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TRAMADOL HYDROCHLORIDE 100 mg Tablet, Extended Release, 30-count

by Proficient Rx LP · 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (63187-597-30)
NDC 63187-0597-30
🏷️ FDA NDC (as labeled) 63187-597-30 billing pads the product segment with a zero
This package
Contains30-count Pack sizes3 compare ↓
Also priced by: Part D plans $1.97/unit — full pricing hub ↓
Also comes in: 60 tablets 63187-0597-60 90 tablets 63187-0597-90
Rx only Generic On market CIV
🗂️ Data synced Jul 24, 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

⚠️
Other active recalls for Tramadol Hydrochloride (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Apr 26, 2024 — Presence of Foreign Tablets: Pharmacist reported a tablet of baclofen in a bottle of 1000-count tramadol (Rubicon Research Private Limited) · FDA recall D-0487-2024
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 63187-597-30
Product NDC 63187-597
11-digit billing NDC 63187059730
NCPDP billing unit EA — each (per item)
RxCUI 833709
UNII 9N7R477WCK
UPC 0363187597900
Application # ANDA201384
SPL Set ID 27495d02-8641-4c92-b5a3-edf50abc2a6f
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 2011-12-12
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance TRAMADOL HYDROCHLORIDE
GPI-14 65100095107520
GPI class traMADol HCl ER
GCN Seq No 060274
GCN 26387
HICL code 008317
Ingredient (HICL) Tramadol Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H3
Therapeutic class — intermediate (HIC2) Analgesics
HIC3 code H3A
Therapeutic class — specific (HIC3) Opioid Analgesics
AHFS code 28:08.08.00
AHFS class Opioid Agonists (28:08)
FDB label name TRAMADOL HCL ER 100 MG TABLET
FDB brand name Tramadol Hcl Er
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 63187-597-30 — 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 → 63187-0597-30. 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.

🏭 Manufacturer & labeler

LabelerProficient Rx LP
Application holderSUN PHARMACEUTICAL INDUSTRIES LTD
FDA applicationANDA201384 (ANDA)
Labeler code63187
First marketedDec 2011
DEA scheduleCIV
Product typeHuman Prescription Drug
Portfolio1,729 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

Label name TRAMADOL HCL ER 100 MG TABLET Ingredient Tramadol Hcl
📖 What it is MedlinePlus · NLM

Tramadol is used to relieve certain types of pain. Tramadol is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Yes — tramadol is a real opioid, though it works a little differently from something like morphine or oxycodone. It's prescribed for adults with pain that's severe enough that regu...
  • What is tramadol actually used for? Is it a real opioid?
  • Swallow it whole, once a day, at roughly the same time every day. This part is really important: never chew, crush, split, or dissolve the tablet — the extended-release design slow...
  • How do I take the extended-release tablet correctly?
📖 Read our full Tramadol guide →

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.

🧪 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.

💲 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 $1.97 $59.02 / 30 tablets
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
Tramadol Hydrochloride 100 mg 33342-0269-07 Macleods 30 tablets $0.894 AB1 Availability likely —
Tramadol Hydrochloride 100 mg 47335-0859-08 Sun 100 tablets — — FDA listed —
Tramadol Hydrochloride 100 mg 50090-5107-00 A-S 30 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 55700-0996-30 Quality 30 tablets — AB1 FDA listed —
Tramadol Hcl Er 100 mg 61919-0818-30 DIRECT 30 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mgthis 63187-0597-30 Proficient 30 tablets — — FDA listed —
Tramadol Hydrochloride 100 mg 63629-8323-01 Bryant 30 tablets — AB1 Discontinued —
Tramadol Hydrochloride 100 mg 67046-1527-03 Coupler 30 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 68071-1671-03 NuCare 30 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 68180-0697-01 Lupin 100 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 68788-8367-02 Preferred 20 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 70518-0942-00 REMEDYREPACK 30 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 71205-0463-30 Proficient 30 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 71335-1675-01 Bryant 30 tablets — — FDA listed —
Tramadol Hydrochloride 100 mg 76420-0244-30 Asclemed 30 tablets — — FDA listed —
Tramadol Hydrochloride 100 mg 76420-0536-30 Asclemed 30 tablets — AB1 FDA listed —
Tramadol HCL ER 100 mg 80425-0108-01 Advanced 30 tablets — AB1 FDA listed —
Tramadol HCL ER 100 mg 80425-0141-01 Advanced 30 tablets — — FDA listed —
Tramadol Hydrochloride 100 mg 82804-0298-30 Proficient 30 tablets — AB1 FDA listed —
Tramadol Hydrochloride 100 mg 47335-0531-08 Sun 100 tablets — — 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

🏛️
2011
On the market since
Dec 2011
📍
2026
Currently FDA-listed
15 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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
63187-0597-30 You're viewing this 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (63187-597-30) 2018-12-01 Active
63187-0597-60 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (63187-597-60) 2018-12-01 Active
63187-0597-90 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (63187-597-90) 2018-12-01 Active

You're viewing the smallest of 3 pack sizes for this product.

Pack size FAQ

What quantity is in NDC 63187-0597-30?
NDC 63187-0597-30 is a 30-count package — 30 tablet, extended release in 1 bottle.
What is the difference between NDC 63187-0597-30 and NDC 63187-0597-60?
Both are TRAMADOL HYDROCHLORIDE 100 mg Tablet, Extended Release — the drug itself is identical. NDC 63187-0597-30 is the 30-count package, while NDC 63187-0597-60 is the 60 tablets package.
What NDC number is used to bill for this package of TRAMADOL HYDROCHLORIDE 100 mg Tablet, Extended Release?
Bill NDC 63187-0597-30 — the 11-digit billing format is 63187059730. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 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 — Not published for this NDC No photo available yet for this listing.
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 FDA registers it as 63187-597-30, 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: 63187-0597-30, written without dashes as 63187059730. 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 63187-0597-30, the first segment (63187) is the labeler code FDA assigned to Proficient Rx LP; the middle segment (0597) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (30) 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 Proficient Rx LP. 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 2 other package presentations of this same product, including 60 tablets (63187-0597-60), 90 tablets (63187-0597-90). 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?
Proficient Rx LP 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.
🎯 Indications and Usage ⏱️ Dosage and Administration ⛔ Contraindications ⚠️ Warnings 🤒 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
🎯 Indications and Usage 34 words ▾

INDICATIONS AND USAGE Tramadol hydrochloride extended-release tablets are indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time.

⏱️ Dosage and Administration ~2 min read ▾

DOSAGE AND ADMINISTRATION Tramadol hydrochloride extended-release tablets should not be used in patients with: • creatinine clearance less than 30 mL/min, • severe hepatic impairment (Child-Pugh Class C) (See PRECAUTIONS, Use in Renal and Hepatic Disease ). Tramadol hydrochloride extended-release tablets must be swallowed whole and must not be chewed, crushed, or split (see WARNINGS, Misuse, Abuse and Diversion of Opioids and DRUG ABUSE AND ADDICTION ). Adults (18 years of age and over) Patients Not Currently on Tramadol Immediate-Release Products For patients not currently treated with tramadol immediate-release (IR) products, tramadol hydrochloride extended-release tablets should be initiated at a dose of 100 mg once daily and titrated up as necessary by 100 mg increments every five days to relief of pain and depending upon tolerability.

Tramadol hydrochloride extended-release tablets should not be administered at a dose exceeding 300 mg per day. Patients Currently on Tramadol Immediate-Release Products For patients maintained on tramadol IR products, calculate the 24-hour tramadol immediate-release (IR) dose and initiate a total daily dose of tramadol hydrochloride extended-release tablets rounded down to the next lowest 100 mg increment. The dose may subsequently be individualized according to patient need.

Due to limitations in flexibility of dose selection with tramadol hydrochloride extended-release tablets, some patients maintained on tramadol IR products may not be able to convert to tramadol hydrochloride extended-release tablets. Tramadol hydrochloride extended-release tablets should not be administered at a dose exceeding 300 mg per day . The concomitant use of tramadol hydrochloride extended-release tablets with other tramadol products is not recommended (see WARNINGS ).

Individualization of Dose Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Start at the lowest possible dose and titrate upward as tolerated to achieve an adequate effect. Clinical studies of tramadol hydrochloride extended-release tablets have not demonstrated a clinical benefit at a total daily dose exceeding 300 mg.

In general, dosing of an elderly patient (over 65 years of age) should be initiated cautiously, 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. Tramadol hydrochloride extended-release tablets should be administered with even greater caution in patients over 75 years, due to the greater frequency of adverse events seen in this population.

⛔ Contraindications 72 words ▾

CONTRAINDICATIONS Tramadol hydrochloride extended-release tablets should not be administered to patients who have previously demonstrated hypersensitivity to tramadol, any other component of this product or opioids. Tramadol hydrochloride extended-release tablets are contraindicated in any situation where opioids are contraindicated, including acute intoxication with any of the following: alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs. Tramadol hydrochloride extended-release tablets may worsen central nervous system and respiratory depression in these patients.

⚠️ Warnings ~3 min read ▾

WARNINGS Seizure Risk Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous postmarketing reports indicate that seizure risk is increased with doses of tramadol above the recommended range. Concomitant use of tramadol increases the seizure risk in patients taking: • Selective serotonin re-uptake inhibitors (SSRI antidepressants or anorectics), • Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), or • Other opioids.

Administration of tramadol may enhance the seizure risk in patients taking: • MAO inhibitors (see also WARNINGS - Use with MAO Inhibitors ), • Neuroleptics, or • Other drugs that reduce the seizure threshold. Risk of convulsions may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizure.

Suicide Risk • Do not prescribe tramadol hydrochloride extended-release tablets for patients who are suicidal or addiction-prone. • Prescribe tramadol hydrochloride extended-release tablets with caution for patients taking tranquilizers or antidepressant drugs and patients who use alcohol in excess. • Tell your patients not to exceed the recommended dose and to limit their intake of alcohol. Serotonin Syndrome Risk The development of a potentially life-threatening serotonin syndrome may occur with use of tramadol products, including tramadol hydrochloride extended-release tablets, particularly with concomitant use of serotonergic drugs such as SSRIs, SNRIs, TCAs, MAOIs and triptans, with drugs which impair metabolism of serotonin (including MAOIs) and with drugs which impair metabolism of tramadol (CYP2D6 and CYP3A4 inhibitors).

This may occur within the recommended dose. (See CLINICAL PHARMACOLOGY - Pharmacokinetics ). Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Tramadol products in excessive doses, either alone or in combination with other CNS depressants, including alcohol, are a major cause of drug-related deaths. Fatalities within the first hour of overdosage are not uncommon. Tramadol should not be taken in doses higher than those recommended by the physician.

The judicious prescribing of tramadol is essential to the safe use of this drug. With patients who are depressed or suicidal, consideration should be given to the use of non-narcotic analgesics. Patients should be cautioned about the concomitant use of tramadol products and alcohol because of potentially serious CNS-additive effects of these agents.

Because of its added depressant effects, tramadol should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. Patients should be advised of the additive depressant effects of these combinations. Many of the tramadol-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation or attempts as well as histories of misuse of tranquilizers, alcohol, and other CNS-active drugs.

Some deaths have occurred as a consequence of the accidental ingestion of excessive quantities of tramadol alone or in combination with other drugs. Patients taking tramadol should be warned not to exceed the dose recommended by their physician. Anaphylactoid Reactions Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving therapy with tramadol.

When these events do occur it is often following the first dose. Other reported…

🤒 Adverse Reactions ~3 min read ▾

ADVERSE REACTIONS Tramadol hydrochloride extended-release tablets were administered to a total of 3108 patients during studies conducted in the U.S. These included four double-blind studies in patients with osteoarthritis and/or chronic low back pain and one open-label study in patients with chronic non-malignant pain. A total of 901 patients were 65 years or older.

The frequency of adverse events generally7 increased with doses from 100 mg to 400 mg in the two pooled, twelve-week, randomized, double-blind, placebo-controlled studies in patients with chronic non-malignant pain (see Table 2 ). Table 2: Incidence (%) of patients with adverse event rates ≥ 5% from two 12-week placebo-controlled studies in patients with moderate to moderately severe chronic pain by dose (N=1811). MedDRA Preferred Term Tramadol Hydrochloride Extended-Release Tablets Placebo 100 mg (N=403) n (%) 200 mg (N=400) n (%) 300 mg (N=400) n (%) 400 mg (N=202) n (%) (N=406) n (%) Dizziness (not vertigo) 64 (15.9) 81 (20.3) 90 (22.5) 57 (28.2) 28 (6.9) Nausea 61 (15.1) 90 (22.5) 102 (25.5) 53 (26.2) 32 (7.9) Constipation 49 (12.2) 68 (17) 85 (21.3) 60 (29.7) 17 (4.2) Headache 49 (12.2) 62 (15.5) 46 (11.5) 32 (15.8) 43 (10.6) Somnolence 33 ( 8.2) 45 (11.3) 29 (7.3) 41 (20.3) 7 (1.7) Flushing 31 (7.7) 40 (10) 35 (8.8) 32 (15.8) 18 (4.4) Pruritus 25 (6.2) 34 (8.5) 30 (7.5) 24 (11.9) 4 (1) Vomiting 20 (5) 29 (7.3) 34 (8.5) 19 (9.4) 11 (2.7) Insomnia 26 (6.5) 32 (8) 36 (9) 22 (10.9) 13 (3.2) Dry Mouth 20 (5) 29 (7.3) 39 (9.8) 18 (8.9) 6 (1.5) Diarrhea 15 (3.7) 27 (6.8) 37 (8.5) 10 (5) 17 (4.2) Asthenia 14 (3.5) 24 (6) 26 (6.5) 13 (6.4) 7 (1.7) Postural hypotension 7 (1.7) 17 (4.3) 8 (2) 11 (5.4) 9 (2.2) Sweating increased 6 (1.5) 8 (2) 15 (3.8) 13 (6.4) 1 (0.2) Anorexia 3 (0.7) 7 (1.8) 21 (5.3) 12 (5.9) 1 (0.2) The following adverse events were reported from all the chronic pain studies (N=3108).

The lists below include adverse events not otherwise noted in Table 2. Adverse events with incidence rates of 1% to <5% Eye disorders: vision blurred Gastrointestinal disorders: abdominal pain upper, dyspepsia, abdominal pain, sore throat General disorders: weakness, pain, feeling hot, influenza like illness, fall, rigors, lethargy, pyrexia, chest pain Infections and infestations: nasopharyngitis, upper respiratory tract infection, sinusitis, influenza, gastroenteritis viral, urinary tract infection, bronchitis Investigations: blood creatine phosphokinase increased, weight decreased Metabolism and nutrition disorders: appetite decreased Musculoskeletal, connective tissue and bone disorders: arthralgia, back pain, pain in limb, neck pain Nervous system disorders: tremor, paresthesia, hypoesthesia Psychiatric disorders: nervousness, anxiety, depression, restlessness Respiratory, thoracic and mediastinal disorders: sneezing, cough, rhinorrhea, nasal congestion, dyspnea, sinus congestion Skin and subcutaneous tissue disorders: sweating increased, dermatitis Vascular disorders: hot flushes, vasodilatation Adverse events with incidence rates of 0.5% to <1% and serious adverse events reported in at least 2 patients.

Cardiac disorders: palpitations, myocardial infarction Ear and labyrinth disorders: tinnitus, vertigo Gastrointestinal disorders: flatulence, toothache, constipation aggravated, appendicitis, pancreatitis General disorders: feeling jittery, edema lower limb, shivering, joint swelling, malaise, drug withdrawal syndrome, peripheral swelling Hepato-biliary disorders: cholelithiasis, cholecystitis Infections and infestations: cellulitis, ear infection, gastroenteritis, pneumonia, viral infection Injury and poisoning: joint sprain, muscle injury Investigations: alanine aminotransferase increased, blood pressure increased, aspartate aminotransferase increased, heart rate increased, blood glucose increased, liver function tests abnormal Musculoskeletal, connective tissue and bone disorders: muscle cramps, muscle spasms, joint stiffness, muscle twitching, myalgia, osteoarthr…

🔄 Drug Interactions ~2 min read ▾

Drug Interactions The formation of the active metabolite, M1, is mediated by CYP2D6. Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme of cytochrome P-450. Based on a population PK analysis of Phase I studies with immediate-release tablets in healthy subjects, concentrations of tramadol were approximately 20% higher in "poor metabolizers" versus "extensive metabolizers," while M1 concentrations were 40% lower.

In vitro drug interaction studies in human liver microsomes indicate that inhibitors of CYP2D6 (fluoxetine, norfluoxetine, amitriptyline, and quinidine) inhibit the metabolism of tramadol to various degrees, suggesting that concomitant administration of these compounds could result in increases in tramadol concentrations and decreased concentrations of M1. The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown. Tramadol is also metabolized by CYP3A4.

Administration of CYP3A4 inhibitors, such as ketoconazole and erythromycin, or inducers, such as rifampin and St. John’s Wort, with tramadol hydrochloride extended-release tablets may affect the metabolism of tramadol leading to altered tramadol exposure (see PRECAUTIONS, Drug Interactions ). Quinidine Tramadol is metabolized to M1 by CYP2D6.

A study was conducted to examine the effect of quinidine, a selective inhibitor of CYP2D6, on the pharmacokinetics of tramadol by administering 200 mg quinidine two hours before the administration of tramadol hydrochloride extended-release tablets 100 mg. The results demonstrated that the exposure of tramadol increased 50 to 60% and the exposure of M1 decreased 50 to 60% (see PRECAUTIONS, Drug Interactions ). In vitro drug interaction studies in human liver microsomes indicate that tramadol has no effect on quinidine metabolism.

Carbamazepine Carbamazepine, a CYP3A4 inducer, increases tramadol metabolism. Patients taking carbamazepine may have a significantly reduced analgesic effect of tramadol. Because of the seizure risk associated with tramadol, concomitant administration of tramadol hydrochloride extended-release tablets and carbamazepine is not recommended (see PRECAUTIONS, Drug Interactions ).

Cimetidine Concomitant administration of tramadol immediate-release tablets with cimetidine does not result in clinically significant changes in tramadol pharmacokinetics. No alteration of the tramadol hydrochloride extended-release tablets dosage regimen with cimetidine is recommended.

👥 Use in Specific Populations ~2 min read ▾

Special Populations Renal Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. The pharmacokinetics of tramadol were studied in patients with mild or moderate renal impairment after receiving multiple doses of tramadol hydrochloride extended-release tablets 100 mg. There is no consistent trend observed for tramadol exposure related to renal function in patients with mild (CLcr: 50 to 80 mL/min) or moderate (CLcr: 30 to 50 mL/min) renal impairment in comparison to patients with normal renal function.

However, exposure of M1 increased 20 to 40% with increased severity of the renal impairment (from normal to mild and moderate). Tramadol hydrochloride extended-release tablets have not been studied in patients with severe renal impairment (CLcr < 30 mL/min). The limited availability of dose strengths of tramadol hydrochloride extended-release tablet does not permit the dosing flexibility required for safe use in patients with severe renal impairment.

Therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe renal impairment (see PRECAUTIONS, Use in Renal and Hepatic Disease and DOSAGE AND ADMINISTRATION ). The total amount of tramadol and M1 removed during a 4-hour dialysis period is less than 7% of the administered dose. Hepatic Pharmacokinetics of tramadol was studied in patients with mild or moderate hepatic impairment after receiving multiple doses of tramadol hydrochloride extended-release tablets 100 mg.

The exposure of (+)- and (-)-tramadol was similar in mild and moderate hepatic impairment patients in comparison to patients with normal hepatic function. However, exposure of (+)- and (-)- M1 decreased ~50% with increased severity of the hepatic impairment (from normal to mild and moderate). The pharmacokinetics of tramadol after the administration of tramadol hydrochloride extended-release tablets has not been studied in patients with severe hepatic impairment.

After the administration of tramadol immediate-release tablets to patients with advanced cirrhosis of the liver, tramadol area under the plasma concentration time curve was larger and the tramadol and M1 half-lives were longer than subjects with normal hepatic function. The limited availability of dose strengths of tramadol hydrochloride extended-release tablets does not permit the dosing flexibility required for safe use in patients with severe hepatic impairment. Therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe hepatic impairment (see PRECAUTIONS, Use in Renal and Hepatic Disease and DOSAGE AND ADMINISTRATION ).

Geriatric The effect of age on the absorption of tramadol from tramadol hydrochloride extended-release tablets in patients over the age of 65 years has not been studied and is unknown (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ). Gender Based on pooled multiple-dose pharmacokinetics studies for tramadol hydrochloride extended-release tablets in 166 healthy subjects (111 males and 55 females), the dose-normalized AUC values for tramadol were somewhat higher in females than in males. There was a considerable degree of overlap in values between male and female groups.

Dosage adjustment based on gender is not recommended.

🤰 Pregnancy 161 words ▾

Pregnancy Teratogenic Effects: Pregnancy Category C Tramadol was not teratogenic at oral dose levels up to 50 mg/kg/day (approximately equivalent to MDHD) in rats and 100 mg/kg (approximately 5-fold MDHD) in rabbits during organogenesis. However, embryo-fetal lethality, reductions in fetal weight and skeletal ossification, and increased supernumerary ribs were observed at a maternal toxic dose of 140 mg/kg in mice (approximately 2-fold MDHD), 80 mg/kg in rats (2-fold MDHD) or 300 mg/kg in rabbits (approximately 15-fold MDHD).

Non-teratogenic Effects Tramadol caused a reduction in neonatal body weight and survival at an oral dose of 80 mg/kg (approximately 2-fold MDHD) when rats were treated during late gestation throughout lactation period. There are no adequate and well-controlled studies in pregnant women. Tramadol hydrochloride extended-release tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported during postmarketing reports with tramadol hydrochloride immediate-release products.

🧒 Pediatric Use 36 words ▾

Pediatric Use The safety and efficacy of tramadol hydrochloride extended-release tablets in patients under 18 years of age have not been established. The use of tramadol hydrochloride extended-release tablets in the pediatric population is not recommended.

🧓 Geriatric Use 136 words ▾

Geriatric The effect of age on the absorption of tramadol from tramadol hydrochloride extended-release tablets in patients over the age of 65 years has not been studied and is unknown (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ).

Geriatric Use Nine-hundred-one elderly (65 years of age or older) subjects were exposed to tramadol hydrochloride extended-release tablets in clinical trials. Of those subjects, 156 were 75 years of age and older. In general, higher incidence rates of adverse events were observed for patients older than 65 years of age compared with patients 65 years and younger, particularly for the following adverse events: constipation, fatigue, weakness, postural hypotension and dyspepsia.

For this reason, tramadol hydrochloride extended-release tablets should be used with great caution in patients older than 75 years of age (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ).

🆘 Overdosage ~1 min read ▾

OVERDOSAGE 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, bradycardia, hypotension, and death. Deaths due to overdose have been reported with abuse and misuse of tramadol, by ingesting, inhaling, or injecting the crushed tablets. 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.

In the treatment of tramadol overdosage, primary attention should be given to the re- establishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.

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 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.

🧬 Clinical Pharmacology ~3 min read ▾

CLINICAL PHARMACOLOGY Mechanism of Action Tramadol hydrochloride is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity 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.

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. The relationship between exposure of tramadol and M1 and efficacy has not been evaluated in the tramadol hydrochloride extended-release tablets clinical studies.

Apart from analgesia, tramadol administration may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of other opioids. In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, tramadol has no effect on heart rate, left-ventricular function or cardiac index.

Orthostatic hypotension has been observed. Pharmacokinetics The analgesic activity of tramadol is due to both parent drug and the M1 metabolite. Tramadol hydrochloride is administered as a racemate and both the [-] and [+] forms of both tramadol and M1 are detected in the circulation.

The pharmacokinetics of tramadol are approximately dose-proportional over a 100 mg to 400 mg dose range in healthy subjects. The observed tramadol AUC values for the 400 mg dose were 26% higher than predicted based on the AUC values for the 200 mg dose. The clinical significance of this finding has not been studied and is not known.

Absorption In healthy subjects, the bioavailability of a tramadol hydrochloride extended-release 200 mg tablet relative to a 50 mg every six hours dosing regimen of the immediate-release dosage form (tramadol) was approximately 85 to 90%. Consistent with the extended-release nature of the formulation, there is a lag time in drug absorption following tramadol hydrochloride extended-release tablets administration. The mean peak plasma concentrations of tramadol and M1 after administration of tramadol hydrochloride extended-release tablets to healthy volunteers are attained at about 12 h and 15 h, respectively, after dosing (see Table 1 and Figure 2).

Following administration of the tramadol hydrochloride extended-release tablets, steady-state plasma concentrations of both tramadol and M1 are achieved within four days with once daily dosing. The mean (%CV) pharmacokinetic parameter values for tramadol hydrochloride extended-release tablets 200 mg administered once daily and tramadol hydrochloride immediate-release 50 mg administered every six hours are provided in Table 1 . Table 1.

Mean (%CV) Steady-State Pharmacokinetic Parameter Values (n=32). Pharmacokinetic Parameter Tramadol M1 Metabolite Tramadol Hydrochloride Extended-Release 200 mg Tablet Once-Daily Immediate-Release Tramadol 50 mg Tablet Every 6 Hours Tramadol Hydrochloride Extended-Release 200 mg Tablet Once-Daily Immediate-Release Tramadol 50 mg Tablet Every 6 Hours AUC 0-24 (ng∙h/mL) 5975 (34) 6613 (27) 1890 (25) 2095 (26) C max (ng/mL) 335 (35) 383 (21) 95 (24) 104 (24) C min (ng/mL) 187 (37) 228 (32) 69 (30) 82 (27) T max (h) 12 (27) 1.5 (42) 15 (27) 1.9 (57) % Fluctuation 61 (57) 59 (35) 34 (72) 26 (47) AUC 0-…

🧬 Mechanism of Action ~1 min read ▾

Mechanism of Action Tramadol hydrochloride is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity 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.

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. The relationship between exposure of tramadol and M1 and efficacy has not been evaluated in the tramadol hydrochloride extended-release tablets clinical studies.

Apart from analgesia, tramadol administration may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of other opioids. In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, tramadol has no effect on heart rate, left-ventricular function or cardiac index.

Orthostatic hypotension has been observed.

📦 How Supplied / Storage and Handling 117 words ▾

HOW SUPPLIED Tramadol hydrochloride extended-release tablets are supplied in the following package and dose strength forms: 100 mg: White, round shape, biconvex, beveled edge, coated tablet with release portal on the center of the tablet on any one side, imprinted “531” with black ink on one side and plain on other side. Bottles of 30's with Child Resistant Cap ……………..NDC 63187-597-30 Bottles of 60's with Child Resistant Cap ……………. NDC 63187-597-60 Bottles of 90's with Child Resistant Cap ……… NDC 63187-597-90 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature].

Dispense in a tight, light resistant container. Warning: keep out of reach of children.

📋 Description 132 words ▾

DESCRIPTION Tramadol hydrochloride is a centrally acting synthetic analgesic in an extended-release formulation. The chemical name is (±) cis -2-[(dimethylamino) methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride. Its structural formula is: Figure 1 The molecular weight of tramadol hydrochloride is 299.84.

It is a white, crystalline powder that is freely soluble in water and methanol, very slightly soluble in acetone and has a pKa of 9.41. The n-octanol/water log partition coefficient (logP) is 1.35 at pH 7. Tramadol hydrochloride extended-release tablets contain 100 mg, 200 mg or 300 mg of tramadol hydrochloride, USP in an extended-release formulation.

The tablets are white in color and contain the inactive ingredients pregelatinized maize starch, hypromellose, mannitol, magnesium stearate, cellulose acetate and polyethylene glycol. Imprinting ink contains, shellac glaze, iron oxide black, N-butyl alcohol, ammonium hydroxide and propylene glycol. tramadol-structure

💬 Information for Patients ~2 min read ▾

Information for Patients • Patients should be informed that tramadol hydrochloride extended-release tablets is for oral use only and should be swallowed whole. The tablets should not be chewed, crushed, or split. • Patients should be informed that tramadol hydrochloride extended-release tablets may cause seizures and/or serotonin syndrome with concomitant use of serotonergic agents (including SRIs, NRIs, and triptans) or drugs that significantly reduce the metabolic clearance of tramadol. • Patients should be informed that tramadol hydrochloride extended-release tablets may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. • Patients should be informed that tramadol hydrochloride extended-release tablets should not be taken with alcohol containing beverages. • Patients should be informed that tramadol hydrochloride extended-release tablets should be used with caution when taking medications such as tranquilizers, hypnotics or other opiate containing analgesics. • Female patients should be instructed to inform the prescriber if they are pregnant, think they might become pregnant, or are trying to become pregnant (see PRECAUTIONS, Labor and Delivery ). • Patients should be educated regarding the single-dose and 24-hour dosing regimen, as exceeding these recommendations can result in respiratory depression, seizures or death.

Use in Drug and Alcohol Addiction Tramadol hydrochloride extended-release tablet is an opioid with no approved use in the management of addictive disorders. Its proper usage in individuals with drug or alcohol dependence, either active or in remission, is for the management of pain requiring opioid analgesia. Drug Interactions CYP2D6 and CYP3A4 inhibitors: Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors (See CLINICAL PHARMACOLOGY - Pharmacokinetics ), such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors), and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events including seizures and serotonin syndrome.

Serotonergic Drugs: There have been postmarketing reports of serotonin syndrome with use of tramadol and SSRIs/SNRIs or MAOIs and α2-adrenergic blockers. Caution is advised when tramadol hydrochloride extended-release tablets are coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as SSRIs, MAOIs, triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, or St. John's Wort.

If concomitant treatment of tramadol hydrochloride extended-release tablets with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see WARNINGS - Serotonin Syndrome ). Triptans: Based on the mechanism of action of tramadol and the potential for serotonin syndrome, caution is advised when tramadol hydrochloride extended-release tablets are coadministered with a triptan. If concomitant treatment of tramadol hydrochloride extended-release tablets with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see WARNINGS - Serotonin Syndrome ).

Use With Carbamazepine Patients taking carbamazepine , a CYP3A4 inducer, may have a significantly reduced analgesic effect of tramadol. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of tramadol hydrochloride extended-release tablets and carbamazepine is not recommended. Use With Quinidine Coadministration of quinidine with tramadol hydrochloride extended-release tablets resulted in a 50% to 60% increase in tramadol exposure and a 50% to 60% decrease in M1 exposure (see CLINICAL PHARMACOLOGY, Drug Interac…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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