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Tramadol Hydrochloride and Acetaminophen 37.5 mg; 325 mg Tablet, Film Coated, 1 tablet — NDC 76420-0105-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Tramadol Hydrochloride and Acetaminophen 37.5 mg; 325 mg Tablet, Film Coated, 1 tablet — NDC 76420-105-01 (Billing 76420-0105-01)

by Asclemed USA, Inc. · 1 TABLET, FILM COATED in 1 BOTTLE

This is a package of 1 tablet of Tramadol Hydrochloride and Acetaminophen 37.5 mg; 325 mg Tablet, Film Coated from Asclemed USA, Inc., marketed since Dec 2012 and currently FDA-listed. It is the main listing for this product, which comes in 5 package sizes.

NDC 76420-0105-01
🏷️ FDA NDC (as labeled) 76420-105-01 billing pads the product segment with a zero
This package
Contains1 tablet Pack sizes5 compare ↓
Also priced by: Part D plans $0.2110/unit — full pricing hub ↓
Main listing for product 76420-105 · Also comes in: 2 tablets 76420-105-02 3 tablets 76420-105-03 10 tablets 76420-105-10 30 tablets 76420-105-30
Rx only Generic On market CIV 🛡 REMS ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Aug 27, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 76420-105-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
76420 labeler · 105 product · 01 package
Package marketed since
Oct 30, 2020
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 7642010501 5
FDA record last changed
Aug 27, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 76420-105-01
Product NDC 76420-105
11-digit billing NDC 76420010501
RxCUI 836395
UNII 9N7R477WCK, 362O9ITL9D
Application # ANDA201952
SPL Set ID 82d8b70f-aebf-4b9a-89b1-183fc9e2ff59
Established class (EPC) Opioid Agonist
Mechanism of action Full Opioid Agonists
DEA schedule CIV
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2012-12-15
Route ORAL
Dosage form TABLET, FILM COATED
Substance TRAMADOL HYDROCHLORIDE; ACETAMINOPHEN
Quick answers
  • RxCUI (RxNorm): 836395
Why two NDCs? The FDA registers this code as 76420-105-01 — a 5-3-2 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 product segment → 76420-0105-01. 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 Opioid Agonist class.

Pharmacologic class Opioid Agonist
Drug family (ATC) Other opioids
How it works Full Opioid Agonists
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.

Clinical

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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.

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 · Q2 2026 $0.2110 $0.21 / 1 tablet
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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
76420-0105-01 You're viewing this Main listing 1 TABLET, FILM COATED in 1 BOTTLE 2020-10-30 — Active
76420-0105-02 76420-105-02 2 TABLET, FILM COATED in 1 BOTTLE 2020-10-30 — Active
76420-0105-03 76420-105-03 3 TABLET, FILM COATED in 1 BOTTLE 2020-10-30 — Active
76420-0105-10 76420-105-10 10 TABLET, FILM COATED in 1 BOTTLE 2020-10-30 — Active
76420-0105-30 76420-105-30 30 TABLET, FILM COATED in 1 BOTTLE 2020-10-30 — Active

You're viewing the smallest of 5 pack sizes for this product.

Pack size FAQ

What quantity is in this package?
This package contains 1 tablet — 1 tablet, film coated in 1 bottle.
How does this package differ from NDC 76420-0105-02?
Both are Tramadol Hydrochloride and Acetaminophen 37.5 mg; 325 mg Tablet, Film Coated — the drug itself is identical. This page's package is the 1 tablet one, while NDC 76420-0105-02 is the 2 tablets package.
What NDC number is used to bill for this package of Tramadol Hydrochloride and Acetaminophen 37.5 mg; 325 mg Tablet, Film Coated?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 50268-0774-15 AvPAK 50 tablets $0.116 AB Availability likely —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 53746-0617-01 Amneal 100 tablets $0.116 AB Availability likely —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 65862-0922-01 Aurobindo 100 tablets $0.116 AB Availability likely —
Tramadol Hydrochloride And Acetaminophen 325 mg/1; 37.5 mg 42571-0119-01 Micro 100 tablets $0.125 — Discontinued —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 45865-0170-60 Medsource 60 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 60760-0922-20 St. 20 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 63187-0084-30 Proficient 30 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 68788-7855-02 Preferred 20 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 70518-4461-00 REMEDYREPACK 60 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 71205-0625-30 Proficient 30 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 71335-0111-01 Bryant 30 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 71335-1742-01 Bryant 30 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 72162-2510-01 Bryant 100 tablets — AB FDA listed —
Tramadol Hydrochloride and Acetaminophen 325 mg/1; 37.5 mg 72189-0382-60 Direct_Rx 60 tablets — AB FDA listed —
Tramadol/APAP 325 mg/1; 37.5 mg 72189-0671-60 Direct_rx 60 tablets — AB FDA listed —
Tramadol Hydrochloride And Acetaminophen 37.5 mg/1; 325 mgthis 76420-0105-01 Asclemed 1 tablet — — FDA listed —
Tramadol Hydrochloride and Acetaminophen 37.5 mg/1; 325 mg 76420-0983-01 Asclemed 1 tablet — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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

🏛️
2012
On the market since
Dec 2012
📍
2026
Currently FDA-listed
14 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

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.

What it looks like

Color yellow
ShapeOval
ImprintI03
Size16 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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.

Manufacturer & labeler

LabelerAsclemed USA, Inc.
Application holderMICRO LABS LTD INDIA
FDA applicationANDA201952 (ANDA)
Labeler code76420
First marketedDec 2012
DEA scheduleCIV
Product typeHuman Prescription Drug
Portfolio652 products on file

More NDCs from Asclemed USA, Inc. labeler code 76420

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.

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 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide
🚨 Boxed Warning ~3 min read ▾

WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF TRAMADOL AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Tramadol hydrochloride and acetaminophen tablets exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death.

Assess each patient’s risk prior to prescribing tramadol hydrochloride and acetaminophen tablets, and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1) ]. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products [see Warnings and Precautions (5.2) ] . Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers.

Healthcare providers are strongly encouraged to complete a REMS-compliant education program, counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products, emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of tramadol hydrochloride and acetaminophen tablets.

Monitor for respiratory depression, especially during initiation of tramadol hydrochloride and acetaminophen tablets or following a dose increase [see Warnings and Precautions (5.3) ]. Accidental Ingestion Accidental ingestion of even one dose of tramadol hydrochloride and acetaminophens tablets, especially by children, can result in a fatal overdose of tramadol [see Warnings and Precautions (5.3) ]. Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children Life-threatening respiratory depression and death have occurred in children who received tramadol.

Some of the reported cases occurred following tonsillectomy and/or adenoidectomy, and in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism [see Warnings and Precautions (5.4) ]. Tramadol hydrochloride and acetaminophen tablet is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4) ]. Avoid the use of tramadol hydrochloride and acetaminophen tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol. [see Warnings and Precautions (5.4) ] Neonatal Opioid Withdrawal Syndrome Prolonged use of tramadol hydrochloride and acetaminophen tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.

If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.5) ]. Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhib…

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions (5.1) ] , reserve tramadol hydrochloride and acetaminophen for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: Have not been tolerated, or are not expected to be tolerated, Have not provided adequate analgesia, or are not expected to provide adequate analgesia.

Tramadol hydrochloride and acetaminophen tablet is a combination of tramadol hydrochloride, an opioid agonist, and acetaminophen, and is indicated for the management of acute pain, severe enough to require an opioid analgesic and for which alternative treatments are inadequate. ( 1 ) Limitations of Use ( 1 ) Tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve tramadol hydrochloride and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: Have not been tolerated, or are not expected to be tolerated.

Have not provided adequate analgesia, or are not expected to provide adequate analgesia.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. ( 2.1 ) Initiate treatment with two tablets every 4 to 6 hours as needed for pain relief; maximum of 8 tablets per day.

( 2.2 ) Do not use with other acetaminophen- or tramadol-containing products. ( 2 , 5.17 ) Severe Renal Impairment : Do not exceed 2 tablets every 12 hours. ( 2.3 ) Do not abruptly discontinue tramadol hydrochloride and acetaminophen tablets in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

( 2.4 )

2.1Important Dosage and Administration Instructions Tramadol hydrochloride and acetaminophen is not approved for use for more than 5 days. Do not exceed the recommended dose of tramadol hydrochloride and acetaminophen. Do not co-administer tramadol hydrochloride and acetaminophen with other tramadol or acetaminophen containing products [see Warnings and Precautions (5.19) ] .

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5.1) ]. Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1) ] . Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with tramadol hydrochloride and acetaminophen and adjust the dosage accordingly [see Warnings and Precautions (5.3) ] .

2.2Initial Dosage The initial dose of tramadol hydrochloride and acetaminophen tablet is 2 tablets every 4 to 6 hours as needed for pain relief up to a maximum of 8 tablets per day.

2.3Dosage Modification in Patients with Renal Impairment In patients with creatinine clearances of less than 30 mL/min, do not exceed 2 tablets every 12 hours.

2.4Safe Reduction or Discontinuation of Tramadol Hydrochloride and Acetaminophen Do not abruptly Do not abruptly discontinue tramadol hydrochloride and acetaminophenin patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When When a decision has been made to decrease the dose or discontinue therapy in an opioid- dependent patient taking tramadol hydrochloride and acetaminophen, there are a variety of factors that should be considered, including the dose of tramadol hydrochloride and acetaminophen the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.

It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder.

Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist. There are There are no standard opioid tapering schedules that…

💊 Dosage Forms and Strengths 46 words ▾

3 DOSAGE FORMS AND STRENGTHS Tramadol hydrochloride and acetaminophen tablets USP, 37.5 mg/325 mg, are light yellow, oblong-shaped, biconvex, film-coated tablets debossed with “I 03" on one side and plain on the other side. Tablets: tramadol hydrochloride 37.5 mg and acetaminophen 325 mg. ( 3 )

⛔ Contraindications ~1 min read ▾

4 CONTRAINDICATIONS Tramadol hydrochloride and acetaminophen is contraindicated for: all children younger than 12 years of age [see Warnings and Precautions (5.4) ] post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.4) ] . Tramadol hydrochloride and acetaminophen is also contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.3) ] . Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.13) ] .

Patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.17) ] . Previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids [see Warnings and Precautions (5.18) ]. Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7) ].

Children younger than 12 years of age ( 4 ) Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. ( 4 ) Significant respiratory depression. ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment.

( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) Previous hypersensitivity to tramadol hydrochloride, acetaminophen, any other component of this product, or opioids. ( 4 ) Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: May be life-threatening. Can occur with use of tramadol alone, with concomitant use of serotonergic drugs, with drugs that impair metabolism of serotonin or tramadol. ( 5.9 ) Risk of Seizure: Can occur at the recommended dose of tramadol.

Concomitant use with other drugs may increase seizure risk. Risk may increase in patients with epilepsy, a history of seizures, and in patients with a recognized risk for seizures. ( 5.10 ) Risk of Suicide: Do not prescribe for suicidal or addiction-prone patients.

( 5.11 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.12 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration. ( 5.13 ) Severe Hypotension: Monitor during dosage initiation and titration.

Avoid use of tramadol hydrochloride and acetaminophen in patients with circulatory shock. ( 5.14 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression. Avoid use of tramadol hydrochloride and acetaminophen in patients with impaired consciousness or coma.

( 5.15 )

5.1Addiction, Abuse and Misuse Tramadol hydrochloride and acetaminophen contains tramadol, a Schedule IV controlled substance. As an opioid, tramadol hydrochloride and acetaminophen exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9) ] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed tramadol hydrochloride and acetaminophen.

Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing tramadol hydrochloride and acetaminophen, and monitor all patients receiving tramadol hydrochloride and acetaminophen for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).

The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as tramadol hydrochloride and acetaminophen, but use in such patients necessitates intensive counseling about the risks and proper use of tramadol hydrochloride and acetaminophen along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Consider these risks when prescribing or dispensing tramadol hydrochloride and acetaminophen. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17) ] . Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

5.2Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) To ensure that To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following: Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includ…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3) ] Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children [see Warnings and Precautions (5.4) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.5) ] Hepatotoxicity [see Warnings and Precautions (5.7) ] Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.8) ] Serotonin Syndrome [see Warnings and Precautions (5.9) ] Seizures [see Warnings and Precautions (5.10) ] Suicide [see Warnings and Precautions (5.11) ] Adrenal Insufficiency [see Warnings and Precautions (5.12) ] Severe Hypotension [see Warnings and Precautions (5.14) ] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.17) ] Hypersensitivity Reactions [see Warnings and Precautions (5.18) ] Withdrawal [see Warnings and Precautions (5.20) ] The most common incidence of treatment-emergent adverse events (≥3%) in patients from clinical trials were constipation, diarrhea, nausea, somnolence, anorexia, dizziness, and sweating increased.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA, Inc. at 1-855-839-8195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common incidence of treatment-emergent adverse events (≥3%) in subjects from clinical trials was constipation, diarrhea, nausea, somnolence, anorexia, dizziness, and sweating increased. Table 1 shows the incidence rate of treatment-emergent adverse events reported in ≥2% of subjects over five days of tramadol hydrochloride and acetaminophen use in clinical trials (subjects took an average of at least 6 tablets per day).

Table 1: Incidence of Treatment-Emergent Adverse Events ( ≥ 2%) Body System Preferred Term Tramadol Hydrochloride and Acetaminophen (N=142) (%) Gastrointestinal System Disorders Constipation 6 Diarrhea 3 Nausea 3 Dry Mouth 2 Psychiatric Disorders Somnolence 6 Anorexia 3 Insomnia 2 Central & Peripheral Nervous System Dizziness 3 Skin and Appendages Sweating Increased 4 Pruritus 2 Reproductive Disorders, Male* Prostatic Disorder 2 * Number of males = 62 Incidence at least 1%, causal relationship at least possible or greater: The following lists adverse reactions that occurred with an incidence of at least 1% in single-dose or repeated-dose clinical trials of tramadol hydrochloride and acetaminophen.

Body as a Whole - Asthenia, fatigue, hot flushes Central and Peripheral Nervous System - Dizziness, headache, tremor Gastrointestinal System - Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, dry mouth, nausea, vomiting Psychiatric Disorders - Anorexia, anxiety, confusion, euphoria, insomnia, nervousness, somnolence Skin and Appendages - Pruritus, rash, increased sweating Selected Adverse events occurring at less than 1%: The following lists clinically relevant adverse reactions that occurred with an incidence of less than 1% in tramadol hydrochloride and acetaminophen clinical trials.

Body as a Whole - Chest pain, rigors, syncope, withdrawal syndrome Cardiovascular Disorders - Hypertension, aggravated hypertension, hypotension Central and Peripheral Nervous System - Ataxia, convulsions, hypertonia, migraine, aggravated migraine, involuntary muscle contractions, paresthesias, stupor, vertigo Gastrointestinal System - Dysphagia, melena, tongue edema Hearing and Vestibular Disorders - Tinnitus Heart Rate and Rhythm Disorders - Arrhythmia, palpitation, tachycardia Liver and Biliary System -…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Table 2 includes clinically significant interactions with tramadol hydrochloride and acetaminophen. Table 2: Clinically Significant Drug Interactions with Tramadol Hydrochloride and Acetaminophen Inhibitors of CYP2D6 Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophenand CYP2D6 inhibitors may result in an increase in the plasma concentration of tramadol and a decrease in the plasma concentration of M1, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride and acetaminophen is achieved.

Since M1 is a more potent µ-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. After stopping a CYP2D6 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease and the M1 plasma concentration will increase which could increase or prolong therapeutic effects but also increase adverse reactions related to opioid toxicity, and may cause potentially fatal respiratory depression [see Clinical Pharmacology (12.3) ] .

Intervention: If concomitant use of a CYP2D6 inhibitor is necessary, follow patients closely for adverse reactions including opioid withdrawal, seizures and serotonin syndrome. If a CYP2D6 inhibitor is discontinued, consider lowering tramadol hydrochloride and acetaminophendosage until stable drug effects are achieved. Follow patients closely for adverse events including respiratory depression and sedation.

Examples: Quinidine, fluoxetine, paroxetine and bupropion Inhibitors of CYP3A4 Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP3A4 inhibitors can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1. Follow patients closely for increased risk of serious adverse events including seizures and serotonin syndrome, and adverse reactions related to opioid toxicity including potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride and acetaminophen is achieved.

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease [see Clinical Pharmacology (12.3) ] , resulting in decreased opioid efficacy and possibly signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Intervention: If concomitant use is necessary, consider dosage reduction of tramadol hydrochloride and acetaminophen until stable drug effects are achieved. Follow patients closely for seizures and serotonin syndrome, and signs of respiratory depression and sedation at frequent intervals.

If a CYP3A4 inhibitor is discontinued, consider increasing the tramadol hydrochloride and acetaminophen dosage until stable drug effects are achieved and follow patients for signs and symptoms of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP3A4 inducers can decrease the plasma concentration of tramadol [see Clinical Pharmacology (12.3) ] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol.

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the tramadol plasma concentration will increase [see Clinical Pharmacology (12.3) ] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression,…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy : May cause fetal harm. ( 8.1 ) Lactation : Breastfeeding not recommended. ( 8.2 )

8.1Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5) ] . Available data with tramadol hydrochloride and acetaminophen in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, the combination of tramadol and acetaminophen decreased fetal weights and increased supernumerary ribs at 1.6 times the maximum recommended human daily dosage (MRHD).

In separate animal reproduction studies, tramadol administration alone during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (MRHD). Tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the MRHD. Reproductive and developmental studies in rats and mice from the published literature identified adverse events at clinically relevant doses with acetaminophen.

Treatment of pregnant rats with doses of acetaminophen approximately 1.3 times the maximum human daily dose (MRHD) showed evidence of fetotoxicity and increases in bone variations in the fetuses. In another study, necrosis was observed in the liver and kidney of both pregnant rats and fetuses at doses approximately 1.9 times the MHDD. 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 [see Data] . Based on animal data, advise pregnant women of the potential risk to a fetus. 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 Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight.

The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms and signs of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.5) ] . Neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol hydrochloride during postmarketing.

Labor or Delivery Tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in the neonate.

Tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including tramadol hydrochloride and acetaminophen, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is n…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5) ] . Available data with tramadol hydrochloride and acetaminophen in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, the combination of tramadol and acetaminophen decreased fetal weights and increased supernumerary ribs at 1.6 times the maximum recommended human daily dosage (MRHD).

In separate animal reproduction studies, tramadol administration alone during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (MRHD). Tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the MRHD. Reproductive and developmental studies in rats and mice from the published literature identified adverse events at clinically relevant doses with acetaminophen.

Treatment of pregnant rats with doses of acetaminophen approximately 1.3 times the maximum human daily dose (MRHD) showed evidence of fetotoxicity and increases in bone variations in the fetuses. In another study, necrosis was observed in the liver and kidney of both pregnant rats and fetuses at doses approximately 1.9 times the MHDD. 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 [see Data] . Based on animal data, advise pregnant women of the potential risk to a fetus. 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 Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight.

The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms and signs of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.5) ] . Neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol hydrochloride during postmarketing.

Labor or Delivery Tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in the neonate.

Tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including tramadol hydrochloride and acetaminophen, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor.

Monitor neonates e…

🧒 Pediatric Use 217 words ▾

8.4Pediatric Use The safety and effectiveness of tramadol hydrochloride and acetaminophen in pediatric patients have not been established. Life-threatening respiratory depression and death have occurred in children who received tramadol [see Warnings and Precautions (5.4) ] . In some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6).

Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. Because of the risk of life-threatening respiratory depression and death: Tramadol hydrochloride and acetaminophen is contraindicated for all children younger than age 12 years of age [see Contraindications (4) ] . Tramadol hydrochloride and acetaminophen is contraindicated for postoperative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4) ] .

Avoid the use of tramadol hydrochloride and acetaminophen in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. Risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

🧓 Geriatric Use 183 words ▾

8.5Geriatric Use Elderly patients (65 years of age or older) may have increased sensitivity to tramadol. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.

Titrate the dosage of tramadol hydrochloride and acetaminophen slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.3) ]. Tramadol and acetaminophen are 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 ~3 min read ▾

10 OVERDOSAGE Clinical Presentation Tramadol hydrochloride and acetaminophen is a combination drug. The clinical presentation of overdose may include the signs and symptoms of tramadol toxicity, acetaminophen toxicity or both. The initial symptoms of tramadol overdosage may include respiratory depression and/or seizures.

The initial symptoms seen within the first 24 hours following an acetaminophen overdose are: anorexia, nausea, vomiting, malaise, pallor and diaphoresis. Tramadol Acute overdosage with tramadol can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, QT prolongation, hypotension, partial or complete airway obstruction, atypical snoring, seizures, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Deaths due to overdose have been reported with abuse and misuse of tramadol [see Warnings and Precautions ( 5.1 )] . Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids. Acetaminophen In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect.

Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia also 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. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise.

Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. Treatment of Overdose A single or multiple drug overdose with tramadol and acetaminophen is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.

Oxygen, intravenous fluids, vasopressors, assisted ventilation, and other supportive measures should be employed as indicated. Tramadol In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated.

Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to tramadol overdose, administer an opioid antagonist.

Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to tramadol overdose. While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with naloxone administration. In animals, convulsions following the administration of toxic doses of tramadol hydrochloride and acetaminophen could be suppressed with barbiturates or benzodiazepines but were increased with naloxone.

Naloxone administration did not change the lethality of an overdose in mice. Hemodialysis is not expected to be helpful in an overdose because it removes less than 7% of the administered dose in a 4-hour dialysis period. Because the duration of opioid reversal is expected to be less than the duration of action of tramadol in tramadol hydrochloride and acetaminophen, carefully monitor the patient until spontaneous respiration is reliably re-established.

If the respo…

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY The following information is based on studies of tramadol alone or acetaminophen alone, except where otherwise noted:

12.1Mechanism of Action Tramadol hydrochloride and acetaminophencontains tramadol, an opioid agonist and inhibitor of norepinephrine and serotonin re-uptake, and acetaminophen. Although the mode of action of tramadol is not completely understood, the analgesic effect of tramadol is believed to be due to both binding to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity of tramadol is due to both low affinity binding of the parent compound and higher affinity binding of the O -demethylated metabolite M1 to µ-opioid receptors.

In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound [see Clinical Pharmacology ( 12.3 )] .

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro , as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol. Acetaminophen is a non-opioid, non-salicylate analgesic.

The site and mechanism for the analgesic effect of acetaminophen has not been determined but is thought to primarily involve central actions.

12.2Pharmacodynamics Effects on the Central Nervous System Tramadol produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. Tramadol causes miosis, even in total darkness.

Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Effects on the Gastrointestinal Tract and Other Smooth Muscle Tramadol causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum.

Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation. Other opioid- induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.

Effects on the Cardiovascular System Tramadol produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. The effect of oral tramadol on the QTcF interval was evaluated in a double-blind, randomized, four-way crossover, placebo-and positive-(moxifloxacin) controlled study in 68 adult male and female healthy subjects.

At a 600 mg/day dose (1.5-fold the maximum immediate-release daily dose), the study demonstrated no significant effect on the QTcF interval. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Warnings and Precautions (5.12) , Adverse Reactions (6.2) ] . Theyalso stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.

Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of…

🧬 Mechanism of Action 211 words ▾

12.1Mechanism of Action Tramadol hydrochloride and acetaminophencontains tramadol, an opioid agonist and inhibitor of norepinephrine and serotonin re-uptake, and acetaminophen. Although the mode of action of tramadol is not completely understood, the analgesic effect of tramadol is believed to be due to both binding to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity of tramadol is due to both low affinity binding of the parent compound and higher affinity binding of the O -demethylated metabolite M1 to µ-opioid receptors.

In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound [see Clinical Pharmacology ( 12.3 )] .

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro , as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol. Acetaminophen is a non-opioid, non-salicylate analgesic.

The site and mechanism for the analgesic effect of acetaminophen has not been determined but is thought to primarily involve central actions.

📦 How Supplied / Storage and Handling 133 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Tramadol hydrochloride and acetaminophen tablets USP, 37.5 mg/325 mg, are light yellow, oblong-shaped, biconvex, film-coated tablets debossed with “I 03” on one side and plain on the other side. They are available as follows: Bottles of 1 tablets NDC 76420-105-01 (repackaged from NDC 42571-119-xx) Bottles of 2 tablets NDC 76420-105-02 (repackaged from NDC 42571-119-xx) Bottles of 3 tablets NDC 76420-105-03 (repackaged from NDC 42571-119-xx) Bottles of 10 tablets NDC 76420-105-10 (repackaged from NDC 42571-119-xx) Bottles of 30 tablets NDC 76420-105-30 (repackaged from NDC 42571-119-xx) Dispense in a tight container.

Store at 20 to 25°C (68 to 77°F); excursions permitted to 15 to 30°C (59 to 86°F). [see USP Controlled Room Temperature]. Store tramadol hydrochloride and acetaminophen tablets securely and dispose of properly [see Patient Counseling Information (17) ].

📋 Description 164 words ▾

11 DESCRIPTION Tramadol hydrochloride and acetaminophen tablets USP combines two analgesics, tramadol hydrochloride and opioid agonist, and acetaminophen. The chemical name for tramadol hydrochloride is (±)cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride. Itsstructural formula is: The molecular weight of tramadol hydrochloride is 299.84.

Tramadol hydrochloride USP is a white, bitter, crystalline, and odorless powder. The chemical name for acetaminophen is N-acetyl-p-aminophenol. Its structural formula is: The molecular weight of acetaminophen is 151.17.

Acetaminophen USP is an analgesic and antipyretic agent which occurs as a white, odorless, crystalline powder, possessing a slightly bitter taste. Tramadol hydrochloride and acetaminophen tablets USP, contain 37.5 mg tramadol hydrochloride USP and 325 mg acetaminophen USP and are light yellow in color. Inactive ingredients in the tablets are powdered cellulose, pregelatinized starch, sodium starch glycolate, corn starch, magnesium stearate and OPADRY ® Light Yellow.

OPADRY ® Light Yellow consists of the following ingredients: Hypromellose 2910 Titanium Dioxide Polyethylene Glycol 400 Iron oxide yellow Polysorbate 80 Meets USP Dissolution Test 2. tramadol structure acetaminophen structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store tramadol hydrochloride and acetaminophen securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions (5.1 , 5.20) , Drug Abuse and Dependence (9.2) ] . Inform patients that leaving tramadol hydrochloride and acetaminophen unsecured can pose a deadly risk to others in the home.

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Inform patients that medicine take-back options are the preferred way to safely dispose of most types of unneeded medicines. If no take back programs or Drug Enforcement Administration (DEA)-registered collectors are available, instruct patients to dispose of tramadol hydrochloride and acetaminophen by following these four steps: Mix tramadol hydrochloride and acetaminophen (do not crush) with an unpalatable substance such as dirt, cat litter, or used coffee grounds; Place the mixture in a container such as a sealed plastic bag; Throw the container in the household trash; Delete all personal information on the prescription label of the empty bottle.

Inform patients that they can visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. Addiction, Abuse, and Misuse Inform patients that the use of tramadol hydrochloride and acetaminophen, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1) ] . Instruct patients not to share tramadol hydrochloride and acetaminophen with others and to take steps to protect tramadol hydrochloride and acetaminophen from theft or misuse.

Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting tramadol hydrochloride and acetaminophen or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.3) ] . Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.3) ] .

Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children Advise caregivers that tramadol hydrochloride and acetaminophen is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Advise caregivers of children 12 to 18 years of age receiving tramadol hydrochloride and acetaminophen to monitor for signs of respiratory depression [see Warnings and Precautions (5.4) ] . Interactions with Benzodiazepines or Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if tramadol hydrochloride and acetaminophen is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.8) , Drug Interactions (7) ] .

Serotonin Syndrome Inform patients that tramadol could cause a rare but potentially life-threatening condition, particularly during concomitant use with serotonergic drugs. Warn patients of the symptoms and signs of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare provider if they are taking, or plan to take serotonergic medications [see Warnings and Precautions (5.9) ] .

MAOI Interaction Inform patients not to take tramadol hydrochloride…

💬 Medication Guide ~3 min read ▾

Medication Guide Tramadol Hydrochloride (TRAM-a-dol HYE-droe-KLOR-ide) and Acetaminophen (ass-eet-ah-MEE-noe-fen) Tablets, CIV Tramadol hydrochloride and acetaminophen Tablet is: A strong prescription pain medicine that contains an opioid (narcotic) that is used for the short-term (five days or less) management of acute pain, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them. An opioid pain medicine that can put you at risk for overdose and death.

Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death. Important information about tramadol hydrochloride and acetaminophen tablet : Get emergency help right away if you take too much tramadol hydrochloride and acetaminophen tablet ( overdose). When you first start taking tramadol hydrochloride and acetaminophentablet, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur.

Tramadol hydrochloride and acetaminophen tabletcan cause severe drowsiness, breathing problems (respiratory depression), coma and death when taken with benzodiazepines or other medicines that depress consciousness. Never give anyone else your tramadol hydrochloride and acetaminophen tablet. They could die from taking it.

Selling or giving away tramadol hydrochloride and acetaminophen tabletis against the law. Store tramadol hydrochloride and acetaminophen tablet securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Get emergency help right away if you take more than 4,000 mg of acetaminophen in 1 day.

Taking tramadol hydrochloride and acetaminophen tablet with other products that contain acetaminophen can lead to serious liver problems and death. Important Information Guiding Use in Pediatric Patients: Do not give tramadol hydrochloride and acetaminophen tablets to a child younger than 12 years of age. Do not give tramadol hydrochloride and acetaminophen tablets to a child younger than 18 years of age after surgery to remove the tonsils and/or adenoids.

Avoid giving tramadol hydrochloride and acetaminophen tablets to children between 12 to 18 years of age who have risk factors for breathing problems such as obstructive sleep apnea, obesity, or underlying lung problems. Do not take tramadol hydrochloride and acetaminophen tablet if you have: Severe asthma, trouble breathing, or other lung problems. A bowel blockage or have narrowing of the stomach or intestines.

An allergy to any of its ingredients (e.g., tramadol hydrochloride or acetaminophen). Taken a Monoamine Oxidase Inhibitor, MAOI, (medicine used for depression) within the last 14 days. Before taking tramadol hydrochloride and acetaminophen tablet , tell your healthcare provider if you have a history of: head injury, seizures liver, kidney, thyroid problems problems urinating pancreas or gallbladder problems abuse of street or prescription drugs, alcohol addiction, or mental health problems.

Tell your healthcare provider if you are: pregnant or planning to become pregnant . Prolonged use of tramadol hydrochloride and acetaminophen tabletduring pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. breastfeeding . Not recommended; it may harm your baby. taking prescription or over-the-counter medicines, vitamins, or herbal supplements.

Taking tramadol hydrochloride and acetaminophen tabletwith certain other medicines can cause serious side effects that could lead to death. When taking tramadol hydrochloride and acetaminophen tablet : Do not change your dose. Take tramadol hydrochloride and acetaminophen tabletexactly as prescribed by your healthcare provider.

Use the lowest dose possible for the shortest time needed. Take your prescribed dose: 2 tablets every 4 to 6 hours as needed for pain r…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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This drug has a REMS. A Risk Evaluation & Mitigation Strategy is an FDA-required safety program. It may require enrollment, counseling, or monitoring to manage a serious risk. See the boxed warning & full label below, and REMS@FDA ↗.

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) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
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 Asclemed USA, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 4 other package presentations of this same product, including 2 tablets (76420-0105-02), 3 tablets (76420-0105-03), 10 tablets (76420-0105-10). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Asclemed USA, 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.
← 76420-0104-10 · Asclemed 76420-0106-16 · Asclemed →
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.