Santramol

Tramadol hydrochloride, paracetamol.

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

Pharmacology: Tramadol is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal test, at least two complementary mechanism appear applicable: binding of parent and M1 metabolite to μ-opioid receptors and weak inhibition of 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 up is to 6 times more potent than Tramadol in producing analgesia and 200 times more potent in μ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both Tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound.
Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in-vitro, as have some other opioid analgesics. These mechanism may contribute independently to the overall analgesic profile of Tramadol.
Apart from analgesia, Tramadol administration may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating, and pruritus) similar to that of other opioids.
Paracetamol is a non-opiate, non-salicylate analgesic.

SANTRAMOL is indicated for short-term treatment of acute pain.

Unless otherwise prescribed, SANTRAMOL should be administered as follows: Adults and Children Over 16 Years: The maximum single dose of SANTRAMOL is 1 to 2 caplets every 4 to 6 hours as needed for pain relief up to a maximum of 8 caplets per day.
SANTRAMOL can be administered without regard to food.
Children Below 16 Years: The safety and effectiveness of SANTRAMOL 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.

SANTRAMOL is combination product. The clinical presentation of overdose may include the signs and symptoms of Tramadol toxicity, Paracetamol toxicity or both. The initial symptoms seen within the first 24 hours following an Paracetamol overdosage may include: gastrointestinal irritability, anorexia, nausea, vomiting, malaise, pallor, and diaphoresis.
Human Experience: Tramadol: Serious potential consequences of overdosage of the Tramadol component are respiratory depression, lethargy, coma, seizure, cardiac arrest, and death.
Paracetamol: Paracetamol in massive overdosage may cause hepatic toxicity in some patients. Early symptoms following a potentially hepatotoxic overdosage may include: gastrointestinal irritability, anorexia, nausea, vomiting, malaise, pallor, and diaphoresis. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to72 hours post-ingestion.
Treatment: A single or multiple overdose with SANTRAMOL 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 overdosage because it removes less than 7% of the administered dose in a 4-hour dialysis period.
In treating an overdosage of SANTRAMOL, primary attention should be given to maintaining adequate ventilation along with general supportive treatment. Measures should be taken to reduce drug absorption. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated dose are used, the the cathartic may be included with alternate doses as required. Hypotension is usually hypovolemic in etiology and should respond to fluids. Vasopressors and other supportive measures should be employed as indicated. A cuffed endo-tracheal tube should be inserted before gastric lavage of the unconscious patient and, when necessary, to provide assisted respiration.
In adult and pediatric patients, any individual presenting with an unknown amount of Paracetamol ingested or with a questionable or unreliable history about the time of ingestion should have a plasma Paracetamol level drawn and be treated with acetylcysteine. If an assay cannot be obtained and the estimated Paracetamol ingestion exceeds 7.5 to 10 grams for adults and adolescents or 150 mg/kg for children, dosing with N-acetylcysteine should be initiated and continued for a full course of therapy.

SANTRAMOL is contraindicated: In patients who have previously demonstrated hypersensitivity to Tramadol, Paracetamol, 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.

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 Other opioids.
Administration of Tramadol may enhance the seizure risk inpatients 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 seizures (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In Tramadol overdose, naloxone administration may increase the risk of seizures.
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 increased risk and therefore should not receive SANTRAMOL (see CONTRAINDICATIONS).
Respiratory Depression: Patient with significant respiratory depression or acute severe bronchial asthma are at increased risk of life-threatening respiratory depression when treated with opioids. SANTRAMOL should only be used in this patient population in a monitored setting and with the availability of resuscitative equipment.
Administer SANTRAMOL cautiously in patients at risk for respiratory depression. In these patients, alternative non-opioid analgesics should be considered. When large doses of Tramadol are administered with anesthetic medications or alcohol, respiratory depression may result. Respiratory depression should be treated as an overdose. If naloxone is to be administered, use cautiously because it may precipitate seizures (see Seizure Risk as previously mentioned, and OVERDOSAGE).
Interaction With Central Nervous System (CNS) Depressants, including Alcohol: The concomitant use of Tramadol (the active substance component in SANTRAMOL) with CNS depressants, including alcohol may cause additive CNS depressant effects, including profound sedation and respiratory depression.
SANTRAMOL should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers, or sedative hypnotics. Tramadol increases the risk of CNS and respiratory depression in these patients (see INTERACTIONS).
Increased Intracranial Pressure or Head Trauma: SANTRAMOL 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 SANTRAMOL (see Respiratory Depression as previously mentioned).
Use with Serotonin Reuptake Inhibitors: Use SANTRAMOL with great caution in patients taking SSRIs. Concomitant use of Tramadol with SSRIs increases the risk of adverse events, including seizure and serotonin syndrome.
Increase Risk of Hepatotoxicity with Alcohol Use: SANTRAMOL should not be used concomitantly with alcohol consumption. The use of SANTRAMOL in patients with liver disease is not recommended.
Use with other Paracetamol-containing Products: Due to the potential for Paracetamol hepatotoxicity as doses higher than the recommendation dose, SANTRAMOL should not be used concomitantly with other Paracetamol-containing products.
Withdrawal: Withdrawal symptoms may occur if SANTRAMOL 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 SANTRAMOL discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience suggest that withdrawal symptoms may be avoided by tapering SANTRAMOL at the time of discontinuation.
Physical Dependence and Abuse: SANTRAMOL contains Tramadol as an active ingredient. A portion of the analgesic effect of SANTRAMOL is attributable to the binding of the active ingredient Tramadol to the μ-opioid receptor. Upon repeated administration of opioids, tolerance physical dependence and psychological dependence may develop even at recommended dosages. Asses each patient's risk for opioid dependence and abuse prior to prescribing SANTRAMOL and monitor all patients receiving SANTRAMOL 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 induce 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 overdosage, primary attention should be given to maintaining adequate ventilation along with general supportive treatment (see OVERDOSAGE).
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.

General: The recommended dose of SANTRAMOL should not be exceeded.
Do not co-administer SANTRAMOL with other Tramadol or Paracetamol products. (See Use with other Paracetamol-containing products and Risk of Overdosage under WARNINGS).
Acute Abdominal Conditions: The administration of SANTRAMOL may complicate the clinical assessment of patients with acute abdominal conditions.
Information for Patients: SANTRAMOL may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
SANTRAMOL should not be taken with alcohol containing beverages.
The patients should be instructed not to take SANTRAMOL in combination with other Tramadol or Paracetamol containing products, including over-the counter preparations.
SANTRAMOL should be used with caution when taking medications such as tranquilizers, hypnotics or other opiate containing analgesics.
The patients should be instructed to inform the physician if they are pregnant, think they might become pregnant, or are trying to become pregnant.
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.
Serious Skin Reaction: Serious skin reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Steven-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN), are reported to be very rare in patients receiving Paracetamol.
Patients should be informed about signs of a serious skin reaction, and if there is use of the drug should be stopped since the first signs of redness appear on the skin or other symptoms associated with hypersensitivity.
Effects on Ability to Drive and Use Machines: SANTRAMOL may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
Use in Renal Disease: SANTRAMOL has not been studied in patients with impaired renal function. Experience with Tramadol suggests that impaired renal function results in a decreased rate and extent of excretion of Tramadol and its active metabolite, M1. In patients with creatinine clearances of less than 30 mL/min, it is recommended that the dosing interval of SANTRAMOL be increased not to exceed 2 caplets every 12 hours.
Use in Hepatic Disease: SANTRAMOL has not been studied in patients with impaired hepatic function. The use of SANTRAMOL in patients with hepatic impairment is not recommended. (See Use with Alcohol under WARNINGS).
Use in Children: The safety and effectiveness of SANTRAMOL has not been studied in the pediatric population.
Use in Elderly: In general, dose selection for an elderly patients should be cautions, reflecting the greater frequency of decreased hepatic, renal, or cardiac function; of concomitant disease and multiple drug therapy.

Tramadol has been shown to cross the placenta.
There are no adequate and well-controlled studies in pregnant women. Safe use in pregnancy has not been established. SANTRAMOL is not recommended for breast-feeding mothers because its safety in infants and newborns has not been studied.
Prolonged use of SANTRAMOL, or other opioids during pregnancy may lead to neonatal opioid withdrawal syndrome. The risk is particularly increased during the last trimester of pregnancy.

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 SANTRAMOL include: Body as a whole: chest pain, rigors, syncope, withdrawal syndrome.
Cardiovascular disorders: hypertension, aggravated hypertension, hypotension.
Central and peripheral nervous system: ataxia, convulsions, hypertonia, migraine, aggravated migraine, involuntary muscle contractions, 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 product 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 serotoninergic 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 hypoglycemia have been reported but are very rare in patients taking Tramadol. Most reports occur in patients with predisposing risk factors, including diabetes or renal insufficiency, or in elderly patients. 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 taking concomitant drugs that can cause hyponatremia.
Other clinically significant adverse experiences previously reported in clinical trials or post-marketing reports with Paracetamol: Allergic reactions (primarily skin rash) or reports of hypersensitivity secondary to Paracetamol are rare and generally controlled by discontinuation of the drug, and when necessary, symptomatic treatment. 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.

Use with MAO Inhibitors: The concomitant use of SANTRAMOL with MAO Inhibitors or use within 14 days of their discontinuation, 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 Reuptake Inhibitors: Concomitant use of Tramadol with SSRI's increases the risk of adverse reactions, including seizures and serotonin syndrome.
Use caution when administering SANTRAMOL inpatients taking SSRI's and monitor for signs of adverse reactions.
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 SANTRAMOL 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 Carbamazepine: 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 SANTRAMOL.
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 SANTRAMOL and warfarin like compounds are administered concurrently due to reports of increased INR in some patients.
Use with Inhibitor CYP2D6: In-vitro drug interaction studies in human liver microsomes indicated 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 SANTRAMOL and Cimetidine has not been studied. Concomitant administration of Tramadol and Cimetidine does not result in clinically significant changes in Tramadol pharmacokinetics.

Store below 30°C.

Analgesics (Opioid)

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

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