DESCRIPTION
id: B38406F8-897F-51BB-16F1-C76ADFDF5C39
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Tramadol hydrochloride tablets are a centrally acting analgesic. The chemical name for tramadol hydrochloride is (±)cis-2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride. Its structural formula is:
Molecular formula: C16H25NO2• HCl Molecular weight: 299.84
Tramadol hydrochloride is a white, bitter, crystalline and odorless powder. It is readily soluble in water and ethanol and has a pKa of 9.41. The n-octanol/water log partition coefficient (logP) is 1.35 at pH 7. Each tablet, for oral administration contains 50 mg of tramadol hydrochloride and is white in color. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate, pregelatinized starch and titanium dioxide.
INDICATIONS AND USAGE
id: 9CE759C3-2849-FC9D-3C6A-329F84DFAFF6
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Tramadol hydrochloride tablets are indicated for the management of moderate to moderately severe pain in adults.
CONTRAINDICATIONS
id: 0386CCC2-9D99-F85A-F950-973C12266BFC
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Tramadol hydrochloride should not be administered to patients who have previously demonstrated hypersensitivity to tramadol, any other component of this product or opioids. Tramadol hydrochloride is 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 may worsen central nervous system and respiratory depression in these patients.
ADVERSE REACTIONS
id: 75A62507-EC8D-7004-8E63-A71127EFEAEA
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Tramadol hydrochloride was administered to 550 patients during the double-blind or open-label extension periods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. Table 2 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days for the most frequent reactions (5% or more by 7 days). The most frequently reported events were in the central nervous system and gastrointestinal system. Although the reactions listed in the table are felt to be probably related to tramadol hydrochloride administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication. The overall incidence rates of adverse experiences in these trials were similar for tramadol hydrochloride and the active control groups, TYLENOL® with Codeine #3 (acetaminophen 300 mg with codeine phosphate 30 mg), and aspirin 325 mg with codeine phosphate 30 mg (Tylenol® with Codeine #3 is the registered trademark of Johnson RW). However, the rates of withdrawals due to adverse events appeared to be higher in the tramadol hydrochloride groups.
Table 2 Cumulative Incidence of Adverse Reactions for Tramadol Hydrochloride in Chronic Trials of Nonmalignant Pain (N = 427)
|
Up to |
Up to |
Up to |
|
7 Days |
30 Days |
90 Days |
| 1 “CNS Stimulation” is a composite of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability and hallucinations. |
| Dizziness/Vertigo |
26% |
31% |
33% |
| Nausea |
24% |
34% |
40% |
| Constipation |
24% |
38% |
46% |
| Headache |
18% |
26% |
32% |
| Somnolence |
16% |
23% |
25% |
| Vomiting |
9% |
13% |
17% |
| Pruritus |
8% |
10% |
11% |
| “CNS Stimulation” 1 |
7% |
11% |
14% |
| Asthenia |
6% |
11% |
12% |
| Sweating |
6% |
7% |
9% |
| Dyspepsia |
5% |
9% |
13% |
| Dry Mouth |
5% |
9% |
10% |
| Diarrhea |
5% |
6% |
10% |
Incidence 1% to less than 5%, possibly causally related: The following lists adverse reactions that occurred with an incidence of 1% to less than 5% in clinical trials, and for which the possibility of a causal relationship with tramadol hydrochloride exists.
Body as a Whole: Malaise.
Cardiovascular: Vasodilation.
Central Nervous System: Anxiety, Confusion, Coordination disturbance, Euphoria, Miosis, Nervousness, Sleep disorder.
Gastrointestinal: Abdominal pain, Anorexia, Flatulence.
Musculoskeletal: Hypertonia.
Skin: Rash.
Special Senses: Visual disturbance.
Urogenital: Menopausal symptoms, Urinary frequency, Urinary retention.Incidence less than 1%, possibly causally related: The following lists adverse reactions that occurred with an incidence of less than 1% in clinical trials and/or reported in post-marketing experience.
Body as a Whole: Accidental injury, Allergic reaction, Anaphylaxis, Death, Suicidal tendency, Weight loss, Serotonin syndrome (mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures and coma).
Cardiovascular: Orthostatic hypotension, Syncope, Tachycardia.
Central Nervous System: Abnormal gait, Amnesia, Cognitive dysfunction, Depression, Difficulty in concentration, Hallucinations, Paresthesia, Seizure (seeWARNINGS), Tremor.
Respiratory: Dyspnea.
Skin: Stevens-Johnson syndrome/Toxic epidermal necrolysis, Urticaria, Vesicles.
Special Senses: Dysgeusia.
Urogenital: Dysuria, Menstrual disorder.Other adverse experiences, causal relationship unknown:
A variety of other adverse events were reported infrequently in patients taking tramadol hydrochloride during clinical trials and/or reported in post-marketing experience. A causal relationship between tramadol hydrochloride and these events has not been determined. However, the most significant events are listed below as alerting information to the physician.Cardiovascular: Abnormal ECG, Hypertension, Hypotension, Myocardial ischemia, Palpitations, Pulmonary edema, Pulmonary embolism.
Central Nervous System: Migraine, Speech disorders.
Gastrointestinal: Gastrointestinal bleeding, Hepatitis, Stomatitis, Liver failure.
Laboratory Abnormalities: Creatinine increase, Elevated liver enzymes, Hemoglobin decrease, Proteinuria.
Sensory: Cataracts, Deafness, Tinnitus.
DRUG ABUSE AND DEPENDENCE
id: 898BED7A-B767-8317-CBA3-22FF06E94124
displayName: DRUG ABUSE & DEPENDENCE SECTION
FDA Article Code: 42227-9
Tramadol hydrochloride may induce psychic and physical dependence of the morphine-type (μ-opioid). (SeeWARNINGS.) Dependence and abuse, including drug-seeking behavior and taking illicit actions to obtain the drug are not limited to those patients with prior history of opioid dependence. The risk in patients with substance abuse has been observed to be higher. Tramadol hydrochloride is associated with craving and tolerance development. Withdrawal symptoms may occur if tramadol hydrochloride is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Other symptoms that have been seen less frequently with tramadol hydrochloride discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience suggests that withdrawal symptoms may be relieved by reinstitution of opioid therapy followed by a gradual, tapered dose reduction of the medication combined with symptomatic support.
OVERDOSAGE
id: 840E551B-5678-7728-1D10-38AE797D4C93
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
Serious potential consequences of overdosage are respiratory depression, lethargy, coma, seizure, cardiac arrest and death. (SeeWARNINGS.) Fatalities have been reported in post marketing in association with both intentional and unintentional overdose with tramadol hydrochloride. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment. While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol hydrochloride, 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.
HOW SUPPLIED
id: 7AB8964D-A0DA-2913-5AA2-B9513DD66599
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Tramadol Hydrochloride Tablets, 50 mg are available as white, round, film coated tablets, debossed with 466 on one side and WATSON on the other. Each tablet contains 50 mg of tramadol hydrochloride. They are supplied in bottles of 100, 500 and 1000 tablets.Store at controlled room temperature 15°-30°C (59°-86°F). [See USP.]Dispense in a tight container as defined in the USP.Watson Laboratories, Inc.
Corona, CA 92880 USA30354-3
Rev: August 2004
