Chlorpheniramine maleate; hydrocodone bitartrate - Generic Drug Details

What are the generic sources for chlorpheniramine maleate; hydrocodone bitartrate and what is the scope of patent protection?

Chlorpheniramine maleate; hydrocodone bitartrate is the generic ingredient in four branded drugs marketed by Acella, Tris Pharma Inc, Persion, Apozeal Pharms, Mayne Pharma Inc, and Padagis Us, and is included in eight NDAs. Additional information is available in the individual branded drug profile pages.

Summary for chlorpheniramine maleate; hydrocodone bitartrate

US Patents:	0
Tradenames:	4
Applicants:	6
NDAs:	8
DailyMed Link:	chlorpheniramine maleate; hydrocodone bitartrate at DailyMed

Anatomical Therapeutic Chemical (ATC) Classes for chlorpheniramine maleate; hydrocodone bitartrate

D04AA	Antihistamines for topical use
D04A	ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
D04	ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
D	Dermatologicals

R05DA	Opium alkaloids and derivatives
R05D	COUGH SUPPRESSANTS, EXCL. COMBINATIONS WITH EXPECTORANTS
R05	COUGH AND COLD PREPARATIONS
R	Respiratory system

R06AB	Substituted alkylamines
R06A	ANTIHISTAMINES FOR SYSTEMIC USE
R06	ANTIHISTAMINES FOR SYSTEMIC USE
R	Respiratory system

US Patents and Regulatory Information for chlorpheniramine maleate; hydrocodone bitartrate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Persion	ZUTRIPRO	chlorpheniramine maleate; hydrocodone bitartrate; pseudoephedrine hydrochloride	SOLUTION;ORAL	022439-001	Jun 8, 2011		DISCN	Yes	No
Tris Pharma Inc	HYDROCODONE BITARTRATE AND CHLORPHENIRAMINE MALEATE	chlorpheniramine maleate; hydrocodone bitartrate	SOLUTION;ORAL	206438-001	Jan 27, 2015		DISCN	No	No
Apozeal Pharms	HYDROCODONE BITARTRATE, CHLORPHENIRAMINE MALEATE AND PSEUDOEPHEDRINE HYDROCHLORIDE	chlorpheniramine maleate; hydrocodone bitartrate; pseudoephedrine hydrochloride	SOLUTION;ORAL	206660-001	May 15, 2017		DISCN	No	No

Chlorpheniramine Maleate and Hydrocodone Bitartrate Market Dynamics, Patent Status, and Financial Outlook

Last updated: September 8, 2026

Chlorpheniramine maleate and hydrocodone bitartrate are mature prescription ingredients used together in extended-release cough products, most notably Tussionex Pennkinetic Extended-Release Suspension. The combination has limited growth potential because its core composition and delivery technology are old, generic competition is established, opioid prescribing is tightly regulated, and the product treats a symptom category with declining reliance on prescription cough medicines.

The commercial opportunity is concentrated in branded and generic extended-release oral suspensions. Revenue exposure is likely modest relative to large pharmaceutical products, but pricing can remain resilient when manufacturing capacity is constrained or when pharmacists substitute among a limited number of approved suppliers.

What drug contains chlorpheniramine maleate and hydrocodone bitartrate?

Tussionex is the principal U.S. product associated with the combination. Its labeled active components are hydrocodone polistirex and chlorpheniramine polistirex. The polistirex complexes provide extended release, while the label expresses the dosage strength in terms equivalent to hydrocodone bitartrate and chlorpheniramine maleate.

Product	Active drug presentation	Dosage form	U.S. regulatory status
Tussionex Pennkinetic Extended-Release Suspension	Hydrocodone polistirex and chlorpheniramine polistirex, equivalent to hydrocodone bitartrate and chlorpheniramine maleate	Extended-release oral suspension	FDA-approved prescription product
Generic hydrocodone polistirex/chlorpheniramine polistirex	Equivalent extended-release suspension	Extended-release oral suspension	Approved ANDA products exist
Hydrocodone bitartrate/chlorpheniramine maleate immediate-release combination	Not the principal branded U.S. product	Varies by product	Limited commercial relevance compared with Tussionex

The usual labeled strength of Tussionex is 10 mg hydrocodone bitartrate equivalent and 8 mg chlorpheniramine maleate equivalent per 5 mL. The product is indicated for relief of cough and upper respiratory symptoms associated with respiratory conditions in adults and children at least six years old, subject to the product label and boxed-warning restrictions (FDA, 2023a).

When does hydrocodone and chlorpheniramine lose exclusivity?

Core composition-of-matter exclusivity has expired. Tussionex was approved decades ago, and the principal commercial barrier is no longer a basic active-ingredient patent. The relevant protection historically centered on the controlled-release delivery system, product formulation, manufacturing process, and regulatory exclusivity.

Exclusivity category	Current assessment
Active ingredients	Long expired
Basic combination	Long expired
Original NDA exclusivity	Expired
Formulation and controlled-release technology	Historical protection; commercially important but no longer a durable barrier to approved generic entry
Pediatric exclusivity	Expired if previously granted
Orphan exclusivity	Not applicable
Biosimilar exclusivity	Not applicable
Current market protection	Primarily manufacturing, supply, regulatory, and controlled-substance compliance barriers

No meaningful patent-based exclusivity remains for the active ingredients themselves. The commercial question is whether an applicant can produce an equivalent extended-release suspension and satisfy FDA requirements for release characteristics, stability, content uniformity, taste, and abuse-control controls.

What patents protect Tussionex and its generic equivalents?

The strongest historical protection involved the Pennkinetic delivery platform rather than chlorpheniramine or hydrocodone as chemical entities. The formulation combines ion-exchange or polymeric complexation concepts with a liquid oral dosage form designed to release the active ingredients over time.

A patent review should distinguish among four layers:

1. The hydrocodone and antihistamine active ingredients.
2. The salt or resin complex.
3. The extended-release suspension formulation.
4. The manufacturing and quality-control process.

The first layer has no remaining strategic value. The second and third layers historically supported branded differentiation, but generic applicants can challenge or design around expired claims. The fourth layer can still create practical barriers when the product requires specialized resin processing, particle-size control, suspension uniformity, or validated release testing.

How strong is the formulation patent estate?

The estate is weak as a long-term exclusivity platform and moderate as a manufacturing barrier.

A generic competitor does not need to reproduce the brand’s exact excipient system if it can demonstrate pharmaceutical equivalence and bioequivalence under the applicable FDA pathway. A formulation patent can delay entry only if it remains enforceable, is listed or otherwise actionable, and covers the generic applicant’s proposed product.

For this product class, manufacturing know-how may matter more than patent duration. Generic companies need controlled-substance handling, a stable liquid suspension, reliable hydrocodone assay results, and a process that avoids dose segregation during storage and administration.

What is the Orange Book status of Tussionex?

Tussionex is an FDA-listed prescription drug, and the Orange Book is the principal public source for its reference-listed-drug status, therapeutic-equivalence codes, and any listed patents or regulatory exclusivities (FDA, 2024a).

The product is not protected by biologic exclusivity. Its generic pathway is an abbreviated new drug application, not a biosimilar application. Orange Book activity is therefore more relevant than the Purple Book.

The practical Orange Book analysis should focus on:

• The reference listed drug and corresponding NDA.
• Approved ANDAs for hydrocodone polistirex/chlorpheniramine polistirex extended-release suspension.
• Any remaining listed patents.
• Therapeutic-equivalence designations.
• Whether an ANDA applicant filed a Paragraph IV certification against a listed patent.

Because the core product is mature, an active Paragraph IV campaign would be more likely to concern a later-added formulation or delivery patent than the original active ingredients.

Which companies are challenging or competing with Tussionex?

Competition comes from generic manufacturers, alternative prescription cough products, and non-opioid therapies rather than from a single direct branded rival.

The competitive set includes:

Competitor category	Examples	Competitive effect
Generic hydrocodone/chlorpheniramine extended-release suspensions	ANDA-approved equivalents	Direct price and formulary pressure
Other opioid cough products	Hydrocodone homatropine and related products	Substitution within prescription cough treatment
Non-opioid prescription products	Benzonatate and other antitussives	Reduce opioid exposure
OTC cough products	Dextromethorphan, guaifenesin, antihistamines	Expand low-cost alternatives
Nonpharmacologic care	Supportive treatment and watchful waiting	Limits prescription demand for uncomplicated cough

The market has no biosimilar risk because the product is a small-molecule oral drug. Generic risk is high, although supply interruptions can prevent a fully commoditized pricing outcome.

What patent litigation affects hydrocodone and chlorpheniramine products?

The principal litigation risk is generic drug patent litigation under the Hatch-Waxman framework. A Paragraph IV certification can trigger a 30-month stay of ANDA approval if the NDA holder or patent owner files suit within the statutory period.

For a mature Tussionex-type product, litigation exposure is likely lower than for recently launched extended-release products. The economic value of delaying generic entry is limited when multiple suppliers already exist or when the branded product has a small prescription base.

No major, current, high-value litigation campaign is central to the commercial outlook of the combination based on the publicly established profile of the product. Litigation risk is better characterized as episodic and product-specific rather than as a continuing market-wide threat.

Are there settlement agreements affecting generic launch?

Any settlement would need to be assessed from FDA records, federal court dockets, and the parties’ public disclosures. Mature combination products generally have less settlement value because generic entry is already possible or because the remaining patents have limited remaining life.

A settlement can still matter if it contains:

• An agreed generic launch date.
• A license to a formulation patent.
• Authorized-generic terms.
• Restrictions on suppliers or dosage strengths.
• A manufacturing or distribution agreement.

No broadly material industry settlement is required to explain the current market structure. Generic availability and opioid controls are more important drivers.

What is the FDA regulatory status?

Hydrocodone is a Schedule II controlled substance in the United States. This classification imposes prescription, ordering, inventory, recordkeeping, quota, distribution, and security requirements. The FDA label also carries opioid warnings, including risks of addiction, abuse, misuse, overdose, respiratory depression, and death (FDA, 2023a; DEA, 2024).

The regulatory profile affects both demand and supply:

• Prescribers face greater scrutiny when selecting opioid cough products.
• Pharmacies must maintain controlled-substance controls.
• Manufacturers require DEA registration and quota allocation.
• Wholesalers manage opioid distribution limits and compliance systems.
• Pediatric use is constrained by opioid safety concerns.
• State-level prescribing laws can be stricter than federal requirements.

The FDA has also warned against opioid cough medicines containing hydrocodone in young children and has required labeling changes reflecting serious respiratory and misuse risks (FDA, 2018).

What is the market size and revenue trajectory?

Public companies generally do not report Tussionex or generic hydrocodone/chlorpheniramine revenue as a separate line item. Product-level revenue estimates from syndicated prescription databases are therefore more reliable than corporate filings for market sizing, but they are not consistently public.

The financial trajectory is structurally mature:

Period	Market condition	Financial implication
Early branded period	Protected extended-release formulation	Higher pricing and stronger brand economics
Generic-entry period	ANDA competition begins	Volume may remain stable, but price and share decline
Current mature period	Generic substitution, opioid restrictions, limited innovation	Lower branded revenue and fragmented supplier economics
Forward period	Continued regulatory pressure and substitution	Flat-to-declining demand, with episodic price increases from shortages

Branded revenue is exposed to generic substitution and declining opioid use. Generic revenue can still be attractive when the number of approved suppliers is small, when competitors experience manufacturing problems, or when pharmacy purchasing favors a limited set of distributors.

The principal financial risks are:

1. Declining prescriptions for opioid cough medicines.
2. Reimbursement pressure and therapeutic substitution.
3. Controlled-substance compliance costs.
4. Product recalls or suspension-quality failures.
5. Limited market size relative to fixed regulatory and manufacturing costs.
6. Shortages that create revenue volatility rather than durable growth.

What generic launch scenarios exist?

Base case: stable generic substitution

Existing generic suppliers retain access, branded share continues to erode, and the market declines gradually in prescription volume. Pricing remains competitive but does not collapse if manufacturing is concentrated.

Downside case: accelerated opioid displacement

Prescribers move toward benzonatate, dextromethorphan, guaifenesin, or nonpharmacologic treatment. Pediatric and primary-care use falls faster, reducing total market volume.

Supply-constrained case: temporary price expansion

A manufacturing interruption, DEA quota issue, or quality-control problem reduces supply. Remaining suppliers capture temporary volume and may obtain higher net pricing. The effect is operational rather than patent-driven.

Upside case: limited

A meaningful upside scenario would require a new delivery system, a reformulated abuse-deterrent product, expanded commercial distribution, or a licensing transaction. The existing ingredients do not provide a credible growth platform by themselves.

How does this combination compare with other prescription cough drugs?

Attribute	Hydrocodone/chlorpheniramine ER	Benzonatate	Dextromethorphan products
Opioid	Yes	No	No
Controlled substance	Hydrocodone is Schedule II	No	Generally not federally scheduled
Abuse liability	High	Lower	Misuse risk exists but different profile
Dosing convenience	Extended release	Typically multiple daily doses	Depends on formulation
Pediatric and primary-care acceptance	Declining	Broader	Broad OTC and prescription use
Patent strength	Weak and mature	Mature	Mature
Growth outlook	Declining to stable	More resilient	Supported by OTC demand

What are the geographic and manufacturing barriers?

The United States is the most commercially significant market because hydrocodone controls and prescription cough economics are especially developed there. International opportunity is constrained by differing opioid schedules, approval requirements, prescribing practices, and product availability.

Manufacturing barriers include:

• Controlled-substance quota management.
• DEA registration and audits.
• Secure warehousing and distribution.
• Extended-release suspension uniformity.
• Hydrocodone assay and impurity controls.
• Stability testing across shelf life.
• Packaging that supports accurate dosing.
• Palatability and pourability requirements.

These barriers can support market concentration even when patent protection has ended.

Key Takeaways

• The commercial reference product is Tussionex, an extended-release suspension using hydrocodone polistirex and chlorpheniramine polistirex.
• The active ingredients and basic combination have long lost patent exclusivity.
• Current competition is primarily generic and regulatory, not patent-driven.
• Hydrocodone’s Schedule II status is the central market constraint.
• FDA approval and Orange Book status matter more than biosimilar rules because this is a small-molecule oral product.
• Generic manufacturing barriers can preserve supplier economics despite expired patents.
• Branded revenue is likely to remain under pressure from generic substitution and non-opioid alternatives.
• The most plausible forward trajectory is flat-to-declining demand with periodic supply-driven pricing volatility.
• A durable growth strategy would require a new formulation, delivery technology, or broader commercial platform.

FAQs

Is chlorpheniramine maleate and hydrocodone bitartrate still commercially available?

Yes. The combination remains associated with FDA-approved extended-release oral suspension products, including Tussionex and generic equivalents, subject to market supply and controlled-substance distribution conditions.

Is Tussionex a generic drug?

Tussionex is the branded reference product. Generic products use equivalent hydrocodone and chlorpheniramine extended-release technology and may be therapeutically equivalent when assigned an FDA rating.

Is hydrocodone chlorpheniramine protected by a current composition patent?

No meaningful composition-of-matter protection remains for the active ingredients. Any residual patent issue would most likely concern formulation, delivery, or manufacturing claims.

Can a generic manufacturer launch without conducting new clinical trials?

An ANDA applicant generally relies on the FDA’s finding of safety and efficacy for the reference listed drug and demonstrates pharmaceutical equivalence and bioequivalence, subject to FDA requirements for the specific dosage form.

Does the product have biosimilar competition?

No. Biosimilar regulation applies to biological products. Hydrocodone/chlorpheniramine extended-release suspension is a small-molecule drug evaluated through the generic-drug framework.

References

1. Drug Enforcement Administration. (2024). Drug scheduling and controlled substances regulations. U.S. Department of Justice.

2. U.S. Food and Drug Administration. (2018). FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older. U.S. Department of Health and Human Services.

3. U.S. Food and Drug Administration. (2023a). Tussionex Pennkinetic extended-release suspension prescribing information. U.S. Department of Health and Human Services.

4. U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.

5. U.S. Food and Drug Administration. (2024b). Approved drug products and abbreviated new drug applications. U.S. Department of Health and Human Services.