TRAMADOL HYDROCHLORIDE 300 mg Tablet, Extended Release, 100-count
Other active recalls for Tramadol Hydrochloride (different manufacturers) — 2 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Opioid Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Tramadol immediate-release tablets and oral solution are used as a short-term treatment to relieve severe pain (pain that begins suddenly, has a specific cause, and is expected to go away when the cause of the pain is healed) in people who are expected to need an opioid pain medication and who cannot be controlled by the use of alternative pain medications. Tramadol extended-release tablets and capsules are used to relieve severe and persistent pain in people who are expected to need an opioid pain medication to relieve pain around-the-clock for a long time and who cannot be treated with other...
Read the full MedlinePlus article ↗- 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?
Patient education
Supplement & herbal interactions
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 5138Q19F1X
Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
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UNII 8PJ61P6TS3
Butyl alcohol is a clear liquid organic solvent derived from petroleum or natural sources. In medicines, it helps dissolve active ingredients and serves as a solvent in liquid formulations and some topical products.
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UNII 3J2P07GVB6
Cellulose acetate is a plant-derived polymer made by chemically modifying cellulose fibers. In medications, it serves as a film-coating material for tablets and capsules to protect the drug, control release, and improve appearance.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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UNII R75537T0T4
Hypromellose 2910 is a plant-derived thickening agent made from cellulose. It serves as a binder that holds tablet ingredients together, a film-coating for pills, and a viscosity controller in liquids.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
11 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 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 system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tramadol Hydrochloride 300 mg 33342-0271-07 | Macleods | 30 tablets | $2.015 | AB1 | Availability likely | — |
| Tramadol Hydrochloride 300 mgthis 47335-0537-08 | Sun | 100 tablets | — | — | FDA listed | — |
| Tramadol Hydrochloride 300 mg 71205-0569-30 | Proficient | 30 tablets | — | AB1 | FDA listed | — |
| Tramadol Hydrochloride 300 mg 71205-0656-30 | Proficient | 30 tablets | — | — | FDA listed | — |
| Tramadol Hydrochloride 300 mg 76420-0246-30 | Asclemed | 30 tablets | — | — | FDA listed | — |
| Tramadol Hydrochloride 300 mg 76420-0538-30 | Asclemed | 30 tablets | — | AB1 | FDA listed | — |
| Tramadol Hydrochloride 300 mg 70518-2795-00 | REMEDYREPACK | 30 tablets | — | AB1 | FDA listed | — |
| Tramadol Hydrochloride 300 mg 68180-0699-01 | Lupin | 100 tablets | — | AB1 | FDA listed | — |
| Tramadol Hydrochloride 300 mg 45865-0184-30 | Medsource | 30 tablets | — | AB1 | FDA listed | — |
| Tramadol Hydrochloride 300 mg 68071-5078-03 | NuCare | 30 tablets | — | AB1 | FDA listed | — |
| Tramadol Hydrochloride 300 mg 47335-0861-08 | Sun | 100 tablets | — | — | FDA listed | — |
| Tramadol Hydrochloride 300 mg 71335-9670-01 | Bryant | 30 tablets | — | AB1 | FDA listed | — |
| Tramadol Hydrochloride 300 mg 63629-8324-01 | Bryant | 30 tablets | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 47335-0537-08 You're viewing this | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (47335-537-08) | 2011-12-30 | Active |
| 47335-0537-18 | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE (47335-537-18) | 2011-12-30 | Active |
| 47335-0537-83 | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (47335-537-83) | 2011-12-30 | Active |
| 47335-0537-88 | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (47335-537-88) | 2011-12-30 | Active |
Pack size FAQ
What quantity is in NDC 47335-0537-08?
What is the difference between NDC 47335-0537-08 and NDC 47335-0537-83?
What NDC number is used to bill for this package of TRAMADOL HYDROCHLORIDE 300 mg Tablet, Extended Release?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — 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. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride extended-release 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 and reassess all patients regularly for the development of these behaviors and conditions [see Warnings] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of tramadol hydrochloride extended-release tablets, especially during initiation or following a dose increase.
To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride extended-release tablets are essential [see Warnings] . Instruct patients to swallow tramadol hydrochloride extended-release tablets whole to avoid exposure to a potentially fatal dose of tramadol. Accidental Ingestion Accidental ingestion of even one dose of tramadol hydrochloride extended-release tablets, especially by children, can result in a fatal overdose of tramadol [see Warnings] .
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of tramadol hydrochloride extended-release tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [ see Warnings, Precautions; Drug Interactions ] . Neonatal Opioid Withdrawal Syndrome (NOWS) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated.
Ensure that management by neonatology experts will be available at delivery [see Warnings ]. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS): Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings] . 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 followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism [see WARNINGS]. Tramadol hydrochloride extended-release tablets are 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]. Avoid the use of tramadol hydrochloride extended-release 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].
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Tramadol Extended-Release Tablets requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1 [see WARNINGS, PRECAUTIONS; Drug Interactions].
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Tramadol hydrochloride extended-release tablets are indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use • Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings] , reserve opioid analgesics, including tramadol hydrochloride extended-release tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. • Tramadol hydrochloride extended-release tablets are not indicated as an as-needed (prn) analgesic.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Tramadol hydrochloride extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. Do not use tramadol hydrochloride extended-release tablets concomitantly with other tramadol products [ see WARNINGS ]. Do not administer tramadol hydrochloride extended-release tablets at a dose exceeding 300 mg per day.
Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [ see Warnings ] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of tramadol hydrochloride extended-release tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [ see Warnings ] Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with tramadol hydrochloride extended-release tablets.
Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings ]. Tramadol hydrochloride extended-release tablets should be taken once daily, at approximately the same time every day. Instruct patients to swallow tramadol hydrochloride extended-release tablets whole [see PRECAUTIONS; Information for Patients ], and to take it with liquid.
Crushing, chewing, splitting, or dissolving tramadol hydrochloride extended-release tablets will result in uncontrolled delivery of tramadol and can lead to overdose or death [ see WARNINGS ] . Tramadol hydrochloride extended-release tablets may be taken without regard to food, it is recommended that it be taken in a consistent manner [see CLINICAL PHARMACOLOGY ] . Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene).
Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see WARNINGS; Addiction, Abuse, and Misuse; Life-Threatening Respiratory Depression; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ].
Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.
Initial Dosage It is safer to underestimate a patient’s 24-hour tramadol requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour tramadol dosage and manage an adverse reaction due to an overdose. While useful tables of opioid equivalents are readily available, there is inter-patient variability in the potency of opioid drugs and opioid formulations. Frequently reevaluate patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to Tramadol Hydrochloride E…
⛔ Contraindications ▾
CONTRAINDICATIONS Tramadol hydrochloride extended-release tablets are contraindicated for: all children younger than 12 years of age [see WARNINGS ]. postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [ see WARNINGS ]. Tramadol hydrochloride extended-release tablets are also contraindicated in patients with: Significant respiratory depression [see WARNINGS ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ] Hypersensitivity to tramadol (e.g., anaphylaxis) [see ADVERSE REACTIONS ] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see PRECAUTIONS; Drug Interactions ]
⚠️ Warnings ▾
WARNINGS Addiction, Abuse, and Misuse Tramadol hydrochloride extended-release tablets contain tramadol, a Schedule IV controlled substance. As an opioid, tramadol hydrochloride extended-release tablets expose users to the risks of addiction, abuse, and misuse [see DRUG ABUSE and DEPENDENCE]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed tramadol hydrochloride extended-release tablets.
Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see ADVERSE REACTIONS; Postmarketing Experience ].
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing tramadol hydrochloride extended-release tablets, and reassess all patients receiving tramadol hydrochloride extended-release tablets for the development of these behaviors or 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 extended-release tablets, but use in such patients necessitates intensive counseling about the risks and proper use of tramadol hydrochloride extended-release tablets along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [see WARNINGS; Life-Threatening Respiratory Depression, DOSAGE and ADMINISTRATION; Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose ].
Abuse or misuse of tramadol hydrochloride extended-release tablets by cutting, breaking, chewing, crushing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tramadol and can result in overdose and death [see OVERDOSAGE ] . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing tramadol hydrochloride extended-release tablets.
Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and proper disposal of unused drug. Contact local state professional licensing board or statecontrolled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents, depending on the patient’s clinical status [see OVERDOSAGE ] . Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of tramadol hydrochloride extended-release tablets, the risk is greatest during the initiation of therapy or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride extended-release tablets are essential [see DOSAGE and ADMINISTRATION ] . Overestimating the tramadol hydrochloride extended-release tablets dosage when converting patients from another opioid product c…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse (see WARNINGS ) Life-Threatening Respiratory Depression (see WARNINGS ) Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children (see WARNINGS ) Neonatal Opioid Withdrawal Syndrome (see WARNINGS ) Interactions with Benzodiazepines or Other CNS Depressants (see WARNINGS ) Opioid-Induced Hyperalgesia and Allodynia (see WARNINGS ) Serotonin Syndrome (see WARNINGS ) Seizures (see WARNINGS ) Suicide (see WARNINGS ) Adrenal Insufficiency (see WARNINGS ) Severe Hypotension (see WARNINGS ) Gastrointestinal Adverse Reactions (see WARNINGS ) Hypersensitivity Reactions (see WARNINGS ) Withdrawal (see WARNINGS ) Clinical 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.
Tramadol hydrochloride extended-release tablets were administered to a total of 2707 subjects (2406 patients and 301 healthy volunteers) during clinical studies, including four randomized double-blind studies (treatment ≥ 12 weeks) and two open-label long-term studies (treatment up to 12 months) in patients with moderate to severe pain due to osteoarthritis of the knee. A total of 844 patients were exposed to tramadol hydrochloride extended-release tablets for 12 weeks, 493 patients for 6 months and 243 patients for 12 months.
Treatment emergent adverse events increased with dose from 100 mg to 300 mg in the three twelve-week, randomized, double-blind, placebo-controlled studies (Table 2). Table 2. Percentage of Patients with Incidence of Adverse Events ≥ 2% from Three 12-week Placebo-Controlled Studies (MDT3-002, MDT3-003 and MDT3-005) ADVERSE EVENTS (MEDRA Preferred Terms) Tramadol Hydrochloride Extended-Release Tablets Placebo 100 mg 200 mg 300 mg Total * N=216 N=311 N=530 N=1095 N=668 Nausea 28 (13%) 42 (14%) 76 (14%) 179 (16%) 37 (6%) Constipation 21 (10%) 36 (12%) 52 (10%) 140 (13%) 26 (4%) Dizziness 16 (7%) 28 (9%) 52 (10%) 106 (10%) 18 (3%) Somnolence 11 (5%) 22 (7%) 23 (4%) 77 (7%) 12 (2%) Vomiting 7 (3%) 16 (5%) 31 (6%) 58 (5%) 4 (1%) Pruritus 9 (4%) 15 (5%) 18 (3%) 51 (5%) 7 (1%) Headache 10 (5%) 9 (3%) 15 (3%) 41 (4%) 21 (3%) Sweating increased 1 (0%) 9 (3%) 14 (3%) 35 (3%) 5 (1%) Dry mouth 7 (3%) 13 (4%) 6 (1%) 32 (3%) 8 (1%) Fatigue 6 (3%) 7 (2%) 9 (2%) 26 (2%) 6 (1%) Anorexia 4 (2%) 4 (1%) 10 (2%) 25 (2%) 2 (0%) Vertigo 2 (1%) 3 (1%) 6 (1%) 21 (2%) 3 (0%) Insomnia 2 (1%) 6 (2%) 9 (2%) 18 (2%) 8 (1%) *Due to the difference in study design of MDT3-005, only the results of the double-blind phase of the study are presented and the dose specific results include maintenance period data only.
The majority of patients who experienced the most common adverse events (≥5%) reported mild to moderate symptoms. Less than 3% of adverse events were rated as severe. Overall, onset of these adverse events usually occurred within the first two weeks of treatment.
Adverse reactions with an incidence of 1.0% to <5.0% Ear and labyrinth disorders: vertigo Gastrointestinal disorders: abdominal pain, diarrhea, dry mouth, dyspepsia, upper abdominal pain General disorders : fatigue, weakness Investigations: weight decreased Metabolism and nutrition disorders : anorexia Musculoskeletal and connective tissue disorders: arthralgia Nervous system disorders : headache, tremor Psychiatric disorders : anxiety, insomnia Skin and subcutaneous tissue disorders : pruritus, sweating increased Vascular disorders: hot flushes Adverse reactions with an incidence of <1.0% Blood and lymphatic system disorders: anemia, thrombocytopenia Cardiac disorders : bradycardia Eye disorders: blurred vision, visual disturbance Gastrointestinal disorders : abdominal discomfort, ab…
🔄 Drug Interactions ▾
Drug Interactions Inhibitors of CYP2D6 The concomitant use of tramadol hydrochloride extended-release tablets and CYP2D6 inhibitors such as quinidine, fluoxetine, paroxetine and bupropion 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 extended-release tablets 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 ] .
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 extended-release tablets dosage until stable drug effects are achieved. Evaluate patients at frequent intervals for adverse events including respiratory depression and sedation.
Inhibitors of CYP3A4 The concomitant use of tramadol hydrochloride extended-release tablets and CYP3A4 inhibitors such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) 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 extended-release tablets is achieved.
After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease [see CLINICAL PHARMACOLOGY ] , resulting in decreased opioid efficacy and possibly signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. If concomitant use is necessary, consider dosage reduction of tramadol hydrochloride extended-release tablets until stable drug effects are achieved. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of seizures, serotonin syndrome, and signs of respiratory depression and sedation.
If a CYP3A4 inhibitor is discontinued, consider increasing the tramadol hydrochloride extended-release tablets dosage until stable drug effects are achieved and evaluate patients at frequent intervals for signs and symptoms of opioid withdrawal. CYP3A4 Inducers The concomitant use of tramadol hydrochloride extended-release tablets and CYP3A4 inducers such as rifampin, carbamazepine, phenytoin can decrease the plasma concentration of tramadol, [see CLINICAL PHARMACOLOGY ] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol [see WARNINGS ] .
After stopping a CYP3A4 inducer, as the effects of the inducer decline, the tramadol plasma concentration will increase [see CLINICAL PHARMACOLOGY ] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause seizures and serotonin syndrome, and potentially fatal respiratory depression. If concomitant use is necessary, consider increasing…
🤰 Pregnancy ▾
Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings ] . Available data with tramadol hydrochloride extended-release tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, tramadol administration 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 [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in 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 ] .
Neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol hydrochloride during post-approval use of tramadol hydrochloride extended release tablets.
🧒 Pediatric Use ▾
Pediatric Use The safety and effectiveness of tramadol hydrochloride extended-release tablets in pediatric patients have not been established. Life-threatening respiratory depression and death have occurred in children who received tramadol [ see WARNINGS ]. 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 or high morphine concentrations).
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 extended-release tablets are contraindicated for all children younger than 12 years of age [ see CONTRAINDICATIONS ]. Tramadol hydrochloride extended-release tablets are contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [ see CONTRAINDICATIONS ].
Avoid the use of tramadol hydrochloride extended-release 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 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 ▾
Geriatric Use In 12-week clinical trials, tramadol hydrochloride extended-release tablets were administered to 534 patients aged 65 years and older. Of those, 68 patients were 75 years of age and older. Comparable incidence rates of patients experiencing adverse events were observed for patients older than 65 years of age compared with younger patients (< 65 years of age), except constipation for which the incidence was higher in older patients.
Tramadol hydrochloride extended-release tablets should be used with caution in patients older than 75 years of age [see CLINICAL PHARMACOLOGY , DOSAGE and ADMINISTRATION ] . 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 coadministered with other agents that depress respiration. Titrate the dosage of tramadol hydrochloride extended-release tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings ] .
Tramadol is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
🆘 Overdosage ▾
OVERDOSAGE Clinical Presentation Acute overdosage with tramadol hydrochloride extended-release tablets 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, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see CLINICAL PHARMACOLOGY ]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication.
Treatment of Overdose In case of overdose, priorities are the reestablishment 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 measures.
For clinically significant respiratory or circulatory depression secondary to tramadol overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. While an opioid overdose reversal agent will reverse some (but not all) symptoms caused by overdosage with tramadol, the risk of seizures is also increased with reversal agent administration. In animals, convulsions following the administration of toxic doses of tramadol hydrochloride extended-release tablets 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 extended-release tablets, carefully monitor the patient until spontaneous respiration is reliably reestablished.
Tramadol hydrochloride extended-release tablets will continue to release tramadol and add to the tramadol load for 24 to 48 hours or longer following ingestion, necessitating prolonged monitoring. If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome.
The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of thereversal agent.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Mechanism of Action Tramadol hydrochloride extended-release tablets, contain tramadol, an opioid agonist inhibitor of norepinenphrine and serotonin re-uptake. Although the mode of action of tramadol is not completely understood, the analgesic effect of tramadol is believed to be due to 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 mu-opioid receptors.
In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in mu-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. Apart from analgesia, tramadol hydrochloride administration may produce various 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.
Pharmacodynamics 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, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED).
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. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS ].
They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time 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 hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see ADVERSE REACTIONS ].
Effects on the Immune System Opioids…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Tramadol hydrochloride extended-release tablets, USP are available as follows: 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 47335-531-83 Bottles of 100’s with Child Resistant Cap………….....NDC 47335-531-88 Bottles of 100’s with Non Child Resistant Cap…….....NDC 47335-531-08 Bottles of 1000’s with Non Child Resistant Cap……...NDC 47335-531-18 200 mg: White, round shape, biconvex, beveled edge, coated tablet with release portal on the center of the tablet on any one side, imprinted “533” with black ink on one side and plain on other side.
Bottles of 30’s with Child Resistant Cap………………NDC 47335-533-83 Bottles of 100’s with Child Resistant Cap……………..NDC 47335-533-88 Bottles of 100’s with Non Child Resistant Cap………..NDC 47335-533-08 Bottles of 1000’s with Non Child Resistant Cap……....NDC 47335-533-18 300 mg: White, round shape, biconvex, beveled edge, coated tablet with release portal on the center of the tablet on any one side, imprinted “537” with black ink on one side and plain on other side. Bottles of 30’s with Child Resistant Cap…...................NDC 47335-537-83 Bottles of 100’s with Child Resistant Cap….................NDC 47335-537-88 Bottles of 100’s with Non Child Resistant Cap….........NDC 47335-537-08 Bottles of 1000’s with Non Child Resistant Cap….......NDC 47335-537-18 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. Store tramadol hydrochloride extended-release tablets securely and dispose of properly [see PRECAUTIONS/ Information for Patients ].
📋 Description ▾
DESCRIPTION Tramadol hydrochloride extended-release tablets, USP are an opioid agonist composed of a matrix delivery system with extended-release characteristics. The chemical name for tramadol hydrochloride, USP is (±) cis -2-[(dimethylamino) methyl]-1-(3 methoxyphenyl) cyclohexanol hydrochloride. Its structural formula is: The molecular weight of tramadol hydrochloride, USP is 299.8.
Tramadol hydrochloride, USP is a white crystalline powder that is freely soluble in water and ethanol. Tramadol hydrochloride extended-release tablets, USP are for oral administration and contain 100 mg, 200 mg or 300 mg of tramadol hydrochloride, USP. The tablets are white in color.
The inactive ingredients in the tablet are pregelatinized maize starch, hypromellose, mannitol, magnesium stearate, cellulose acetate and polyethylene glycol. Imprinting ink contains shellac glaze, iron oxide black, N-butyl alcohol, propylene glycol and ammonium hydroxide. Meets USP dissolution test 4. spl-tramadol-structure
💬 Information for Patients ▾
Information for Patients/Caregivers 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 extended-release tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see WARNINGS, DRUG ABUSE and DEPENDENCE ] . Inform patients that leaving tramadol hydrochloride extended-release tablets 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 DEA-registered collectors are available, instruct patients to dispose of tramadol hydrochloride extended-release tablets by following these four steps: Mix tramadol hydrochloride extended-release tablets (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; Remove 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 extended-release tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS] . Instruct patients not to share tramadol hydrochloride extended-release tablets with others and to take steps to protect tramadol hydrochloride extended-release tablets 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 extended-release tablets or when the dosage is increased, and that it can occur even at recommended dosages.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see WARNINGS; Life Threatening Respiratory Depression]. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see WARNINGS] . Interactions with Benzodiazepines or Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if tramadol hydrochloride extended-release tablets are used with benzodiazepines or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), and not to use these concomitantly unless supervised by a healthcare provider [see WARNINGS and PRECAUTIONS; Drug Interactions ].
Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.
Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see WARNINGS, DOSAGE AND ADMINISTRATION]. Educate patients and caregive…
💬 Medication Guide ▾
Medication Guide Tramadol Hydrochloride ( tram a dol hye droe klor ide) Extended-Release Tablets, USP, C-IV Tramadol hydrochloride extended-release tablets are: A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine when other pain medicines do not treat your pain well enough or you cannot tolerate them. A long-acting (extended-release) 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. Not to be taken on an “as needed” basis. Important information about tramadol hydrochloride extended-release tablets: Get emergency help or call 911 right away if you take too many tramadol hydrochloride extended-release tablets (overdose) .
When you first start taking tramadol hydrochloride extended-release tablets, when your dose is changed, or if you take too many (overdose), serious or life-threatening breathing problems that can lead to death may occur. Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse an opioid overdose. Taking tramadol hydrochloride extended-release tablets with other opioid medicines, benzodiazepines, gabapentinoids (gabapentin or pregabalin), alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.
Never give anyone else your tramadol hydrochloride extended-release tablets. They could die from taking them. Selling or giving away tramadol hydrochloride extended-release tablets is against the law.
Store tramadol hydrochloride extended-release tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Important Information Guiding Use in Pediatric Patients: Do not give tramadol hydrochloride extended-release tablets to a child younger than 12 years of age. Do not give tramadol hydrochloride extended-release tablets to a child younger than 18 years of age after surgery to remove the tonsils and/or adenoids.
Avoid giving tramadol hydrochloride extended-release 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 extended-release tablets if you have: severe asthma, trouble breathing, or other lung problems. a bowel blockage or have narrowing of the stomach or intestines. Before taking tramadol hydrochloride extended-release tablets, 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, opioid overdose, or mental health problems.
Tell your healthcare provider if you: notice your pain getting worse. If your pain gets worse after you take tramadol hydrochloride extended-release tablets, do not take more of tramadol hydrochloride extended-release tablets without first talking to your healthcare provider. Talk to your healthcare provider if the pain that you have increases, if you feel more sensitive to pain, or if you have new pain after taking tramadol hydrochloride extended-release tablets.
Are pregnant or planning to become pregnant . Use of tramadol hydrochloride extended-release tablets for an extended period of time during 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. living in a household where there are small children or someone who has abused street or prescription drugs taking prescription or over-the-counter medicines, vitamins, or herbal supplement…