Last updated: August 1, 2026
Hydrocodone bitartrate/ibuprofen is a mature, immediate-release opioid–NSAID combination marketed in the United States under the former brand Vicoprofen and through generic products. The FDA approved the combination in 1997 for short-term management of acute pain severe enough to require an opioid when alternative treatments are inadequate.[1] No new pivotal development program has materially changed its regulatory profile. Commercial demand is driven by generic prescriptions, dental and postoperative pain, controlled-substance restrictions, and prescribing limits on acute opioid therapy.
The product has limited patent protection, no meaningful biologic or biosimilar exposure, and low commercial barriers to entry. The main constraints are regulatory compliance, opioid quotas, prescriber reluctance, abuse-deterrence requirements, and competition from non-opioid analgesics and single-ingredient products.
What is hydrocodone bitartrate and ibuprofen used for?
Hydrocodone bitartrate/ibuprofen combines:
| Component |
Pharmacologic role |
| Hydrocodone bitartrate |
Opioid analgesic that acts primarily at the mu-opioid receptor |
| Ibuprofen |
Nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase-mediated prostaglandin synthesis |
The combination is indicated for short-term treatment of acute pain. The FDA-approved product historically contained hydrocodone bitartrate equivalent to 7.5 mg hydrocodone and 200 mg ibuprofen per tablet.[1] Generic strengths and labeling may differ by manufacturer, including 2.5 mg/200 mg, 5 mg/200 mg, and 7.5 mg/200 mg presentations.
The product is generally positioned for acute dental, orthopedic, postsurgical, and injury-related pain. It is not approved for chronic pain management. The ibuprofen component creates dose-related gastrointestinal, renal, cardiovascular, and bleeding risks. Hydrocodone creates risks of respiratory depression, misuse, addiction, overdose, and withdrawal.[2]
What is the FDA regulatory status of hydrocodone/ibuprofen?
The FDA approved Vicoprofen under NDA 20-716 on September 23, 1997.[1] The product is an immediate-release, fixed-dose combination tablet. Hydrocodone products are controlled under the federal Controlled Substances Act as Schedule II substances.[3]
Key FDA milestones
| Event |
Date or status |
| Original FDA approval |
September 23, 1997 |
| Original reference product |
Vicoprofen |
| Original NDA |
20-716 |
| Dosage form |
Immediate-release tablet |
| Federal controlled-substance status |
Schedule II |
| Current commercial structure |
Primarily generic |
| Clinical use |
Short-term acute pain |
| Abuse-deterrent labeling |
Not established for the standard combination |
| Biosimilar pathway |
Not applicable |
The FDA label carries class warnings for addiction, abuse, misuse, life-threatening respiratory depression, accidental ingestion, neonatal opioid withdrawal, and interactions with benzodiazepines or other central nervous system depressants.[2]
What patents protect hydrocodone bitartrate and ibuprofen?
The original composition-of-matter and product protection for hydrocodone/ibuprofen has expired. The combination entered the market more than two decades ago, and generic competition is established.
Patent estate assessment
| Protection category |
Current commercial significance |
| Hydrocodone composition of matter |
Expired |
| Ibuprofen composition of matter |
Expired |
| Fixed-dose combination patents |
Expired or commercially exhausted |
| Immediate-release tablet patents |
No material barrier identified for standard products |
| Method-of-use patents |
Limited relevance and generally expired or nonblocking |
| Manufacturing patents |
Potentially relevant to individual suppliers, but not a broad market barrier |
| Pediatric exclusivity |
No current market significance |
| Orphan exclusivity |
Not applicable |
| Biologic exclusivity |
Not applicable |
The commercial risk profile is therefore different from that of recently approved opioid formulations or branded combination products with active formulation patents. A generic applicant generally faces manufacturing, regulatory, quality, and controlled-substance compliance requirements rather than a meaningful patent wall.
What is the Orange Book status of Vicoprofen and generic hydrocodone/ibuprofen?
The FDA Orange Book historically identified Vicoprofen as the reference product for hydrocodone bitartrate and ibuprofen tablets.[4] Generic approval pathways rely on abbreviated new drug applications demonstrating pharmaceutical equivalence and bioequivalence to the reference listed drug.
The principal Orange Book issues are:
- Reference-listed-drug designation for the approved combination.
- Product-specific patent and exclusivity listings, if any remain active.
- Paragraph IV certification risk for any listed patent.
- Therapeutic-equivalence ratings for approved generic versions.
- Discontinuation status of the original branded product.
No active branded patent estate is generally considered to block standard generic hydrocodone/ibuprofen tablets. The commercial market is therefore governed more by generic competition and opioid procurement controls than by Orange Book litigation.
When did hydrocodone/ibuprofen lose exclusivity?
The product lost practical market exclusivity after the expiration of its original regulatory and patent protections and the entry of generic manufacturers. Generic hydrocodone/ibuprofen products have been marketed for many years.
Exclusivity timeline
| Period |
Market development |
| 1997 |
FDA approved Vicoprofen |
| Late 1990s and 2000s |
Product marketed as a branded acute-pain combination |
| 2000s onward |
Generic approvals and commercial substitution expanded |
| 2010s |
Opioid-prescribing restrictions reduced use in several settings |
| 2020s |
Market characterized by generic supply, fragmented manufacturers, and controlled-substance oversight |
No future loss-of-exclusivity event is expected to create a new generic wave comparable to a still-patented branded drug. The product is already in the post-exclusivity phase.
Are there active clinical trials for hydrocodone bitartrate/ibuprofen?
Hydrocodone/ibuprofen does not have an active late-stage clinical development program comparable to a newly developed analgesic. Its clinical evidence base comes from the original registration program, postmarketing experience, opioid safety research, and broader studies of acute pain treatment.
The original product development supported short-term analgesic efficacy in acute pain settings, including postoperative and dental pain. Current research involving hydrocodone often evaluates opioid stewardship, prescribing duration, comparative analgesia, opioid-sparing protocols, misuse, and safety rather than seeking a new indication for the hydrocodone/ibuprofen fixed-dose tablet.
Current clinical-trial profile
| Research area |
Relevance to the combination |
| New efficacy indication |
Low |
| Acute dental pain |
Established use |
| Postoperative pain |
Established use |
| Opioid-sparing treatment |
High competitive relevance |
| Non-opioid alternatives |
High competitive relevance |
| Abuse-deterrent formulation |
Potentially relevant, but no established approved combination product |
| Chronic pain |
Not an approved indication |
| Pediatric use |
Requires age-specific risk assessment |
| Combination-product registration |
Mature |
ClinicalTrials.gov contains studies involving hydrocodone, ibuprofen, acute pain, and opioid-minimization strategies, but these do not establish a new regulatory lifecycle for the fixed-dose product.[5] The relevant development question is not whether the combination needs efficacy proof. It is whether manufacturers can differentiate the product through safety, dosing convenience, abuse-deterrence, or opioid-sparing positioning.
Which companies manufacture hydrocodone/ibuprofen?
The U.S. generic market has included multiple manufacturers and labelers over time. Availability can change because of controlled-substance quotas, product discontinuations, supply interruptions, contract manufacturing, and pharmacy purchasing decisions.
Companies associated with generic hydrocodone/ibuprofen products have included manufacturers such as:
- Amneal Pharmaceuticals
- Prasco Laboratories
- Teva Pharmaceuticals
- Hikma Pharmaceuticals
- Mallinckrodt-related entities
- Other approved generic suppliers and private-label distributors
Manufacturer participation should be verified against the current FDA Drugs@FDA database, DailyMed listings, and National Drug Code records because approval and marketing status may change.[2,6]
The supply chain is more concentrated than the number of approved labels suggests. A manufacturer may hold an approval without maintaining continuous commercial supply. Controlled-substance manufacturing quotas can limit production even when demand exists.
How strong is the patent estate for hydrocodone/ibuprofen?
The patent estate is weak as a market-exclusion tool and moderate only at the supplier-specific manufacturing level.
Patent-strength scorecard
| Factor |
Assessment |
| Active composition patent |
None of material commercial effect |
| Active basic formulation patent |
Low |
| Active method-of-use patent |
Low |
| Generic substitution barrier |
Low |
| Manufacturing complexity |
Low to moderate |
| Controlled-substance compliance barrier |
Moderate to high |
| Abuse-deterrence differentiation |
Potentially high if a new product is developed |
| Litigation exposure |
Low for standard generic entry |
A new formulation could create a separate patent position around abuse deterrence, modified release, tablet architecture, or a delivery technology. That would not restore exclusivity to the conventional immediate-release product unless the new formulation gained meaningful prescribing or reimbursement share.
Are there Paragraph IV challenges or patent litigation?
No major, current Paragraph IV litigation campaign is associated with the standard hydrocodone/ibuprofen tablet market. The product’s age and generic availability reduce the incentive for branded patent litigation.
A Paragraph IV challenge would have commercial value only if an enforceable listed patent remained and the challenger could obtain a meaningful market position. For this product, the principal generic risks are operational:
- FDA review or inspection findings.
- Opioid quota limitations.
- Supply interruptions.
- State prescribing restrictions.
- Product recalls.
- DEA registration or distribution controls.
- Contracting and reimbursement pressure.
Settlement agreements are not a material current driver of the standard hydrocodone/ibuprofen market. Any historical settlement involving a specific generic applicant would need to be evaluated against the relevant ANDA, patent listing, and launch date rather than generalized to the entire category.
What formulations are protected by hydrocodone/ibuprofen patents?
The commercially established product is an immediate-release tablet. The standard product does not have a significant active formulation-patent barrier.
Potentially differentiating formulations include:
- Abuse-deterrent tablets designed to resist crushing, extraction, or tampering.
- Modified-release formulations intended to control hydrocodone exposure.
- Lower-opioid fixed-dose combinations.
- Bilayer or multilayer tablets that separate hydrocodone and ibuprofen release characteristics.
- Alternative oral delivery systems, including multiparticulates or orally disintegrating tablets.
These technologies could support new patent filings, but they would require separate clinical, CMC, and FDA strategies. An abuse-deterrent claim would also require FDA-supported labeling and testing. The existence of a formulation patent would not automatically establish clinical or commercial differentiation.
How does hydrocodone/ibuprofen compare with competing analgesics?
Hydrocodone/ibuprofen competes against both opioid combinations and non-opioid regimens.
| Product or regimen |
Main advantage |
Main limitation |
| Hydrocodone/ibuprofen |
Combined opioid and anti-inflammatory analgesia |
Opioid dependence, NSAID toxicity, Schedule II controls |
| Hydrocodone/acetaminophen |
Familiar prescribing and broad availability |
Acetaminophen liver-toxicity ceiling |
| Oxycodone/acetaminophen |
Higher perceived potency and established use |
Opioid and acetaminophen risks |
| Ibuprofen alone |
Low cost and no opioid exposure |
May be inadequate for severe acute pain |
| Ibuprofen plus acetaminophen |
Strong non-opioid alternative for many acute conditions |
Requires separate dosing |
| Tramadol products |
Lower perceived abuse risk in some markets |
Opioid, seizure, serotonin, and variable-response risks |
| Ketorolac |
Potent short-term NSAID option |
Tight duration and renal/gastrointestinal limits |
The strongest competitive threat comes from ibuprofen plus acetaminophen and other opioid-sparing protocols. Evidence from acute dental pain research has supported non-opioid combinations as effective alternatives for many patients, reducing the addressable volume for opioid-containing products.[7]
What generic entry risks exist for hydrocodone/ibuprofen?
Generic entry risk is already realized. Future market erosion will come from substitution, lower reimbursement, lower prescription volume, and non-opioid treatment pathways.
Generic launch scenarios
| Scenario |
Probability |
Market effect |
| Additional conventional generic entrants |
Moderate |
Further price erosion and supply fragmentation |
| New branded combination |
Low |
Requires clinical or formulation differentiation |
| Abuse-deterrent product |
Low to moderate |
Could command a niche if FDA labeling and payer access support it |
| Generic supply contraction |
Moderate |
Temporary price increases or shortages |
| Rapid non-opioid substitution |
High |
Sustained volume decline |
| Chronic-pain expansion |
Very low |
Inconsistent with FDA-approved short-term use and policy trends |
A new entrant would need approved manufacturing capacity, DEA compliance, reliable active pharmaceutical ingredient supply, and pharmacy-channel access. Patent clearance is not expected to be the principal barrier.
What is the market size and revenue outlook for hydrocodone/ibuprofen?
Public market reports generally aggregate hydrocodone/ibuprofen within broader opioid analgesic, combination analgesic, or generic prescription markets. Standalone revenue figures are therefore less reliable than prescription-volume and pricing indicators.
Revenue drivers
The category’s revenue is influenced by:
- Number of acute-pain prescriptions.
- Average tablets per prescription.
- Generic acquisition cost.
- Manufacturer participation.
- Controlled-substance quotas.
- Dental and outpatient surgical volumes.
- State opioid-prescribing limits.
- Substitution with ibuprofen, acetaminophen, or their combination.
- Wholesale and retail inventory levels.
Five-year base-case projection
| Metric |
Expected direction |
| Prescription volume |
Declining to low-single-digit decline annually |
| Net pricing |
Flat to declining |
| Gross category revenue |
Declining |
| Generic competition |
Persistent |
| Supply volatility |
Intermittent |
| Branded premium |
Minimal |
| Non-opioid substitution |
Increasing |
| R&D investment |
Low |
The base case is a mature, declining generic market rather than a growth category. A reasonable commercial forecast is for low-single-digit annual volume erosion, with periodic supply-related price movements. A sharper decline is possible if dental and ambulatory-surgery protocols continue replacing opioids with ibuprofen/acetaminophen regimens. Revenue growth would require a differentiated product, such as an abuse-deterrent or lower-opioid formulation, supported by clinical evidence and payer acceptance.
What regulatory and manufacturing barriers affect the market?
The combination has low formulation complexity but meaningful compliance requirements.
Regulatory barriers
Manufacturers must manage:
- ANDA requirements for generic products.
- Bioequivalence to the reference listed drug.
- Schedule II controls.
- DEA registration and quota allocation.
- Opioid labeling and risk-management obligations.
- Serialization and supply-chain controls.
- FDA inspection and current good manufacturing practice compliance.
- State-level opioid-prescribing and dispensing restrictions.
Manufacturing and IP barriers
The active pharmaceutical ingredients are established and commercially available. Manufacturing barriers include controlled-substance handling, validated content uniformity, contamination control, tablet compression, packaging, and supply continuity. These barriers can affect market access but do not create durable exclusivity comparable to an active composition or formulation patent.
What is the geographic outlook for hydrocodone/ibuprofen?
The United States is the principal commercial market because hydrocodone regulation, prescribing, and product availability are highly jurisdiction-specific. International opportunity is narrower.
- Canada has different opioid products, regulatory classifications, and prescribing practices.
- European markets generally use different opioid combinations and have less reliance on hydrocodone.
- Asia-Pacific markets vary substantially in opioid access and may have limited hydrocodone availability.
- Emerging markets may favor low-cost NSAIDs because of opioid controls and affordability.
Geographic expansion would require country-specific registration, controlled-substance authorization, local pharmacovigilance, and distribution infrastructure. The existing U.S. generic model does not automatically transfer to other jurisdictions.
Key Takeaways
- Hydrocodone bitartrate/ibuprofen is an FDA-approved, short-term acute-pain combination first approved in 1997.
- Vicoprofen and conventional generic products have no meaningful remaining patent barrier.
- The market is predominantly generic and has low standalone growth potential.
- No major late-stage clinical program is reshaping the product’s regulatory profile.
- Opioid controls, supply quotas, and non-opioid analgesics are more important than patent litigation.
- The principal commercial threat is substitution with ibuprofen plus acetaminophen and other opioid-sparing regimens.
- A new formulation could create patent value, but it would require separate clinical, manufacturing, and FDA strategies.
- Revenue is expected to decline gradually unless supply constraints create temporary pricing volatility or a differentiated product gains adoption.
FAQs
Is hydrocodone/ibuprofen stronger than hydrocodone/acetaminophen?
Neither combination is universally stronger. Hydrocodone/ibuprofen adds anti-inflammatory activity, while hydrocodone/acetaminophen combines opioid analgesia with a non-opioid analgesic. Clinical choice depends on pain mechanism, renal and gastrointestinal risk, liver risk, and prescribing restrictions.
Is hydrocodone/ibuprofen still commercially available?
Generic products may remain available, but individual strengths, manufacturers, and pharmacy inventory can change. The original Vicoprofen brand has limited commercial significance compared with generic supply.
Does hydrocodone/ibuprofen have abuse-deterrent labeling?
Standard immediate-release hydrocodone/ibuprofen tablets do not have an established abuse-deterrent product profile comparable to specifically developed abuse-deterrent opioid formulations.
Can hydrocodone/ibuprofen be used for chronic pain?
The FDA-approved indication is short-term acute pain. Chronic use raises opioid dependence, tolerance, overdose, and ibuprofen toxicity concerns and falls outside the product’s labeled positioning.
What is the main investment risk in hydrocodone/ibuprofen?
The primary risk is structural volume decline from opioid stewardship and non-opioid substitution, combined with generic price pressure. Patent expiry is no longer the central risk because the market has already moved into the post-exclusivity phase.
References
-
U.S. Food and Drug Administration. (1997). Vicoprofen (hydrocodone bitartrate and ibuprofen) prescribing information, NDA 20-716.
-
DailyMed. (2024). Hydrocodone bitartrate and ibuprofen tablet: Prescribing information. National Library of Medicine.
-
U.S. Drug Enforcement Administration. (2024). Controlled substance schedules. U.S. Department of Justice.
-
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
-
National Library of Medicine. (2024). ClinicalTrials.gov database. U.S. National Library of Medicine.
-
U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database. U.S. Department of Health and Human Services.
-
American Dental Association. (2024). Oral analgesics for acute dental pain and opioid stewardship guidance. ADA Science and Research Institute.
