Tracy

Each film-coated tablet contains: Paracetamol 325 mg, Tramadol HCl 37.5 mg.
Paracetamol is used in the symptomatic management of pain and fever. It possesses weak anti-inflammatory activity. Tramadol HCl is an opioid analgesic. It also has noradrenergic and serotonergic properties that may contribute to its analgesic activity. Paracetamol + Tramadol HCl (Tracy) is characterized by peach to light orange to orange colored film-coated capsule shape tablet, plain on one side and bisected on the other side.

Pharmacology: Pharmacodynamics: Tramadol HCl is a centrally-acting analgesic compound. At least 2 complementary mechanisms appear applicable, binding of parent and M1 metabolite to u-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Paracetamol is another centrally-acting analgesic. The exact site and mechanism of its analgesic action is not clearly defined. When evaluated in a standard animal model, the combination of Tramadol and Paracetamol exhibited a synergistic effect.
Pharmacokinetics: Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentration occurring about 10-60 minutes after oral administration. Paracetamol is distributed into the most body tissues. It crosses the placenta and is present in the breast milk. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. The elimination half-life of Paracetamol varies from about 1 to 3 hours. Paracetamol is metabolized predominantly in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates less than 5% is excreted as unchanged Paracetamol. A minor hydroxylated metabolite (N-acetyl-p-benzoquinoneimine), which is usually produced in very small amounts by mixed function oxidases in the liver and kidney and which is usually detoxified by conjugation with glutathione may accumulate following Paracetamol overdosage and cause tissue damage.
Tramadol HCl is readily absorbed following oral administration but is subject to first-pass metabolism. Tramadol HCl is metabolized by N- and O-demethylation, glucuronidation or sulfation in the liver. The metabolite O-desmethyltramadol is pharmacologically active. Tramadol HCl is excreted mainly in the urine, predominantly as metabolites. Tramadol is widely distributed, crosses the placenta, and appears in small amounts in breast milk. The elimination half-life following oral administration is about 6 hours.

Indicated for moderate to severe acute pain.

Adults and Children over 16 years: 1 to 2 tablets every 4 to 6 hours up to a maximum of 8 tablets per day or as prescribed by the physician.

Paracetamol + Tramadol HCl (Tracy) is a combination product. The clinical presentation of overdose may include the signs and symptoms of Tramadol HCl toxicity, Paracetamol toxicity or both. The initial symptoms of Tramadol HCl overdosage may include respiratory depression and/or seizures. The initial symptoms seen within the first 24 hrs following a Paracetamol overdose may include: Gastrointestinal irritability, anorexia, nausea, vomiting, malaise, pallor, and diaphoresis.
Human Experience: Tramadol HCl: Serious potential consequences of overdosage of the Tramadol HCl component are respiratory depression, lethargy, coma, seizure, cardiac arrest and death.
Paracetamol: Paracetamol in massive overdosage may cause hepatic toxicity in some patients. Early symptoms following a potentially hepatotoxic overdosage may include: Gastrointestinal irritability, anorexia, nausea, vomiting, malaise, pallor, and diaphoresis. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48-72 hrs post-ingestion.
Treatment: A single or multiple overdose of Tramadol HCl + Paracetamol may be a potentially lethal polydrug overdose, and appropriate expert consultation, if available, is recommended. While naloxone will reverse some, but not all, symptoms caused by overdosage with Tramadol HCl, the risk of seizures is also increased with naloxone administration. Based on experience with Tramadol HCl, hemodialysis is not expected to be helpful in an overdose because it removes <7% of the administered dose in a 4-hr dialysis period. In treating an overdosage of Tramadol HCl + Paracetamol, primary attention should be given to maintaining adequate ventilation along with general supportive treatment. Measures should be taken to reduce drug absorption. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g per kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic in etiology and should respond to fluids. Vasopressors and other supportive measures should be employed as indicated. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and, when necessary, to provide assisted respiration. In adult and pediatric patients, any individual presenting with an unknown amount of Paracetamol ingested or with questionable or unreliable history about the time of ingestion should have a plasma Paracetamol level drawn and be treated with acetylcysteine. If an assay cannot be obtained and the estimated Paracetamol ingestion exceeds 7.5-10 g for adults and adolescents or 150 mg per kg for children, dosing with N-acetylcysteine should be initiated and continued for a full course of therapy.

Hypersensitivity to Tramadol HCl, Paracetamol, any other component of this product. It is also contraindicated in cases of acute intoxication with alcohol, hypnotics, narcotics, centrally acting-analgesics, opioids or psychotropic.

Seizures: Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing 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 Reuptake Inhibitors (SSRIs antidepressants or anorectics), Tricyclic Antidepressants (TCAs), and other tricyclic compounds (eg, cyclobenzaprine, promethazine, etc.), or opioids.
Administration of tramadol may enhance the seizure risk in patients taking: 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 (e.g., head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infection). In tramadol overdose, naloxone administration may increase the risk of seizure.
Anaphylactoid Reactions: Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive Paracetamol + Tramadol HCl.
Respiratory Depression: Administer Paracetamol + Tramadol HCl cautiously in patients at risk for respiratory depression. When large doses of tramadol are administered with anesthetic medications or alcohol, respiratory depression may result. Treat such cases as an overdose. If naloxone is to be administered, use cautiously because it may precipitate seizures.
Use with CNS Depressants: Paracetamol + Tramadol HCl should be used with caution and in reduced dosages when administered to patients receiving CNS depressant (e.g., alcohol, opioids, anesthetic agents, phenothiazines, tranquilizers or sedative hypnotics).
Increased Intracranial Pressure or Head Trauma: Paracetamol + Tramadol HCl should be used with caution in patients with increased intracranial pressure or head injury.
Use in Opioid-Dependent Patients: Paracetamol + Tramadol HCl should not be used in opioid-dependent patients. Tramadol has been shown to reinitiate physical dependence in some patients that have been previously dependent on other opioids.
Use with Alcohol: Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive paracetamol use.
Withdrawal: Withdrawal symptoms may occur if Paracetamol + Tramadol HCl is discontinued abruptly. Panic attacks, severe anxiety, hallucinations, paresthesia, tinnitus and unusual CNS symptoms have also been rarely reported with abrupt discontinuation of Tramadol HCl. Clinical experience suggests that withdrawal symptoms may be relieved by tapering the medication.
Use with MAO Inhibitors and Selective Serotonin Reuptake Inhibitors: Use Paracetamol + Tramadol HCl with great caution in patients taking monoamine oxidase inhibitors. Concomitant use of tramadol with MAO inhibitors or SSRIs increases the risk of adverse events, including seizure and serotonin syndrome.
Use in Renal Disease: Paracetamol + Tramadol HCl has not been studied in patients with impaired renal function. In patients with creatinine clearance of <30 mL per min, it is recommended that the dosing interval of Paracetamol + Tramadol HCl be increased not to exceed 2 tablets every 12 hrs.
Use in Hepatic Disease: The use of Paracetamol + Tramadol HCl in patients with severe hepatic impairment is not recommended.
Serious Skin Reactions: Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN), have been reported very rarely in patients receiving paracetamol. Patients should be informed about the signs of serious reactions, and use of the drug should be discontinued at the first appearance of skin rash or any sign of hypersensitivity.
Hyponatremia: Has been reported very rarely with the use of Paracetamol + Tramadol HCl, usually in patients using concomitant medications that may cause hyponatremia. In some reports, this hyponatremia appeared to be result of the Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) and resolve with discontinuation of Paracetamol + Tramadol HCl and appropriate treatment (e.g, fluid restriction). During Tramadol HCl + Paracetamol treatment, monitoring for signs and symptoms of hyponatremia is recommended for patients with predisposing risk factors.
General Precautions: The recommended dose of Paracetamol + Tramadol HCl should not be exceeded. This product, Tracy, should not be co-administered with other tramadol or paracetamol-containing products.

Tramadol HCl has been shown to cross the placenta. There are no adequate and well-controlled studies in pregnant women. Safe use in pregnancy has not been established. Paracetamol + Tramadol HCl is not recommended for nursing mothers because its safety in infants and newborns has not been studied.

Paracetamol adverse effects are rare and usually mild, although haematological reactions including thrombocytopenia, leucopenia, pancytopenia, neutropenia, and agranulocytosis have been reported. Skin rashes, and other hypersensitivity reactions occur occasionally. Overdosage with Paracetamol can result in severe liver damage and sometimes acute renal tubular necrosis. Prompt treatment with acetylcysteine or methionine is essential. The most common side effects of Tramadol HCl are nausea, vomiting, constipation, drowsiness and confusion; tolerance to these (except constipation) generally develops with long-term use. Micturition may be difficult and there may be ureteric or biliary spasm; there is also an antidiuretic effect. Dry mouth, dizziness, sweating, facial flushings, headache, vertigo, bradycardia, tachycardia, palpitations, orthostatic hypotension, hypothermia, restlessness, changes of mood, decreased libido or potency, hallucinations, and miosis also occur. These effects tend to occur more commonly in ambulant patients than in those at rest in bed and in those without severe pain. Raised intracranial pressure occurs in some patients. Muscle rigidity has been reported following high doses. The euphoric activity of opioids has led to their abuse.

Use with MAO inhibitors and SSRIs: Interaction with MAO inhibitors have been reported for some centrally-acting drugs. (See Precautions.)
Use with Carbamazepine: Concomitant administration of Tramadol HCl and carbamazepine causes a significant increase in Tramadol HCl metabolism. Patients taking carbamazepine may have a significantly reduced analgesic effect from the Tramadol HCl component of Tracy.
Use with Quinidine: Tramadol HCl is metabolized to M1 by CYP2D6. Concomitant administration of quinidine and Tramadol HCl results in increased concentrations of Tramadol HCl. The clinical consequences of these findings are unknown.
Use with Warfarin-Like Compounds: As medically appropriate, periodic evaluation of prothrombin time should be performed when Paracetamol + Tramadol HCl and these agents are administered concurrently due to reports of increased International Normalized Ratio (INR) in some patients.
Use with Inhibitors of CYP2D6: In vitro interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 (e.g., fluoxetine, paroxetine and amitriptyline) could result in some inhibition of the metabolism of Tramadol HCl.
Use with Cimetidine: Concomitant administration of Paracetamol + Tramadol HCl and cimetidine has not been studied. Concomitant administration of Tramadol HCl and cimetidine does not result in clinically significant changes in Tramadol HCl pharmacokinetics.

Store at temperatures not exceeding 30°C.

Analgesics (Opioid)

N02AJ13 - tramadol and paracetamol ; Belongs to the class of opioids in combination with other non-opioid analgesics. Used to relieve pain.

Rx