A slight, but statistically significant, increase in two common murine tumors, pulmonary and hepatic, was observed in an NMRI mouse carcinogenicity study, particularly in aged mice. Mice were dosed orally up to 30 mg/kg in the drinking water (0.36 times the MRHD) for approximately two years, although the study was not done with the Maximum Tolerated Dose. This finding is not believed to suggest risk in humans. No evidence of carcinogenicity was noted in a rat 2-year carcinogenicity study testing oral doses of up to 30 mg/kg in the drinking water, 0.73 times the MRHD.
Tramadol was mutagenic in the presence of metabolic activation in the mouse lymphoma assay. Tramadol was not mutagenic in the in vitro bacterial reverse mutation assay using Salmonella and E. coli (Ames), the mouse lymphoma assay in the absence of metabolic activation, the in vitro chromosomal aberration assay, or the in vivo micronucleus assay in bone marrow.
Impairment of Fertility
No effects on fertility were observed for tramadol at oral dose levels up to 50 mg/kg in male rats and 75 mg/kg in female rats. These dosages are 1.2 and 1.8 times the maximum recommended human daily dose based on body surface area, respectively.
Tramadol hydrochloride tablets have been given in single oral doses of 50, 75 and 100 mg to patients with pain following surgical procedures and pain following oral surgery (extraction of impacted molars).
In single-dose models of pain following oral surgery, pain relief was demonstrated in some patients at doses of 50 mg and 75 mg. A dose of 100 mg tramadol hydrochloride tablets tended to provide analgesia superior to codeine sulfate 60 mg, but it was not as effective as the combination of aspirin 650 mg with codeine phosphate 60 mg.
Tramadol hydrochloride tablets have been studied in three long-term controlled trials involving a total of 820 patients, with 530 patients receiving tramadol hydrochloride tablets. Patients with a variety of chronic painful conditions were studied in double-blind trials of one to three months duration. Average daily doses of approximately 250 mg of tramadol hydrochloride tablets in divided doses were generally comparable to five doses of acetaminophen 300 mg with codeine phosphate 30 mg (TYLENOL with Codeine #3) daily, five doses of aspirin 325 mg with codeine phosphate 30 mg daily, or two to three doses of acetaminophen 500 mg with oxycodone hydrochloride 5 mg (TYLOX) daily.
In a randomized, blinded clinical study with 129 to 132 patients per group, a 10-day titration to a daily tramadol hydrochloride tablets dose of 200 mg (50 mg four times per day), attained in 50 mg increments every 3 days, was found to result in fewer discontinuations due to dizziness or vertigo than titration over only 4 days or no titration. In a second study with 54 to 59 patients per group, patients who had nausea or vomiting when titrated over 4 days were randomized to re-initiate tramadol hydrochloride tablets therapy using slower titration rates.
Tramadol hydrochloride tablets, USP 50 mg are available as white capsule shaped film coated tablets, debossed with “377” on one side and plain on the other side.
PACKAGING: 100 in 1 BOTTLE PLASTIC
PACKAGING: 60 in 1 BOTTLE PLASTIC
Dispense in a tight container.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [see USP Controlled Room Temperature].
Store tramadol hydrochloride tablets securely and dispose of properly [see Patient Counseling Information (17)].
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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 tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions (5.1, 5.17), Drug Abuse and Dependence (9.2)] . Inform patients that leaving tramadol hydrochloride 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 Drug Enforcement Administration (DEA)-registered collectors are available, instruct patients to dispose of tramadol hydrochloride tablets by following these four steps:
- Mix tramadol hydrochloride 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;
- Delete all personal information on the prescription label of the empty bottle.
Inform patients that they can visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.
Addiction, Abuse, and Misuse
Inform patients that the use of tramadol hydrochloride tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1)]. Instruct patients not to share tramadol hydrochloride tablets with others and to take steps to protect tramadol hydrochloride 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 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 and Precautions (5.3)].
Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose
Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with tramadol hydrochloride tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) [see Dosage and Administration (2.2),Warnings and Precautions (5.3)].
Educate patients and caregivers on how to recognize the signs and symptoms of an overdose.
Explain to patients and caregivers that naloxone’s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered [see Overdosage (10)].
If naloxone is prescribed, also advise patients and caregivers:
- How to treat with naloxone in the event of an opioid overdose
- To tell family and friends about their naloxone and to keep it in a place where family and friends can access it in an emergency
- To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do.
Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.3)].
Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children
Advise caregivers that tramadol hydrochloride 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. Advise caregivers of children ages 12 to 18 years of age receiving tramadol hydrochloride tablets to monitor for signs of respiratory depression [see Warnings and Precautions (5.4)].
Interactions with Benzodiazepines and Other CNS Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if tramadol hydrochloride tablets are used with benzodiazepines, CNS depressants, including alcohol, or some illicit drugs and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.7); Drug Interactions (7)].
Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome, and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare provider if they are taking, or plan to take serotonergic medications [see Warnings and Precautions (5.8)].
Inform patients that tramadol hydrochloride tablets may cause seizures with concomitant use of serotonergic agents (including SSRIs, SNRIs, and triptans) or drugs that significantly reduce the metabolic clearance of tramadol [see Warnings and Precautions (5.9)].
Inform patients not to take tramadol hydrochloride tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking tramadol hydrochloride tablets [see Drug Interactions (7)].
Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions (5.11)].
Important Administration Instructions
- Instruct patients how to properly take tramadol hydrochloride tablets. [see Dosage and Administration (2)].
- Advise patients not to adjust the dose of tramadol hydrochloride tablets without consulting with a physician or other healthcare professional.
Important Discontinuation Instructions
In order to avoid developing withdrawal symptoms, instruct patients not to discontinue tramadol hydrochloride tablets without first discussing a tapering plan with the prescriber [see Dosage and Administration ( 2.5)] .
Inform patients that tramadol hydrochloride tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.13)].
Inform patients that anaphylaxis has been reported with ingredients contained in tramadol hydrochloride tablets. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4); Warnings and Precautions (5.16); Adverse Reactions (6)].
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that prolonged use of tramadol hydrochloride tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated and that the patient should inform their healthcare provider if they have used opioids at any time during their pregnancy, especially near the time of birth. [ see Warnings and Precautions (5.5); Use in Specific Populations (8.1)].
Inform female patients of reproductive potential that tramadol hydrochloride tablets may cause fetal harm and to inform the healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].
Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3)].
Driving or Operating Heavy Machinery
Inform patients that tramadol hydrochloride tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.18)].
Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6)].
Maximum single-dose and 24-hour dose
Advise patients not to exceed the single-dose and 24-hour dose limit and the time interval between doses, since exceeding these recommendations can result in respiratory depression, seizures and death [see Dosage and Administration (2); Warnings and Precautions (5.3)].
Repackaged By / Distributed By: RemedyRepack Inc.
625 Kolter Drive, Indiana, PA 15701
Tramadol Hydrochloride Tablets, USP
(TRAM a dol hye” droe cklo’ ride”), CIV
Tramadol hydrochloride tablets are:
Important information about tramadol hydrochloride tablets:
Important information guiding use in pediatric patients:
Do not take tramadol hydrochloride tablets if you have:
Before taking tramadol hydrochloride tablets, tell your healthcare provider if you have a history of:
Tell your healthcare provider if you are:
When taking tramadol hydrochloride tablets:
While taking tramadol hydrochloride tablets DO NOT:
The possible side effects of tramadol hydrochloride tablets:
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Repackaged By / Distributed By: RemedyRepack Inc.
625 Kolter Drive, Indiana, PA 15701
DRUG: tramadol hydrochloride
GENERIC: tramadol hydrochloride
SCORE: No score
SIZE: 13 mm
PACKAGING: 100 in 1 BOTTLE, PLASTIC
PACKAGING: 60 in 1 BOTTLE, PLASTIC
- TRAMADOL HYDROCHLORIDE 50mg in 1
- STARCH, CORN
- ANHYDROUS LACTOSE
- MAGNESIUM STEARATE
- MICROCRYSTALLINE CELLULOSE
- POLYETHYLENE GLYCOL, UNSPECIFIED
- SODIUM STARCH GLYCOLATE TYPE A POTATO
- TITANIUM DIOXIDE
|TRAMADOL HYDROCHLORIDE tramadol hydrochloride tablet|
|Labeler — REMEDYREPACK INC. (829572556)|
Revised: 05/2021 REMEDYREPACK INC.
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