Duocetz

Duocetz

tramadol + paracetamol

Manufacturer:

Mega Lifesciences

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Paracetamol, tramadol hydrochloride.
Description
Each film-coated tablet contains 2 analgesics, paracetamol 325 mg and tramadol HCl 37.5 mg. It also contains the following excipients: Corn starch, povidone K30, sodium starch glycolate, microcrystalline cellulose PH 101, magnesium stearate, opadry II yellow, purified water.
Tramadol HCl is a white, bitter, crystalline and odorless powder. Its chemical name is (±)cis-2-[(dimethylamino)methyl]-1-(3-methoxy phenyl) cyclohexanol HCl and has a molecular weight of 299.84.
Paracetamol is an analgesic and antipyretic agent which occurs as a white, odorless, crystalline powder, possessing a slightly bitter taste. Its chemical name is N-acetyl-p-aminophenol and has a molecular weight of 151.17.
Action
Pharmacology: Pharmacodynamics: Tramadol is a centrally-acting synthetic opioid analgesic. Although its mode of action is not completely understood, at least 2 complementary mechanisms appear applicable: Binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of re-uptake of norepinephrine and serotonin.
Paracetamol is a non-opiate, non-salicylate analgesic.
Pharmacokinetics: Tramadol is administered as a racemate and both the (-) and (+) forms of both tramadol and M1 are detected in the circulation. The pharmacokinetics of plasma tramadol and paracetamol following oral administration of 1 tablet are shown in the Table as follows. Tramadol has a slower absorption and longer half-life when compared to paracetamol. (See Table.)

Click on icon to see table/diagram/image

Absorption: Tramadol HCl has a mean absolute bioavailability of approximately 75% following administration of a single 100 mg oral dose of tramadol tablets. The mean peak plasma concentration of racemic tramadol and M1 after administration of 2 Doucetz occurs at approximately 2 and 3 hrs, respectively, post-dose.
Peak plasma concentrations of paracetamol occur within 1 hr and are not affected by co-administration with tramadol. Oral absorption of paracetamol following administration occurs primarily in the small intestine.
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 IV dose. The binding of tramadol to human plasma proteins is approximately 20% and binding also appears to be independent of concentration up to 10 mcg/mL. Saturation of plasma protein binding occurs only at concentrations outside the clinically relevant range.
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 (approximately 20%) of paracetamol is bound to plasma protein.
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 P-450. 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 eg, 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 (SRIs) and monoamine oxidase inhibitors (MAOIs) may enhance the risk of adverse events, including seizure and serotonin syndrome.
Paracetamol is primarily metabolized in the liver by 1st-order kinetics and involves 3 principal separate pathways: Conjugation with glucuronide; conjugation with sulfate; and oxidation via the cytochrome P-450-dependent, mixed-function oxidase enzyme pathway to a reactive intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates. The principal cytochrome P-450 isoenzyme involved appears to be CYP2E1, with CYP1A2 and CYP3A4 as additional pathways.
In adults, the majority of paracetamol 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 hrs, respectively, after administration of Duocetz. The apparent plasma elimination half-life of racemic tramadol increased to 7-9 hrs upon multiple dosing of Duocetz.
The half-life of paracetamol is about 2-3 hrs in adults. It is somewhat shorter in children and somewhat longer in neonates and in cirrhotic patients. Paracetamol is eliminated from the body primarily by formation of glucuronide and sulfate conjugates in a dose-dependent manner. Less than 9% of paracetamol is excreted unchanged in the urine.
Special Populations: Renal Impairment: The pharmacokinetics of Duocetz 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 <30 mL/min, adjustment of dosing regimen in this patient population is recommended. The total amount of tramadol and M1 removed during a 4-hr dialysis period is <7% of the administered dose based on studies using tramadol alone.
Hepatic Impairment: The pharmacokinetics and tolerability of Duocetz in patients with impaired hepatic function has not been studied. Since tramadol and paracetamol are both extensively metabolized by the liver, the use of Duocetz 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 Duocetz which included 55 patients between 65 and 75 years and 19 patients >75 years, showed no significant changes in pharmacokinetics of tramadol and paracetamol in elderly patients with normal renal and hepatic function.
Gender: Tramadol clearance was 20% higher in female subjects compared to males on 4 phase I studies of Duocetz in 50 male and 34 female healthy subjects. The clinical significance of this difference is unknown.
Pediatric: Pharmacokinetics of Duocetz has not been studied in pediatric patients <16 years.
Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: There are no animal or laboratory studies on the Duocetz to evaluate carcinogenesis, mutagenesis or impairment of fertility.
Teratogenic Effects: No drug-related teratogenic effects were observed in the progeny of rats treated orally with tramadol and paracetamol. The Duocetz was shown to be embryotoxic and fetotoxic in rats at a maternally toxic dose, 50/434 mg/kg tramadol/paracetamol (300/2604 mg/m2 or 1.6 times the maximum daily human tramadol/paracetamol dosage of 185/1591 mg/m2), but was not teratogenic at this dose level. Embryo and fetal toxicity consisted of decreased fetal weights and increased supernumerary ribs.
Non-Teratogenic Effects: Tramadol alone was evaluated in peri- and postnatal studies in rats. Progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (300 mg/m2 or 1.6 times the maximum daily human tramadol dosage) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (480 mg/m2 or 2.6 times the maximum daily human tramadol dosage).
There are no adequate and well-controlled studies in pregnant women. Duocetz should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported with tramadol HCl during post-marketing.
Indications/Uses
For management of moderate to severe pain.
Dosage/Direction for Use
Adults and Children >16 Years: 1-2 tabs every 4-6 hrs as needed for pain relief up to a maximum of 8 tabs/day.
Elderly: No overall differences with regard to safety or pharmacokinetics were noted between subjects ≥65 years and younger subjects.
Overdosage
The clinical presentation of overdose may include the signs and symptoms of tramadol toxicity, acetaminophen toxicity or both. The initial symptoms of tramadol overdosage may include respiratory depression and/or seizures. The initial symptoms seen within the first 24 hrs following an acetaminophen overdose are: Anorexia, nausea, vomiting, malaise, pallor and diaphoresis. An overdosage of Duocetz may be a potentially lethal polydrug overdose and consultation with a regional poison control center is recommended.
Tramadol: Acute overdosage with tramadol can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, seizures, bradycardia, hypotension, cardiac arrest and death.
Deaths due to overdose have been reported with abuse and misuse of tramadol. Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids.
In the treatment of tramadol overdosage, primary attention should be given to the re-establishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.
While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with naloxone administration. In animals convulsions following the administration of toxic doses of Duocetz 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 <7% of the administered dose in a 4-hr dialysis period.
Paracetamol: Serious potential consequences of overdosage with acetaminophen are hepatic centrilobular necrosis, leading to hepatic failure and death. Renal tubular necrosis, hypoglycemia and coagulation defects also may occur. Early symptoms following a potentially hepatotoxic overdose may include: Nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48-72 hrs post ingestion. Standard recommendations should be followed for the treatment of paracetamol overdose.
Contraindications
Hypersensitivity to tramadol, paracetamol, any other component of Duocetz or opioids. It 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. It may worsen central nervous system (CNS) and respiratory depression in these patients.
Warnings
Seizure 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 re-uptake inhibitors (SSRI antidepressants or anorectics); tricyclic antidepressants (TCAs) and other tricyclic compounds (eg, cyclobenzaprine, promethazine, etc); or other 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 (eg, head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizure.
Suicide Risk: Do not prescribe Duocetz for patients who are suicidal or addiction-prone.
Prescribe Duocetz with caution for patients taking tranquilizers or antidepressant drugs and patients who use alcohol in excess and who suffer from emotional disturbance or depression.
The judicious prescribing of tramadol is essential to the safe use of this drug. With patients who are depressed or suicidal, consideration should be given to the use of non-narcotic analgesics.
Tramadol-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation or attempts, as well as histories of misuse of tranquilizers, alcohol and other CNS-active drugs.
Serotonin Syndrome Risk: The development of a potentially life-threatening serotonin syndrome may occur with the use of tramadol products, including Duocetz, particularly with concomitant use of serotonergic drugs eg, SSRIs, SNRIs, TCAs, MAOIs, and triptans, with drugs which impair metabolism of serotonin (including MAOIs) and with drugs which impair metabolism of tramadol (CYP2D6 and CYP3A4 inhibitors). This may occur within the recommended dose.
Serotonin syndrome may include mental-status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination) and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea).
Anaphylactoid Reactions: Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving therapy with tramadol. When these events do occur it is often following the 1st 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 Duocetz.
Respiratory Depression: Administer Duocetz 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.
Interaction With Central Nervous System (CNS) Depressants: Duocetz should be used with caution and in reduced dosages when administered to patients receiving CNS depressants eg, alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers or sedative hypnotics. Tramadol increases the risk of CNS and respiratory depression in these patients.
Interactions with Alcohol and Drugs of Abuse: Tramadol may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.
Increased Intracranial Pressure or Head Trauma: Duocetz 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, pupillary 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 reaction when evaluating altered mental status in these patients if they are receiving Duocetz.
Use in Ambulatory Patients: Tramadol may impair the mental and or physical abilities required for the performance of potentially hazardous tasks eg, driving a car or operating machinery. The patient using this drug should be cautioned accordingly.
Use With MAO Inhibitors and Serotonin Re-uptake Inhibitors: Use Duocetz 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: Duocetz should not be used concomitantly with alcohol consumption. The use of Duocetz 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, Duocetz should not be used concomitantly with other paracetamol-containing products.
Misuse, Abuse and Diversion: Tramadol has mu-opioid agonist activity. Duocetz, a tramadol-containing product, can be sought by drug abusers and people with addiction disorders and may be subject to criminal diversion. The possibility of illegal or illicit use should be considered when prescribing or dispensing Duocetz in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Misuse or abuse poses a significant risk to the abuser that could result in overdose and death.
Concerns about abuse, addiction and diversion should not prevent the proper management of pain. The development of addiction to opioid analgesics in properly managed patients with pain has been reported to be rare. However, data are not available to establish the true incidence of addiction in chronic pain patients.
Risk of Overdosage: Patients taking tramadol should be warned not to exceed the dose recommended by their physician. Tramadol products in excessive doses, either alone or in combination with other CNS depressants, including alcohol, are a cause of drug-related deaths. Patients should be cautioned about the concomitant use of tramadol products and alcohol because of potentially serious CNS additive effects of these agents. Because of its added depressant effects, tramadol should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, tricyclic antidepressants or other CNS depressant drugs. Patients should be advised of the additive depressant effects of these combinations.
Serious potential consequences of overdosage with tramadol are CNS depression, respiratory depression and death. Some deaths have occurred as a consequence of the accidental ingestion of excessive quantities of tramadol alone or in combination with other drugs. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment.
Serious potential consequences of overdosage with paracetamol 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.
Withdrawal: Withdrawal symptoms may occur if Duocetz are discontinued abruptly. 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 tramadol HCl and acetaminophen tablet discontinuation include: Panic attacks, severe anxiety and paresthesias.
Clinical experience suggests that withdrawal symptoms may be avoided by tapering Duocetz at the time of discontinuation.
Special Precautions
General: The recommended dose of Duocetz should not be exceeded.
Do not co-administer Duocetz with other tramadol or paracetamol-containing products.
Acute Abdominal Conditions: The administration of DUOCETZ may complicate the clinical assessment of patients with acute abdominal conditions.
Renal Impairment: Tramadol HCl and paracetamol tablets have 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 <30 mL/min, it is recommended that the dosing interval of Duocetz be increased not >2 tablets every 12 hrs.
Hepatic Impairment: Tramadol HCl and paracetamol tablets have not been studied in patients with impaired hepatic function. The use of Duocetz in patients with hepatic impairment is not recommended.
Information for Patients: Patients should be informed that Duocetz may cause seizures and/or serotonin syndrome with concomitant use of serotonergic agents (including SSRIs, SNRIs, and triptans) or drugs that significantly reduce the metabolic clearance of tramadol.
Duocetz should not be taken with alcohol containing beverages. The patient should be instructed not to take Duocetz in combination with other tramadol or paracetamol-containing products, including over-the-counter preparations. Duocetz should be used with caution when taking medications eg, tranquilizers, hypnotics or other opiate containing analgesics. The patient should be instructed to inform the physician if they are pregnant, think they might become pregnant or are trying to become pregnant. The patient should understand the single-dose and 24-hr dose limit and the time interval between doses, since exceeding these recommendations can result in respiratory depression, seizures, hepatic toxicity and death.
Effects on the Ability to Drive or Operate Machinery: Duocetz may impair mental or physical abilities required for the performance of potentially hazardous tasks eg, driving a car or operating machinery.
Labor and Delivery: Duocetz should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks. Safe use in pregnancy has not been established. Chronic use during pregnancy may lead to physical dependence and post-partum withdrawal symptoms in the newborn.
Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor. The effect of tramadol HCl and acetaminophen tablets, if any, on the later growth, development and functional maturation of the child is unknown.
Use in Pregnancy: There are no adequate and well-controlled studies in pregnant women. Duocetz should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported with tramadol HCl during post-marketing.
Use in Lactation: Following a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hrs post-dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of M1.
Use in Children: The safety and effectiveness of Duocetz has not been studied in the pediatric population.
Use in the Elderly: In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function; of concomitant disease and multiple drug therapy.
Use In Pregnancy & Lactation
Use in Pregnancy: There are no adequate and well-controlled studies in pregnant women. Duocetz should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported with tramadol HCl during post-marketing.
Use in Lactation: Following a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hrs post-dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of M1.
Adverse Reactions
Common adverse reactions reported in clinical trials are constipation, nausea, diarrhea, dry mouth, psychiatric disorders, somnolence, anorexia, insomnia, dizziness, increased sweating, pruritus, prostatic disorder.
Drug Abuse and Dependence: Abuse: Tramadol has mu-opioid agonist activity. Duocetz, a tramadol-containing product, can be abused and may be subject to criminal diversion.
Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial and environmental factors influencing its development and manifestations. Drug addiction is characterized by behaviors that include 1 or more of the following: Impaired control over drug use, compulsive use, use for non-medical purposes, continued use despite harm or risk of harm and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.
“Drug-seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics, include emergency calls or visits near the end of office hrs, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of tramadol HCl and acetaminophen tablets can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances.
Concerns about abuse and addiction should not prevent the proper management of pain. However, all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Proper assessment of the patient and periodic re-evaluation of therapy are appropriate measures that help to limit the potential abuse of Duocetz.
Duocetz are intended for oral use only.
Dependence: Tolerance is the need for increasing doses of drugs to maintain a defined effect eg, analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist.
The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: Restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia and mydriasis. Other symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea or increased blood pressure, respiratory rate or heart rate.
Generally, tolerance and/or withdrawal are more likely to occur the longer a patient is on continuous therapy with Duocetz.
Drug Interactions
CYP2D6 and CYP3A4 Inhibitors: Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors eg, quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors) and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events, including seizures and serotonin syndrome.
Serotonergic Drugs: There have been post-marketing reports of serotonin syndrome with use of tramadol and SSRIs/SNRIs or MAOIs and α2-adrenergic blockers. Caution is advised when Duocetz are co-administered with other drugs that may affect the serotonergic neurotransmitter systems eg, SSRIs, MAOIs, triptans, linezolid (an antibiotic which is a reversible nonselective MAOI), lithium or St. John’s Wort. If concomitant treatment of Duocetz with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
Triptans: Based on the mechanism of action of tramadol and the potential for serotonin syndrome, caution is advised when Duocetz are co-administered with a triptan. If concomitant treatment of tramadol HCl and paracetamol tablets with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
Use With Carbamazepine: Patients taking carbamazepine may have a significantly reduced analgesic effect of tramadol. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of Duocetz and carbamazepine is not recommended.
Use With Quinidine: Tramadol is metabolized to M1 by CYP2D6. Quinidine is a selective inhibitor of that isoenzyme, so that concomitant administration of quinidine and tramadol results in increased concentrations of tramadol and reduced concentrations of M1. The clinical consequences of these findings are unknown. In vitro drug interaction studies in human liver microsomes indicate that tramadol has no effect on quinidine metabolism.
Potential for Other Drugs to Affect Tramadol: In vitro drug interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 eg, fluoxetine, paroxetine and amitriptyline could result in some inhibition of the metabolism of tramadol. Administration of CYP3A4 inhibitors eg, ketoconazole and erythromycin or inducers eg, rifampin and St. John’s Wort, with Duocetz, may affect the metabolism of tramadol leading to altered tramadol exposure.
Potential for Tramadol to Affect Other Drugs: In vitro studies indicate that tramadol is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when tramadol is administered concomitantly at therapeutic doses. Tramadol does not appear to induce its own metabolism in humans, since observed maximal plasma concentrations after multiple oral doses are higher than expected based on single-dose data. Tramadol is a mild inducer of selected drug metabolism pathways measured in animals.
Use With Cimetidine: Concomitant administration of Duocetz and cimetidine has not been studied. Concomitant administration of tramadol and cimetidine does not result in clinically significant changes in tramadol pharmacokinetics. Therefore, no alteration of the Duocetz dosage regimen is recommended.
Use With Digoxin: Tramadol has revealed rare reports of digoxin toxicity.
Use With Warfarin-Like Compounds: Both tramadol and paracetamol individual products have revealed rare alterations of warfarin effect, including elevation of prothrombin times.
While such changes have been generally of limited clinical significance for the individual products, periodic evaluation of prothrombin time should be performed when Duocetz and warfarin-like compounds are administered concurrently.
Storage
Do not store above 30°C.
Shelf-life: 24 months.
MIMS Class
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 (yellow, oblong) 3 x 10's.
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