Trap

Trap

tramadol + paracetamol

Manufacturer:

Cadila Healthcare

Distributor:

Metro Drug

Marketer:

Zydus Healthcare Phils
Full Prescribing Info
Contents
Paracetamol, tramadol hydrochloride.
Description
Each film-coated tablet contains: Paracetamol 325 mg, Tramadol Hydrochloride 37.5 mg.
Tramadol hydrochloride is a centrally acting opioid analgesic, used in treating moderate to moderately severe pain. The drug has a wide range of applications, including treatment for restless leg syndrome, acid reflux, and fibromyalgia. Tramadol possesses weak agonist actions at the μ-opioid receptor, releases serotonin, and inhibits the reuptake of norepinephrine.
Paracetamol is an odorless, slightly bitter taste white crystalline powder. It is soluble in organic solvents such as methanol and ethanol but slightly soluble in water and ether. It's pH range is 5.5-6.5 based on saturated aqueous solution. It, chemically N-(4-Hydroxyphenyl) acetamide, is derived from the interaction of p-aminophenol and an aqueous solution of acetic anhydride.
Action
Pharmacology: Pharmacokinetics: Tramadol is administered in racemic form and the [-] and [+] forms of tramadol and its metabolite M1, are detected in the blood. Although tramadol is rapidly absorbed after administration, its absorption is slower (and its half-life longer) than that of paracetamol.
For acetaminophen, Cmax was measured as µg/mL. A single dose pharmacokinetic study of Tramadol Hydrochloride & Paracetamol Tablets in volunteers showed no drug interactions between tramadol and acetaminophen. Upon multiple oral dosing to steady state, however, the bioavailability of tramadol and metabolite M1 was lower for the combination tablets compared to tramadol administered alone. The de-crease in AUC was 14% for (+)-tramadol, 10.4% for (-)-tramadol, 11.9% for (+)-M1 and 24.2% for (-)-M1. The cause of this reduced bioavailability is not clear. Following single or multiple dose administration of Tramadol Hydrochloride & Paracetamol Tablets, no significant change in acetaminophen pharmacokinetics was observed when compared to acetaminophen given alone.
After a single oral administration of a tramadol/paracetamol (37.5 mg/325 mg) tablet, peak plasma concentrations of 64.3/55.5 ng/ml [(+)-tramadol/(-)-tramadol] and 4.2 µg/ml (paracetamol) are reached after 1.8 h [(+)-tramadol/(-)-tramadol] and 0.9 h (paracetamol) respectively. The mean elimination half-lives t½ are 5.1/4.7 h [(+)-tramadol/(-)-tramadol] and 2, 5 h (paracetamol).
During pharmacokinetic studies in healthy volunteers after single and repeated oral administration of Tramadol Hydrochloride & Paracetamol Tablets, no clinical significant change was observed in the kinetic parameters of each active ingredient compared to the parameters of the active ingredients used alone.
Absorption: Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean absolute bioavailability of a single 100 mg dose is approximately 75 %. After repeated administration, the bioavailability is increased and reaches approximately 90%. The mean peak plasma concentration of racemic tramadol and M1 after administration of two Tramadol Hydrochloride & Paracetamol Tablets occurs at approximately two and three hours, respectively, post-dose.
After administration of Tramadol Hydrochloride & Paracetamol Tablets, the oral absorption of paracetamol is rapid and nearly complete and takes place mainly in the small intestine. Peak plasma concentrations of paracetamol are reached in one hour and are not modified by concomitant administration of tramadol.
The oral administration of Tramadol Hydrochloride & Paracetamol Tablets with food has no significant effect on the peak plasma concentration or extent of absorption of either tramadol or paracetamol so that Tramadol Hydrochloride & Paracetamol Tablets can be taken independently of meal times.
Food Effects: When Tramadol Hydrochloride & Paracetamol Tablets was administered with food, the time to peak plasma concentration was delayed for approximately 35 minutes for tramadol and almost one hour for acetaminophen. However, peak plasma concentration or the extent of absorption of either tramadol or acetaminophen were not affected. The clinical significance of this difference is unknown.
Distribution: The volume of distribution of tramadol was 2.6 and 2.9 L/kg in male and female subjects, respectively, following a 100 mg intravenous dose. The binding of tramadol to human plasma proteins is approximately 20% and binding also appears to be independent of concentration up to 10 µg/mL. Saturation of plasma protein binding occurs only at concentrations outside the clinically relevant range. Acetaminophen appears to be widely distributed throughout most body tissues except fat. Its apparent volume of distribution is about 0.9 L/kg. A relative small portion (~20%) of acetaminophen is bound to plasma protein. Paracetamol appears to be widely distributed throughout most body tissues except fat. Its apparent volume of distribution is about 0.9 l/kg. A relative small portion (~20%) of paracetamol is bound to plasma proteins.
Metabolism: Following oral administration, tramadol is extensively metabolized by a number of pathways, including CYP2D6 and CYP3A4, as well as by conjugation of parent and metabolites. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites. The major metabolic pathways appear to be N- and O-demethylation and glucuronidation or sulfation in the liver. Metabolite M1 (O-desmethyltramadol) is pharmacologically active in animal models. Formation of M1 is dependent on CYP2D6 and as such is subject to inhibition, which may affect the therapeutic response. Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme of cytochrome P450. These individuals are "poor metabolizers" of debrisoquine, dextromethorphan, tricyclic antidepressants, among other drugs. Based on a population PK analysis of Phase 1 studies in healthy subjects, concentrations of tramadol were approximately 20% higher in "poor metabolizers" versus "extensive metabolizers", while M1 concentrations were 40% lower. In vitro drug interaction studies in human liver microsomes indicates that inhibitors of CYP2D6 such as fluoxetine and its metabolite norfluoxetine, amitriptyline and quinidine inhibit the metabolism of tramadol to various degrees. The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown. Concomitant use of serotonin re-uptake inhibitors and Mao Inhibitors may enhance the risk of adverse events, including seizure and serotonin syndrome.
Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways: a) conjugation with glucuronide; b) conjugation with sulfate; and c) oxidation via the cytochrome, P450-dependent, mixed-function oxidase enzyme pathway to form a reactive intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates. The principal cytochrome P450 isoenzyme involved appears to be CYP2E1, with CYP1A2 and CYP3A4 as additional pathways.
In adults, the majority of acetaminophen is conjugated with glucuronic acid and, to a lesser extent, with sulfate. These glucuronide-, sulfate-, and glutathione-derived metabolites lack biologic activity. In premature infants, newborns, and young infants, the sulfate conjugate predominates.
Elimination: Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. The plasma elimination half-lives of racemic tramadol and M1 are approximately 5-6 and 7 hours, respectively, after administration of Tramadol Hydrochloride & Paracetamol Tablets. The apparent plasma elimination half-life of racemic tramadol increased to 7-9 hours upon multiple dosing of Tramadol Hydrochloride & Paracetamol Tablets.
The half-life of acetaminophen is about 2 to 3 hours in adults. It is somewhat shorter in children and somewhat longer in neonates and in cirrhotic patients.
Acetaminophen is eliminated from the body primarily by formation of glucuronide and sulfate conjugates in a dose-dependent manner. Less than 9% of acetaminophen is excreted unchanged in the urine.
Special Populations: Renal: The pharmacokinetics of Tramadol Hydrochloride & Paracetamol Tablets in patients with renal impairment has not been studied. Based on studies using tramadol alone, excretion of tramadol and metabolite M1 is reduced in patients with creatinine clearance of less than 30 mL/min, adjustment of dosing regimen in this patient population is recommended. The total amount of tramadol and M1 removed during a 4- hour dialysis period is less than 7% of the administered dose based on studies using tramadol alone.
Hepatic: The pharmacokinetics and tolerability of Tramadol Hydrochloride & Paracetamol Tablets in patients with impaired hepatic function has not been studied. Since tramadol and acetaminophen are both extensively metabolized by the liver, the use of Tramadol Hydrochloride & Paracetamol Tablets in patients with hepatic impairment is not recommended.
Geriatric: A population pharmacokinetic analysis of data obtained from a clinical trial in patients with chronic pain treated with Tramadol Hydrochloride & Paracetamol Tablets which included 55 patients between 65 and 75 years of age and 19 patients over 75 years of age, showed no significant changes in pharmacokinetics of tramadol and acetaminophen in elderly patients with normal renal and hepatic function.
Gender: Tramadol clearance was 20% higher in female subjects compared to males on four phase I studies of Tramadol Hydrochloride & Paracetamol tablets in 50 male and 34 female healthy subjects. The clinical significance of this difference is unknown.
Pediatric: Pharmacokinetics of Tramadol Hydrochloride & Paracetamol tablets has not been studied in pediatric patients below 16 years of age.
Clinical Studies Single Dose Studies for Treatment of Acute Pain: In pivotal single-dose studies in acute pain, two tablets of Tramadol Hydrochloride & Paracetamol Tablets administered to patients with pain following oral surgical procedures provided greater relief than placebo or either of the individual components given at the same dose. The onset of pain relief after Tramadol Hydrochloride & Paracetamol tablets was faster than tramadol alone. Onset of analgesia occurred in less than one hour. The duration of pain relief after Tramadol Hydrochloride & Paracetamol tablets was longer than acetaminophen alone. Analgesia was generally comparable to that of the comparator, ibuprofen. Pharmacodynamics: Tramadol is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. 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 is up 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, as have 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. Acetaminophen Acetaminophen is a non-opiate, non-salicylate analgesic.
Indications/Uses
Tramadol Hydrochloride & Paracetamol tablets are indicated for the symptomatic treatment of moderate to severe pain. The use of Tramadol Hydrochloride & Paracetamol tablets should be restricted to patients whose moderate to severe pain is considered to require a combination of Tramadol and Paracetamol.
Dosage/Direction for Use
An initial dose of two tablets of Tramadol 37.5 mg and paracetamol 325 mg tablets is recommended. Additional doses can be taken as needed, not exceeding 8 tablets (equivalent to 300 mg Tramadol and 2600 mg Paracetamol) per day.
The dosing interval should not be less than six hours.
An initial dose of two tablets of Tramadol Hydrochloride & Paracetamol tablets is recommended. Additional doses can be taken as needed, not exceeding 8 tablets (equivalent to 300 mg Tramadol and 2600 mg Paracetamol) per day.
The dosing interval should not be less than six hours.
Tramadol 37.5 and paracetamol 325 mg tablets should under no circumstances be administered for longer than is strictly necessary. If repeated use or long term treatment with Tramadol 37.5 and paracetamol 325 mg tablets is required as a result of the nature and severity of the illness, then careful, regular monitoring should take place (with breaks in the treatment, where possible), to assess whether continuation of the treatment is necessary.
Children: The effective and safe use of Tramadol 37.5 and paracetamol 325 mg tablets has not been established in children below the age of 12 years. Treatment is therefore not recommended in this population.
Elderly patients: The usual dosages may be used although it should be noted that in volunteers aged over 75 years the elimination half life of tramadol was increased by 17% following oral administration. In patients over 75 years old, it is recommended that the minimum interval between doses should be not less than 6 hours, due to the presence of tramadol.
Renal insufficiency: Because of the presence of tramadol, the use of Tramadol Hydrochloride & Paracetamol tablets is not recommended in patients with severe renal insufficiency (creatinine clearance < 10 ml/min). In cases of moderate renal insufficiency (creatinine clearance between 10 and 30 ml/min), the dosing should be increased to 12-hourly intervals. As tramadol is removed only very slowly by haemodialysis or by haemofiltration, post dialysis administration to maintain analgesia is not usually required. Hepatic insufficiency: In patients with severe hepatic impairment Tramadol Hydrochloride & Paracetamol tablets should not be used. In moderate cases prolongation of the dosage interval should be carefully considered.
Method of administration: Oral use. Tablets must be swallowed whole, with a sufficient quantity of liquid. They must not be broken or chewed.
Overdosage
Tramadol Hydrochloride & Paracetamol tablets is a fixed combination of active ingredients. In case of overdose, the symptoms may include the signs and symptoms of toxicity of tramadol or paracetamol or of both these active ingredients.
Symptoms of overdose from tramadol: In principle, on intoxication with tramadol, symptoms similar to those of other centrally acting analgesics (opioids) are to be expected. These include in particular, miosis, vomiting, cardiovascular collapse, consciousness disorders up to coma, convulsions and respiratory depression up to respiratory arrest. Symptoms of overdose from paracetamol: An overdose is of particular concern in young children. Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Liver damage is possible in adults who have taken 7.5-10 g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.
Emergency treatment: Transfer immediately to a specialised unit.
Maintain respiratory and circulatory functions.
Prior to starting treatment, a blood sample should be taken as soon as possible after overdose in order to measure the plasma concentration of paracetamol and tramadol and in order to perform hepatic tests.
Perform hepatic tests at the start (of overdose) and repeat every 24 hours. An increase in hepatic enzymes (ASAT, ALAT) is usually observed, which normalizes after one or two weeks.
Empty the stomach by causing the patient to vomit (when the patient is conscious) by irritation or gastric lavage.
Supportive measures such as maintaining the patency of the airway and maintaining cardiovascular function should be instituted; naloxone should be used to reverse respiratory depression; fits can be controlled with diazepam.
Tramadol is minimally eliminated from the serum by haemodialysis or haemofiltration. Therefore treatment of acute intoxication with Tramadol Hydrochloride & Paracetamol Tablets with haemodialysis or haemofiltration alone is not suitable for detoxification.
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any adult or adolescent who had ingested around 7.5 g or more of paracetamol in the preceding 4 hours or any child who has ingested ≥150 mg/kg of paracetamol in the preceding 4 hours should undergo gastric lavage. Paracetamol concentrations in blood should be measured later than 4 hours after overdose in order to be able to assess the risk of developing liver damage (via the paracetamol overdose nomogram). Administration of oral methionine or intravenous N-acetylcysteine (NAC) which may have a beneficial effect up to at least 48 hours after the overdose, may be required. Administration of intravenous NAC is most beneficial when initiated within 8 hours of overdose ingestion. However, NAC should still be given if the time to presentation is greater than 8 hours after overdose and continued for a full course of therapy. NAC treatment should be started immediately when massive overdose is suspected. General supportive measures must be available. Irrespective of the reported quantity of paracetamol ingested, the antidote for paracetamol, NAC, should be administered orally or intravenously, as quickly as possible, if possible, within 8 hours following the overdose.
Contraindications
Hypersensitivity to tramadol, paracetamol or to any of the excipients of the medicinal product.
Acute intoxication with alcohol, hypnotic drugs, centrally-acting analgesics, opioids or psychotropic drugs.
Tramadol Hydrochloride & Paracetamol tablets should not be administered to patients who are receiving monoamine oxidase inhibitors or within two weeks of their withdrawal. Severe hepatic impairment.
Epilepsy not controlled by treatment.
Special Precautions
Warnings: In adults and adolescents 12 years and older. The maximum dose of 8 tablets of Tramadol Hydrochloride & Paracetamol tablets should not be exceeded. In order to avoid inadvertent overdose, patients should be advised not to exceed the recommended dose and not to use any other paracetamol (including over the counter) or tramadol hydrochloride containing products concurrently without the advice of a physician.
In severe renal insufficiency (creatinine clearance <10 ml/mm), Tramadol Hydrochloride & Paracetamol tablets is not recommended.
In patients with severe hepatic impairment Tramadol Hydrochloride & Paracetamol tablets should not be used. The hazards of paracetamol overdose are greater in patients with non-cirrhotic alcoholic liver disease. In moderate cases prolongation of dosage interval should be carefully considered.
In severe respiratory insufficiency, Tramadol Hydrochloride & Paracetamol tablets is not recommended.
Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms.
Convulsions have been reported in tramadol-treated patients susceptible to seizures or taking other medications that lower the seizure threshold, especially selective serotonin re-uptake inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local anaesthesia. Epileptic patients controlled by a treatment or patients susceptible to seizures should be treated with Tramadol Hydrochloride & Paracetamol tablets only if there are compelling circumstances. Convulsions have been reported in patients receiving tramadol at the recommended dose levels. The risk may be increased when doses of tramadol exceed the recommended upper dose limit.
Concomitant use of opioid agonists-antagonists (nalbuphine, buprenorphine, pentazocine) is not recommended.
Precautions for use: Tramadol Hydrochloride & Paracetamol tablets should be used with caution in opioid dependent patients, or in patients with cranial trauma, in patients prone to convulsive disorder, biliary tract disorders, in a state of shock, in an altered state of consciousness for unknown reasons, with problems affecting the respiratory center or the respiratory function, or with an increased intracranial pressure.
Paracetamol in overdosage may cause hepatic toxicity in some patients.
At therapeutic doses, tramadol has the potential to cause withdrawal symptoms.
Rarely, cases of dependence and abuse have been reported. Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal may occur.
In one study, use of tramadol during general anaesthesia with enflurane and nitrous oxide was reported to enhance intra-operative recall. Until further information is available, use of tramadol during light planes of anaesthesia should be avoided.
Effects on ability to drive and use machines: Tramadol may cause drowsiness or dizziness, which may be enhanced by alcohol or other CNS depressants. If affected, the patient should not drive or operate machinery.
Use in Pregnancy: Since Tramadol Hydrochloride & Paracetamol tablets is a fixed combination of active ingredients including tramadol, it should not be used during pregnancy. Data regarding paracetamol: Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosages.
Data regarding tramadol: Tramadol should not be used during pregnancy as there is inadequate evidence available to assess the safety of tramadol in pregnant women.
Tramadol administered before or during birth does not affect uterine contractility. In neonates it may induce changes in the respiratory rate which are usually not clinically relevant. Long-term treatment during pregnancy may lead to withdrawal symptoms in the newborn after birth, as a consequence of habituation.
Use in Lactation: Since Tramadol Hydrochloride & Paracetamol tablets is a fixed combination of active ingredients including tramadol, it should not be ingested during breast feeding.
Data regarding paracetamol: Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding by women using single ingredient medicinal products containing only paracetamol.
Data regarding tramadol: Tramadol and its metabolites are found in small amounts in human breast milk. An infant could ingest about 0.1% of the dose given to the mother. Tramadol should not be ingested during breast feeding.
Use In Pregnancy & Lactation
Pregnancy: Since Tramadol Hydrochloride & Paracetamol tablets is a fixed combination of active ingredients including tramadol, it should not be used during pregnancy.
Data regarding paracetamol: Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosages.
Data regarding tramadol: Tramadol should not be used during pregnancy as there is inadequate evidence available to assess the safety of tramadol in pregnant women.
Tramadol administered before or during birth does not affect uterine contractility. In neonates it may induce changes in the respiratory rate which are usually not clinically relevant. Long-term treatment during pregnancy may lead to withdrawal symptoms in the newborn after birth, as a consequence of habituation.
Lactation: Since Tramadol Hydrochloride & Paracetamol tablets is a fixed combination of active ingredients including tramadol, it should not be ingested during breast feeding. Data regarding paracetamol: Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding by women using single ingredient medicinal products containing only paracetamol.
Data regarding tramadol: Tramadol and its metabolites are found in small amounts in human breast milk. An infant could ingest about 0.1% of the dose given to the mother. Tramadol should not be ingested during breast feeding.
Adverse Reactions
The most commonly reported undesirable effects during the clinical trials performed with the paracetamol/tramadol combination were nausea, dizziness and somnolence, observed in more than 10 % of the patients.
Tramadol: Postural hypotension, bradycardia, collapse (tramadol).
Post-marketing surveillance of tramadol has revealed rare alterations of warfarin effect, including elevation of prothrombin times.
Psychic side-effects may occur following administration of tramadol which vary individually in intensity and nature (depending on personality and duration of medication). These include changes in mood, (usually elation occasionally dysphoria), changes in activity (usually suppression occasionally increase) and changes in cognitive and sensorial capacity (e.g. decision behaviour perception disorders).
Paracetamol: Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
There have been several reports that suggest that paracetamol may produce hypoprothrombinemia when administered with warfarin-like compounds. In other studies, prothrombin time did not change.
Drug Interactions
Concomitant use is contraindicated with: Non-selective MAO Inhibitors.
Risk of serotoninergic syndrome: diarrhoea, tachycardia, sweating, trembling, confusion, even coma.
Selective-MAO Inhibitors: Tramadol Hydrochloride & Paracetamol from non-selective MAO inhibitors.
Risk of serotoninergic syndrome: diarrhoea, tachycardia, sweating, trembling, confusion, even coma.
Selective-B MAO Inhibitors: Central excitation symptoms evocative of a serotoninergic syndrome: diarrhoea, tachycardia, sweating, trembling, confusion, even coma.
In case of recent treatment with MAO inhibitors, a delay of two weeks should occur before treatment with tramadol.
Concomitant use is not recommended with: Alcohol: Alcohol increases the sedative effect of opioid analgesics.
The effect on alertness can make driving of vehicles and the use of machines dangerous.
Avoid intake of alcoholic drinks and of medicinal products containing alcohol.
Carbamazepine and other enzyme inducers.
Risk of reduced efficacy and shorter duration due to decreased plasma concentrations of tramadol.
Opioid agonists-antagonists (buprenorphine, nalbuphine, pentazocine) Decrease of the analgesic effect by competitive blocking effect at the receptors, with the risk of occurrence of withdrawal syndrome.
Concomitant use which needs to be taken into consideration: In isolated cases there have been reports of Serotonin Syndrome in a temporal connection with the therapeutic use of tramadol in combination with other serotoninergic medicines such as selective serotonin re-uptake inhibitors (SSRIs) and triptans. Signs of Serotonin Syndrome may be for example, confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus and diarrhoea.
Other opioid derivatives (including antitussive drugs and substitutive treatments), benzodiazepines and barbiturates.
Increased risk of respiratory depression which can be fatal in cases of overdose.
Other central nervous system depressants, such as other opioid derivatives (including antitussive drugs and substitutive treatments), barbiturates, benzodiazepines, other anxiolytics, hypnotics, sedative antidepressants, sedative antihistamines, neuroleptics, centrally-acting antihypertensive drugs, thalidomide and baclofen.
These drugs can cause increased central depression. The effect on alertness can make driving of vehicles and the use of machines dangerous.
As medically appropriate, periodic evaluation of prothrombin time should be performed when Tramadol Hydrochloride & Paracetamol tablets and warfarin like compounds are administered concurrently due to reports of increased INR.
Other drugs known to inhibit CYP3A4, such as ketoconazole and erythromycin, might inhibit the metabolism of tramadol (N-demethylation) probably also the metabolism of the active O-demethylated metabolite. The clinical importance of such an interaction has not been studied.
Medicinal products reducing the seizure threshold, such as bupropion, serotonin reuptake inhibitor antidepressants, tricyclic antidepressants and neuroleptics. Concomitant use of tramadol with these drugs can increase the risk of convulsions. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
In a limited number of studies the pre- or postoperative application of the antiemetic 5- HT3 antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain.
Storage
Store at temperatures not exceeding 30°C. Protect from light and moisture.
MIMS Class
Analgesics (Non-Opioid) & Antipyretics
ATC Classification
N02AJ13 - tramadol and paracetamol ; Belongs to the class of opioids in combination with other non-opioid analgesics. Used to relieve pain.
Presentation/Packing
FC tab 100's.
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