Tacrolimus - Generic Drug Details

What are the generic drug sources for tacrolimus and what is the scope of patent protection?

Tacrolimus is the generic ingredient in five branded drugs marketed by Astellas, Chengdu, Accord Hlthcare, Ajenat Pharms, Alkem Labs Ltd, Biocon Pharma, Concord Biotech Ltd, Dr Reddys Labs Ltd, Glenmark Pharms Ltd, Hangzhou Zhongmei, Heritage Pharma Avet, Mylan, Panacea, Sandoz, Strides Pharma, Hospira, Nexus, Leo Pharma As, Encube, Fougera Pharms Inc, and Veloxis Pharms Inc, and is included in twenty-six NDAs. There are ten patents protecting this compound and three Paragraph IV challenges. Additional information is available in the individual branded drug profile pages.

Tacrolimus has thirty patent family members in sixteen countries.

There are twenty drug master file entries for tacrolimus. Thirty-four suppliers are listed for this compound.

Summary for tacrolimus

International Patents:	30
US Patents:	10
Tradenames:	5
Applicants:	21
NDAs:	26
Drug Master File Entries:	20
Finished Product Suppliers / Packagers:	34
Raw Ingredient (Bulk) Api Vendors:	65
Clinical Trials:	1,384
Drug Prices:	Drug price trends for tacrolimus
Drug Sales Revenues:	Drug sales revenues for tacrolimus
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for tacrolimus
What excipients (inactive ingredients) are in tacrolimus?	tacrolimus excipients list
DailyMed Link:	tacrolimus at DailyMed

See drug prices for tacrolimus

See drug sales revenues for tacrolimus

Recent Clinical Trials for tacrolimus

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

Sponsor	Phase
Shalamar Institute of Health Sciences	PHASE3
Sung Won Choi	PHASE2
Milton S. Hershey Medical Center	PHASE2

See all tacrolimus clinical trials

Pharmacology for tacrolimus

Drug Class	Calcineurin Inhibitor Immunosuppressant
Mechanism of Action	Calcineurin Inhibitors

Medical Subject Heading (MeSH) Categories for tacrolimus

Calcineurin Inhibitors

Immunosuppressive Agents

Anatomical Therapeutic Chemical (ATC) Classes for tacrolimus

D11AH	Agents for dermatitis, excluding corticosteroids
D11A	OTHER DERMATOLOGICAL PREPARATIONS
D11	OTHER DERMATOLOGICAL PREPARATIONS
D	Dermatologicals

L04AD	Calcineurin inhibitors
L04A	IMMUNOSUPPRESSANTS
L04	IMMUNOSUPPRESSANTS
L	Antineoplastic and immunomodulating agents

Paragraph IV (Patent) Challenges for TACROLIMUS

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
ENVARSUS XR	Extended-release Tablets	tacrolimus	0.75 mg, 1 mg and 4 mg	206406	1	2022-03-31
ASTAGRAF XL	Extended-release Capsules	tacrolimus	0.5 mg, 1 mg, and 5 mg	204096	1	2013-09-24
PROTOPIC	Ointment	tacrolimus	0.03%	050777	1	2010-11-22
PROTOPIC	Ointment	tacrolimus	0.10%	050777	1	2010-09-09

US Patents and Regulatory Information for tacrolimus

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Encube	TACROLIMUS	tacrolimus	OINTMENT;TOPICAL	212387-001	Oct 10, 2023	BX	RX	No	No
Leo Pharma As	PROTOPIC	tacrolimus	OINTMENT;TOPICAL	050777-002	Dec 8, 2000	AB	RX	Yes	Yes
Accord Hlthcare	TACROLIMUS	tacrolimus	CAPSULE;ORAL	091195-001	Aug 31, 2011	BX	RX	No	No
Hospira	TACROLIMUS	tacrolimus	INJECTABLE;INJECTION	203900-001	Aug 25, 2017		DISCN	No	No
Accord Hlthcare	TACROLIMUS	tacrolimus	CAPSULE;ORAL	091195-003	Aug 31, 2011	BX	RX	No	No
Biocon Pharma	TACROLIMUS	tacrolimus	CAPSULE;ORAL	212297-003	Nov 10, 2020	AB	RX	No	No
Astellas	PROGRAF	tacrolimus	CAPSULE;ORAL	050708-002	Apr 8, 1994	AB	RX	Yes	Yes

Expired US Patents for tacrolimus

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Veloxis Pharms Inc	ENVARSUS XR	tacrolimus	TABLET, EXTENDED RELEASE;ORAL	206406-001	Jul 10, 2015	8,591,946
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-003	Jul 19, 2013	6,576,259
Leo Pharma As	PROTOPIC	tacrolimus	OINTMENT;TOPICAL	050777-002	Dec 8, 2000	5,385,907
Veloxis Pharms Inc	ENVARSUS XR	tacrolimus	TABLET, EXTENDED RELEASE;ORAL	206406-002	Jul 10, 2015	9,757,362
Veloxis Pharms Inc	ENVARSUS XR	tacrolimus	TABLET, EXTENDED RELEASE;ORAL	206406-001	Jul 10, 2015	8,486,993
Veloxis Pharms Inc	ENVARSUS XR	tacrolimus	TABLET, EXTENDED RELEASE;ORAL	206406-002	Jul 10, 2015	11,077,096
Veloxis Pharms Inc	ENVARSUS XR	tacrolimus	TABLET, EXTENDED RELEASE;ORAL	206406-001	Jul 10, 2015	8,617,599

EU/EMA Drug Approvals for tacrolimus

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Astellas Pharma Europe B.V.	Modigraf	tacrolimus	EMEA/H/C/000954Prophylaxis of transplant rejection in adult and paediatric, kidney, liver or heart allograft recipients.Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult and paediatric patients.	Authorised	no	no	no	2009-05-15
Astellas Pharma Europe BV	Advagraf	tacrolimus	EMEA/H/C/000712Prophylaxis of transplant rejection in adult kidney or liver allograft recipients.Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients.	Authorised	no	no	no	2007-04-23
Chiesi Farmaceutici S.p.A.	Envarsus	tacrolimus	EMEA/H/C/002655Prophylaxis of transplant rejection in adult kidney or liver allograft recipients. Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients.	Authorised	no	no	no	2014-07-18
LEO Pharma A/S	Protopic	tacrolimus	EMEA/H/C/000374Flare treatmentAdults and adolescents (16 years of age and above)Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids.Children (two years of age and above)Treatment of moderate to severe atopic dermatitis in children (two years of age and above) who failed to respond adequately to conventional therapies such as topical corticosteroids.Maintenance treatmentMaintenance treatment of moderate to severe atopic dermatitis for the prevention of flares and the prolongation of flare-free intervals in patients experiencing a high frequency of disease exacerbations (i.e. occurring four or more times per year) who have had an initial response to a maximum of six weeks treatment of twice daily tacrolimus ointment (lesions cleared, almost cleared or mildly affected).	Authorised	no	no	no	2002-02-27
Teva B.V.	Tacforius	tacrolimus	EMEA/H/C/004435Prophylaxis of transplant rejection in adult kidney or liver allograft recipients.Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients.	Authorised	yes	no	no	2017-12-08
Astellas Pharma GmbH	Protopy	tacrolimus	EMEA/H/C/000375Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids. Treatment of moderate to severe atopic dermatitis in children (2 years of age and above) who failed to respond adequately to conventional therapies such as topical corticosteroids.Maintenance treatment of moderate to severe atopic dermatitis for the prevention of flares and the prolongation of flare-free intervals in patients experiencing a high frequency of disease exacerbations (i.e. occurring 4 or more times per year) who have had an initial response to a maximum of 6 weeks treatment of twice daily tacrolimus ointment (lesions cleared, almost cleared or mildly affected).	Withdrawn	no	no	no	2002-02-28

International Patents for tacrolimus

Country	Patent Number	Title	Estimated Expiration
Eurasian Patent Organization	027869	СТАБИЛИЗИРОВАННАЯ КОМПОЗИЦИЯ ТАКРОЛИМУСА (STABILIZED TACROLIMUS COMPOSITION)
Spain	2634153
Poland	2575769
Serbia	55118	STABILIZOVANA TAKROLIMUS KOMPOZICIJA (STABILIZED TACROLIMUS COMPOSITION)
Canada	2688381	FORME PHARMACEUTIQUE ORALE A ADMINISTRER UNE FOIS PAR JOUR COMPORTANT DU TACROLIMUS (ONCE DAILY ORAL DOSAGE FORM COMPRISING TACROLIMUS)
Hungary	E028847
Canada	2729948	TACROLIMUS POUR TRAITEMENT AMELIORE DE PATIENTS TRANSPLANTES (TACROLIMUS FOR IMPROVED TREATMENT OF TRANSPLANT PATIENTS)

Market Dynamics and Financial Trajectory for the Pharmaceutical Drug: Tacrolimus

Last updated: July 27, 2025

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Introduction

Tacrolimus, a calcineurin inhibitor primarily used for immunosuppression, stands as a cornerstone in transplant medicine, notably in preventing organ rejection. Its complex market landscape is shaped by evolving clinical needs, regulatory reforms, patent expirations, and competitive innovation. Understanding tacrolimus's market dynamics and financial trajectory offers vital insights for healthcare providers, pharmaceutical companies, and investors aiming to navigate this high-stakes domain effectively.

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Pharmacological Profile and Clinical Applications

Tacrolimus, marketed under brand names such as Prograf and Astragraf, modulates immune responses by inhibiting T-lymphocyte activation. Approved initially in the 1990s, it has become integral in preventing rejection post-renal, hepatic, and cardiac transplants [1]. Its therapeutic scope extends to autoimmune disorders and off-label uses, expanding its clinical footprint.

The drug’s efficacy, however, is tempered by significant adverse effects, notably nephrotoxicity, neurotoxicity, and heightened infection risk. Such safety considerations influence prescribing patterns and patient management strategies, impacting market penetration and growth potential.

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Market Landscape Analysis

Market Size and Growth Trends

The global tacrolimus market was valued at approximately USD 4.0 billion in 2022, with projections indicating a compound annual growth rate (CAGR) of around 4.4% through 2030 [2]. Asia-Pacific markets, driven by increasing transplant procedures and expanding healthcare infrastructure, represent a rapidly growing segment, accounting for a significant share of the market expansion.

Key Players and Patent Dynamics

Major pharmaceutical companies, including Astellas Pharma (original developer), Novartis (generic formulations), and Sandoz, maintain significant market shares. Patent expirations for original formulations, notably in North America and Europe by the late 2010s, catalyzed an influx of generic versions, resulting in price erosion and increased accessibility.

Notably, Astellas Pharma’s patent protections expired in key markets around 2017–2018, opening the door for generics. This transition has introduced pricing competition, lowering average treatment costs and expanding patient access, while simultaneously pressuring branded drug revenues.

Regulatory Environment and Biosimilar Entry

Regulatory agencies such as the FDA and EMA have expedited approval pathways for biosimilars, including tacrolimus variants, emphasizing safety and efficacy equivalence. Biosimilar entrants, particularly from Indian, Chinese, and European manufacturers, have gained market footholds, intensifying competition.

Furthermore, regulatory scrutiny over immunosuppressant indications and safety profiles influences market access strategies and post-market surveillance investments.

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Market Drivers

• Increasing Transplant Procedures: Rising incidences of end-stage renal and hepatic diseases globally bolster demand for immunosuppressants, with transplant rates growing annually [3].
• Expanding Indications: Broader application in autoimmune conditions, such as psoriasis and atopic dermatitis, fosters incremental growth.
• Technological Innovations: Development of novel formulations (e.g., extended-release formulations) and combination therapies aim to optimize therapeutic outcomes and reduce side effects.
• Healthcare Infrastructure Development: Especially in emerging economies, improved transplant facilities contribute to higher consumption.

Market Challenges

• Safety Concerns and Adverse Effects: The risk profile of tacrolimus necessitates vigilant monitoring, limiting its use in specific patient populations.
• Pricing Pressure and Generic Competition: Post-patent expiry, aggressive pricing strategies by generics compress profit margins.
• Variability in Therapeutic Monitoring: Narrow therapeutic window mandates frequent blood level assessments, increasing treatment costs and complexity.
• Regulatory Hurdles for Biosimilars: Stringent requirements for biosimilar approval can delay market entry and influence market share distribution.

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Financial Trajectory and Future Outlook

Revenue Trends and Profitability

Following patent expirations, revenue from branded tacrolimus products in developed markets declined sharply, aligning with larger market trends for off-patent biotech drugs. Generic formulations, introduced at significantly lower prices, dominated the market share, leading to a circa 30–50% reduction in branded drug revenues in North America and Europe by 2020 [4].

However, in emerging economies, high transplant volumes sustain robust revenues, partially offsetting declines elsewhere. Investments in biosimilars, with patents expected to evolve over the next 5–10 years, indicate potential future revenue streams.

Innovation and Pipeline Development

Pharmaceutical companies are investing in next-generation calcineurin inhibitors with improved safety profiles and pharmacokinetics. For instance, proprietary formulations that mitigate nephrotoxicity are under development, signaling opportunities for premium pricing and market differentiation.

Moreover, combination therapies coupling tacrolimus with other immunosuppressants aim to enhance efficacy and safety, expanding the therapeutic landscape.

Market Penetration and Expansion Strategies

• Geographic Expansion: Targeting emerging markets with rising transplantation rates.
• Formulation Diversification: Developing extended-release and localized delivery systems.
• Biosimilar Adoption: Accelerating biosimilar approval and commercialization to capture cost-sensitive segments.

Looking ahead, the market is poised for a gradual recovery in branded revenues via niche applications, personalized medicine approaches, and innovations that address safety concerns.

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Impact of Regulations and Reimbursement Policies

Government policies on drug pricing, reimbursement, and biosimilar acceptance shape the financial trajectory. For example, the implementation of biosimilar substitution policies in Europe, such as in Germany and the UK, has led to rapid uptake of tacrolimus biosimilars, pressuring branded product margins [5].

In the US, CMS reimbursement adjustments and clinical guidelines influence prescribing habits and market stability.

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Conclusion

The tacrolimus market faces a complex interplay of patent expirations, generic proliferation, safety concerns, and regulatory dynamics. While near-term revenues for original formulations decline, long-term growth is driven by pipeline innovations, emerging indications, and expanding global transplant procedures. Strategic investments in biosimilar development and formulation advancements are vital for sustaining profitability and market relevance.

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Key Takeaways

• Market Evolution: Patent expiries catalyzed a shift from branded to generic dominance, compelling pricing adjustments and competitive strategies.
• Growth Opportunities: Emerging markets, biosimilar proliferation, and new formulations will underpin future revenue streams.
• Innovation Focus: Addressing safety profiles and improving therapeutic windows through technological advancements remains critical.
• Regulatory Environment: Navigating complex approval pathways and reimbursement policies is essential for market expansion.
• Investment Outlook: Companies investing in biosimilars and next-generation formulations can capitalize on long-term growth prospects amid current downward pricing pressures.

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FAQs

1. How does patent expiry affect tacrolimus’s market?
Patent expiry opens the market to generic manufacturers, significantly reducing prices, diminishing revenues for branded versions, but increasing accessibility and volume.

2. What are the primary safety concerns with tacrolimus?
Nephrotoxicity, neurotoxicity, and increased infection risk are key concerns, influencing prescribing practices and post-market monitoring.

3. How are biosimilars impacting the tacrolimus market?
Biosimilars offer cost-effective alternatives, gaining rapid acceptance in regions with favorable regulatory regimes, thereby intensifying competition.

4. What innovations are in development to improve tacrolimus therapy?
Extended-release formulations, combination therapies, and safer analogs aim to enhance efficacy, reduce side effects, and support personalized treatment.

5. What are the future growth prospects for tacrolimus?
Growth hinges on expanding indications, geographic penetration, biosimilar adoption, and technological improvements that address safety and convenience.

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References

[1] Kahan BD. Tacrolimus: a review of its pharmacology and clinical use. Transplant Proc. 1997.
[2] MarketWatch. "Global Tacrolimus Market Size, Status and Forecast 2022-2030."
[3] United Network for Organ Sharing (UNOS). "Transplant Trends." 2022.
[4] IQVIA. "Impact of Patent Expiry on Tacrolimus Market Sales." 2021.
[5] European Medicines Agency. "Biosimilar Tacrolimus Approval and Market Penetration." 2022.