HomeNDC LookupIngredientsAcetaminophen And Ibuprofen › 68788-4181-01
Combogesic ACETAMINOPHEN and IBUPROFEN 325 mg; 97.5 mg Tablet, Film Coated, 120-count — NDC 68788-4181-01 package photo

Combogesic ACETAMINOPHEN and IBUPROFEN 325 mg; 97.5 mg Tablet, Film Coated, 120-count

by Preferred Pharmaceuticals Inc. · 120 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (68788-4181-1)
NDC 68788-4181-01
🏷️ FDA NDC (as labeled) 68788-4181-1 billing pads the package segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 10, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 68788-4181-1
Product NDC 68788-4181
11-digit billing NDC 68788418101
RxCUI 2675760, 2675765
UNII 362O9ITL9D, WK2XYI10QM
Application # NDA209471
SPL Set ID f3cee991-19ef-4a1c-bb14-cbc8b6f32776
Established class (EPC) Nonsteroidal Anti-inflammatory Drug
Mechanism of action Cyclooxygenase Inhibitors
Chemical class Anti-Inflammatory Agents, Non-Steroidal
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2026-08-20
Route ORAL
Dosage form TABLET, FILM COATED
Substance ACETAMINOPHEN; IBUPROFEN
Why two NDCs? The FDA registers this code as 68788-4181-1 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 68788-4181-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Anilides class.

Drug family (ATC) Anilides
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerPreferred Pharmaceuticals Inc.
Application holderAFT PHARMACEUTICALS US INC
FDA applicationNDA209471 (NDA)
Labeler code68788
First marketedAug 2026
Product typeHuman Prescription Drug
Portfolio825 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

📗 Our plain-language guide HelloPharmacist
  • That's a smart question. The idea behind combining them is that they work through different pathways, so together they may give you broader pain relief. For everyday mild to modera...
  • Can I take this combination instead of just acetaminophen or just ibuprofen?
  • You'll want to be cautious. Drinking 3 or more alcoholic beverages a day while using this product significantly raises your risk of liver damage from the acetaminophen, and also in...
  • Is it safe to take this with a drink or two?
📖 Read our full Acetaminophen / Ibuprofen guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color White
ShapeOval
ImprintCG
Size18 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII 36SFW2JZ0W
    Hypromellose 2910 is a plant-based thickening agent derived from cellulose. In medicines, it forms a protective coating on tablets or capsules and controls how quickly the drug dissolves and releases into your body.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII 7CVR7L4A2D
    A starch-derived carbohydrate produced by breaking down corn, potato, or tapioca starch. It functions as a filler and binder to give the medicine bulk and texture, and sometimes as a mild sweetener or texture enhancer in powders and tablets.
  • UNII C9H2L21V7U
    A fat derived from coconut or palm oil containing shorter fatty acid chains. It serves as a solvent and carrier to help dissolve or suspend active ingredients, improving absorption and stability in liquid formulations.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII VH2XOU12IE
    Polydextrose is a synthetic polymer made from dextrose (sugar) that acts as a bulking agent and filler in medicines. It helps give tablets and capsules proper volume and texture while often adding slight sweetness.
  • UNII U725QWY32X
    Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
  • UNII 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

12 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Combogesic 325 mg/1; 97.5 mg 00143-9432-27 Hikma 250 tablets FDA listed
Combogesic 325 mg/1; 97.5 mg 68788-4009-01 Preferred 120 tablets FDA listed
Combogesic 325 mg/1; 97.5 mg 72260-0129-01 AFT 250 tablets FDA listed
Combogesic 325 mg/1; 97.5 mg 71335-3161-01 Bryant 30 tablets FDA listed
Combogesic 325 mg/1; 97.5 mgthis 68788-4181-01 Preferred 120 tablets FDA listed
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2023
First FDA approval
Mar 2023
📍
2026
Currently FDA-listed
3 years listed
🛡️
2039
Latest patent/protection listed
not a guaranteed launch date
Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Feb 2039. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Mar 1, 2023 RLD RS ⏳ ~12.4 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 11534407 — method of use (U-3553)
US 11197830 — method of use (U-3553)
Exclusivity NP
2023 2025 2027 2029 2031 2033 2035 2037 2039
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (2)
PatentTypeUse codeExpires
US 11534407 ↗ Method of use U-3553 Feb 27, 2039
US 11197830 ↗ Method of use U-3553 Feb 27, 2039
FDA exclusivity
CodeWhat it grantsExpires
NPNew ProductMar 1, 2026
Common questions
Is there a generic version of this drug?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for this drug. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
68788-4181-01 You're viewing this 120 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (68788-4181-1) 2026-08-20 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 68788-4181-1, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 68788-4181-01, written without dashes as 68788418101. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 68788-4181-01, the first segment (68788) is the labeler code FDA assigned to Preferred Pharmaceuticals Inc.; the middle segment (4181) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Preferred Pharmaceuticals Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Preferred Pharmaceuticals Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning ~2 min read

WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK, AND GASTROINTESTINAL RISK WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK AND GASTROINTESTINAL RISK See full prescribing information for complete boxed warning . • COMBOGESIC contains acetaminophen, which has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with doses of acetaminophen that exceed 4,000 milligrams per day, and often involve more than one acetaminophen containing product ( 5.1 ). • Nonsteroidal anti-inflammatory drugs (NSAIDS), like the ibuprofen in COMBOGESIC, cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal.

This risk may occur early in treatment and may increase with duration of use ( 5.2 ). • COMBOGESIC tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery ( 5.2 ). • NSAIDS, like the ibuprofen in COMBOGESIC, cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events ( 5.3 ).

HEPATOTOXICITY COMBOGESIC contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product [see Warnings and Precautions (5.1) ] .

CARDIOVASCULAR RISK COMBOGESIC contains ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions (5.2) ] .

COMBOGESIC is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.2) ] . GASTROINTESTINAL RISK NSAIDS cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms.

Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings and Precautions (5.3) ] .

🎯 Indications and Usage 51 words

1 INDICATIONS AND USAGE COMBOGESIC is indicated in adults for the short-term management of mild to moderate acute pain. COMBOGESIC is a combination of acetaminophen and ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and is indicated in adults for the short term management of mild to moderate acute pain ( 1 ).

⏱️ Dosage and Administration 138 words

2 DOSAGE AND ADMINISTRATION • Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5) ]. • Do not exceed the recommended dose of COMBOGESIC in 24 hours [see (2) below]. • Do not co-administer COMBOGESIC with other acetaminophen- or NSAID-containing products [see Warnings and Precautions (5.1 , 5.2 , 5.3) ]. The recommended dose of COMBOGESIC is 3 tablets every 6 hours as needed for pain relief, up to a maximum of 12 tablets per day. • Use the lowest effective dosage for shortest duration consistent with individual patient treatment goals ( 2 ). • Do not administer with other acetaminophen-containing products ( 2 ).

Three tablets every 6 hours as needed for pain relief, up to a maximum of 12 tablets per day ( 2 ).

💊 Dosage Forms and Strengths 48 words

3 DOSAGE FORMS AND STRENGTHS Tablets: white, biconvex, capsule-shaped, film-coated tablets, debossed with the letters "CG" on one side and plain on the other side, each containing 325 mg acetaminophen and 97.5 mg ibuprofen. • Film-coated tablet containing 325 mg acetaminophen and 97.5 mg ibuprofen ( 3 ).

Contraindications 159 words

4 CONTRAINDICATIONS COMBOGESIC is contraindicated in: • patients with a known hypersensitivity (e.g., anaphylactic reactions, serious skin reactions) to acetaminophen, ibuprofen, other NSAIDs, or to any of the excipients in this product [see Warnings and Precautions (5.7 , 5.8 , 5.9) ]. • patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDS [see Warnings and Precautions (5.7 and 5.8) ] . • the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.2) ] .

COMBOGESIC is contraindicated in: • patients with known hypersensitivity to acetaminophen, ibuprofen, other NSAIDs, or to any of the excipients in this product ( 4 ). • patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients ( 4 ). • the setting of coronary artery bypass graft (CABG) surgery ( 4 ).

⚠️ Warnings and Cautions ~3 min read

5 WARNINGS AND PRECAUTIONS • Hypertension : Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure ( 5.4 ). • Heart Failure and Edema : Avoid use of COMBOGESIC in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure ( 5.5 ). • Renal Toxicity : Long-term administration of NSAIDs, including the ibuprofen component of COMBOGESIC, has resulted in renal papillary necrosis and other renal injury ( 5.6 ). • Anaphylactic Reactions : Seek emergency help if an anaphylactic reaction occurs ( 5.7 ). • Exacerbation of Asthma Related to Aspirin Sensitivity : COMBOGESIC is contraindicated in patients with aspirin-sensitive asthma.

Monitor patients with preexisting asthma (without aspirin sensitivity) ( 5.8 ). • Serious Skin Reactions : Discontinue COMBOGESIC at first appearance of skin rash or other signs of hypersensitivity ( 5.9 ). • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) : Discontinue and evaluate clinically ( 5.10 ). • Fetal Toxicity : Limit use of NSAID-containing products, including COMBOGESIC, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAID-containing products, including COMBOGESIC in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus ( 5.11 ). • Hematologic Toxicity : Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia ( 5.12 ).

5.1Hepatotoxicity Acetaminophen COMBOGESIC contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involved more than one acetaminophen-containing product.

The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products. The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen. Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen.

Instruct patients to seek medical attention immediately upon ingestion of more than 4,000 milligrams of acetaminophen per day, even if they feel well. Ibuprofen Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported.

Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with NSAIDs including ibuprofen. Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue COMBOGESIC immediately, and perform a clinical evaluation of the patient.

COMBOGESIC has not been studied in patients with impaired hepatic function. The use of COMBOGESIC in patients with hepatic impairment is not recommended.

5.2Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear th…

🤒 Adverse Reactions ~2 min read

6 ADVERSE REACTIONS The following clinically significant adverse reactions to ibuprofen or acetaminophen are described elsewhere in other sections of the labelling. • Hepatotoxicity [see Warnings and Precautions (5.1) ] • Cardiovascular Thrombotic Events [see Warnings and Precautions (5.2) ] • Gastrointestinal Bleeding, Ulceration, and Perforation [see Warnings and Precautions (5.3) ] • Hypertension [see Warnings and Precautions (5.4) ] • Heart Failure and Edema [see Warnings and Precautions (5.5) ] • Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6) ] • Anaphylaxis and Other Hypersensitivity Reactions [see Warnings and Precautions (5.7) ] • Serious Skin Reactions [see Warnings and Precautions (5.9) ] • Hematologic Toxicity [see Warnings and Precautions (5.12) ] The most common adverse reactions (incidence of ≥ 2% for patients receiving COMBOGESIC) are: nausea, vomiting, headache, dizziness, somnolence, post-procedural hemorrhage, and swelling of the face (Table 1).

The most common adverse reactions (greater than or equal to 2%) are nausea, vomiting, headache, dizziness, somnolence, post-procedural hemorrhage, and swelling of the face ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact AFT Pharmaceuticals US, Inc at 01-248-631-4810 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to the rates reported from clinical trials of another drug and may not reflect the rates observed in practice. The clinical trials of COMBOGESIC have been conducted in patients with postoperative pain following dental and arthroscopic procedures, who received double-blind treatment every 6 hours for 24 or 48 hours. Most commonly (≥2%) reported adverse reactions by organ system during double-blind treatment are listed in the table below.

Adverse reactions are closely related to the extent (the level and length) of exposure. The incidences of overall and individual adverse reactions reported during the double-blind treatment period did not suggest an increase of risks associated with short-term (up to one or two days) use of the combination drug, COMBOGESIC in comparison to each individual component, acetaminophen or ibuprofen, and to placebo. Table 1: Most commonly (≥2%) reported adverse reactions by organ system during double-blind treatment COMBOGESIC Acetaminophen Ibuprofen Placebo N=261 N=231 N=231 N=199 Total number of AEs 145 142 101 133 % of patients with ≥1 AE 30 38 29 37 Gastrointestinal disorders Nausea 15 19 12 23 Vomiting 7 10 3 10 Constipation 1 2 1 1 Dyspepsia 0.4 1 2 1 Injury, poisoning and procedural complications Post Procedural Hemorrhage 2 0.4 1 2 Nervous system disorders Headache 5 6 4 7 Dizziness 3 4 4 5 Somnolence 2 1 0 1 Skin and subcutaneous tissue disorders Swelling face 2 4 4 3 Pruritus 0.4 0.4 0.4 3

6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of acetaminophen and ibuprofen. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Appendages: Exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

🔄 Drug Interactions ~3 min read

7 DRUG INTERACTIONS Table 2: Clinically Significant Drug Interactions with COMBOGESIC Drugs That Interfere with Hemostasis Clinical Impact: • Ibuprofen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of ibuprofen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. • Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.

Intervention: Monitor patients with concomitant use of COMBOGESIC with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [ see Warnings and Precautions (5.12) ]. Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [ see Warnings and Precautions (5.3) ].

Intervention: Concomitant use of COMBOGESIC and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [ see Warnings and Precautions (5.3) ]. COMBOGESIC is not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: • NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). • In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure.

These effects are usually reversible. Intervention: • During concomitant use of COMBOGESIC and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. • During concomitant use of COMBOGESIC and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [ see Warnings and Precautions (5.6) ] . • When these drugs are administered concomitantly, patients should be adequately hydrated.

Assess renal function at the beginning of the concomitant treatment and periodically thereafter. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.

Intervention: During concomitant use of COMBOGESIC with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions (5.4 and 5.6) ]. Digoxin Clinical Impact: The concomitant use of ibuprofen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Intervention: During concomitant use of COMBOGESIC and digoxin, monitor serum digoxin levels.

Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance . The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.

Intervention: During concomitant use of COMBOGESIC and lithium, monitor pati…

👥 Use in Specific Populations ~3 min read

8 USE IN SPECIFIC POPULATIONS • Infertility: NSAID-containing products, including COMBOGESIC, are associated with reversible infertility. Consider withdrawal of COMBOGESIC tablets in women who have difficulties conceiving. ( 8.3 ) • Renal or hepatic impairment: Not recommended ( 5.1 , 5.6 , 8.6 , 8.7 ).

8.1Pregnancy Risk Summary Ibuprofen Use of NSAID-containing products, including COMBOGESIC, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of COMBOGESIC use between about 20 and 30 weeks of gestation and avoid COMBOGESIC use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations , Data ). Premature Closure of Fetal Ductus Arteriosus: Use of NSAID-containing products, including COMBOGESIC, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment: Use of NSAID-containing products, including COMBOGESIC, at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimester of pregnancy are inconclusive. In published animal reproduction studies, there were no clear developmental effects at doses up to 2.7-times the maximum human daily dose (MHDD) in the rabbit and 1.5-times in the MHDD rat when dosed throughout gestation.

In contrast, an increase in membranous ventricular septal defects was reported in rats treated on Gestation Days 9 & 10 with 2.2-times the MHDD. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as ibuprofen, resulted in increased pre- and post-implantation loss.

Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. Acetaminophen Prolonged experience with acetaminophen in pregnant women over several decades, based on published observational epidemiological studies and case reports, did not identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes (see Data ) .

Reproductive and developmental studies in rats and mice from the published literature have identified adverse events at clinically relevant doses of acetaminophen. Fetotoxicity, increases in bone variations in the fetuses, and necrosis in the fetus liver and kidney have been noted in studies in rats. In mice treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproduction were seen in a continuous breeding study.

A reduction in number of litters of the parental mating pair was observed as well as retarded growth and abnormal sperm in their offspring and reduced birth weight in the next generation. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAID-containing products, including COMBOGESIC, in women at about 30 weeks gestation and later in pregnancy, because NSAID-containing products, including COMBOGESIC, ca…

🤰 Pregnancy ~3 min read

8.1Pregnancy Risk Summary Ibuprofen Use of NSAID-containing products, including COMBOGESIC, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of COMBOGESIC use between about 20 and 30 weeks of gestation and avoid COMBOGESIC use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations , Data ). Premature Closure of Fetal Ductus Arteriosus: Use of NSAID-containing products, including COMBOGESIC, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment: Use of NSAID-containing products, including COMBOGESIC, at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimester of pregnancy are inconclusive. In published animal reproduction studies, there were no clear developmental effects at doses up to 2.7-times the maximum human daily dose (MHDD) in the rabbit and 1.5-times in the MHDD rat when dosed throughout gestation.

In contrast, an increase in membranous ventricular septal defects was reported in rats treated on Gestation Days 9 & 10 with 2.2-times the MHDD. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as ibuprofen, resulted in increased pre- and post-implantation loss.

Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. Acetaminophen Prolonged experience with acetaminophen in pregnant women over several decades, based on published observational epidemiological studies and case reports, did not identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes (see Data ) .

Reproductive and developmental studies in rats and mice from the published literature have identified adverse events at clinically relevant doses of acetaminophen. Fetotoxicity, increases in bone variations in the fetuses, and necrosis in the fetus liver and kidney have been noted in studies in rats. In mice treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproduction were seen in a continuous breeding study.

A reduction in number of litters of the parental mating pair was observed as well as retarded growth and abnormal sperm in their offspring and reduced birth weight in the next generation. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAID-containing products, including COMBOGESIC, in women at about 30 weeks gestation and later in pregnancy, because NSAID-containing products, including COMBOGESIC, can cause premature closure of the fetal ductus arteriosus (see Data ) .

Oligohydramnios/Neonatal Renal Impairment: If, after consideration of alternative treatments for pain management, an NSAID-containing product, including COMBOGESIC, is necessary at about 20 weeks gestation or later in pregnancy, limit…

🧒 Pediatric Use 27 words

8.4Pediatric Use The safety and effectiveness of COMBOGESIC in pediatric patients have not been established. COMBOGESIC is not approved for patients under 18 years of age.

🧓 Geriatric Use 123 words

8.5Geriatric Use Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see Warnings and Precautions (5.1 , 5.2 , 5.3 , 5.4 , 5.5 , 5.6 )]. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

🆘 Overdosage ~2 min read

10 OVERDOSAGE COMBOGESIC is a combination product. The clinical presentation of overdose may include the signs and symptoms of acetaminophen toxicity, ibuprofen toxicity, or both. Acetaminophen The initial symptoms seen within the first 24 hours following an acetaminophen overdose are: anorexia, nausea, vomiting, malaise, pallor and diaphoresis.

Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects also may occur.

Plasma acetaminophen levels >300 mcg/mL at 4 hours after oral ingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are <150 mcg/mL or <37.5 mcg/mL at 12 hours after ingestion. If an acetaminophen overdose is suspected, obtain a serum acetaminophen assay as soon as possible, but no sooner than 4 hours following oral ingestion. Obtain liver function studies initially and repeat at 24-hour intervals.

Administer the antidote N-acetylcysteine (NAC) as early as possible. As a guide to treatment of acute ingestion, the acetaminophen level can be plotted against time since oral ingestion on a nomogram Rumack-Matthew). The lower toxic line on the nomogram is equivalent to 150 mcg/mL at 4 hours and 37.5 mcg/mL at 12 hours.

If serum level is above the lower line, administer the entire course of NAC treatment. Withhold NAC therapy if the acetaminophen level is below the lower line. Ibuprofen Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care.

Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [ see Warnings and Precautions (5.1 , 5.2 , 5.3 , 5.4 , 5.6 , 5.14 ) ]. Manage patients with symptomatic and supportive care following an NSAID overdosage.

There are no specific antidotes. It is advisable to contact a poison control center (1-800-222-1222) to determine the latest recommendations because strategies for the management of overdose are continually evolving. If gastric decontamination may benefit the patient, e.g., short time since ingestion or a large overdosage (5 to 10 times the recommended dosage), consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or an osmotic cathartic in symptomatic patients if clinically appropriate.

🧬 Clinical Pharmacology ~3 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Analgesia COMBOGESIC contains acetaminophen and ibuprofen. Acetaminophen is a non-opiate, non-salicylate analgesic. The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to primarily involve central actions.

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). Its mechanism of action for analgesia, like that of other NSAIDs, is not completely understood, but involves inhibition of cyclooxygenase (COX-1 and COX-2). Ibuprofen is a potent inhibitor of prostaglandin synthesis in vitro.

Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because ibuprofen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

12.2Pharmacodynamics Hematological Effects NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible.

12.3Pharmacokinetics Absorption Peak plasma concentration following the administration of three COMBOGESIC tablets occurs at approximately 45 minutes and 1 hour 15 minutes after administration for acetaminophen and ibuprofen, respectively, under fasting condition. In the same study, the peak plasma concentration (C max ) and the extent of absorption (AUC 0-inf ) are 14.88 mcg/mL and 47.44 mcg.h/mL for acetaminophen and 25.58 mcg/mL and 95.62 mcg.h/mL for ibuprofen, respectively. The C max and AUC 0-inf values for both acetaminophen and ibuprofen increase dose proportionally to increases in COMBOGESIC doses from one, to two, to three tablets.

A single-dose pharmacokinetic study of COMBOGESIC in volunteers showed no drug interactions between acetaminophen and ibuprofen. Food effects When COMBOGESIC was administered with food, the time to peak plasma concentration was delayed by approximately 30 minutes for acetaminophen and was approximately the same when compared to fasting conditions for ibuprofen. The peak plasma concentration of acetaminophen was reduced by approximately 30%, but the extent of absorption was not affected.

Peak plasma concentration and the extent of absorption were not affected for ibuprofen. Distribution Acetaminophen appears to be widely distributed throughout most body tissues except fat. Its apparent volume of distribution is about

0.9L/kg. A relatively small portion (~20%) of acetaminophen is bound to plasma protein. Elimination The half-life of acetaminophen is about 2 to 3 hours in adults.

It is somewhat shorter in children and somewhat longer in neonates and in cirrhotic patients. Acetaminophen is eliminated from the body primarily by formation of glucuronide and sulfate conjugates in a dose-dependent manner. Ibuprofen is rapidly metabolized and eliminated in the urine.

The elimination half-life of ibuprofen is in the range of 1.9 to 2.2 hours. Metabolism Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways: 1. conjugation with glucuronide; 2. conjugation with sulfate; and 3. oxidation via the cytochrome, P450-dependent, mixed-function oxidase enzyme pathway to form a reactive intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates.

The principal cytochrome P450 isoenzyme involved appears to be CYP2E1, with CYP1A2 and CYP3A4 as additional pathways. In adults, the majority of acetaminophen is conjugated with glucuronic acid and, to a lesser extent, with sulfate. These glucuronide-, sulfate-, and glutathione-derived metabolites lack biologic activity.

In premature infants, newborns, and young infants, the sulfate conjugate predominates. Excretion Less than 9% of acetaminophen is excreted unchanged in the urine. The exc…

🧬 Mechanism of Action 120 words

12.1Mechanism of Action Analgesia COMBOGESIC contains acetaminophen and ibuprofen. Acetaminophen is a non-opiate, non-salicylate analgesic. The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to primarily involve central actions.

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). Its mechanism of action for analgesia, like that of other NSAIDs, is not completely understood, but involves inhibition of cyclooxygenase (COX-1 and COX-2). Ibuprofen is a potent inhibitor of prostaglandin synthesis in vitro.

Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because ibuprofen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

📦 How Supplied / Storage and Handling 76 words

16 HOW SUPPLIED/STORAGE AND HANDLING COMBOGESIC tablets with acetaminophen 325 mg and ibuprofen 97.5 mg are white, biconvex, capsule-shaped film coated tablets, debossed with the letters "CG" on one side and plain on the other side and are available as follows: NDC 68788-4181-1 1 bottle containing 120 tablets Store at 20°C to 25°C (68°F to 77°F) with excursions permitted within USP controlled room temperature of 15°C to 30°C (59°F to 86°F). Protect from moisture and light.

📦 Storage and Handling 28 words

Store at 20°C to 25°C (68°F to 77°F) with excursions permitted within USP controlled room temperature of 15°C to 30°C (59°F to 86°F). Protect from moisture and light.

📋 Description 189 words

11 DESCRIPTION COMBOGESIC tablets are a combination of acetaminophen, an analgesic and antipyretic, and ibuprofen, a non-steroidal anti-inflammatory drug (NSAID). The chemical name for acetaminophen is N -acetyl- p -aminophenol. The molecular formula is C 8 H 9 NO 2 and the structural formula is: The molecular weight of acetaminophen is 151.17.

Acetaminophen is a white, odorless, crystalline powder, possessing a slightly bitter taste. Acetaminophen is soluble in boiling water and 1N sodium hydroxide, and is freely soluble in alcohol. The chemical name for ibuprofen is (±)-2-(p-isobutylphenyl) propionic acid.

The molecular formula is C 13 H 18 O 2 and the structural formula is: The molecular weight of ibuprofen is 206.29. Ibuprofen is a white powder with a melting point of 74-77°C and is very slightly soluble in water (<1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone. COMBOGESIC tablets contain 325 mg acetaminophen and 97.5 mg ibuprofen and are white in color.

The inactive ingredients in the tablet are croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, maltodextrin, medium chain triglycerides, microcrystalline cellulose, polydextrose, povidone-30, sodium lauryl sulfate, talc, titanium dioxide. Chemical Structure Chemical Structure

💬 Information for Patients ~3 min read

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Important Dosage and Administration Information : • Clearly explain to patients the single-dose and 24-hour dose limit and the time interval between doses. Explain that exceeding these recommendations can result in hepatic toxicity and/or gastrointestinal bleeding, ulceration, and perforation [See Dosage and Administration (2) , Warnings and Precautions (5.1 , 5.3) ]. • Inform patients that the concomitant use of COMBOGESIC with other NSAIDs, acetaminophen-containing products, or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of hepatic and gastrointestinal toxicity, and little or no increase in efficacy [see Warnings and Precautions (5.1 , 5.3) , Drug Interactions (7) ].

Alert patients that these may be present in "over the counter" medications for treatment of colds, fever, or insomnia. • Alert patients that NSAIDs and acetaminophen may be present in "over the counter" medications for treatment of colds, fever, or insomnia. Hepatotoxicity : Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness and "flu-like" symptoms). Instruct patients to stop therapy and seek immediate medical assistance if these occur [see Warnings and Precautions (5.1) ] .

Alcohol : Advise patients not to take COMBOGESIC concomitantly with alcohol-containing beverages [see Warnings and Precautions (5.1) ] . Cardiovascular Thrombotic Effects : Inform patients that COMBOGESIC, like other NSAID-containing medications, may cause serious CV side effects such as MI or stroke, which may result in hospitalization and even death. Advise patients to be alert for chest pain, shortness of breath, weakness, and slurring of speech, and to seek medical assistance when observing any sign or symptom indicative of CV effects [see Warnings and Precautions (5.2) ] .

Gastrointestinal Bleeding, Ulceration, and Perforation : Inform patients that COMBOGESIC, like other NSAID-containing medications, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Advise patients to be alert for the signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and to seek medical assistance should these symptoms occur [see Warnings and Precautions (5.3) ] . Heart Failure and Edema : Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see Warnings and Precautions (5.5) ] .

Weight Gain and Edema : Advise patients to promptly report unexplained weight gain or edema to their physicians [see Warnings and Precautions (5.5) ] . Anaphylactic Reactions : Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [see Warnings and Precautions (5.7) ] .

Serious Skin Reactions, including DRESS : Advise patients to stop taking COMBOGESIC immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [see Warnings and Precautions (5.9 , 5.10) ]. Female Fertility : Advise females of reproductive potential who desire pregnancy that NSAID containing products, including COMBOGESIC tablets, may be associated with a reversible delay in ovulation [see Use in Specific Populations (8.3) ]. Fetal Toxicity : Inform pregnant women to avoid use of COMBOGESIC and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus.

If treatment with COMBOGESIC is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need t…

💬 Medication Guide ~3 min read

Medication Guide COMBOGESIC ( kom-boh-JEE-zik ) (acetaminophen and ibuprofen) tablets This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: 06/2026 COMBOGESIC is a combination prescription medicine that contains acetaminophen and ibuprofen (a nonsteroidal anti-inflammatory drug [NSAID]).

What is the most important information I should know about COMBOGESIC? COMBOGESIC may cause serious side effects, including: • Severe liver problems. Acetaminophen, one of the ingredients in COMBOGESIC, has caused severe and life-threatening acute liver failure which caused the need for a liver transplant and has caused death. o Taking COMBOGESIC with other products that contain acetaminophen can lead to serious severe liver problems and death.

Do not take COMBOGESIC with other acetaminophen containing products. o You should not take more than 3 COMBOGESIC tablets in one dose or more than 12 COMBOGESIC tablets in one day. o If you take too much COMBOGESIC or acetaminophen, call your healthcare provider or Poison Control Center at 1-800-222-1222, or go to the nearest hospital emergency room right away. • Increased risk of a heart attack or stroke that can lead to death . This risk may happen early in treatment and may increase :Do not take COMBOGESIC right before or after a heart surgery called a "coronary artery bypass graft (CABG)." Avoid taking COMBOGESIC after a recent heart attack unless your healthcare provider tells you to.

You may have an increased risk of another heart attack if you take COMBOGESIC after a recent heart attack. o with increasing doses of medicines containing NSAIDs o with longer use of medicines containing NSAIDs • Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:The risk of getting an ulcer or bleeding increases with:COMBOGESIC should only be taken exactly as prescribed, at the lowest dose possible for your treatment, and for the shortest time needed. o anytime during use o without warning symptoms o that may cause death o past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs o taking medicines called "corticosteroids", "anticoagulants", "SSRIs", or "SNRIs" o increasing doses of NSAIDs o longer use of NSAIDs o smoking o drinking alcohol o older age o poor health o advanced liver disease o bleeding problems What is COMBOGESIC?

COMBOGESIC is a combination prescription medicine that contains acetaminophen and ibuprofen (a non-steroidal anti-inflammatory drug [NSAID]) used in adults for the short-term management of mild to moderate acute pain. It is not known if COMBOGESIC is safe and effective for use in children. Do not take COMBOGESIC: • If you are allergic to acetaminophen, ibuprofen, other NSAIDs, or to any of the ingredients in COMBOGESIC.

See the end of this Medication Guide for a complete list of ingredients in COMBOGESIC. • If you have had an asthma attack, hives, or other allergic reactions after taking aspirin or any other NSAIDs. • Right before or after heart bypass surgery. Before taking COMBOGESIC, tell your healthcare provider about all of your medical conditions, including if you: • have liver or kidney problems • have high blood pressure • have asthma • have heart problems • have bleeding problems • have or have had ulcers • drink alcohol • are pregnant or plan to become pregnant.

Taking COMBOGESIC at about 20 weeks of pregnancy or later may harm your unborn baby. o If you need to take NSAIDs for more than 2 days when you are between 20 and 30 weeks of pregnancy, your healthcare provider may need to monitor the amount of fluid in your womb around your baby. You should not take NSAIDs after about 30 weeks of pregnancy. o NSAID containing products, including COMBOGESIC, may cause reversible fertility problems in females, which may temporarily affect your ability to become pregnant during treatment with COMBOGESIC.

Talk to your healthcare provider…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.