Tramadol retard instructions for use. Medicinal reference book geotar

international and chemical name:tramadol; (±) -trans-2 - [(dimethyl amino) methyl] -1- (3-methoxyphenyl) cyclohexanol hydrochloride;

basic physical and chemical properties:white oval biconvex film-coated tablets;

composition:1 tablet contains 100 mg of tramadol hydrochloride;

excipients: lactose monohydrate, microcrystalline cellulose, hypromellose 4.000, hypromellose 100.000, hypromellose 6, povidone, colloidal anhydrous silicon dioxide, magnesium stearate, talc, macrogol, titanium dioxide.

Release form

Extended-release tablets.

Pharmacotherapeutic group

Analgesics. Tramadol. ATC code N02A X02.

Pharmacological properties

Pharmacodynamics. Tramadol retard is a strong central analgesic. The analgesic effect is carried out in two ways: it induces weak stimulation central system to inhibit pain by binding to opioid nimi receptors, thereby reducing the sensation of pain, and it also acts on the monoaminergic system by increasing the inhibition of the transmission of pain impulses in the spine. This analgesic effect is the result of the synergistic activity of both mechanisms of action. Tramadol does not cause respiratory depression and cardiovascular disorders. The action comes quickly and lasts several hours. Tramadol retard in the form of sustained release tablets active substance is a special pharmaceutical form that provides a long-term therapeutic hypostatic concentration of tramadol in the blood.

Pharmacokinetics. After oral administration, Tramadol retard is rapidly and almost completely absorbed in the gastrointestinal tract. Therapeutic concentration is reached after about 2 hours, reaches a maximum after 4 hours and lasts for up to 12 hours. Plasma protein binding is 20%. Tramodol penetrates through the placenta, and its concentration in the umbilical blood is 80% of the concentration in the mother's blood.

90% of tramadol and its metabolites are excreted by the kidneys, and the remainder is excreted in the feces. The elimination half-life is 5-6 hours and is the same for tramadol and its metabolites.

Indications for use

Severe to moderate pain of various origins.

Method of administration and dosage

The dose is determined depending on the severity of the patient's pain.

1 - 2 tablets of Tramadol retard twice a day. The interval between dosing should be 12 hours, basically, regardless of the meal, the tablet is taken in the morning and the tablet in the evening, with a small amount of liquid. It is not recommended to use a daily dose of more than 400 mg of Tramadol, except in cases of pain relief in patients with cancer and in patients with severe postoperative pain, for which the daily dose can be increased to 600 mg.

For patients with renal or hepatic impairment, it is recommended to reduce the dose and increase the interval between doses. For patients with creatinine clearance less than 30 ml / min. it is recommended at the beginning of treatment to double the interval between injections.

Side effect

The most common adverse effects are gastrointestinal and central nervous system... They occur in approximately 5-30% of patients taking tramadol in therapeutic doses.

Undesirable effects that occur in more than 5% of patients include dizziness, nausea, constipation, headache, drowsiness, vomiting, itching, stimulation of the central nervous system, asthenia, sweating, shortness of breath, dry mouth, diarrhea.

Others unwanted effectsthat occur in more than 1% of patients:

central nervous system: anxiety, confusion, lack of coordination, euphoria, emotional instability, sleep disturbance;

gastrointestinal tract: abdominal pain, loss of appetite, flatulence;

skin: skin rashes;

genitourinary system: urinary retention, frequent urination, menopausal signs;

cardiovascular system: vasodilation;

sense organs: visual impairment.

Adverse effects that occur in less than 1% of patients and may be associated with the use of tramadol:

central nervous system: convulsions, paresthesia, impaired cognitive function, hallucinations, tremors, amnesia, impaired concentration, impaired gait;

skin: urticaria;

genitourinary system: dysuria, menstrual disorders;

cardiovascular system: syncope, orthostatic hypotension, tachycardia, palpitation, hypertension, cardiovascular collapse;

other undesirable effects: increased muscle tone, impaired swallowing, weight loss.

Contraindications

Hypersensitivity to tramadol or other ingredients of the drug. Extended-release tablets should not be given to children under 14 years of age. Acute intoxication with central nervous system inhibitors (alcohol, antidepressants, antipsychotics, sedatives, anxiolytics, hypnotics). Treatment with MAO inhibitors.

Overdose

When using the drug in doses significantly exceeding the recommended doses, signs of intoxication may occur: impaired consciousness (including coma), generalized convulsions, hypotension, tachycardia, narrowing or dilated pupils, respiratory depression. In case of severe intoxication with tramadol, which is accompanied by loss of consciousness and shallow breathing, it is recommended to administer naloxone, and convulsions must be eliminated internally. intravenous administration diazepam.

Application features

Tramadol can be used to treat opioid hypersensitive patients, but with caution. Tramadol is not recommended for patients prone to abuse (alcoholism, drug abuse and drug dependence).

During treatment, as well as for some time after treatment, it is recommended to carefully monitor patients with cerebral seizures.

Tramadol retard is not used as a substitution therapy for opioid retention.

With prolonged use of tramadol, the possibility of drug dependence cannot be completely excluded.

For patients with renal insufficiency (creatinine clearance less than 30 ml / min), for an increase in the elimination half-life, it is recommended to double the interval between injections at least at the beginning of treatment.

For patients with hepatic impairment due to decreased hepatic clearance, increased serum concentration and increased elimination half-life, it is recommended to reduce the dose or increase the interval between doses.

Tramadol can be used in patients with increased internal cranial pressure (for example, with traumatic brain injury) or pulmonary disease, but with caution.

Pregnancy and lactation

The safety of using the drug during pregnancy has not been established. High doses can be damaging to the fetus and newborn baby. In some urgent cases, the use of the drug is allowed only under close medical supervision and if the expected benefits of treatment for the mother justify possible risk for the fetus.

When using the drug during lactation, it should be borne in mind that approximately 0.1% of the drug passes into breast milk. With a single use of Tramadoluretard, it is generally not necessary to stop breastfeeding.

Influence on the ability to drive a car and other mechanical means

This drug has a powerful effect on psychophysical activity. Therefore, during treatment, patients are prohibited from driving a car or working with mechanical devices.

Interaction with other medicinal products

Tramadol is not recommended for use with MAO inhibitors. With the simultaneous use of tramadol with drugs acting on the central nervous system (anesthetics, antidepressants, antipsychotics, sedatives, anxiolytics, hypnotics), or with alcoholic beverages synergy is possible, which manifests itself in an increase in the sedative effect or a stronger analgesic effect. With simultaneous use with carbamazepine, the metabolism of tramadol slows down, which requires an increase in the dose of tramadol. The simultaneous administration of tramadol and specific serotonin reuptake inhibitors, tricyclic antidepressants and antipsychotics may increase the risk of seizures.

Terms and conditions of zberigan

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children. The shelf life is 5 years.

Composition and release form of the drug

Sustained-release film-coated tablets white or nearly white, round, round, biconvex; in cross section, the core is white or almost white.

Excipients: hypromellose (hydroxypropyl methylcellulose) K15M CR - 64 mg, microcrystalline cellulose (type 200) - 52.8 mg, colloidal silicon dioxide (Aerosil) - 1.6 mg, magnesium stearate - 1.6 mg.

Shell composition: opadry white (85F28751) or another film-forming system - 10 mg: (polyvinyl alcohol - 4 mg, talc - 1.48 mg, macrogol (polyethylene glycol) - 2.02 mg, titanium dioxide - 2.5 mg).

10 pieces. - contour cell packaging (1) - cardboard packs.
10 pieces. - contour cell packages (2) - cardboard packs.
10 pieces. - contour cell packages (3) - cardboard packs.

pharmachologic effect

Opioid, a derivative of cyclohexanol. Non-selective agonist of μ-, Δ- and κ-receptors in the central nervous system. It is a racemate of (+) and (-) isomers (50% each), which are involved in various ways in the analgesic effect. Isomer (+) is a pure agonist of opioid receptors, has a low tropism and does not have a pronounced selectivity in relation to various receptor subtypes. Isomer (-), inhibiting neuronal uptake, activates descending noradrenergic influences. Due to this, the transmission of pain impulses to the gelatinous substance of the spinal cord is disrupted.

Calls out sedation... In therapeutic doses, it practically does not depress respiration. It has an antitussive effect.

Pharmacokinetics

After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract (about 90%). C max is reached 2 hours after oral administration. Bioavailability with a single dose is 68% and increases with repeated use.

Plasma protein binding - 20%. Tramadol is widely distributed in tissues. V d after oral administration and intravenous administration is 306 l and 203 l, respectively. Penetrates through the placental barrier at a concentration equal to the concentration of the active substance in plasma. 0.1% is excreted in breast milk.

It is metabolized by demethylation and conjugation of up to 11 metabolites, of which only 1 is active.

It is excreted by the kidneys - 90% and through the intestines - 10%.

Indications

Moderate and severe pain syndrome of various origins (including with malignant tumors, acute heart attack myocardium, neuralgia, trauma). Carrying out painful diagnostic or therapeutic procedures.

Contraindications

Acute intoxication with alcohol and drugs that have a depressing effect on the central nervous system, children under 1 year of age, hypersensitivity to tramadol.

Dosage

For adults and children over 14 years of age, a single dose for oral administration is 50 mg, rectally - 100 mg, intravenously slowly or intramuscularly - 50-100 mg. If, with parenteral administration, the effectiveness is insufficient, then after 20-30 minutes, oral administration in a dose of 50 mg is possible.

For children aged 1 to 14 years, the dose is set at the rate of 1-2 mg / kg.

The duration of treatment is determined individually.

Maximum dose: adults and children over 14 years old, regardless of the route of administration - 400 mg / day.

Side effects

From the side of the central nervous system: dizziness, weakness, drowsiness, confusion; in some cases - seizures of cerebral genesis (with intravenous administration in high doses or with the simultaneous administration of antipsychotics).

From the side of cardio-vascular system: tachycardia, orthostatic hypotension, collapse.

From the side digestive system: dry mouth, nausea, vomiting.

From the side of metabolism: increased sweating.

From the musculoskeletal system: muscle weakness.

Drug interactions

With simultaneous use with drugs that have a depressing effect on the central nervous system, with ethanol, an increase in the inhibitory effect on the central nervous system is possible.

With simultaneous use with MAO inhibitors, there is a possibility of developing serotonin syndrome.

With simultaneous use with reuptake inhibitors, tricyclic antidepressants, antipsychotics, and other drugs that lower the seizure threshold, the risk of seizures increases.

With simultaneous use, the anticoagulant effect of warfarin and phenprocoumon is enhanced.

With simultaneous use with decreases the concentration of tramadol in the blood plasma and its analgesic effect.

With simultaneous use with paroxetine, cases of the development of serotonin syndrome, seizures are described.

With simultaneous use with sertraline, cases of the development of serotonin syndrome have been described.

With simultaneous use, there is a possibility of a decrease in the analgesic effect of opioid analgesics. Long-term use opioid analgesics or barbiturates stimulates the development of cross-tolerance.

Naloxone activates respiration, eliminating analgesia after using opioid analgesics.

special instructions

It should be used with caution in case of seizures of central genesis, drug addiction, confusion, in patients with impaired renal and liver function, as well as in hypersensitivity to other agonists of opioid receptors.

Tramadol should not be used for longer than the period justified from a therapeutic point of view. In the case of long-term treatment, the possibility of drug dependence cannot be ruled out.

Avoid combination with MAO inhibitors.

During the period of treatment, avoid alcohol consumption.

Influence on the ability to drive vehicles and use mechanisms

Pregnancy and lactation

During pregnancy, long-term use of tramadol should be avoided due to the risk of developing addiction in the fetus and the occurrence of withdrawal syndrome in the neonatal period.

If necessary, use during lactation ( breastfeeding) it must be borne in mind that tramadol is excreted in small quantities in breast milk.

Pediatric use

Contraindicated in childhood up to 1 year. For children aged 1 to 14 years, the dose is set at the rate of 1-2 mg / kg.

Tramadol in the form dosage forms prolonged action should not be used in children under 14 years of age.

With impaired renal function

It should be used with caution in patients with impaired renal function.

For violations of liver function

It should be used with caution in patients with impaired liver function.

Instructions for medical use

drug

TRAMADOL RETARD

Tradename

Tramadol retard

International non-proprietary name

Tramadol

Dosage form

Sustained-release film-coated tablets, 100 mg

Composition

One tablet contains

active substance - tramadol hydrochloride 0.1 g

excipients: hypromellose 4.000 cps, hypromellose 100.000 cps, microcrystalline cellulose, lactose monohydrate, povidone, anhydrous colloidal silicon dioxide, magnesium stearate,

shell composition: hypromellose 6 cps, talc, macrogol 6000, titanium dioxide (E 171)

Description

Oval tablets, film-coated white, biconvex. At the break, the tablets have a white, uneven surface

Pharmacotherapeutic group

Analgesics. Opioids. Other opioids. Tramadol

ATX code N02AX02

Pharmacological properties

Pharmacokinetics

Suction

After oral administration, tramadol is rapidly and almost completely absorbed into
the gastrointestinal tract. The average oral bioavailability is approximately 68%. Food intake does not significantly affect the rate and extent of absorption. Whey concentration 100 ng / L (minimum effective analgesic concentration) is reached approximately 0.7 hours after ingestion and lasts for 9 hours.

The therapeutic concentration after taking the extended-release tablets is reached after about 2 hours, reaches a maximum after 4 hours and lasts for 12 hours.

Distribution
The volume of distribution after oral and intravenous administration is approximately 306 and 203 liters, respectively. Plasma protein binding is about 20%. Tramadol crosses the placenta and its concentration in the umbilical cord blood is 80% of the concentration in the mother's blood.

Metabolism
Approximately 85% of tramadol is metabolized. Tramadol is metabolized by N- and O-demethylation. With the exception of the O-demethylated metabolite (M1), all metabolites are pharmacologically inactive.

Withdrawal

90% of tramadol and its metabolites are excreted through the kidneys, the rest is excreted in feces. The half-life is 5-6 hours and is the same for both tramadol and its metabolites.

In case of impaired renal function, the volume and rate of excretion decrease, therefore, in patients with creatinine clearance less than 0.5 ml / s, it is recommended to reduce the dosage and increase the intervals between dosing.

The metabolism of tramadol and M 1 is reduced in patients with severe cirrhosis of the liver, and therefore the dosage should be adjusted.

In patients over 75 years of age, the peak concentration of tramadol in blood plasma increases slightly and the half-life is longer, therefore dose adjustment is required.

Pharmacodynamics

The analgesic effect of tramadol is carried out in two ways: it induces weak stimulation of the central system for inhibition of pain by binding to μ-opioid receptors, thereby reducing the sensation of pain, and it also acts on the monoaminergic system by increasing inhibition of the transmission of pain impulses in the spine. This analgesic effect is the result of the synergistic activity of both mechanisms of action. The intensity of the analgesic effect is comparable to pethidine and codeine and ten times lower than that of morphine.

Tramadol in therapeutic doses has practically no effect on the cardiovascular system (it does not have a depressing effect and does not increase pressure in pulmonary artery), does not cause spasm of smooth muscles, release of histamine, therefore, anaphylactic reactions are rare. The effect on respiration is minimal and can only appear at higher doses. The development of addiction and addiction is also very rare.

Indications for use

Moderate and severe pain syndrome of various etiologies:

With injuries

With malignant tumors

When performing painful diagnostic or therapeutic procedures

Postoperative pain

Method of administration and dosage

The dosage should be selected individually and adjusted depending on the severity of the pain syndrome.

Adults and adolescents over 12 years old

1 - 2 tablets 100 mg Tramadol retard twice a day. The interval between doses is 12 hours, usually in the morning and in the evening, regardless of food intake and with plenty of fluids.

Patients with renal failure /for sick on hemodialysis and patients with liver failure

In patients with renal insufficiency and / or with hepatic insufficiency, tramadol excretion is slowed down. In such patients, it is necessary to individually select the interval between doses of the drug in accordance with the patient's well-being.

Elderly patients

In elderly patients up to 75 years old, without clinical manifestation hepatic or renal failure, dose adjustment is not required. Elderly patients after the age of 75 years may slow down the elimination of the drug. In such cases, it is necessary to increase the interval between doses of the drug in accordance with the patient's well-being.

Children

Tramadol retard, film-coated tablets with prolonged release, is not approved for use in children under 12 years of age.

Side effects

Very often (\u003e 1/10)

• dizziness
• nausea

Often (\u003e 1/100 -<1/10)

• headache
• clouding of consciousness
• dry mouth, vomiting, constipation
• sweating
• extreme tiredness

Uncommon (\u003e 1/1000 -<1/100)

• palpitations, tachycardia, orthostatic hypotension, cardiovascular

vascular insufficiency

• urge to vomit, gastrointestinal irritation (eg, feeling

heaviness in the stomach, flatulence), diarrhea

• itching, rash, urticaria

Rarely (\u003e 1 / 10,000 -< 1/1000)

• hallucinations, confusion
• sleep disturbances, nightmares
• euphoria, sometimes dysphoria
• changes in activity (usually decrease, sometimes increase)
• changes in cognitive and sensory perception (eg, decision making, cognitive disorders)
• drug addiction
• changes in appetite
• paresthesia, tremor
• respiratory depression
• seizures of cerebral origin (observed in almost all cases,

when antipsychotics were prescribed at the same time)

• involuntary muscle contractions, impaired coordination of movements
• fainting, bradycardia, arterial hypertension
• epileptiform seizures
• decreased visual acuity
• dyspnea
• muscle weakness
• urinary disorders (difficulty urinating, dysuria and urinary retention)
• allergic reactions (dyspnea, bronchospasm, wheezing, angioedema), anaphylaxis

Very rarely (< 1/10 000)

• increased activity of liver enzymes

In isolated cases

• difficulty swallowing fluids

Respiratory depression can occur when the recommended dose is significantly exceeded or when other drugs that affect the central nervous system are used concurrently

(see section "Drug interactions").

Epileptiform seizures mainly occur after the use of high doses of Tramadol or with the simultaneous use of drugs that lower the seizure threshold (see section "Drug interactions").

In patients suffering bronchial asthma, deterioration is possible. However, a causal relationship with the use of tramadol has not been established.

Possible withdrawal symptoms are similar to those with opiates. These symptoms include agitation, anxiety, nervousness, sleep disturbances, hyperkinesia, tremors, and gastrointestinal symptoms. Other symptoms that are very rare when Tramadol is discontinued include: panic attacks, severe anxiety, hallucinations, paresthesia, ringing in the ears.

Contraindications

• hypersensitivity to tramadol and / or drug ingredients

and other opioid analgesics

• acute intoxication with central nervous system depressants

(alcohol, antidepressants, antipsychotics, sedatives,

tranquilizers, hypnotics)

• severe renal failure (creatinine clearance less than 10 ml / min)
• severe liver failure
• simultaneous use of MAO inhibitors (and within 14 days

after canceling them)

• patients with epilepsy, the course of which cannot adequately

monitored

• drug withdrawal syndrome
• children and adolescents up to 12 years old

Drug interactions

With the simultaneous use of tramadol with drugs that have a depressing effect on the central nervous system, and with ethanol, mutual strengthening of their action is possible.

Application carbamazepine, barbiturates and other inducers of microsomal enzymes can lead to a weakening of the analgesic effect of tramadol.

Long-term use of tramadol stimulates the development of cross-tolerance to other opioid analgesics.

Anxiolytics increase the severity of the analgesic effect of tramadol, the duration of anesthesia increases when combined with barbiturates. Naloxone activates breathing, eliminating analgesia after using opioid analgesics.

With the simultaneous use of tramadol with inhibitors MAO, furazolidone, procarbazine, neuroleptics there is a risk of seizures (lowering the seizure threshold

Quinidine increases the plasma concentration of tramadol and reduces the content of the metabolite of mono-O-desmethyltramadol due to competitive inhibition of the isoenzyme CYP2D6.

With joint or preliminary using cimetidine (an enzyme inhibitor) clinically significant interactions are unlikely.
Combining opioid receptor agonists / antagonists(eg, buprenofine, nalbuphine, pentazocine) and tramadol is not recommended, since the analgesic effect of a pure agonist is reduced under these conditions.

Perhaps the development of serotonin syndrome associated with the use of tramadol in combination with other serotonergic substances, such as selective serotonin reuptake inhibitors. Symptoms of serotonin syndrome: confusion, dysphoria, hyperthermia, sweating, ataxia, hyperreflexia, myoclonus, and diarrhea. Withdrawal of serotonergic drugs causes rapid relief of symptoms.

With the simultaneous use of tramadol with selective inhibitors serotonin reuptake (SSRI), tricyclic antidepressants, antipsychotics, and other drugs that lower the seizure threshold (eg, bupropion, mirtazapine, tetrahydrocannabinol), the risk of seizures increases.

Particular care should be taken with the simultaneous use of tramadol and coumarins (eg , warfarin) due to the risk of a decrease in prothrombin time with the development of bleeding and bruising.

Other inhibitorsCYP3 A4 , eg , ketoconazole and erythromycin, can inhibit the metabolism of tramadol (N-demethylation) and active O-desmethyltramadol.

A limited number of studies have found that pre- or postoperative use of the antiemetic agent, the 5-HT3 antagonist, ondansetron, increased the need for tramadol for postoperative pain.

special instructions

Tramadol should be used with extreme caution

With kidney and liver diseases

In patients with traumatic brain injury

With increased intracranial pressure

In patients with epilepsy

In patients with opioid dependence

For abdominal pain of unknown origin ("acute abdomen")

With confusion of unclear origin

In case of disorders of the respiratory center or respiratory function

In shock

Tramadol has a low potential for the development of addiction. With prolonged use, addiction, mental and physical dependence can develop. In patients with a tendency to abuse drugs or with dependence on drugs tramadol treatment should only be carried out for a short period under the strict supervision of a physician.

In addition, tramadol may increase the risk of seizures in patients taking other drugs, which lowers the seizure threshold. Tramadol treatment for patients with epilepsy or a predisposition to seizures should be considered only if compelling circumstances exist. Patients with cerebral seizures should be closely monitored during and for some time after treatment. Tramadol is not suitable as substitution therapy opioid dependence, does not suppress morphine withdrawal symptoms. With long-term use of tramadol, the development of drug dependence and cross-tolerance to other opioid drugs cannot be completely ruled out. Therefore, only the doctor should decide whether to continue or interrupt treatment. Patients should be warned about the need to adhere to the dose and duration of treatment prescribed by the doctor and not to transfer the drug to others. Long-term treatment of chronic pain syndrome should be carried out only under strict indications. The use of alcohol should be excluded when using any dosage form of tramadol.

Pregnancy

There is insufficient clinical data on the use of the drug in women during pregnancy and lactation. Tramadol crosses the placental barrier. Very high doses of tramadol affect development internal organs, bone growth and neonatal mortality rate. There were no teratogenic effects of the drug. Tramadol does not affect uterine contractility during labor.

Tramadol should not be used during pregnancy.

Prescribing the drug is possible only for health reasons, the use of tramadol should be limited only to a single dose.

Lactation

Tramadol should not be used during lactation.

During lactation, the appointment of tramadol is possible only for health reasons, the use should be limited only to a single dose.

After a single use of tramadol, there is usually no need to interrupt breastfeeding. In this regard, after a single use of tramadol, it is necessary to express the first portion breast milk and do not use expressed milk for feeding.

With the introduction of the drug to the mother, the newborns have a risk of changes in the frequency of respiratory movements, which is usually not clinically significant.

Features of the effect of the drug on the ability to manage vehicle or potentially dangerous mechanisms

During the period of treatment, it is forbidden to drive a car or work with potentially dangerous mechanisms.

Overdose

Symptoms of a tramadol overdose are similar to those that may occur with the use of other centrally acting analgesics (opioids).

Symptoms:constriction or dilation of pupils, vomiting, collapse, fall blood pressure, palpitations, depression of consciousness (up to coma), epileptic seizures, difficulty breathing, up to a stop (apnea).

Treatment:

Basic general measures

Diagnostics (breathing, blood circulation, consciousness), maintenance / restoration of vital functions of respiration and blood circulation, gastric lavage.

Special measures

Convulsions: protection of the patient from concomitant bruises, intravenous administration of diazepam or other benzodiazepines in the form of injections.

Hypotension: horizontal position of the patient's body, if necessary, intravascular infusion of electrolyte solutions, vasopressors.

Anaphylactic shock: contact a doctor emergency assistance; give the patient a horizontal position, raise lower part body, start an intensive infusion of electrolyte solutions.

Heart failure: immediate cardiopulmonary resuscitation, contact an emergency doctor.

Stop breathing: immediate cardiopulmonary resuscitation, contact an emergency doctor, naloxone is an antidote to depression of the respiratory center.

Dosage Form: & nbsp

Sustained-release film-coated tablets.

Composition:

1 tablet contains:

CORE:

Active substance:

Tramadol hydrochloride 0.1 g

Excipients:

Hypromellose 4,000 kpc, hypromellose 100,000 kpc, microcrystalline cellulose, lactose monohydrate, povidone, colloidal silicon dioxide, anhydrous, magnesium stearate,

SHELL:

Hypromellose 6 kpc, talc, macrogol 6000, titanium dioxide.

Description: Oval biconvex white film-coated tablets. At the break, the tablets have a white, uneven surface. Pharmacotherapeutic group:Analgesic with a mixed mechanism of action. ATX: & nbsp

N.02.A.X.02 Tramadol

Pharmacodynamics:

The drug belongs to the list No. 1 of potent substances of the Standing Committee on Drug Control of the Ministry of Health of the Russian Federation.

An opioid synthetic analgesic with central action and action on the spinal cord (promotes the opening of K and Ca 2+ channels, causes hyperpolarization of membranes and inhibits the conduct of pain impulses), enhances the effect of sedatives(JIC). Activates opioid receptors (mu-, delta-, kappa-) on the pre- and postsynaptic membranes of afferent fibers of the nociceptive system in the brain and gastrointestinal tract. Slows down the destruction of catecholamines, stabilizes their concentration in the central nervous system (CNS). It is a racemic mixture of two enantiomers - dextrorotatory (+) and levorotatory (-), each of which exhibits a different receptor affinity from the others. is a selective agonist of µ-opioid receptors, and also selectively inhibits neuronal reuptake of serotonin. inhibits the reverse neuronal seizure of norepinephrine. Mono-O-desmethyltramadol(M 1 -metabolite) also selectively stimulates µ-opioid receptors.

The analgesic effect is due to a decrease in the activity of the nociceptive and an increase in the antinociceptive systems of the body.

In therapeutic doses, it does not significantly affect hemodynamics and respiration, does not change the pressure in the pulmonary artery, slightly slows down intestinal peristalsis, without causing constipation. It has some antitussive and sedative effects. Inhibits the respiratory center, excites the starting zone of the vomiting center, the nucleus of the oculomotor nerve.

With prolonged use, tolerance may develop. The analgesic effect develops 15-30 minutes after ingestion and lasts up to 6 hours.

Pharmacokinetics:

After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract. The average bioavailability after oral administration is about 65-68%. Simultaneous food intake does not significantly affect the duration and completeness of absorption. The therapeutic concentration is observed approximately 2 hours after taking the drug, reaches a maximum after 4 hours and lasts up to 12 hours.

The volume of distribution is 306 liters. Connection with plasma proteins - 20%. penetrates the placental and blood-brain barriers.

In the liver, about 85% of tramadol is metabolized. byN - and O-demethylation followed by conjugation with glucuronic acid. 11 metabolites have been identified, of which mono-O-desmethyltramadol(M 1) possesses pharmacological activity. The isoenzyme is involved in the metabolism of the drugCYP 2 D 6.

90% of tramadol and its metabolites are excreted by the kidneys (25-35% unchanged), 10%

- intestines. The half-life (T 1/2) for tramadol and its metabolites is 6

7 o'clock.

With renal failure, T 1/2 is lengthened, with CC less than 30 ml / min or 0.5 ml / s, a dose reduction and an increase in the time intervals between doses of the drug are recommended.

Tramadol metabolism andM 1 decreased in patients with severe liver cirrhosis (with cirrhosis of the liver, tramadol is 13.3 ± 4.9 h and T1 / 2 M1 - 18.5 ± 9.4 h, in severe cases - 19.5 h and 43.2 h, respectively ), in connection with which the concentration of the drug in the blood plasma increases and T 1/2 increases, therefore, such patients need a dose reduction and an increase in the time intervals between doses of the drug. In patients over 75 years of age, the value of the maximum concentration of the drug in the blood plasma slightly increases and T 1/2 of tramadol (7.4 h) is lengthened. In this case, you need to reduce the dose of the drug.

Delayed release of the active substance from the tablet leads to its slow, constant entry into the blood plasma and long-term action... This makes it possible to take the drug twice a day. About 7% of the drug is excreted by hemodialysis.

Indications: Moderate and severe pain syndrome of various etiologies ( postoperative period, trauma, pain in cancer patients, during diagnostic or therapeutic manipulations). Contraindications:

Hypersensitivity to tramadol, other components of the drug and other opioids.

Conditions accompanied by respiratory depression or severe depression of the central nervous system (CNS) (acute intoxication with alcohol, hypnotics and sedatives, narcotic analgesics, antidepressants, anxiolytics, neuroleptics, psychotropic drugs).

Severe hepatic or renal impairment.

Simultaneous use of monoamine oxidase (MAO) inhibitors and within two weeks after their withdrawal.

Children under 14 years of age.

Hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.

Carefully:

Dysfunction of the kidneys and liver, traumatic brain injury (TBI), intracranial hypertension, convulsive syndrome, drug dependence, incl. to opioids, alcohol dependence, impaired consciousness of various origins.

Pregnancy and lactation:The safety of using the drug during pregnancy has not been studied. High doses of tramadol can be unsafe for the fetus and newborn. Therefore, it is not recommended for use during pregnancy. , prescribed before or during childbirth, does not affect uterine contractility. In newborns, slow breathing may occur, which is not clinically significant. excreted in very small amounts (about 0.1% of the intravenous dose) in breast milk. Therefore, it should not be used while breastfeeding. Method of administration and dosage:

Inside, with a sufficient amount of liquid, regardless of meal time. The dosage regimen of the drug is selected individually, depending on the severity of the pain syndrome and the sensitivity of the patient. The duration of treatment is determined individually; the duration of therapy must be justified. Tramadol retard is recommended for adults and children over 14 years of age, 1-2 tablets of 100 mg twice a day (morning and evening). The drug should be taken at twelve hour intervals, unless otherwise recommended by the attending physician. The maximum daily dose is 400 mg (4 tablets).

In patients with renal and / or hepatic insufficiency, it is recommended to reduce the dose or lengthen the interval between doses of the drug. In Patients with creatinine clearance (CC) less than 30 ml / min or 0.5 ml / s, it is recommended at the beginning of treatment to double the time interval between taking the drug.

In elderly patients (aged 65 to 75 years), the recommendations are the same as for renal and liver failure... Patients over the age of 75 are advised to reduce the daily dose to 300 mg.

Side effects:

From the central (CNS) and peripheral nervous system: very often (\u003e 1/10)

- dizziness; often (\u003e 1/100 to< 1/10) - вертиго, головная боль; нечасто (от > 1/1000 to< 1/100) - беспокойство, сонливость, анорексия; редко (от >1/10000 to< 1/1000)

- paradoxical stimulation of the central nervous system (nervousness, agitation, anxiety, tremor, muscle spasms), hallucinations, euphoria, emotional lability, sleep disturbances, cognitive function, depression, amnesia, impaired coordination of movement, seizures of central origin (with the simultaneous administration of antipsychotics), paresthesias, impaired concentration, impaired gait, asthenia, weakness, increased fatigue, lethargy, confusion.

From the digestive system: very often (\u003e 1/10) - nausea; often (\u003e 1/100 to< 1/10) - запор, рвота, диарея, сухость во рту; нечасто (от > 1/1000 to< 1/100) - диспепсия, метеоризм, боль в животе; редко (от >1/10000 to< 1/1000) - затруднение при глотании.

On the part of the cardiovascular system: rarely (from\u003e 1/10000 to< 1/1000) - проявления вазодилятацйи (тахикардия, ортостатическая гипотензия, коллапс, синкопе); артериальная гипертензия; сердцебиение.

Allergic reactions: infrequently (from\u003e 1/1000 to< 1/100) - кожная сыпь,.кожный зуд; редко (от >1/10000 to< 1/1000) - ангионевротический отек, крапивница, экзантема, буллезная сыпь.

On the part of the musculoskeletal system: rarely (from\u003e 1/10000 to< 1/1000) - повышение мышечного тонуса.

From the side genitourinary system: infrequently (from\u003e 1/1000 to< 1/100) - задержка мочи, частое мочеиспускание, нарушение menstrual cycle, symptoms of menopause; rarely (from\u003e 1/10000 to< 171000) - дизурия, затруднение мочеиспускания.

From the senses: very rare (from\u003e 1/10000 to< 1/1000) - нарушение зрения, вкуса.

From the respiratory system: very rare (from\u003e 1/10000 to< 1/1000) - одышка. Others: often (\u003e 1/100 to< 1/10) - повышенное потоотделение; редко (от >1/10000 to< 1/1000) - снижение веса.

With prolonged use, drug dependence may develop; with abrupt cancellation, the development of a withdrawal syndrome is not excluded.

Overdose:

Symptoms: impaired consciousness (including coma), miosis, vomiting, collapse, convulsions, decreased blood pressure, tachycardia, constriction or dilation of the pupil, depression of the respiratory center, apnea.

Treatment:ensuring passability respiratory tract, maintenance of respiration and activity of the cardiovascular system; opiate-like effects can be stopped with morphine antagonists (), convulsions - with drugs from the benzodiazepine group (). Hemodialysis or hemofiltration is ineffective.

Interaction:

Tramadol retard should not be used simultaneously with MAO inhibitors and within 2 weeks after their withdrawal.

Strengthens the effect of drugs that have a depressing effect on the central nervous system (alcohol, hypnotics and sedatives, narcotic analgesics, antidepressants, anxiolytics, antipsychotics, psychotropic drugs).

Microsomal oxidation inducers (including barbiturates) increase the metabolism of tramadol, as a result, the severity of the analgesic effect and the duration of action decrease. In this case, a dose adjustment of Tramadol retard is necessary. Long-term use of opioid analgesics or barbiturates stimulates the development of cross-tolerance. Anxiolytics increase the severity of the analgesic effect. activates breathing, eliminating analgesia after using opioid analgesics.

Isolated cases of serotonergic syndrome (agitation, fever, sweating, ataxia, hyperreflexia, myoclonus, or diarrhea) have been reported while taking tramadol and serotonergic drugs (eg, antidepressants). Concomitant use with selective serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, MAO inhibitors, furazolidone and procarbazine may increase the risk of seizures.