower-potency prescription analgesic segment. Its alternatives included acetaminophen alone, nonsteroidal anti-inflammatory drugs, tramadol, codeine combinations, and other opioid products.
| Product class | Competitive advantage over propoxyphene | Key limitation |
|---|---|---|
| Acetaminophen | No opioid exposure | Liver toxicity at excessive doses |
| NSAIDs | Strong anti-inflammatory activity | Gastrointestinal, renal, and cardiovascular risks |
| Tramadol | Different analgesic profile and broad use | Dependence, seizure, serotonin, and overdose risks |
| Codeine combinations | Established opioid efficacy | Sedation, respiratory depression, misuse |
| Other short-acting opioids | Greater analgesic potency | Higher abuse and overdose risk |
Propoxyphene lost competitive relevance because its analgesic benefit was modest while its cardiac toxicity was clinically consequential. The product did not have a defensible risk-adjusted position after the FDA’s review.
Is there biosimilar risk for propoxyphene napsylate and acetaminophen?
No. Biosimilar risk does not apply because propoxyphene napsylate and acetaminophen is a synthetic small-molecule combination, not a biologic. The relevant competitive framework is generic-drug entry, not biosimilar interchangeability.
The practical risk is the opposite: there is no credible generic re-entry pipeline because the product was withdrawn for safety reasons.
What licensing deals affected the product?
The most relevant historical commercial arrangement was Xanodyne’s marketing control over Darvon and Darvocet in the United States at the time of withdrawal. Public information does not support a current licensing opportunity with meaningful revenue potential.
Any legacy license or distribution agreement would have been commercially impaired by:
- FDA withdrawal.
- Product discontinuation.
- Absence of current U.S. sales.
- Expired patent protection.
- Product-liability exposure.
- Availability of alternative analgesics.
There is no current strategic licensing thesis based on the original product.
What geographic markets remain?
The U.S. market was eliminated in 2010. European regulators had already taken action against propoxyphene-containing products, with the European Medicines Agency recommending withdrawal from the European Union in 2009.[2]
Country-level availability outside the United States and European Union has varied historically, but any residual market is subject to local regulatory status, controlled-substance rules, and product-specific registration. It does not create a meaningful global growth opportunity comparable to an active branded pharmaceutical franchise.
What manufacturing and intellectual-property barriers remain?
The manufacturing process for an immediate-release combination tablet is technically established. It does not present a major innovation barrier. The dominant barriers are regulatory and commercial:
- Demonstrating an acceptable benefit-risk profile.
- Addressing known cardiac conduction effects.
- Establishing an approvable labeling strategy.
- Managing controlled-substance distribution.
- Carrying product-liability and pharmacovigilance costs.
- Competing against established alternatives with better current regulatory support.
The active ingredients are not protected by a meaningful modern patent estate. Manufacturing capability alone would not support a viable launch.
Key Takeaways
- Propoxyphene napsylate and acetaminophen, including Darvocet-N 50 and Darvocet-N 100, has no active U.S. market.
- The FDA requested withdrawal of all propoxyphene-containing products on November 19, 2010, citing serious cardiac toxicity.[1]
- The product has no meaningful current patent, Orange Book, or regulatory exclusivity.
- Generic-entry risk is minimal because the product’s regulatory withdrawal, not patent protection, blocks commercial re-entry.
- No biosimilar framework applies; this is a discontinued small-molecule combination.
- Public disclosures do not provide a reliable standalone revenue history.
- The financial trajectory progressed from mature analgesic sales to generic erosion, safety-driven decline, and effectively zero U.S. revenue after withdrawal.
- Any future development would face high regulatory, liability, and commercial risk despite low patent risk.
FAQs About Propoxyphene Napsylate and Acetaminophen
Is propoxyphene napsylate and acetaminophen still available by prescription?
No. Propoxyphene-containing products were withdrawn from the U.S. market in 2010 after the FDA determined that cardiac risks outweighed treatment benefits.[1]
What was the difference between Darvocet-N 50 and Darvocet-N 100?
Darvocet-N 50 contained 50 mg of propoxyphene napsylate and 325 mg of acetaminophen. Darvocet-N 100 contained 100 mg of propoxyphene napsylate and 650 mg of acetaminophen.
Can a company file a generic application for Darvocet today?
A company could pursue a regulatory submission, but a conventional generic launch would face the FDA’s safety-based withdrawal and the need to address propoxyphene-associated cardiac toxicity. Expired patents would not resolve that regulatory barrier.
Did the FDA withdraw only Darvocet, or all propoxyphene products?
The FDA requested withdrawal of all propoxyphene-containing products, including Darvocet, Darvon, and generic propoxyphene products.[1]
Does propoxyphene have any current pharmaceutical investment value?
The original product has no meaningful U.S. revenue or exclusivity value. Any investment thesis would depend on a new regulatory strategy, a materially different formulation, or a changed safety assessment, not on the legacy Darvocet franchise.
References
- U.S. Food and Drug Administration. (2010, November 19). FDA recommends against continued use of propoxyphene. https://www.fda.gov
- European Medicines Agency. (2009). European Medicines Agency recommends withdrawal of dextropropoxyphene-containing medicines. https://www.ema.europa.eu
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