Rutram® (Rutram)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceParacetamol + TramadolParacetamol + Tramadol
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  • Zaldiar
    pills inwards 
    Grünenthal GmbH     Germany
  • Rutram®
    pills inwards 
    BALTIMOR FK, LLC     Russia
  • TRAMACETTE
    capsules inwards 
    K.O. Ромфарм Компани С.Р.Л.     Romania
    • Dosage form: & nbspfilm-coated tablets
    Composition:

    Composition per 1 tablet:

    Active substances:

    Paracetamol (Paracetamol DS) - 361.1 mg (corresponding to paracetamol 325 mg and pregelatinized corn starch 36.1 mg)

    Tramadol (tramadol hydrochloride) 37.5 mg

    Excipients:

    Microcrystalline cellulose - 45.4 mg

    Carboxymethyl starch sodium (type A) 28.8 mg

    Silicon dioxide colloidal anhydrous - 2.4 mg

    Magnesium stearate 4.8 mg

    The cover of Advantia Prime 144900 BAAO 1 - 15.0 mg

    Composition of the cover Advantia Prime 144900BA01:

    Gipromellose 2910 6sP (hydroxypropylmethylcellulose) - 9.375 mg

    Macrogol 400 (polyethylene glycol) - 1.875 mg

    Titanium dioxide (E 171) - 3,600 mg

    The iron oxide is yellow (E 172) - 0.150 mg.

    Description:Tablets of oblong form, biconvex, covered with a film membrane, from light yellow to light yellow with a slight brownish hue. On the fracture - a homogeneous mass from white to almost white.
    Pharmacotherapeutic group:Analgesic combined (analgesic with a mixed mechanism of action + analgesic non-narcotic agent)
    ATX: & nbsp

    N.02.A.X   Other opioids

    N.02.A.X.52   Tramadol in combination with other drugs

    Pharmacodynamics:

    Combined drug containing tramadol and paracetamol. Tramadol - an opioid analgesic with a central mechanism of action, a non-selective complete agonist of μ-, δ- and κ-opioid receptors with a high affinity for μ-receptors. Another mechanism of action of tramadol, which enhances its analgesic effect, is the suppression of norepinephrine reuptake by neurons and increased release of serotonin.

    Tramadol has antitussive action. In contrast to morphine in therapeutic doses does not depress respiration, almost does not affect intestinal motility. Influence on the cardiovascular system is weakly expressed. The analgesic potential of tramadol is 1/10 -1/6 of the activity of morphine.

    The exact mechanism of analgesic action of paracetamol is not fully established, most likely, it affects the central nervous system (CNS) and peripheral tissues.

    Combination tramadolparacetamol is an analgesic II step in the treatment of pain according to the classification of the World Health Organization, is applied as prescribed by the doctor.

    Pharmacokinetics:

    Tramadol and paracetamol quickly and almost completely absorbed in the gastrointestinal tract. Tramadol is used in racemic form, blood is defined as (+) and (-) forms and metabolite Ml. Although tramadol quickly absorbed after ingestion, its absorption is somewhat slower, and the duration of the half-life is longer than that of paracetamol. After a single oral administration of tramadol hydrochloride / paracetamol tablets (37.5 mg / 325 mg), the maximum plasma tramadol concentrations of 64.3 / 55.5 ng / ml (+ and - forms, respectively) are determined after 1.8 hours, and paracetamol 4.2 μg / ml after 0.9 h. The half-life period (T1/2) is 5.1 / 4.7 h for tramadol [(+) -tramadol / (-) - tramadol] and 2.5 h for paracetamol.

    Suction

    Tramadol is quickly and almost completely absorbed after ingestion. The average absolute bioavailability is approximately 75% with a single admission of 100 mg tramadol inside. With repeated administration of tramadol, bioavailability increases to approximately 90%. After taking tramadolparacetamol Inside the absorption of paracetamol occurs quickly and almost completely, mainly in the small intestine.Maximum concentrations of paracetamol in the blood plasma are achieved within one hour and do not change with simultaneous application with tramadol. Receiving tramadol +paracetamol inside during meals does not have a significant effect on the maximum concentration of active substances in the blood plasma or on the degree of absorption of tramadol or paracetamol in the gastrointestinal tract, which allows you to take tramadolparacetamol, both during a meal, and regardless of food intake.

    Distribution

    Tramadol has a high affinity for the tissues (Vd,β=203 + 40 l). Binding to plasma proteins is approximately 20%.

    Paracetamol is widely distributed in most body tissues (except for fat). Its apparent volume of distribution is about 0.9 l / kg. A relatively small part (about 20%) of paracetamol binds to blood plasma proteins.

    Metabolism

    Tramadol after oral administration is actively metabolized. About 30% of the dose is excreted unchanged in the urine, 60% of the dose is excreted as metabolites. Tramadol metabolized by O-demethylation (catalyzed by isoenzyme CYP2D6) to the metabolite Ml (O-demethyltramadol) and by N-detylation (catalyzed by isoenzyme CYP3A) to metabolite M2 (Na-methylated metabolite). Metabolite Ml metabolized by N-detylation followed by conjugation with glucuronic acid.

    The half-life of the metabolite Ml is 7 hours.

    Analgesic activity of metabolite Ml surpasses tramadol. The concentration of metabolite M1 in blood plasma is several times lower than the concentration of tramadol, therefore, for multiple applications the value of this metabolite in the overall clinical effectiveness of the drug does not change. Paracetamol is metabolized primarily in the liver in two main ways: glucuronidation and sulfation. The latter can be quickly saturated when taking doses of the drug, exceeding therapeutic. An insignificant part of the dose (less than 4%) is metabolized by cytochrome P450 to the active metabolite, N-acetyl-benzoquinonimine, which, when the drug is used in therapeutic doses, is quickly rendered harmless by reduced glutathione and is excreted in the urine after conjugation with cysteine ​​and mercapturic acid.With an overdose of paracetamol, the concentration N-acetyl-benzoquinonimine in blood plasma significantly increases.

    Excretion

    Tramadol and its metabolites are mainly excreted in the urine. In adults, the half-life of paracetamol is approximately 2 to 3 hours. The half-life of the drug in children is shorter; in newborns and patients with cirrhosis of the liver is slightly longer. Paracetamol is mainly excreted from the body by the dose-dependent formation of glucuronated and sulfo-conjugated derivatives.

    Less than 9% of paracetamol is excreted unchanged in the urine. With renal failure, the half-life of tramadol and paracetamol increases.

    Indications:

    Pain syndrome of medium and high intensity of different etiology (if necessary combined therapy with tramadol and paracetamol).

    Contraindications:

    - Hypersensitivity to any of the components of the drug;

    - acute intoxication with alcohol; hypnotics; narcotic analgesics; opioids and psychotropic drugs;

    - simultaneous use of monoamine oxidase (MAO) inhibitors and within two weeks after their withdrawal;

    - severe hepatic insufficiency;

    - severe renal failure (creatinine clearance (CK) <10 ml / min);

    - children under 12 years of age (no special studies to evaluate efficacy and safety in this age group);

    - pregnancy;

    - the period of breastfeeding;

    - epilepsy, not controlled by treatment.

    Carefully:

    Rutram® should be administered with caution to patients with opioid dependence, with craniocerebral trauma, patients prone to convulsive syndrome, with diseases of the bile ducts, to patients in shock, oppression of unclear origin, respiratory depression or respiratory center depression, with intracranial hypertension; during general anesthesia with enflurane and dinitrogen oxide; patients with alcoholic liver damage; patients prone to seizures or taking other medications that lower the threshold of convulsive readiness; simultaneous use of opioid agonist-antagonists (nalboufine, buprenorphine, pentazocine).

    Pregnancy and lactation:

    BVariability

    The use of Rutram® during pregnancy is not recommended,since one of the active substances is tramadol.

    Paracetamol

    Epidemiological studies in which paracetamol was used in pregnant women, did not reveal any negative consequences. However, when using paracetamol in pregnancy, it is recommended that you consult your doctor beforehand.

    Tramadol

    At present, there is insufficient data to evaluate the safety of tramadol in pregnant women. The appointment of tramadol before or during labor does not affect the contractile capacity of the uterus, but it can cause changes in the frequency of respiratory movements in newborns, which is not clinically significant. Chronic use of tramadol in pregnant women can lead to the development of symptoms of "cancellation" in a newborn.

    Breastfeeding period

    The use of Rutram® during breastfeeding is not recommended, since one of the active substances is tramadol.

    Paracetamol

    Paracetamol is excreted in breast milk in quantities that are not clinically significant. In the period of breastfeeding, paracetamol is not contraindicated.

    Tramadol

    In breast milk, 0.1% of the maternal dose of tramadol is found. At a daily maternal dose of 400 mg of tramadol, in the postpartum period in breast milk, up to 3% of the maternal dose of tramadol is detected. Concerning tramadol should not be given during breastfeeding, or, alternatively, breastfeeding should be discontinued during the administration of tramadol.

    In the case of a single application of tramadol, termination of breastfeeding is not required.

    Dosing and Administration:

    Take inside. Swallow the whole tablet with a sufficient amount of water. You can not break or chew the pill.

    The dose is selected individually depending on the severity of the pain syndrome and the patient's response to ongoing therapy. In this case, you should always choose the minimum effective dose.

    The maximum daily dose is 8 tablets (equivalent to 300 mg of tramadol and 2600 mg of paracetamol).

    The interval between Rutram® should not be less than 6 hours.

    Dosing regimen:

    Adults and adolescents (12 years and over)

    The recommended initial dose is 2 tablets (equivalent to 75 mg of tramadol and 650 mg of paracetamol).

    If repeated or prolonged use of Rutram® is required, treatment should be carried out under close supervision of the physician (if possible with interruptions in treatment courses) to determine whether to continue therapy.

    Pediatric population (up to 12 years)

    Special studies to evaluate the effectiveness and safety of Rutram® in this age group was not conducted.

    Rutram® is not recommended for use in children under 12 years of age.

    Elderly patients

    In patients under the age of 75 years, in the absence of clinical manifestations of hepatic and renal insufficiency, dose adjustment is not required. In patients older than 75 years, excretion slows down. In this regard, if necessary, the interval between doses of the drug should be increased.

    Renal failure / dialysis

    The drug Rutram® is contraindicated in patients with severe renal insufficiency (CC <10 mL / min). In patients with moderate renal insufficiency (KK 10-30 ml / min), the interval between oral administration should be increased to 12 hours. Since hemodialysis or hemofiltration tramadol is very slow, the administration of the drug after the dialysis procedure to maintain an analgesic effect is usually not required.

    Liver failure

    The drug Rutram® is contraindicated in patients with severe hepatic impairment. With hepatic failure of moderate severity, excretion of tramadol from the body is slow. In such patients, the interval between doses should be increased according to the patient's condition.

    Side effects:

    More than 10% of patients with a combination of tramadol and paracetamol have nausea, dizziness and drowsiness.

    The incidence of adverse reactions listed below was determined according to the following (World Health Organization classification): very often -> 1/10; often from> 1/100 to <1/10; infrequently - from> 1/1000 to <1/100; rarely - from> 1/10 000 to <1/1000; very rarely - from <1/10 000; the frequency is unknown (the frequency can not be estimated from the available data).

    Disorders of the psyche: often confusion, mood changes, anxiety, nervousness, euphoria, sleep disturbances; infrequently - depression, hallucinations, nightmares; rarely - delirium, drug dependence; very rarely - abuse (postmarketing observations).

    Impaired nervous system: very often - dizziness, drowsiness; often - headache, tremor; infrequent - involuntary contractions of muscles, paresthesia, amnesia; rarely - ataxia, convulsions, fainting, speech disorders.

    Disorders from the side of the organ of vision: rarely - "blurred" vision, miosis, mydriasis.

    Hearing disorders and labyrinthine disturbances: infrequent - ringing in the ears.

    Heart Disease: infrequent - a feeling of palpitation, tachycardia, arrhythmia.

    Vascular disorders: infrequently - arterial hypertension, hot flushes.

    Disturbances from the respiratory system, organs of the thorax and mediastinum: infrequently - shortness of breath.

    Disorders from the gastrointestinal tract: very often - nausea; often - vomiting, constipation, dry mouth, diarrhea, abdominal pain, indigestion, flatulence; infrequently - dysphagia. melena.

    Disturbances from the skin and subcutaneous tissues: often - sweating, itchy skin; infrequently - skin reactions (rashes, hives).

    Disorders from the kidneys and urinary tract: infrequently - albuminuria, disorders of urination (dysuria and urinary retention).

    General disorders and disorders at the site of administration: infrequently - chills, pain in the chest.

    Impact on laboratory and instrumental research results: infrequently - increased activity of transaminases; frequency is unknown - hypoglycemia.

    The occurrence of the following undesirable reactions, known to be associated with the use of tramadol or paracetamol, can not be ruled out.

    Tramadol:

    - Orthostatic hypotension, bradycardia, collapse;

    - a change in the warfarin effect, including an increase in prothrombin time;

    - allergic reactions with respiratory symptoms (such as dyspnea, bronchospasm, wheezing, angioedema) and anaphylaxis;

    - change in appetite, motor weakness, respiratory depression;

    - mental disorders of varying severity and nature (depending on the type of person and duration of treatment). These include mood changes (usually euphoria, sometimes dysphoria), changes in activity (usually fatigue, less increased physical activity), impairment of cognitive functions and perceptions (eg, decision making, perception disorders);

    - reported a possible exacerbation of asthma symptoms, although a causal relationship was not established;

    - the symptoms of the "withdrawal" syndrome can be manifested as anxiety, anxiety, nervousness, insomnia, hyperkinesia, tremor and disorders from the gastrointestinal tract. Other symptoms that were extremely rare with a sharp discontinuation of tramadol treatment include panic attacks, anxiety, hallucinations, paresthesia, ringing in the ears, and unusual CNS symptoms.

    Paracetamol:

    side effects are rare, possible: hypersensitivity reactions to the drug, including skin rash; hematopoiesis disorders including thrombocytopenia and agranulocytosis, however, a causal relationship with paracetamol has not been established;

    - there is evidence that simultaneous use of paracetamol with indirect anticoagulants (eg, warfarin) may lead to hypoprothrombinemia; in other studies, prothrombin time did not change;

    - in very rare cases, serious skin reactions have been reported.

    Overdose:

    Symptoms of drug overdose may include symptoms of an overdose of both tramadol and paracetamol or both.

    Symptoms of an overdose of tramadol

    With an overdose of tramadol, symptoms may occur when an overdosage of other opioid analgesics occurs, for example: miosis, vomiting, collapse, impaired consciousness up to coma, convulsions, respiratory failure until breathing stops.

    Symptoms of an overdose of paracetamol

    Overdosage is more often observed in childhood. Symptoms of an overdose of paracetamol in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Lesions of the liver can occur 12-48 hours after an overdose of paracetamol. There may be violations of glucose metabolism and metabolic acidosis. With a significant overdose, liver failure can progress to encephalopathy, coma, and death. Acute renal failure with acute tubular necrosis can develop even in the absence of severe liver damage. Heart rhythm disturbances and pancreatitis are possible.

    In adults, liver damage is possible after ingestion of 7.5-10 g or more of paracetamol. It has been established that an excessive amount of a toxic metabolite (which, when applied with paracetamol in recommended doses, is rendered harmless by glutathione),irreversibly binds to the liver tissue.

    Treatment

    - immediate admission to a specialized department;

    - maintenance of respiratory function and circulation;

    - Before the beginning of therapy it is necessary to conduct a blood test to determine the concentration of tramadol and paracetamol in the blood plasma and to determine biochemical markers of liver damage;

    - laboratory determination of biochemical markers of liver damage is performed when a patient receives an overdose and repeats every 24 hours. There is an increase in the activity of liver enzymes in the blood plasma: aspartate aminotransferase (ACT), alanine aminotransferase (ALT), which is normalized within one or two weeks;

    - emptying the stomach, causing vomiting (if the patient is conscious) or performing a gastric lavage;

    - it is necessary to ensure the patency of the airways and maintain the function of the cardiovascular system, if breathing is abused naloxone, in case of seizures - diazepam. Diazepam should be used with caution, as it may increase the risk of respiratory depression;

    - tramadol is poorly excreted from blood serum during hemodialysis or hemofiltration,therefore, hemodialysis or hemofiltration is not an effective method of therapy of a tramadol overdose.

    When symptoms of paracetamol overdose occur, an immediate start of therapy is required. Even in the absence of early symptoms of an overdose, the patient should be urgently hospitalized for medical care. Gastric lavage is required if, within the preceding 4 hours, an adult or adolescent took ≥ 7.5 g of paracetamol or a child ≥ 150 mg / kg of paracetamol. After 4 hours after an overdose it is necessary to determine the concentration of paracetamol in the blood plasma in order to assess the likelihood of developing toxic hepatitis (according to a nomogram of paracetamol). The most effective use of acetylcysteine ​​intravenously within the first 8 hours after an overdose. Nevertheless, acetylcysteine should be prescribed even after 8 hours after an overdose, until the end of therapy. If you suspect a massive overdose, you should immediately begin the injection of acetylcysteine. In addition, general maintenance therapy is required.

    Regardless of the dose of paracetamol, the antidote of paracetamol (acetylcysteine) should be started inside or intravenously as soon as possible. If possible, within the first 8 hours after an overdose.

    Interaction:

    Contraindicated concomitant use

    - with MAO inhibitors (non-selective, A and B-selective).

    Possible development of serotonin syndrome or symptoms similar to the clinical picture of serotonin syndrome; diarrhea, tachycardia, sweating, tremors, confusion, coma. Rutram® may be prescribed no earlier than 2 weeks after the abolition of MAO inhibitors.

    It is not recommended to use simultaneously

    - with alcohol. Alcohol potentiates the sedative effect of opioid analgesics, impaired concentration, the ability to drive and work with machinery. It is necessary to avoid the use of alcoholic beverages and medicinal products. preparations containing alcohol;

    - with carbamazepine and other inducers of microsomal liver enzymes. Possible decrease in the effectiveness and duration of analgesic effects, due to a decrease in the concentration of tramadol in the blood plasma;

    - with agonist antagonists or partial agonists of opioid receptors (buprenorphine, nalboufine, pentazocine).It is possible to reduce the analgesic effect due to competitive blocking of receptors, the risk of development of the "withdrawal" syndrome.

    Caution is necessary when simultaneously appointing

    - with drugs that reduce the threshold of convulsive readiness (such as bupropion, mirtazapine, tetrahydrocannabinol), selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, tricyclic antidepressants, and antipsychotics. There may be seizures;

    - with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SSRIs), MAO inhibitors. tricyclic antidepressants and mirtazapine. Perhaps the development of serotonin syndrome: involuntary muscle contractions, oculogic crisis with agitation or increased sweating, tremor and hyperreflexia, arterial hypertension and an increase in body temperature> 38 ° C in combination with an oculogic crisis. The abolition of serotonergic drugs causes rapid disappearance of symptoms.The necessary therapy is determined by the clinical picture and the severity of the symptoms;

    - with other opioids (including antitussives and agents for the treatment of withdrawal syndrome), benzodiazepines and barbiturates. Combination with these drugs increases the risk of breathing, which can be fatal in case of an overdose;

    - with other drugs depressing the central nervous system, such as other opioids (including antitussives and drugs for the treatment of withdrawal), barbiturates, benzodiazepines, anxiolytics, hypnotics, antidepressants with sedatives, blockers H1-receptors with sedative effect, antipsychotics, antihypertensive drugs with a central mechanism of action, thalidomide and baclofen. These drugs can increase the CNS depression. Reducing concentration can make driving and working with machinery dangerous;

    - with indirect anticoagulants (for example, warfarin). Periodic monitoring of prothrombin time is required in accordance with standards of medical practice, since it is possible to increase the international standardized ratio (INR);

    - with antiemetic agents of the group of serotonin 5-HT3 receptor blockers (for example, ondansetron). Co-administration requires higher doses of tramadol in patients with postoperative pain syndrome.

    Special instructions:

    Precautions for use

    Paracetamol is hepatotoxic in high doses. To avoid accidental overdose, patients should be informed that the recommended dose should not be exceeded or at the same time other drugs containing paracetamol (including those sold without a prescription) or tramadol, without consulting a doctor.

    Tramadol can cause a withdrawal syndrome, even when used in therapeutic doses and for a short time. Gradual reduction of the dose, especially after prolonged use, prevents the occurrence of the "withdrawal" syndrome. In patients with opioid dependence or drug abuse in history, treatment should be conducted under close supervision of the doctor with interruptions in treatment courses.

    Tramadol is not used as an agent for the treatment of the "withdrawal" syndrome in patients with opioid dependence.Although tramadol is an agonist of opioid receptors, he can not suppress the "cancellation" syndrome.

    Do not use tramadol at the initial stages of the surgical stage of anesthesia, since the introduction of tramadol during general anesthesia with enflurane and dinitrogen oxide can be accompanied by spontaneous memories of intraoperative events. Exceeding the dose of paracetamol can lead to hepatotoxicity. In patients with non-cirrhotic alcoholic liver damage, the risk of overdose with paracetamol is increased. It is possible to develop a convulsive syndrome in the appointment of tramadol to patients prone to seizures or taking other medications that lower the threshold of convulsive readiness (eg, selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, analgesics with a central mechanism of action or preparations for local anesthesia). In patients with drug-controlled epilepsy or patients prone to seizure syndrome, Rutram® can be used only for vital signs. The occurrence of convulsive syndrome is possible in such patients with admission tramadol in the recommended therapeutic dose. The risk increases significantly when the maximum allowable doses of the drug are exceeded.

    Effect on the ability to drive transp. cf. and fur:

    Because the tramadol may cause drowsiness and dizziness, aggravated by taking alcohol and drugs that depress the central nervous system, patients taking this medication should refrain from driving and working with potentially dangerous mechanisms requiring rapid psychomotor reactions and increased attention.

    Form release / dosage:

    The film-coated tablets are 325 mg + 37.5 mg.

    Packaging:

    10 tablets are placed in a contour mesh box made of a polyvinylchloride film and aluminum foil.

    1, 2, 3, 5, 6 or 9 contour mesh packages together with the instruction for use are placed in a pack of cardboard for consumer containers.

    Storage conditions:

    In a sheltered spot, at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004781
    Date of registration:03.04.2018
    Expiration Date:03.04.2023
    The owner of the registration certificate:BALTIMOR FK, LLCBALTIMOR FK, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp25.04.2018
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