Ulcetra

Each film-coated caplet contains: Tramadol HCl 37.5 mg, Paracetamol 325 mg.

Pharmacology: Pharmacodynamics: Tramadol is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal test, at least two complementary mechanism appear applicable: binding of parent and M1 metabolite to μ-opioid receptors and weak inhibition of norepinephrine and serotonin reuptake.
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 up is 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, like some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of Tramadol.
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.
Paracetamol: Paracetamol is a non-opiate, non-salicylate analgesic.
Food Effects: When Ulcetra is administered with food, the time to peak plasma concentration was delayed for approximately 35 minutes for Tramadol and almost one hour for Paracetamol. However, peak plasma concentration, and the extents of absorption, of Tramadol and acetaminophen were not affected. The clinical significance of this difference is unknown.

Ulcetra is indicated for the short-term management of acute pain.

Unless otherwise specified, Ulcetra shall be provided as follows: Adults and Children More than 16 years old: For the short-term (five days or less) management of acute pain, the recommended dose of Ulcetra is 1 to 2 tablets every 4 to 6 hours as needed for pain relief up to a maximum of 8 tablets per day.
Ulcetra can be given before or after meals.
Pediatrics (Children Under 16 years of age): The safety and effectiveness of Ulcetra have not been established in children population.
Elderly (Geriatric): In general, there are no differences related to safety or pharmacokinetics recorded between subjects aged > 65 years and younger subjects.

Ulcetra is a combination product. Clinical presentation of an overdose may include signs and symptoms of Tramadol toxicity, Paracetamol toxicity or both. Early symptoms seen in the first 24 hours after Paracetamol overdose may include: gastrointestinal irritation, anorexia, nausea, vomiting, malaise, pallor, and diaphoresis.
Human experience: Tramadol: Potential and serious consequences of an overdose of the Tramadol component are respiratory depression, lethargy, coma, convulsions, cardiac arrest and death.
Paracetamol: Severe overdose of Paracetamol can cause liver toxicity in some patients. Initial symptoms following potential overdose resulting in hepatotoxicity may include: gastrointestinal irritation, anorexia, nausea, vomiting, malaise, pallor, and diaphoresis. Clinical and laboratory evidence of liver toxicity may not be apparent until 48-72 hours after consumption.
Treatment: Single or multiple overdoses with Ulcetra may potentially lead to a deadly multi-drug overdose and it is recommended to consult an expert. Although naloxone can overcome some of the poisoning symptoms, but not all of the symptoms caused by Tramadol overdose can be managed. The risk of seizures also increases with the administration of naloxone. Based on experience, hemodialysis did not gave result as expected because it can only eliminate less than 7% dose of Tramadol taken in the dialysis period of 4 hours. In treating Ulcetra overdose, a major concern should be given to maintaining adequate ventilation (breathing) along with supportive therapy. Steps should be taken to reduce drug absorption. Vomiting should be mechanically induced, or with ipecac syrup, if the patient is conscious (adequate pharyngeal and laryngeal reflexes). The activated charcoal orally (1 g/kg) should be given after the gastric emptying action. The first dose should be accompanied by proper catharsis. If repeated doses are used, catharsis may be included with the necessary alternative dosage. Hypotension is usually caused by hypovolemic conditions and should be treated with fluids. Vasopressors and other support measures should be used as indicated. A balloon endotracheal tube should be inserted before gastric rinse in unconscious patient and, when necessary, to provide respiratory relief.
In adult and pediatric patients, any individual who presents with Paracetamol ingestion but unknown amount or history or timing, it should be attempted to determine plasma Paracetamol level and treated with acetylcysteine. If a measurement can not be obtained and the estimated consumption of Paracetamol exceeds 7.5-10 grams for adults and adolescents or 150 mg/kg for children, then dosing with N-acetylcysteine should be started and continued with overall therapy.

Ulcetra should not be administered to patients who have previously demonstrated hypersensitivity to Tramadol, Paracetamol, any other component of this product or opioids. The drug 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.

Seizures Risk: 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 (SSRI anti depressants or anorectics), Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), or Other opioids.
Administration of Tramadol may increase the seizure risk in patients taking: MAO inhibitors (see Use with MAO Inhibitors as follows), Neuroleptics, or Other drugs that lower 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.
Anaphylactoid Reactions: Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving therapy with Tramadol. When these events occurred it is often following the first dose. Other reported allergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis, and Stevens-Johnson syndrome. Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive Ulcetra (see CONTRAINDICATIONS).
Respiratory Depression: Administer Ulcetra cautiously in patients at risk for respiratory depression. In these patients, alternative non-opioid analgesics should be considered. When large doses of Tramadol are administered with anesthetic medications or alcohol, respiratory depression may result. Respiratory depression should be treated as an overdose. If naloxone is to be administered, use cautiously because it may precipitate seizures (see Seizure Risk as previously mentioned, and OVERDOSAGE).
Ultra-Rapid CYP2D6 Metabolism of Tramadol: Patients who are CYP2D6 ultra-rapid metabolizers can convert Tramadol into its active metabolite (M1) faster and more complete than other patients. This rapid conversion can lead to higher than expected M1 serum levels that may lead to an increased risk of respiratory depression (see Human Experience: Tramadol under OVERDOSAGE). Alternative treatments, dose reduction and/or intensive monitoring of Tramadol overdosage signs, such as respiratory depression are recommended in patients known to be CYP2D6 ultra-rapid metabolizers.
Interaction with Central Nervous System (CNS) Depressants: Ulcetra should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers, or sedatives. Tramadol increases the risk of CNS and respiratory depression in these patients.
Increased Intracranial Pressure or Head Trauma: Ulcetra should be used with caution in patients with increased intracranial pressure or head injury. The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure and may be markedly exaggerated in these patients. Additionally, pupil changes (miosis) from Tramadol may obscure the existence, extent, or course of intracranial pathology. Clinicians should also maintain a high index of suspicion for adverse drug reactions when evaluating altered mental status in these patients if they are receiving Ulcetra (see Respiratory Depression as previously mentioned).
Use in Ambulatory Patients: Tramadol may impair mental and or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Patients using this drug should be cautioned accordingly.
Use with MAO Inhibitors and Serotonin Re-uptake Inhibitors: Use Ulcetra with great caution in patients taking monoamine oxidase inhibitors. Animal studies have shown increased deaths with combined administration of MAO inhibitors and tramadol. Concomitant use of Tramadol with MAO inhibitors or SSRIs increases the risk of adverse events, including seizure and serotonin syndrome.
Use with Alcohol: Ulcetra should not be used concomitantly with alcohol consumption. The use of Ulcetra in patients with liver disease is not recommended.
Use With Other Paracetamol-containing Products: Due to the potential for Paracetamol hepatotoxicity at doses higher than the recommended dose, Ulcetra should not be used concomitantly with other Paracetamol-containing products.
Withdrawal: Withdrawal symptoms may occur if Ulcetra is discontinued abruptly (see also Drug Abuse And Dependency as follows). Reported symptoms have included anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Other symptoms that have been reported less frequently with Ulcetra discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience indicated that withdrawal symptoms may be avoided by tapering Ulcetra at the time of discontinuation.
Physical Dependability and Abuse: Tramadol can cause physical dependence from its morphine type (m-opiod). Tramadol should not be used in opioid-dependent patients. Tramadol has been shown to restart physical dependence on some patients who have previously been dependent on other opioids. Dependency and abuse, including drug addiction behaviors and unlawful acts to obtain drugs are not limited to patients with a prior history of opioid dependency.
Risk of Overdosage: Serious potential consequences of overdosage with Tramadol are central nervous system depression, respiratory depression, and death. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment (see OVERDOSAGE). Serious potential consequences of overdosage with acetaminophen are hepatic (centrilobular) necrosis, leading to hepatic failure and death. Emergency help should be sought immediately and treatment initiated immediately if overdose is suspected, even if symptoms are not apparent.
Hyponatremia: Hyponatremia has been reported but very rarely with the use of Ulcetra, usually in patients with predisposing risk factors, such as elderly patients and/or patients taking concurrent drugs that may cause hyponatremia. In some reports, this hyponatremia appears to be the result of the syndrome of antidiuretic hormone secretion syndrome (SIADH) and is treated with Ulcetra termination and appropriate treatment (eg fluid restriction). During treatment with Ulcetra, monitoring of signs and symptoms of hyponatremia is recommended for patients with predisposing risk factors.

General: The recommended dose of Ulcetra should not be exceeded.
Do not co-administer Ulcetra with other Tramadol or Paracetamol-containing products. (see Use with Other Paracetamol-containing Products and Risk of Overdosage under WARNINGS).
Acute Abdominal Disorder: The administration of Ulcetra may complicate the clinical assessment of patients with acute abdominal condition.
Serious Skin Reactions: Serious skin reactions such as Acute Generalized Exanthematous Pustulosis (AGEP), Steven-Johnson syndrome (SJS), and Toxic Epidermal Necrolysis (TEN), have been reported but are very rare in patients receiving Paracetamol. Patients should be informed of any signs of serious skin reactions, and drug use should be discontinued on the first appearance of skin rashes or other signs of hypersensitivity.
Patient's Information: Ulcetra may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
Ulcetra should not be taken with alcohol containing beverages.
Patients should be instructed not to take Ulcetra in combination with other Tramadol or Paracetamol-containing products, including over-the-counter medications.
Ulcetra should be used with caution when taking medications such as tranquilizers, hypnotics or other opiate containing analgesics.
Patients should be instructed to inform the physician if they are pregnant, think they might become pregnant, or are trying to become pregnant.
Patients should understand the single-dose and 24-hour dose limit and the time interval between doses, since exceeding these recommendations can result in respiratory depression, seizures, hepatic toxicity and death.
Effects on Driving and Operating Machine: Ulcetra can disrupt the mental or physical capabilities required for the performance of potentially dangerous tasks such as driving a car or operating a machine.
Use in Renal Disease: Ulcetra has not been studied in patients with impaired renal function. Experience with Tramadol suggests that impaired renal function results in a decreased rate and extent of excretion of Tramadol and its active metabolite, M1. In patients with creatinine clearances of less than 30 mL/min, it is recommended that the dosing interval of Ulcetra be increased not to exceed 2 tablets every 12 hours.
Use in Hepatic Disease: Ulcetra has not been studied in patients with impaired hepatic function. The use of Ulcetra in patients with hepatic impairment is not recommended. (see Use with Alcohol under WARNINGS).
Use in Children: The safety and effectiveness of Ulcetra have not been studied in pediatric population.
Use in Elderly: In general, dose selection for an elderly patients should be cautions, reflecting the greater frequency of decreased hepatic, renal, or cardiac function; of concomitant disease and multiple drug therapy.

Tramadol has been shown to pass through the placental blood barrier.
There is no adequate controlled clinical trials study in pregnant women.
Safe use in pregnancy has not been established. Ulcetra is not recommended for breastfeeding mothers because safety in infants and newborns has not been studied.

The most frequently reported incidents are those originating from the central nervous system and the digestive system. The most common reported symptoms are nausea, dizziness, and drowsiness.
In addition, the following effects have been frequently observed, although in general the frequency is lower: Body as a whole: asthenia, fatigue, hot flushes.
Central and peripheral nervous system: headache, tremor.
Gastrointestinal system: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, dry mouth, vomiting.
Psychiatric disorders: anorexia, anxiety, confusion, euphoria, insomnia, nervousness.
Skin and appendages: pruritus, rash, increased sweating.
Clinically significant but infrequently reported adverse experiences and at least possible cause-and-effect relationships with Ulcetra include: Body as a whole: chest pain, rigors, syncope, withdrawal syndrome.
Cardiovascular disorders: hypertension, aggravated hypertension, hypotension.
Central and peripheral nervous system: ataxia, convulsions, hypertonia, migraine, aggravated migraine, involuntary muscle contractions, paresthesias, stupor coma, vertigo.
Gastrointestinal system: dysphagia, melena, tongue edema.
Hearing and vestibular disorders: tinnitus.
Heart rate and rhythm disorders: arrhythmia, palpitation, tachycardia.
Liver and biliary system: abnormal hepatic function.
Metabolic and nutritional disorders: weight decrease.
Psychiatric disorders: amnesia, depersonalization, depression, drug abuse, emotional lability, hallucination, impotence, paroniria, abnormal thinking.
Red blood cell disorders: anemia.
Respiratory system: dyspnea.
Urinary system: albuminuria, micturition disorder, oliguria, urinary retention.
Vision disorder: abnormal vision.
Other clinically significant adverse events or events previously reported in clinical trials or post marketing reports with Tramadol hydrochloride: Other events which have been reported with the use of Tramadol products include: Orthostatic hypotension, allergic reactions (including anaphylaxis and urticaria, Stevens-Johnson syndrome/TENS), cognitive dysfunction, suicidal tendency, and hepatitis.
Reported laboratory abnormalities included elevated creatinine. Serotonin syndrome (whose symptoms may include fever, excitation, chills, and agitation) has been reported with Tramadol when used concomitantly with other serotoninergic agents such as SSRIs and MAO inhibitors.
Post-marketing experiences with the use of products containing Tramadol include the rarely reported delirium, miosis, midriasis, and speech disorders, and very rare movement disorders. Post-marketing surveillance of Tramadol has shown a rare change in the effects of warfarin, including elevated prothrombin time. Hypoglycemic cases have been reported but are very rare in patients taking Tramadol. Most reports occurred in patients with predisposing risk factors, including diabetes or renal insufficiency, or in elderly patients. Hyponatremia and/or SIADH cases have been reported very rarely in patients taking Tramadol, usually in patients with predisposing risk factors, such as the elderly or used concomitantly with drugs that may cause hyponatremia.
Other clinically significant adverse experiences previously reported in clinical trials or post-marketing reports with Paracetamol: Allergic reactions (primarily skin rash) or reports of secondary hypersensitivity to Paracetamol are rare and generally managed by discontinuation of the drug, and when necessary, symptomatic treatment.
There have been several reports showing that Paracetamol can lead to hypoprothrombinemia when administered along with compounds such as warfarin. In other studies, prothrombin time did not change.

Concomitant Use with MAO Inhibitor and Serotonin Reuptake Inhibitor: Interactions with MAO inhibitors have been reported for some drugs that work centrally (in the central nervous system).
Use with Carbamazepine: Co-administration between Tramadol hydrochloride and carbamazepine leads to a significant increase in Tramadol metabolism. Patients taking carbamazepine may be significantly lessen the analgesic effect of Tramadol Ulcetra component.
Usage with Quinidine: Tramadol is metabolized into M1 by CYP2D6. Co-administration of quinidine and Tramadol resulted in increased concentrations of Tramadol. The clinical consequences of these findings are unknown.
Co-administration with Warfarin-like Compounds: In order to be medically correct, periodic evaluation of prothrombin time should be made if Ulcetra and these drugs are administered concomitantly due to reports of an increase in INR in some patients.
Use with CYP2D6 Inhibitor: The study of in-vitro drug interactions on human liver microsomes showed that concomitant administration with CYP2D6 inhibitors such as fluoxetine, paroxetine, and amitriptyline could lead to inhibition of Tramadol metabolism.
Use with Cimetidine: Co-administration Ulcetra with cimetidine has not been studied. Co-administration of Tramadol with cimetidine did not result in clinically significant changes in Tramadol pharmacokinetics.

Store below 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.

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