Methotrexate - Generic Drug Details

What are the generic sources for methotrexate and what is the scope of freedom to operate?

Methotrexate is the generic ingredient in eighteen branded drugs marketed by Accord Hlthcare, Shorla, Assertio Speclty, Medexus, Nordic Grp, Abic, Pharmacia And Upjohn, Hospira, Fresenius Kabi Usa, Abraxis Pharm, Hikma, Norbrook, Pharmachemie Usa, Eugia Pharma Speclts, Extrovis, Pharmachemie Bv, Sagent Pharms Inc, Sandoz, Bristol, Bristol Myers, Bristol Myers Squibb, Azurity, Alembic, Amneal Pharms, Barr, Daito, Duramed Pharms Barr, Elite Labs Inc, Eugia Pharma, Lotus Pharm Co Ltd, Mylan, Strides Pharma Intl, Sun Pharm, and Zydus Pharms, and is included in fifty-eight NDAs. There are twenty-five patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Methotrexate has ninety-two patent family members in twenty-nine countries.

There are twenty drug master file entries for methotrexate. Four suppliers are listed for this compound.

Summary for methotrexate

International Patents:	92
US Patents:	25
Tradenames:	18
Applicants:	34
NDAs:	58
Drug Master File Entries:	20
Finished Product Suppliers / Packagers:	4
Raw Ingredient (Bulk) Api Vendors:	100
Clinical Trials:	2,221
Patent Applications:	6,734
Drug Prices:	Drug price trends for methotrexate
Drug Sales Revenues:	Drug sales revenues for methotrexate
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for methotrexate
What excipients (inactive ingredients) are in methotrexate?	methotrexate excipients list
DailyMed Link:	methotrexate at DailyMed

See drug prices for methotrexate

See drug sales revenues for methotrexate

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for methotrexate

Constraining patent/regulatory exclusivity:

9,629,959

Dosage:

SOLUTION;SUBCUTANEOUS

Constraining patent/regulatory exclusivity:

8,664,231

Dosage:

SOLUTION;SUBCUTANEOUS

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for methotrexate

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

Sponsor	Phase
Children's Oncology Group	PHASE2
Sung Won Choi	PHASE2
Juno Therapeutics, Inc., a Bristol-Myers Squibb Company	PHASE2

See all methotrexate clinical trials

Pharmacology for methotrexate

Drug Class	Folate Analog Metabolic Inhibitor
Mechanism of Action	Folic Acid Metabolism Inhibitors

Medical Subject Heading (MeSH) Categories for methotrexate

Abortifacient Agents, Nonsteroidal

Antimetabolites, Antineoplastic

Antirheumatic Agents

Dermatologic Agents

Enzyme Inhibitors

Folic Acid Antagonists

Immunosuppressive Agents

Nucleic Acid Synthesis Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for methotrexate

L01BA	Folic acid analogues
L01B	ANTIMETABOLITES
L01	ANTINEOPLASTIC AGENTS
L	Antineoplastic and immunomodulating agents

L04AX	Other immunosuppressants
L04A	IMMUNOSUPPRESSANTS
L04	IMMUNOSUPPRESSANTS
L	Antineoplastic and immunomodulating agents

US Patents and Regulatory Information for methotrexate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Extrovis	METHOTREXATE SODIUM PRESERVATIVE FREE	methotrexate sodium	INJECTABLE;INJECTION	201530-001	Mar 29, 2012		DISCN	No	No
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-005	Nov 7, 2014		DISCN	Yes	No	12,357,642		Y
Barr	TREXALL	methotrexate sodium	TABLET;ORAL	040385-004	Mar 21, 2001		RX	No	Yes
Medexus	RASUVO	methotrexate	SOLUTION;SUBCUTANEOUS	205776-002	Jul 10, 2014		RX	Yes	Yes	8,664,231
Abraxis Pharm	METHOTREXATE SODIUM	methotrexate sodium	INJECTABLE;INJECTION	088935-001	Oct 11, 1985		DISCN	No	No
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-003	Oct 11, 2013		DISCN	Yes	No	8,945,063		Y
Sagent Pharms Inc	METHOTREXATE SODIUM PRESERVATIVE FREE	methotrexate sodium	INJECTABLE;INJECTION	203407-001	Aug 9, 2018	AP	RX	No	No

Expired US Patents for methotrexate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-003	Oct 11, 2013	RE44847
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-002	Oct 11, 2013	RE44847
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-001	Oct 11, 2013	7,744,582
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-007	Mar 24, 2016	RE44847
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-004	Oct 11, 2013	RE44846
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-004	Oct 11, 2013	RE44847
Assertio Speclty	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-004	Oct 11, 2013	7,744,582

EU/EMA Drug Approvals for methotrexate

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Nordic Group B.V.	Nordimet	methotrexate	EMEA/H/C/003983Nordimet is indicated for the treatment of:active rheumatoid arthritis in adult patients,polyarthritic forms of severe, active juvenile idiopathic arthritis (JIA), when the response to nonsteroidal anti-inflammatory drugs (NSAIDs) has been inadequate,moderate to severe plaque psoriasis in adults who are candidates for systemic therapy, and severe psoriatic arthritis in adult patients, induction of remission in moderate steroid-dependent Crohn's disease in adult patients, in combination with corticosteroids and for maintenance of remission, as monotherapy, in patients who have responded to methotrexate.	Authorised	no	no	no	2016-08-18
Therakind (Europe) Limited	Jylamvo	methotrexate	EMEA/H/C/003756In rheumatological and dermatological diseasesActive rheumatoid arthritis in adult patients.Polyarthritic forms of active, severe juvenile idiopathic arthritis (JIA) in adolescents and children aged 3 years and over when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate.Severe, treatment-refractory, disabling psoriasis which does not respond sufficiently to other forms of treatment such as phototherapy, psoralen and ultraviolet A radiation (PUVA) therapy and retinoids, and severe psoriatic arthritis in adult patients.In oncologyMaintenance treatment of acute lymphoblastic leukaemia (ALL) in adults, adolescents and children aged 3 years and over.	Authorised	no	no	no	2017-03-29

International Patents for methotrexate

Country	Patent Number	Title	Estimated Expiration
World Intellectual Property Organization (WIPO)	2009114542
Serbia	51688
European Patent Office	2990067	DISPOSITIF DE SÉCURITÉ D'INJECTEUR (INJECTOR SAFETY DEVICE)
Australia	2007276387
China	102612381	Hazardous agent injection system
China	116747190
Montenegro	01940

Market Dynamics and Financial Trajectory for Methotrexate: An Industry Overview

Last updated: July 27, 2025

Introduction

Methotrexate, a ralent-prevailing immunosuppressant and chemotherapeutic agent, has maintained a pivotal role in the treatment landscape for rheumatoid arthritis, psoriasis, and certain cancers since its approval in the 1950s. As a folate analog, it inhibits dihydrofolate reductase, disrupting DNA synthesis, cell replication, and immune responses. Its enduring clinical utility underscores a complex interplay of market forces influencing its dynamics and financial trajectory.

Global Market Landscape

Market Size and Growth Projections

The global methotrexate market was valued at approximately $XXX million in 2022, with projections indicating a Compound Annual Growth Rate (CAGR) of X% over the next five years. This growth is driven predominantly by expanded indications, increasing prevalence of autoimmune diseases, and the entry of biosimilar versions in key markets. Despite its age, the drug's widespread familiarity ensures sustained demand, especially in regions with limited access to newer biologics.

Therapeutic Domains and Market Segments

Methotrexate primarily operates within two domains:

• Oncology: Used at higher doses for hematologic malignancies, including leukemia and lymphoma.
• Autoimmune Diseases: Employed at lower doses for rheumatoid arthritis, psoriasis, and related conditions.

The autoimmune segment constitutes X% of the total market, driven by rising global incidence rates and increased diagnosis. Conversely, the oncology segment, although smaller, benefits from its established efficacy in specific chemotherapeutic protocols.

Market Drivers

Growing Prevalence of Autoimmune Diseases

The global burden of rheumatoid arthritis (RA) is estimated at XX million cases, with an annual rise of X%. This trend propels demand for disease-modifying antirheumatic drugs (DMARDs), among which methotrexate remains a first-line therapy due to its proven efficacy and cost-effectiveness [1].

Cost-Effectiveness and Healthcare Policies

Methotrexate’s long-standing patent expiry and presence of generic formulations have rendered it a cost-effective option, influencing prescribing practices, especially in emerging markets. Insurance reimbursements and government initiatives favor its continued utilization.

Introduction of Biosimilars and Generics

Patent expirations have catalyzed the introduction of biosimilars and generics, reducing prices and expanding access. Several manufacturing companies now produce high-quality methotrexate formulations, intensifying market competition [2].

Advances in Drug Delivery and Formulation

Innovations such as subcutaneous injections and targeted delivery systems enhance patient compliance and safety, broadening its therapeutic appeal. These developments support steady prescription rates.

Market Challenges

Safety Concerns and Toxicity

Methotrexate carries risks of hepatotoxicity, bone marrow suppression, and pulmonary toxicity. These safety concerns necessitate rigorous monitoring, which can deter its use in adverse scenarios or among vulnerable populations.

Emergence of Targeted Biologics

Biologics, such as TNF-alpha inhibitors, offer superior efficacy and safety profiles for autoimmune conditions, challenging methotrexate’s dominance. The high cost of biologics, however, limits their accessibility in some regions, maintaining methotrexate’s relevance.

Regulatory and Legal Factors

Stringent post-marketing surveillance, manufacturing standards, and evolving regulatory frameworks influence market accessibility and pricing strategies, potentially impacting revenue streams.

Financial Trajectory and Business Strategies

Revenue Trends

While the total revenue for methotrexate faced a plateau in mature markets due to the dominance of biologics, the expansion in developing economies — fueled by affordability and unmet needs — supplies a growth avenue. Generics and biosimilars purchasing collectively contribute approximately $XXX million in annual sales, with a projected CAGR of X%.

Market Entry and Competition

Companies focusing on biosimilar development, such as [Company A] and [Company B], have capitalized on patent expirations, leading to aggressive pricing and increased market share. Strategic alliances and licensing agreements facilitate broader distribution.

Pipeline Developments

Limited pipeline innovations suggest that growth will rely heavily on market expansion, formulation improvements, and possibly new indications. Manufacturers are exploring combination therapies and alternative delivery methods to enhance therapeutic profiles.

Regional Market Insights

• North America: Dominates the market due to high prevalence of autoimmune diseases and healthcare infrastructure.
• Europe: Characterized by mature markets with significant biosimilar penetration.
• Asia-Pacific: Exhibiting the fastest growth, driven by expanding healthcare access, increasing autoimmune disease burden, and rising pharmaceutical manufacturing capacity.

Regulatory Outlook

Agencies such as the FDA and EMA are emphasizing biosimilar approvals, which streamline access and affordability. The regulatory environment favors approval pathways for biosimilars, impacting competitive dynamics.

Future Outlook

Methotrexate’s market sustainability hinges on its continued role as a cost-effective first-line treatment, adaptation to new formulations, and the strategic positioning against emerging biologics. Innovators and generic manufacturers alike must navigate safety profiles, regulatory landscapes, and competitive pressures to capitalize on future opportunities.

Key Takeaways

• The methotrexate market remains vital, particularly in policy-driven regions prioritizing affordable therapeutics.
• Biosimilar proliferation plays a crucial role in commoditizing supply and driving price erosion.
• Emerging safety concerns and the rise of targeted biologics constitute key challenges but do not diminish current demand, especially in resource-constrained settings.
• Regional trends reveal robust growth in Asia-Pacific, where expanding healthcare infrastructure and disease prevalence drive demand.
• Strategic innovation in delivery methods, combination therapies, and indication expansion offers pathways for sustained revenue.

FAQs

1. How has the patent expiry of methotrexate influenced its pricing and market share?
   Patent expiry led to the surge of generics, significantly reducing prices and increasing accessibility, particularly in emerging markets, thus sustaining overall market share despite competition from newer therapies.

2. What are the major safety concerns associated with methotrexate therapy?
   Risks include hepatotoxicity, bone marrow suppression, pulmonary toxicity, and teratogenicity. Regular monitoring is essential to mitigate adverse effects.

3. How do biosimilars impact the future landscape of methotrexate?
   Biosimilars drive down costs, expand access, and stimulate competitive pricing, ensuring the drug's continued relevance and affordability in global markets.

4. In which regions is methotrexate expected to see the highest growth?
   Asia-Pacific is projected for the highest growth, owing to increasing disease burden, healthcare access, and favorable regulatory reforms.

5. What innovations are on the horizon for methotrexate formulations?
   Innovations include subcutaneous delivery options, combination therapies, and sustained-release formulations aimed at improving patient compliance and reducing toxicity.

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Sources:
[1] Global Burden of Disease Study, 2021.
[2] Market Research Future, 2022 Report.