SYMPROIC Drug Patent Profile

When do Symproic patents expire, and what generic alternatives are available?

Symproic is a drug marketed by Bdsi and is included in one NDA. There are five patents protecting this drug.

The generic ingredient in SYMPROIC is naldemedine tosylate. There is one drug master file entry for this compound. One supplier is listed for this compound. Additional details are available on the naldemedine tosylate profile page.

DrugPatentWatch^® Generic Entry Outlook for Symproic

Symproic was eligible for patent challenges on March 23, 2021.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be November 11, 2031. This may change due to patent challenges or generic licensing.

Indicators of Generic Entry

Summary for SYMPROIC

US Patents:	5
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	14
Patent Applications:	32
Drug Prices:	Drug price information for SYMPROIC
What excipients (inactive ingredients) are in SYMPROIC?	SYMPROIC excipients list
DailyMed Link:	SYMPROIC at DailyMed

See drug prices for SYMPROIC

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

NDA:

208854

Dosage:

TABLET;ORAL

^*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.

Pharmacology for SYMPROIC

Drug Class	Opioid Antagonist
Mechanism of Action	Opioid Antagonists

US Patents and Regulatory Information for SYMPROIC

SYMPROIC is protected by five US patents.

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Bdsi	SYMPROIC	naldemedine tosylate	TABLET;ORAL	208854-001	Mar 23, 2017		RX	Yes	Yes			Y	Y
Bdsi	SYMPROIC	naldemedine tosylate	TABLET;ORAL	208854-001	Mar 23, 2017		RX	Yes	Yes			Y	Y
Bdsi	SYMPROIC	naldemedine tosylate	TABLET;ORAL	208854-001	Mar 23, 2017		RX	Yes	Yes			Y	Y

International Patents for SYMPROIC

When does loss-of-exclusivity occur for SYMPROIC?

Based on analysis by DrugPatentWatch, the following patents block generic entry in the countries listed below:

Australia

Brazil

Canada

China

Croatia

Cyprus

Denmark

European Patent Office

Hungary

Israel

Japan

Lithuania

Mexico

Philippines

Poland

Portugal

Russian Federation

Serbia

Slovenia

South Africa

South Korea

Spain

Taiwan

Ukraine

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

See the table below for additional patents covering SYMPROIC around the world.

Country	Patent Number	Title	Estimated Expiration
Canada	2873961	PREPARATION CONTENANT UN DERIVE DE 7-CARBAMOYLMORPHINANE 6,7-INSATURE (PREPARATION CONTAINING 6,7-UNSATURATED-7-CARBAMOYL MORPHINAN DERIVATIVES)
Denmark	2851075
European Patent Office	2851075	PRÉPARATION CONTENANT UN DÉRIVÉ DE 7-CARBAMOYLMORPHINANE 6,7-INSATURÉ (PREPARATION CONTAINING 6,7-UNSATURATED-7-CARBAMOYLMORPHINAN DERIVATIVE)

Supplementary Protection Certificates for SYMPROIC

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1889848	300996	Netherlands		PRODUCT NAME: NALDEMEDINE DAN WEL EEN FARMACEUTISCH AANVAARDBAAR ZOUT OF SOLVAAT DAARVAN, IN HET BIJZONDER HET TOSYLAATZOUT; REGISTRATION NO/DATE: EU/1/18/1291 20190220
1889848	2019C/533	Belgium		PRODUCT NAME: NALMEDINE OF EEN FARMACEUTISCH AANVAARDBAAR ZOUT OF SOLVAAT HIERVAN, IN BIJZONDER HET TOSYLAATZOUT; AUTHORISATION NUMBER AND DATE: EU/1/18/1291 20190220
1889848	122019000063	Germany		PRODUCT NAME: NALDEMEDINE ODER EIN PHARMAZEUTISCH VERTRAEGLICHES SALZ ODER SOLVAT DAVON, EINSCHLIESSLICH DAS TOSYLAT SALZ; REGISTRATION NO/DATE: EU/1/18/1291 20190218

SYMPROIC Market Dynamics, Financial Trajectory, Patent Exclusivity, and Generic Risk

Last updated: August 11, 2026

SYMPROIC, the U.S. brand for naldemedine, is a prescription peripherally acting mu-opioid receptor antagonist for opioid-induced constipation in adults with chronic non-cancer pain. Shionogi developed and commercializes the product in the United States. Its commercial profile is supported by clinical differentiation against laxatives and by an extended patent estate, but growth is constrained by declining opioid utilization, payer controls, competition from MOVANTIK and RELISTOR, and the absence of a large new indication.

Shionogi does not report standalone U.S. SYMPROIC revenue in its consolidated disclosures. It reports naldemedine revenue across markets and brands, including SYMPROIC in the United States and RIZMOIC in Japan and Europe. This limits direct calculation of U.S. product profitability and market share from public filings.

What is SYMPROIC and how does naldemedine work?

SYMPROIC contains naldemedine, a derivative of naltrexone that blocks peripheral mu-opioid receptors in the gastrointestinal tract. It is designed to reduce opioid-induced constipation without materially reversing opioid analgesia in the central nervous system.

The FDA approved SYMPROIC on March 23, 2017, under NDA 208854. The approved indication covers opioid-induced constipation in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent opioid dosage escalation.[1]

Product attribute	SYMPROIC
Active ingredient	Naldemedine
Drug class	Peripherally acting mu-opioid receptor antagonist
FDA approval	March 23, 2017
U.S. NDA	208854
Dosage form	0.2 mg oral tablet
Primary indication	Opioid-induced constipation
U.S. developer and commercial rights holder	Shionogi Inc.
Key international brand	RIZMOIC
Primary competitors	MOVANTIK, RELISTOR, generic laxatives, AMITIZA in relevant use cases

SYMPROIC is administered once daily and competes primarily on oral convenience, indication breadth within chronic non-cancer pain, and clinical positioning for patients who remain constipated despite opioid therapy.

How large is the SYMPROIC market?

The addressable market is narrower than the total opioid-induced constipation population because many patients are managed with inexpensive over-the-counter laxatives. Prescription treatment is concentrated among patients with persistent symptoms, high opioid exposure, chronic pain, cancer-related pain, or inadequate response to conventional bowel regimens.

The main market forces are:

1. Chronic opioid prescribing remains substantial, but U.S. opioid dispensing has declined from its peak.
2. Opioid-induced constipation remains a predictable adverse effect among long-term opioid users.
3. Prescription adoption is limited by step therapy and payer requirements for laxative failure.
4. Oral agents compete with injectable or rectal options used in more severe cases.
5. Generic and low-cost bowel regimens create price pressure even when branded products retain patent protection.

SYMPROIC's commercial opportunity is therefore a treatment-share opportunity within a mature and price-sensitive category, rather than a rapidly expanding disease market.

How does SYMPROIC compare with MOVANTIK and RELISTOR?

Product	Ingredient	Route	Manufacturer or marketer	Core commercial position
SYMPROIC	Naldemedine	Oral tablet	Shionogi	Chronic non-cancer pain and selected prior-cancer pain patients
MOVANTIK	Naloxegol	Oral tablet	AstraZeneca originator; commercial rights have changed by market	Oral treatment for opioid-induced constipation
RELISTOR	Methylnaltrexone	Oral tablet and injection	Bausch Health/Salix	Oral and injectable options, including advanced illness and palliative-care use
AMITIZA	Lubiprostone	Oral capsule	Takeda originator	Constipation indications, including opioid-induced constipation in adults with chronic non-cancer pain
Laxatives	Multiple ingredients	Oral and rectal	Generic and consumer-health companies	First-line, low-cost management

SYMPROIC's most direct branded competition is MOVANTIK because both are once-daily oral prescription products for opioid-induced constipation. RELISTOR has a broader route-of-administration profile, including injection, which supports use in patients who cannot rely on oral therapy.

What is the financial trajectory of SYMPROIC and naldemedine?

Shionogi's public financial statements disclose naldemedine sales at a consolidated or product-family level rather than separating U.S. SYMPROIC revenue from international RIZMOIC revenue. The disclosed trajectory is therefore best evaluated using naldemedine's reported global sales contribution and the commercial performance of Shionogi's broader prescription portfolio.

The product has several financial characteristics:

• Revenue is recurring because chronic opioid therapy can continue for months or years.
• Prescription volume is more defensive than growth-oriented.
• Net price is shaped by formulary rebates, specialty pharmacy arrangements, and payer step edits.
• International RIZMOIC sales provide diversification from the U.S. reimbursement environment.
• Product revenue is exposed to patent timing and potential generic naldemedine launches.
• The product does not have a high-cost biologic manufacturing profile, so the principal barriers are regulatory, clinical, commercial, and intellectual-property barriers rather than complex manufacturing.

Shionogi's reporting separates major products such as XOF​LUZA, FETCROJA/FETROJA, and HIV-related royalty income in greater detail than it separates SYMPROIC. As a result, analysts should not treat a naldemedine figure in a Shionogi annual report as U.S. SYMPROIC sales.

What drives SYMPROIC revenue growth?

Revenue growth depends on four variables:

Driver	Effect on SYMPROIC
Opioid-treated patient population	Determines the underlying eligible pool
Conversion from laxatives to prescription therapy	Determines market penetration
Reimbursement access	Determines realized volume and net price
Patent and generic timing	Determines duration of branded pricing

The strongest commercial opportunity is in patients who have persistent constipation despite prophylactic laxatives. The weakest segment is low-risk opioid use where patients and prescribers accept inexpensive stool softeners, stimulant laxatives, polyethylene glycol, or dietary measures.

When does SYMPROIC lose exclusivity?

SYMPROIC's U.S. exclusivity is governed by a combination of FDA regulatory exclusivity and Orange Book-listed patents. The five-year new chemical entity exclusivity period associated with the 2017 approval has expired. Commercial protection therefore depends principally on listed patents and any applicable pediatric extension or other statutory protection.

The FDA Orange Book is the controlling public source for current listed patents, expiration dates, patent-use codes, and any certification history.[2] Patent expiration should not be treated as an automatic generic launch date. A generic applicant may file an ANDA before patent expiry and challenge listed patents through Paragraph IV certification.

The practical exclusivity timeline is:

Period	Commercial relevance
2017	FDA approval and launch of SYMPROIC
2022	Expiration of five-year new chemical entity exclusivity
2020s	Patent-based protection remains the primary barrier
Before patent expiry	ANDA applicants may submit Paragraph IV certifications
After valid patent expiry	FDA approval and commercial launch become legally possible, subject to litigation and regulatory status

Exact patent expiration dates must be taken from the current FDA Orange Book because listed patents, pediatric extensions, delistings, and patent-use information can change.

What patents protect SYMPROIC?

SYMPROIC protection is expected to rely on patents covering naldemedine, pharmaceutical compositions, and methods of treating opioid-induced constipation. The relevant categories are:

Drug-substance and composition patents

These patents protect naldemedine or pharmaceutical compositions containing the active ingredient. Composition claims generally create the strongest barrier because a generic product containing the same active ingredient may be unable to avoid infringement if the claims remain valid and enforceable.

Formulation and dosage-form patents

SYMPROIC is a 0.2 mg oral tablet. Formulation protection may cover excipient combinations, tablet characteristics, stability, manufacturing parameters, or dosage forms. Formulation patents typically provide narrower protection than composition patents, but they can delay or complicate generic development.

Method-of-use patents

Method patents may cover treatment of opioid-induced constipation in defined patient populations, including adults receiving opioids for chronic pain. Their commercial value depends on the scope of the claims, the Orange Book patent-use code, and the ability to enforce the patent against a generic product marketed with a permissible label.

A generic applicant may pursue a section viii statement that omits a patented method from its labeling rather than challenge the patent. This can reduce the practical value of method-of-use patents if the remaining label still supports substantial non-infringing use.

Are there Paragraph IV challenges to SYMPROIC?

A Paragraph IV challenge is a certification by an ANDA applicant that an Orange Book-listed patent is invalid, unenforceable, or will not be infringed by the proposed generic product. A challenge can trigger patent litigation and, in some circumstances, a 30-month stay of FDA approval under the Hatch-Waxman Act.[3]

Publicly available regulatory and litigation sources should be checked for any current SYMPROIC ANDA certifications, notices, district-court complaints, settlements, or FDA tentative approvals. A Paragraph IV filing is not equivalent to a generic launch. The sequence usually involves:

1. ANDA submission.
2. Notice to the patent holder.
3. Patent litigation, if filed within the statutory period.
4. Possible 30-month approval stay.
5. Court judgment, settlement, or patent expiry.
6. FDA final approval and commercial launch.

The absence of an identified launch does not eliminate future generic risk. Naldemedine's oral dosage form is technically less complex than an injectable biologic or a device-based product, which reduces development barriers for ANDA applicants.

What is the FDA regulatory and Orange Book status of SYMPROIC?

SYMPROIC is an FDA-approved small-molecule prescription drug listed in the Orange Book under NDA 208854.[1,2] It is not a biologic and does not face biosimilar competition. Any future generic would follow the ANDA pathway rather than the biosimilar pathway.

Regulatory risks include:

• Labeling differences that affect the scope of a generic launch.
• Product-specific bioequivalence requirements.
• Patent certifications and litigation.
• FDA review of tablet formulation and inactive ingredients.
• Potential manufacturing or supply-chain deficiencies at an ANDA applicant.
• Substitution rules determined by state pharmacy law and product-level FDA ratings.

Because SYMPROIC is an oral tablet, manufacturing risk is lower than for sterile injectables. The main manufacturing issues are active-ingredient supply, tablet uniformity, dissolution, stability, and quality-system compliance.

Which companies could challenge SYMPROIC?

Potential challengers would most likely include generic manufacturers with established ANDA operations in oral solid-dose products. The commercial attractiveness depends on the remaining patent term, expected branded net price, market size, and the number of potential entrants.

Likely competitive categories include:

• Large generic companies with opioid-related or gastrointestinal portfolios.
• Contract development and manufacturing organizations partnering with ANDA sponsors.
• Specialty pharmaceutical companies targeting chronic pain and gastrointestinal products.
• Existing competitors seeking formulary leverage rather than direct generic entry.

A single first generic entrant could face a meaningful revenue opportunity if it receives 180-day exclusivity after a successful Paragraph IV challenge. Multiple later entrants would likely accelerate price erosion and reduce the value of the branded franchise.

What generic entry risks exist for SYMPROIC?

The principal generic-entry scenarios are:

Scenario	Likely commercial effect
No ANDA challenge before core patent expiry	Continued branded sales until the earliest approved generic
Paragraph IV litigation with patent-holder victory	Delayed entry and continued SYMPROIC pricing
Paragraph IV settlement	Entry date depends on settlement terms
First generic launch	Rapid unit share transfer and net-price erosion
Multiple generic launches	Accelerated price compression and reduced branded volume
Authorized generic launch	Potential defense of market share but lower combined economics

SYMPROIC's risk is greater than that of a complex biologic because naldemedine is a small molecule in an oral tablet. Its defense depends on patent validity, enforcement, settlement terms, payer behavior, and the strength of prescriber preference.

What licensing deals affect SYMPROIC?

Shionogi retains the central role in the SYMPROIC franchise. The international brand RIZMOIC expands the product's geographic reach, but public reporting does not provide a separate, consistently reported revenue stream for each territory.

Licensing and commercialization analysis should distinguish:

• U.S. SYMPROIC rights held by Shionogi.
• International naldemedine commercialization under the RIZMOIC brand.
• Any local distribution or co-promotion arrangements.
• Royalty economics, if applicable, in individual jurisdictions.

No major transaction comparable to an acquisition of the entire naldemedine franchise is central to the public commercial history of SYMPROIC. The asset remains principally associated with Shionogi.

How strong is the SYMPROIC patent estate?

The estate is commercially meaningful but not comparable to a broad platform estate with multiple independent product families. Its strength rests on the combination of an approved oral product, a defined active ingredient, composition protection, potential formulation protection, and method-of-use claims.

Strengths include:

• FDA approval for a clear prescription indication.
• A differentiated prescription option in a persistent adverse-effect market.
• Oral once-daily administration.
• Multiple potential patent claim categories.
• International commercialization through RIZMOIC.

Weaknesses include:

• Expired five-year regulatory exclusivity.
• Declining U.S. opioid exposure.
• Substitution by inexpensive laxatives.
• Small-molecule ANDA accessibility.
• Potentially narrow method-of-use claims.
• Limited public disclosure of standalone U.S. revenue.

Key Takeaways

• SYMPROIC is Shionogi's U.S. naldemedine brand for opioid-induced constipation.
• FDA approval occurred on March 23, 2017, under NDA 208854.
• The product competes mainly with MOVANTIK, RELISTOR, AMITIZA, and low-cost laxatives.
• Shionogi does not publicly report standalone U.S. SYMPROIC revenue, so global naldemedine figures should not be used as U.S. sales.
• The five-year new chemical entity exclusivity period has expired.
• Current commercial protection depends on Orange Book-listed patents, Paragraph IV activity, and any settlements.
• SYMPROIC is a small-molecule oral tablet and does not face biosimilar risk.
• Generic entry could produce rapid price erosion because the product is not a biologic or highly complex delivery system.
• The long-term market is mature and reimbursement-sensitive, with recurring demand tied to chronic opioid therapy.

FAQs

Is SYMPROIC the same drug as RIZMOIC?

Yes. Both contain naldemedine, although Shionogi uses SYMPROIC as the principal U.S. brand and RIZMOIC in several international markets.

Can SYMPROIC be used for constipation unrelated to opioids?

No. Its FDA-approved indication is opioid-induced constipation in adults with chronic non-cancer pain and specified related patient populations. Use for other constipation conditions would be outside the approved indication.

Is there a generic version of SYMPROIC?

The availability of a generic depends on FDA approval, patent status, and any litigation or settlement restrictions. The Orange Book and FDA approval records are the controlling sources for current generic availability.

Does SYMPROIC have biosimilar competition?

No. Naldemedine is a small-molecule drug, so any follow-on product would be regulated as a generic under the ANDA pathway, not as a biosimilar.

What would most reduce SYMPROIC's value to Shionogi?

The largest risks are generic entry, sustained decline in opioid prescribing, payer preference for lower-cost alternatives, and failure to expand prescription use beyond patients who do not respond adequately to laxatives.

References

1. U.S. Food and Drug Administration. (2017). SYMPROIC (naldemedine) prescribing information.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Food and Drug Administration. (2017). ANDA submissions: Amendments and supplements to ANDAs, generics, and related regulatory guidance.
4. Shionogi & Co., Ltd. (2024). Integrated report and annual financial results materials.
5. U.S. Food and Drug Administration. (2024). Drugs@FDA: SYMPROIC application record, NDA 208854.

DrugChatter Q&A for SYMPROIC

Symproic generic?
Symproic vs movantik?