Ultracet

Ultracet

tramadol + paracetamol

Manufacturer:

Johnson & Johnson
Full Prescribing Info
Contents
Tramadol hydrochloride, acetaminophen.
Description
ULTRACET is available as tablets for oral administration containing 37.5 mg tramadol hydrochloride and 325 mg acetaminophen (N-acetyl-p-aminophenol).
Chemical Names: Tramadol Hydrochloride: (±)cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride.
Acetaminophen: N-acetyl-p-aminophenol (4-hydroxyacetanilide).
Excipients/Inactive Ingredients: Inactive ingredients in the tablet are powdered cellulose, pregelatinized starch, sodium starch glycolate, starch, purified water, magnesium stearate, OPADRY Light Yellow, and carnauba wax.
Action
Pharmacotherapeutic Group: Analgesics, Opioids in combination with non-opioid analgesics. ATC Code: N02AJ13.
Pharmacology: Pharmacodynamics: Pharmacodynamic effects: 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 binding 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 (see Pharmacology: Pharmacokinetics under Actions).
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.
Clinical Studies: Single Dose Studies for Treatment of Acute Pain: In pivotal single-dose studies in acute pain, two tablets of ULTRACET 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 ULTRACET was faster than tramadol alone. Onset of analgesia occurred in less than one hour. The duration of pain relief after ULTRACET was longer than acetaminophen alone. Analgesia was generally comparable to that of the comparator, ibuprofen.
Pharmacokinetics: General: 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 acetaminophen following oral administration of one ULTRACET tablet are shown in table as follows. Tramadol has a slower absorption and longer half-life when compared to acetaminophen. (See table.)


Click on icon to see table/diagram/image


A single dose pharmacokinetic study of ULTRACET 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 decrease 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 Ultracet, no significant change in acetaminophen pharmacokinetics was observed when compared to acetaminophen given alone.
Absorption: The absorption bioavailability of tramadol from ULTRACET tablets has not been determined. Tramadol hydrochloride has a mean absolute bioavailability of approximately 75% following administration of a single 100 mg oral dose of ULTRACET tablets. The mean peak plasma concentration of racemic tramadol and M1 after administration of two ULTRACET tablets occurs approximately two and three hours, respectively, post-dose.
Peak plasma concentrations of acetaminophen occur within one hour and are not affected by co-administration with tramadol. Oral absorption of acetaminophen following administration of ULTRACET occurs primarily in the small intestine.
Food effects: When ULTRACET 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.
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 appears to be N- and O-demethylation and glucoronidation or sulfation in the liver. Metabolite M1 (O-desmethyltramadol) is pharmacologically active in animal models. Formation of M1 on CYP2D6 and as such is subject to inhibition, which may affect the therapeutic response (see Precautions and Interactions).
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 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, amitriptylline 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 (see Warnings) and serotonin syndrome.
Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways: conjugation with glucuronide; conjugation with sulfate; and oxidation via cytochrome P450 enzyme pathway, 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 CYP2A2 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 ULTRACET. The apparent plasma elimination half-life of racemic tramadol increased to 7-9 hours upon multiple dosing of Ultracet. 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 ULTRACET in patients with renal impairment have 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. (See Dosage & Administration.) 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 ULTRACET in patients with impaired hepatic function has not been studied. Since tramadol and acetaminophen are both extensively metabolized by the liver, the use of ULTRACET in patients with hepatic impairment is not recommended (see Dosage & Administration and Precautions).
Geriatric: A population pharmacokinetic analysis of data obtained from a clinical trial in patients with chronic pain treated with ULTRACET 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 (see Geriatric Use under Precautions).
Gender: Tramadol clearance was 20% higher in female subjects compared to males on four phase I studies of ULTRACET in 50 male and 34 female healthy subjects. The clinical significance of this difference is unknown.
Pediatric: Pharmacokinetics of ULTRACET tablets have not been studied in pediatric patients below 16 years of age.
Indications/Uses
ULTRACET is indicated for short-term treatment of acute pain.
Dosage/Direction for Use
Unless otherwise prescribed, ULTRACET should be administered as follows: Adults and Children Over 16 Years: The maximum single dose of ULTRACET is 1 to 2 tablets every 4 to 6 hours as needed for pain relief up to a maximum of 8 tablets per day.
ULTRACET can be administered without regard to food.
Pediatric (Children Below 16 Years): The safety and effectiveness of ULTRACET has not been established in the pediatric population.
Elderly (Geriatric): No overall differences with regard to safety or pharmacokinetics were noted between subjects ≥65 years of age and younger subjects.
Overdosage
Symptoms and signs: ULTRACET is a combination product. The clinical presentation of overdose may include the signs and symptoms of tramadol toxicity, acetaminophen toxicity or both. The initial symptoms seen within the first 24 hours following an acetaminophen overdose may include: gastrointestinal irritability, anorexia, nausea, vomiting, malaise, pallor and diaphoresis.
Tramadol: Serious potential consequences of overdosage of the tramadol component are respiratory depression, lethargy, coma, seizure, cardiac arrest and death. In addition, cases of QT prolongation have been reported during overdose.
Acetaminophen: Acetaminophen 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 to 72 hours post-ingestion.
Treatment: A single or multiple overdose with ULTRACET 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, the risk of seizures is also increased with naloxone administration. Based on experience with tramadol, hemodialysis is not expected to be helpful in an overdose because it removes less than 7% of the administered dose in a 4-hour dialysis period.
In treating an overdosage of ULTRACET, primary attention should be given to maintaining adequate ventilation along with general supportive treatment. Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center (where available) to determine the latest recommendations for the management of an overdose. Hypotension is usually hypovolemic in etiology and should respond to fluids. Vasopressors and other supportive measures should be employed as indicated. A cuffed endo-tracheal tube should be inserted when necessary, to provide assisted respiration.
In adult and pediatric patients, any individual presenting with an unknown amount of acetaminophen ingested or with a questionable or unreliable history about the time of ingestion should have a plasma acetaminophen level drawn and be treated with acetylcysteine. If an assay cannot be obtained and the estimated acetaminophen ingestion exceeds 7.5 to 10 grams for adults and adolescents or 150 mg/kg for children, dosing with N-acetylcysteine should be initiated and continued for full course of therapy.
Contraindications
ULTRACET is contraindicated: in patients who have previously demonstrated hypersensitivity to tramadol, acetaminophen, any other component of this product or opioids.
in any situation where opioids are contraindicated, including acute intoxication without of the following in cases of acute intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs.
in patients using monoamine oxidase inhibitors (MAOIs) concurrently or within the last 14 days.
Warnings
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 antidepressants or anorectics), tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), or opioids.
Administration of tramadol may enhance the seizure risk in patients taking: monoamine oxidase (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 (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 do occur 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 in creased risk and therefore should not receive Ultracet (see Contraindications).
Respiratory Depression: Patients with significant respiratory depression or acute, severe bronchial asthma are at increased risk of life-threatening respiratory depression when treated with opioids. ULTRACET should only be used in this patient population in a monitored setting and with the availability of resuscitative equipment.
Administer ULTRACET cautiously in patient 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 Seizures Risk previously mentioned and Overdosage).
CYP2D6 Ultra-Rapid Metabolism of Tramadol: Patients who are CYP2D6 ultra-rapid metabolizers may convert tramadol to its active metabolite (M1) more rapidly and completely than other patients. This rapid conversion may result in higher than expected serum M1 levels which could lead to an increased risk of respiratory depression (see Symptoms and signs, Tramadol under Overdosage). Alternative medication, dose reduction and/or increased monitoring for signs of tramadol overdose, such as respiratory depression is recommended in patients known to be CYP2D6 ultra-rapid metabolizers.
Interaction with Central Nervous System (CNS) Depressants, including alcohol: The concomitant use of tramadol (an active ingredient in Ultracet) with CNS depressants, including alcohol, may cause additive CNS depressant effects, including profound sedation and respiratory depression.
ULTRACET should be used with caution and in reduced dosages when administered to patients receiving CNS depressants. Tramadol increases the risk of CNS and respiratory depression in these patients (see Interactions).
Increased Intracranial Pressure or Head Trauma: ULTRACET 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, papillary 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 ULTRACET (see Respiratory Depression as previously mentioned).
Use in Ambulatory Patients: Tramadol may impair the mental and or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patients using this drug should be cautioned accordingly.
Use with Serotoning Re-Uptake Inhibitors: Use ULTRACET with great caution in patients taking SSRIs. Concomitant use of tramadol with SSRI's increases the risk of adverse events, including seizure and serotonin syndrome.
Increase risk of Hepatotoxicity with alcohol use: ULTRACET should not be used concomitantly with alcohol consumption. The use of Ultracet in patients with liver disease is not recommended.
Use with Other Acetaminophen-containing Products: Due to the potential for acetaminophen hepatotoxicity at doses higher than the recommended dose, ULTRACET should not be used concomitantly with other acetaminophen-containing products.
Withdrawal: Withdrawal symptoms may occur if ULTRACET is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Other symptoms that have been seen less frequently with ULTRACET discontinuation include: panic attacks, severe anxiety and paresthesias, tinnitus and unusual CNS symptoms. Clinical experience suggests that withdrawal symptoms may be avoided by tapering ULTRACET at the time of discontinuation.
Physical Dependence and Abuse: ULTRACET contains tramadol as an active ingredient. A portion of the analgesic effect of ULTRACET is attributable to the binding of the active ingredient, tramadol, to the mu-opioid receptor. Upon repeated administration of opioids, tolerance, physical dependence, and psychological dependence may develop, even at recommended dosages. Assess each patient's risk for opioid dependence and abuse prior to prescribing ULTRACET and monitor all patients receiving ULTRACET for development of these behaviors. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g. major depression).
Tramadol may include physic and physical dependence of the morphine-type (μ-opioid). Tramadol 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. Dependence and abuse, including drug-seeking behavior and taking illicit actions to obtain the drug are not limited to those patients with prior history of opioid dependence.
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 very rarely with the use of ULTRACET, usually in patients with predisposing risk factors, such as elderly patients and/or patients using concomitant medications that may cause hyponatremia. In some reports, this hyponatremia appeared to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and resolved with discontinuation of ULTRACET and appropriate treatment (e.g. fluid restriction). During ULTRACET treatment, monitoring for signs and symptoms of hyponatremia is recommended for patients with predisposing risk factors.
Special Precautions
General: The recommended dose of ULTRACET should not be exceeded.
Do not co-administer ULTRACET with other tramadol or acetaminophen-containing products (see Use with other acetaminophen-containing products and Risk of Overdosage under Warnings).
Acute Abdominal Conditions: The administration of ULTRACET may complicate the clinical assessment of patients with acute abdominal conditions.
Use in Renal Disease: ULTRACET has not been studied in patients with impaired renal function. Experience with tramadol suggest 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 ULTRACET be increased not to exceed 2 tablets every 12 hours.
Use in Hepatic Disease: ULTRACET has not been studied in patients with impaired hepatic function. The use of ULTRACET in patients with hepatic impairment is not recommended (see Use with alcohol under Warnings).
Information for Patients: ULTRACET may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
ULTRACET should not be taken with alcohol containing beverages.
The patient should be instructed not to take ULTRACET in combination with other tramadol or acetaminophen-containing products, including over-the-counter preparations.
ULTRACET should be used with caution when taking medications such as 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 (see Use in Pregnancy & Lactation).
The 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 Ability to Drive and Use Machines: ULTRACET may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
Use in Children: The safety and effectiveness of ULTRACET has not been studied in the pediatric population.
Use in 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.
Acute Abdominal Conditions: The administration of ULTRACET may complicate the clinical assessment of patients with acute abdominal conditions.
Use In Pregnancy & Lactation
PREGNANCY: Tramadol 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.
Prolonged use of ULTRACET, or other opioids, during pregnancy may lead to a neonatal opioid withdrawal syndrome. This risk is particularly increased during the last trimester of pregnancy.
BREAST-FEEDING: ULTRACET is not recommended for breast-feeding mothers because its safety in infants and newborns has not been studied.
Adverse Reactions
The most frequently reported events were in the central nervous system and gastrointestinal system.
The most common reported events were nausea, dizziness, and somnolence.
In addition, the following effects have been frequently observed, though the frequency is general 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.
Uncommon reported clinically significant adverse experiences with at least a possible causal link to Ultracet include: Body as a whole: chest pain, rigors, syncope, withdrawal syndrome.
Cardiovascular disorders: hypertension, aggravated hypertension, hypotension.
Central and peripheral nervous sytem: ataxia, convulsions, hypertonia, migraine, aggravated migraine, involuntary muscle contractions, paraesthesia, stupor, vertigo.
Gastrointestinal system: dysphagia, melena, tongue edema.
Hearing and vestibular disorders: tinnitus.
Heart rate and rhythm disorders: arrhythmia, palpitation, tachycardia.
Liver and biliary system: liver test abnormalities.
Metabolic and nutritional disorders: weight decrease.
Psychiatric disorders: amnesia, depersonalization, depression, drug abuse, emotional lability, hallucination, impotence, bad dreams, abnormal thinking.
Red blood cell disorders: anemia.
Respiratory system: dyspnea.
Urinary system: albuminuria, micturition disorder, oliguria, urinary retention.
Vision disorders: abnormal vision.
Other clinically significant adverse experiences 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, shivering and agitation) has been reported with tramadol when used concomitantly with other serotonergic agents such as SSRIs and MAO inhibitors. Post-marketing surveillance of tramadol has revealed rare alterations of warfarin effect, including elevation of prothrombin times. Cases of hyponatremia and/or SIADH have been reported very rarely in patients taking tramadol, usually in patients with predisposing risk factors, such as the elderly or those using concomitant medications that may cause hyponatremia.
Other clinically significant adverse experience previously reported in clinical trials or post-marketing reports with acetaminophen: Allergic reactions (primarily skin rash) or reports of hypersensitivity secondary to acetaminophen are rare and generally controlled by discontinuation of the drug and when necessary, symptomatic treatment. There have been several reports that suggest that acetaminophen may produce hypoprothrombinemia when administered with warfarin like compounds. In other studies, prothrombin time did not change.
Drug Interactions
Use with MAO Inhibitors: The concomitant use of Ultracet with MAO inhibitors, or use within 14 days of their discontination, is contraindicated due to the increased risk of seizures and serotonin syndrome. Animal studies have shown increased deaths with combined administration of MAO inhibitors and tramadol (see Contraindications).
Use with serotonin re-uptake inhibitors: Concomitant use of tramadol with SSRI's increases the risk of adverse events, including seizures and serotonin syndrome. Use caution when administering ULTRACET in patients taking SSRIs and monitor for signs of adverse events.
Central Nervous System (CNS) depressants, including alcohol: The concomitant use of tramadol with central nervous system depressants, such as benzodiazepines and other sedatives/hypnotics, anesthetic agents, phenothiazines, tranquilizers, opioids or alcohol, may produce additive CNS depressant effects, such as profound sedation and respiratory depression. If concomitant use of ULTRACET with a CNS depressant is clinically necessary, prescribe the lowest effective dosages and minimum duration for both drugs, and follow patients closely for signs of respiratory depression.
Use with Carabamazepine: Concomitant administration of tramadol hydrochloride and carbamazepine causes a significant increase in tramadol metabolism. Patients taking carbamazepine may have a significantly reduced analgesic effect from the tramadol component of ULTRACET.
Use with Quinidine: Tramadol is metabolized to M1 by CYP12D6. Concomitant administration of quinidine and tramadol results in increased concentrations of tramadol. 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 Ultracet and these agents are administered concurrently due to reports of increased INR in some patients.
Use with Inhibitors of CYP2D6: In-vitro drug interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 such as fluoxetine, paroxetine, and amitriptyline could result in some inhibition of the metabolism of tramadol.
Use with Cimetidine: Concomitant administration of ULTRACET and cimetidine has not been studied. Concomitant administration of tramadol and cimetidine does not result in clinically significant changes in tramadol pharmacokinetics.
Caution For Usage
Incompatibilities: None known.
Storage
Do not store above 25°C. Store in the original package.
Shelf-Life: 3 years.
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
Tab 3 x 10's.
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