ETRAFON-A Drug Patent Profile

When do Etrafon-a patents expire, and what generic alternatives are available?

Etrafon-a is a drug marketed by Schering and is included in one NDA.

The generic ingredient in ETRAFON-A is amitriptyline hydrochloride; perphenazine. There are thirteen drug master file entries for this compound. One supplier is listed for this compound. Additional details are available on the amitriptyline hydrochloride; perphenazine profile page.

Summary for ETRAFON-A

US Patents:	0
Applicants:	1
NDAs:	1
DailyMed Link:	ETRAFON-A at DailyMed

US Patents and Regulatory Information for ETRAFON-A

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Schering	ETRAFON-A	amitriptyline hydrochloride; perphenazine	TABLET;ORAL	014713-002	Approved Prior to Jan 1, 1982		DISCN	No	No

Expired US Patents for ETRAFON-A

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Schering	ETRAFON-A	amitriptyline hydrochloride; perphenazine	TABLET;ORAL	014713-002	Approved Prior to Jan 1, 1982

ETRAFON-A: Market Dynamics and Financial Trajectory Analysis

Last updated: February 19, 2026

ETRAFON-A, a fixed-dose combination of the antidepressant amitriptyline and the antipsychotic perphenazine, has experienced a fluctuating market presence due to evolving therapeutic landscapes and patent expirations. The drug's primary indication is for the treatment of moderate to severe depression associated with anxiety. Its initial market entry saw significant traction, but subsequent competition from single-agent antidepressants and newer atypical antipsychotics has reshaped its market share.

What is the Current Market Status of ETRAFON-A?

The current market status of ETRAFON-A is characterized by a declining prescription volume and a narrowed therapeutic niche. Developed by Schering-Plough (now part of Merck & Co.), ETRAFON-A was a prominent treatment option in the mid-to-late 20th century. However, the introduction of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the late 1980s and 1990s offered improved side-effect profiles and perceived efficacy for many patients, leading to a shift in prescribing patterns.

As of the most recent available data, ETRAFON-A is primarily prescribed for patients who have not responded to other antidepressant therapies or for whom the combination of antidepressant and anxiolytic effects is deemed clinically necessary and beneficial. Its market presence is largely confined to specific geographic regions and patient populations that have not fully transitioned to newer drug classes.

Key factors influencing its current market status include:

• Competition: The market is saturated with antidepressants offering better tolerability and fewer side effects. Examples include fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro), and venlafaxine (Effexor XR). Newer antipsychotics, such as risperidone and olanzapine, are also used adjunctively in treatment-resistant depression but with different risk-benefit profiles.
• Patent Expirations: The original patents for ETRAFON-A have long since expired, allowing for the availability of generic versions. This has significantly reduced the drug's price and market exclusivity for the innovator.
• Clinical Guidelines: Current psychiatric treatment guidelines often prioritize newer drug classes for first-line and second-line treatment of depression and anxiety, relegating older combination therapies to specific circumstances.
• Side Effect Profile: Amitriptyline is known for its anticholinergic side effects (dry mouth, constipation, blurred vision, urinary retention), sedative effects, and potential for cardiac toxicity in overdose. Perphenazine carries risks of extrapyramidal symptoms, tardive dyskinesia, and weight gain. These side effects can limit its use in a broader patient population compared to SSRIs and SNRIs.

The market for ETRAFON-A is therefore limited to a segment of patients with treatment-resistant depression or comorbid anxiety where the specific properties of amitriptyline and perphenazine are considered beneficial by the prescribing physician.

What are the Key Patents and Exclusivity Periods for ETRAFON-A?

ETRAFON-A's intellectual property landscape is characterized by the expiration of its foundational patents. The drug, originally developed by Schering Corporation (later Schering-Plough), was introduced to the market in the late 1950s.

• Original Composition of Matter Patents: The initial patents covering the composition of matter for amitriptyline hydrochloride and perphenazine expired decades ago. These patents would have been filed in the 1950s, with typical patent terms of 17 years from the date of grant at that time.
• Formulation and Combination Patents: While specific formulations or combination patents may have existed for ETRAFON-A, these too have long since expired. For instance, a patent for a specific tablet formulation or manufacturing process would have a limited term.
• Exclusivity Periods: Regulatory exclusivities, such as New Drug Application (NDA) exclusivity awarded by the U.S. Food and Drug Administration (FDA), are tied to the approval of a specific drug product. Given ETRAFON-A's long history, any such exclusivities have also lapsed.
• Generic Entry: The expiration of all relevant patents and exclusivities has paved the way for generic manufacturers to produce and market their own versions of ETRAFON-A. This has led to a significant decrease in the drug's price and has made it more accessible to a wider range of patients, but it has also eliminated any premium pricing opportunities for the innovator.

A comprehensive review of patent databases (e.g., USPTO, Espacenet) would reveal specific patent numbers and their filing/expiration dates. However, given the drug's introduction in the 1950s, it is highly improbable that any patents related to its core composition or initial formulations remain in force in major markets. The market for ETRAFON-A today is essentially a generics market.

How has ETRAFON-A's Financial Trajectory Evolved?

The financial trajectory of ETRAFON-A has followed a typical pattern for pharmaceuticals: initial growth driven by market introduction and unmet need, followed by a decline due to patent expiry, generic competition, and the emergence of superior therapeutic alternatives.

• Early Growth (1960s-1980s): During this period, ETRAFON-A was a significant product for Schering-Plough. Its combination of an antidepressant and an anxiolytic addressed a prevalent therapeutic need, leading to substantial sales. Specific sales figures from this era are difficult to isolate in public reports due to company reporting structures and the long duration since the drug's peak. However, it was a cornerstone of the company's psychiatric portfolio.
• Peak Sales and Patent Expiry (1990s): While precise peak sales figures for ETRAFON-A are not readily available in current public financial statements, the 1990s likely represented a period of sustained, albeit potentially declining, revenue. The advent of SSRIs began to erode its market share, but it retained a patient base. Patent expirations in this period would have opened the door for generic competition, initiating price erosion.
• Generic Dominance and Declining Revenue (2000s-Present): Following comprehensive patent expiry, the market for ETRAFON-A became dominated by generic manufacturers. The innovator product's revenue would have plummeted, becoming negligible as physicians and payers shifted to lower-cost generic options. The financial performance of ETRAFON-A is now primarily reflected in the aggregate sales of its generic equivalents, which are often difficult to track precisely due to the fragmented nature of the generic market. Schering-Plough's (and subsequently Merck's) financial reports would no longer highlight ETRAFON-A as a significant revenue driver.

The financial trajectory is a classic example of a drug lifecycle:

1. Introduction & Growth: High sales as a novel treatment.
2. Maturity: Sustained sales, potential for line extensions or new indications.
3. Decline: Patent expiration, generic entry, price erosion, and loss of market share to newer competitors.

For ETRAFON-A, the decline phase is protracted due to its niche application in treatment-resistant cases, but the overall financial impact for the original innovator is now minimal.

Who are the Key Manufacturers and Generic Competitors?

The landscape of ETRAFON-A manufacturers has shifted significantly from its originator to a more fragmented generic market.

• Innovator:

  • Schering-Plough (now Merck & Co.): Developed and initially marketed ETRAFON-A under its brand name. While Merck & Co. continues to market some older products, ETRAFON-A is not a prominent revenue generator for the company.

• Key Generic Competitors: The market is served by numerous generic pharmaceutical companies that produce affordable versions of the fixed-dose combination. Identifying a definitive "key" competitor is challenging as market presence can vary by region and distribution agreements. However, companies that typically engage in the production of generic antidepressants and antipsychotics are likely to be involved. Examples of companies that have historically manufactured or currently offer generic psychotropic medications include:

  • Teva Pharmaceutical Industries: A major global generic drug manufacturer with a broad portfolio.
  • Mylan N.V. (now Viatris): Another large player in the generics space.
  • Apotex Inc.: A significant Canadian-based generic pharmaceutical company.
  • Sun Pharmaceutical Industries Ltd.: A global pharmaceutical company with a strong presence in generics.
  • Various smaller regional manufacturers: Many smaller and regional generic companies also supply ETRAFON-A in specific markets.

The availability of generic ETRAFON-A means that the market is highly competitive on price. Manufacturers primarily compete based on cost-effectiveness, supply chain reliability, and regulatory compliance. The branding and marketing efforts for these generic products are minimal compared to branded drugs, focusing on physician and pharmacist awareness of availability and cost.

What is the Projected Market Demand and Therapeutic Outlook?

The projected market demand for ETRAFON-A is expected to remain low and potentially decline further, reflecting its diminishing role in mainstream psychiatric treatment. The therapeutic outlook is similarly constrained.

• Projected Market Demand:

  • Niche Application: Demand is driven by a specific subset of patients with treatment-resistant depression, particularly those with comorbid anxiety where the combined action is clinically favored by the prescriber.
  • Ageing Patient Population: A portion of the demand may come from older patients who have been on the medication for extended periods and have not experienced significant adverse effects, preferring to maintain their established regimen.
  • Limited New Prescriptions: The drug is unlikely to see significant new prescriptions due to the availability of newer agents with more favorable safety and tolerability profiles.
  • Generic Market Size: The overall market size for generic ETRAFON-A is small compared to blockbuster antidepressants and antipsychotics. Market research reports focusing on psychiatric drugs often exclude such older, niche medications from detailed projections.
  • Geographic Variation: Demand may be higher in regions with less access to newer, more expensive medications or where older prescribing habits persist.

• Therapeutic Outlook:

  • Declining Therapeutic Relevance: ETRAFON-A's therapeutic relevance has decreased with advancements in psychopharmacology. Newer antidepressants (SSRIs, SNRIs, atypicals) and adjunctive treatments offer more targeted mechanisms of action and better side-effect profiles for the majority of patients.
  • Combination Therapy Limitations: While combination therapy can be effective, the specific combination of amitriptyline and perphenazine is associated with a higher burden of side effects than many contemporary treatments. This limits its use as a preferred option.
  • Focus on Personalized Medicine: The trend in psychiatry is towards more personalized treatment approaches, often involving genetic testing or a stepwise escalation of therapies based on individual response and tolerability. ETRAFON-A, as a broad-acting, older agent, fits less neatly into this paradigm.
  • Potential for Withdrawal: As clinical knowledge advances and more data on long-term effects of older drugs emerges, there may be increased pressure to transition patients off older combinations like ETRAFON-A if safer alternatives are available and effective.

In summary, ETRAFON-A is expected to retain a small, stable demand within its defined niche. However, it is unlikely to experience growth and may face gradual erosion as treatment standards continue to evolve towards newer pharmacological agents.

What are the Key Regulatory Considerations for ETRAFON-A?

The regulatory considerations for ETRAFON-A are primarily governed by the generic drug regulations in different markets. As a long-standing medication with expired patents, the focus is on ensuring the quality, safety, and bioequivalence of generic versions.

• U.S. Food and Drug Administration (FDA):

  • Abbreviated New Drug Application (ANDA): Generic manufacturers must file an ANDA to demonstrate that their product is bioequivalent to the reference listed drug (RLD), which is typically the original branded ETRAFON-A. This involves demonstrating comparable pharmacokinetic profiles and therapeutic effects.
  • Manufacturing Standards: Generic drug manufacturing must adhere to Current Good Manufacturing Practices (CGMP) to ensure product quality, purity, and consistency. Regular FDA inspections of manufacturing facilities are standard.
  • Labeling: Generic labeling must be the same as the RLD's labeling, including indications, contraindications, warnings, precautions, and adverse reactions. Any differences must be justified and approved by the FDA.
  • Post-Marketing Surveillance: Like all drugs, ETRAFON-A and its generics are subject to pharmacovigilance and adverse event reporting through systems like FDA's MedWatch.

• European Medicines Agency (EMA) and National Competent Authorities:

  • Generic Marketing Authorisation Applications (MAA): In Europe, generic manufacturers apply for MAAs, which require demonstrating bioequivalence and quality.
  • Harmonization: While national authorities grant authorizations, the EMA provides guidance and facilitates harmonization across member states.
  • Quality Standards: Similar to the US, adherence to GMP and stringent quality control is mandatory.

• Other Regulatory Bodies (e.g., Health Canada, PMDA Japan):

  • Each jurisdiction has its own regulatory framework for generic drugs, requiring similar principles of bioequivalence, quality, and safety.

• Specific Considerations for ETRAFON-A:

  • Fixed-Dose Combination: The combination nature of ETRAFON-A necessitates careful evaluation of the stability and compatibility of both active pharmaceutical ingredients (APIs) within the formulation.
  • Side Effect Management: Given the known side effect profiles of amitriptyline and perphenazine, regulatory bodies pay close attention to warnings and precautions in the drug's labeling to ensure appropriate patient selection and monitoring.
  • Drug Interactions: The labeling must comprehensively detail potential drug interactions for both components.

The regulatory pathway for generic ETRAFON-A is well-established. The primary challenges for manufacturers lie in efficient and cost-effective ANDA/MAA submissions and maintaining high-quality manufacturing processes to remain competitive in the generics market.

What are the Opportunities and Risks for Market Participants?

For current and potential market participants involved with ETRAFON-A, the opportunities are limited and primarily reside within the generics sector, while the risks are associated with market decline and regulatory scrutiny.

Opportunities

• Low-Cost Generic Production: The primary opportunity lies in the efficient and cost-effective production of generic ETRAFON-A. Manufacturers who can achieve economies of scale and optimize their supply chains can secure a portion of the remaining market demand at a profit.
• Underserved Geographies: In certain emerging markets or regions with limited access to newer, more expensive medications, generic ETRAFON-A may remain a viable treatment option for a longer period. Generic companies with established distribution networks in these areas can capitalize on this demand.
• Niche Patient Base: While small, the dedicated patient population for ETRAFON-A represents a stable, albeit shrinking, revenue stream. Generic manufacturers can target this niche by ensuring consistent availability and competitive pricing.
• Combination Therapy Expertise: Companies with expertise in developing and manufacturing fixed-dose combination products may find opportunities in maintaining a portfolio that includes older, established combinations.

Risks

• Market Erosion: The most significant risk is the continued decline in market demand as newer, more favored treatments become standard of care and as generic competition intensifies, driving down prices further.
• Regulatory Scrutiny: Although patents have expired, ETRAFON-A is subject to ongoing regulatory oversight concerning product quality, manufacturing, and post-marketing safety surveillance. Any adverse event reports or changes in regulatory guidance could impact its availability or market status.
• Competition from Newer Agents: The constant innovation in psychopharmacology means that ETRAFON-A will continue to face competition from drugs with improved efficacy, safety, and tolerability profiles.
• Pricing Pressure: The generic nature of ETRAFON-A subjects it to intense pricing pressure from payers, pharmacy benefit managers, and other healthcare systems aiming to reduce costs. This can severely limit profit margins.
• Supply Chain Disruptions: Like any pharmaceutical product, generic ETRAFON-A is susceptible to supply chain disruptions (e.g., API shortages, manufacturing issues) which can lead to temporary stockouts and loss of market share.
• Limited R&D Investment: There is no incentive for significant R&D investment in ETRAFON-A, meaning market participants must focus on manufacturing efficiency rather than product innovation.

Market participants must carefully assess these factors, focusing on operational excellence and cost management to maintain profitability in this mature and declining product segment.

Key Takeaways

• ETRAFON-A, a fixed-dose combination of amitriptyline and perphenazine, has a declining market presence due to competition from newer antidepressants and antipsychotics.
• All foundational patents and regulatory exclusivities for ETRAFON-A have expired, leading to a generics-dominated market.
• The financial trajectory has moved from early growth to a significant decline, with current revenue primarily from generic versions.
• Key manufacturers are now predominantly generic drug companies such as Teva, Viatris, and Apotex, with the innovator being Merck & Co.
• Projected market demand is low and expected to further decrease, catering to a niche of treatment-resistant depression patients, with a constrained therapeutic outlook against modern alternatives.
• Regulatory focus for ETRAFON-A centers on generic bioequivalence, quality, and adherence to CGMP, with no active intellectual property protection.
• Opportunities for market participants lie in efficient generic production and serving specific geographic niches, while risks include significant market erosion, pricing pressure, and competition from newer therapies.

Frequently Asked Questions

1. Is ETRAFON-A still considered a first-line treatment for depression?

No, ETRAFON-A is not considered a first-line treatment for depression. Current psychiatric guidelines generally recommend selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) as first-line options due to their more favorable side-effect profiles and perceived efficacy. ETRAFON-A is typically reserved for patients with moderate to severe depression associated with anxiety who have not responded to other treatments.

2. What are the main side effects associated with ETRAFON-A?

ETRAFON-A combines amitriptyline, which can cause anticholinergic effects (dry mouth, constipation, blurred vision), sedation, and cardiovascular issues, with perphenazine, which carries risks of extrapyramidal symptoms, tardive dyskinesia, and weight gain. The combination necessitates careful monitoring for these potential adverse effects.

3. Can ETRAFON-A be used for anxiety disorders alone?

While ETRAFON-A is indicated for depression associated with anxiety, it is not typically prescribed as a monotherapy for anxiety disorders. Its primary indication is depression, and its use for anxiety is as a comorbid condition alongside depression.

4. Who is the original manufacturer of ETRAFON-A?

The original manufacturer of ETRAFON-A was Schering Corporation, which later became part of Schering-Plough. Schering-Plough was subsequently acquired by Merck & Co.

5. What is the primary reason for ETRAFON-A's declining market share?

The primary reasons for ETRAFON-A's declining market share are the development and widespread adoption of newer antidepressant medications (SSRIs, SNRIs) with improved tolerability and fewer side effects, coupled with the expiration of its patents, which allowed for extensive generic competition.

Citations

[1] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-approved-drug-products-therapeutic-equivalence-evaluations

[2] European Medicines Agency. (n.d.). Generic medicines. Retrieved from https://www.ema.europa.eu/en/medicines/human/generic-medicines

[3] U.S. Patent and Trademark Office. (n.d.). Search Patent Databases. Retrieved from https://www.uspto.gov/patents/search

[4] Espacenet. (n.d.). Espacenet patent search. Retrieved from https://worldwide.espacenet.com/

[5] Merck & Co., Inc. (n.d.). Our History. Retrieved from https://www.merck.com/company-overview/our-history/