Tramadol-Plekhiko - instructions for use, doses, side effects, contraindications

Opioid synthetic analgesic, which has central action and action on the spinal cord (contributes to the discovery of K + and Ca2 + -channels, causes hyperpolarization of membranes and inhibits pain impulses), enhances the action of sedative drugs. Activates opioid receptors (mu, delta, kappa) on the pre- and postsynaptic membranes of the 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.

It is a racemic mixture of 2 enantiomers - dextrorotatory (+) and levorotatory (-), each of which exhibits a different receptor affinity.

(+) Tramadol is a selective agonist of mu-opioid receptors, and selectively inhibits the reverse neuronal capture of serotonin. (-) Tramadol inhibits the reverse neuronal seizure of norepinephrine. Mono-O-desmethyltramadol (Ml metabolite) also selectively stimulates mu-opioid receptors.

The analgesic effect is due to a decrease in nociceptive activity and an increase in the activity of the antinociceptive systems of the body. In therapeutic doses, it does not significantly affect haemodynamics and breathing, does not change the pressure in the pulmonary artery, slightly slows down the intestinal motility without causing constipation. Has some antitussive and sedative effect. Oppresses the respiratory center, excites the start zone of the vomiting center, the nucleus of the oculomotor nerve.

With prolonged use, the development of tolerance is possible. Analgesic effect develops 15-30 minutes after ingestion and lasts up to 6 hours.

Pharmacokinetics:

Absorption is 100% with intramuscular injection. Time to reach the maximum concentration (TC_m_Oh) with a / m introduction 45 min, Ml metabolite - 3 hours.

Penetrates through the blood-brain barrier and the placenta, 0.1% excreted in breast milk. The volume of distribution with iv injection 203 liters, with oral - 306 liters. Connection with plasma proteins - 20%.

Metabolised in the liver by N- and O-demethylation followed by conjugation with glucuronic acid.Identified 11 metabolites, of which mono-O-desmethyltramadol (Ml) has pharmacological activity. In the metabolism of the drug takes part isoenzyme CYP2D6.

T_1/2 in the second phase -6h (tramadol), 7.9 hours (Ml); in patients older than 75 years - 7.4 h (tramadol); with cirrhosis of the liver - 13.3 ± 4.9 h (tramadol), 18.5 ± 9.4 h (Ml), in severe cases - 22.3 hours and 36 hours, respectively. It is excreted by the kidneys (25-35% unchanged), the average cumulative index of renal excretion is 94%.

Indications:

- moderate and severe pain syndrome of different etiology (postoperative period, trauma, pain in cancer patients);

- anesthesia in the conduct of painful diagnostic and therapeutic measures.

Contraindications:

- hypersensitivity to the drug and other opioids;

- conditions accompanied by respiratory depression or severe central nervous system depression (including alcohol poisoning, hypnotic drugs, narcotic analgesics and other psychoactive drugs);

- simultaneous use of monoamine oxidase inhibitors (and within 14 days after their application);

- pharmacovirus-resistant epilepsy;

- severe renal and / or hepatic insufficiency (creatinine clearance less than 10 ml / min);

- use of tramadol as a drug for the treatment of drug withdrawal;

- pregnancy;

- the period of breastfeeding;

- children's age (up to 1 year).

Carefully:With caution appoint a drug to people with impaired liver and kidney function, drug (especially opioid), alcohol dependence, a violation of consciousness of various genesis, craniocerebral trauma, intracranial hypertension, a violation of consciousness of different genesis, epilepsy, patient against abdominal pain unclear genesis ("acute abdomen").

Dosing and Administration:

The solution for injections is administered intravenously (slowly!), Intramuscularly or subcutaneously.

For adults and teenagers over 14 years of age single dose is 50-100 mg. If after a single application there is no satisfactory analgesia, then after 30-60 minutes, you can repeat the administration of the drug at a dose of 50 mg. In severe pain, 100 mg can be used as the initial dose. If necessary, re-administration is prescribed, but not earlier than 6-8 hours.Usually the daily dose should not exceed 400 mg.

Children aged 1 to 14 years the drug is prescribed in a single dose at a rate of 1-2 mg / kg body weight. It is necessary to select the minimum dose that causes anesthesia. The daily dose should not exceed 4-8 mg / kg or 400 mg per day.

In patients with renal and / or hepatic impairment it is recommended to reduce the dose or lengthen the time interval between doses of the drug. When creatinine clearance is less than 30 ml / min or 0.5 ml / s at the beginning of treatment, doubling the time interval between doses of the drug is recommended.

In elderly patients (65 - 75 years) The recommendations are the same as for renal and hepatic insufficiency.

Patients older than 75 years are recommended to reduce the daily dose to 300 mg.

Side effects:The most common side effects with tramadol are nausea and dizziness.

The cardiovascular system.

Palpitations, tachycardia, orthostatic hypotension or collapse. These effects can occur with intravenous administration and in weakened patients.

Bradycardia, increased blood pressure.

Nervous system.

Dizziness, headache, drowsiness, changes in appetite, paresthesia, tremor, respiratory depression, epileptiform seizures, involuntary muscle contractions, coordination disorders, fainting. In the case of a significant excess of the recommended dose or with the simultaneous use of other drugs that have an effect on the central nervous system, respiratory depression can be observed. Epileptiform seizures can mainly occur after applying high doses of tramadol or with simultaneous use of drugs lowering the threshold of convulsive readiness. In some cases, speech disorders may occur.

Mental disorders.

Hallucinations, confusion, sleep disorders, anxiety and nightmares. After the use of tramadol, there may be various side effects of a mental nature (depending on the personality characteristics of the patient and the duration of treatment). These effects include mood changes (euphoria, sometimes dysphoria), changes in activity (usually a decrease, sometimes an increase), changes in cognitive and sensory perceptions (eg, decision making, perceptual disorders).There may be a development of drug dependence.

Disorders of vision.

Decreased visual acuity. In some cases, mydriasis may occur.

Respiratory system.

Impaired breathing.

There was a deterioration in bronchial asthma; but the cause-and-effect relationship was not established.

Gastrointestinal tract.

Difficulty in swallowing, nausea, constipation, dry mouth, vomiting, vomiting

desires, a feeling of heaviness in the epigastrium, flatulence, diarrhea.

Skin and subcutaneous tissue.

Sweating, itching, rash, hives.

Musculoskeletal system.

Muscle weakness.

Liver and biliary tract.

In several cases there was an increase in the level of liver enzymes. Other: disorders of urination (difficulty with urination and urinary retention), fatigue, allergic reactions (eg, respiratory failure, bronchospasm, wheezing, angioedema) and anaphylaxis.

Violations of the menstrual cycle.

Possible withdrawal symptoms are similar to those when using opioids: agitation, anxiety, nervousness, sleep disorders, hyperkinesia, tremor and gastrointestinal symptoms (abdominal pain, diarrhea, nausea).

Other symptoms that occur with the elimination of tramadol include: panic attacks, severe anxiety, hallucinations, paresthesia, ringing in the ears and paradoxical symptoms from the central nervous system (confusion, hallucinations, depersonalization, derealization, paranoia).

Overdose:

Symptoms: miosis or mydriasis, vomiting, collapse, consciousness up to coma, convulsions, respiratory center depression up to apnea.

Treatment. Providing airway patency. Maintain the respiration and activity of the cardiovascular system depending on the symptomatology present.

The antidote of depression of the respiratory center is naloxone. When convulsions should be intravenously administered drugs benzodiazepine series. Hemodialysis and hemofiltration with an overdose are ineffective. Removal with hemodialysis is about 7%.

Interaction:

The drug is pharmaceutically incompatible with solutions of diclofenac, indomethacin, phenylbutazone, diazepam, flunitrazepam, nitroglycerin. Strengthens the effect of drugs that depress the central nervous system and ethanol, increases the toxicity of digoxin.Inductors of microsomal oxidation (including carbamazepine, barbiturates) reduce the severity of the analgesic effect and the duration of the drug.

Long-term use of opioid analgesics or barbiturates stimulates the development of cross tolerance.

With simultaneous use with tramadol inhibitors of monoamine oxidase, tricyclic antidepressants, bromperidol, cyclobenzoprine, furazolidone, procarbazine, antipsychotic drugs (antipsychotics), the risk of convulsions increases (reduction of the convulsive threshold). Also life-threatening interactions that affect the central nervous system, respiratory and cardiovascular functions are possible.

In some cases, the development of serotonin syndrome associated with the use of tramadol in combination with other herrotonergic substances, such as selective serotonin reuptake inhibitors (SSRIs) or MAO inhibitors, has been noted. Symptoms of serotonin syndrome: confusion, agitation, hyperthermia, sweating, ataxia, hyperreflexia, myoclonus and diarrhea. The abolition of serotonergic drugs causes a rapid relief of symptoms.With the simultaneous use of tramadol and coumarin derivatives (eg, warfarin), careful monitoring of patients is necessary, as some of them increase the prothrombin time with the development of bleeding and subcutaneous hemorrhage.

Anxiolytics, erythromycin, ketoconazole increase the severity of the analgesic effect; The duration of anesthesia increases with their combination with barbiturates. Naloxone activates breathing, eliminating analgesia obtained as a result of the use of opioid analgesics. Quinidine increases the plasma concentration of tramadol and reduces the M1 metabolite content due to competitive inhibition of isoenzyme CYP2D6.

Pre- or post-operative use of an anti-emetic agent of 5-HTZ-one-receptor antagonist increased the need for tramadol in patients with postoperative pain syndrome.

Special instructions:

Care should be taken during vehicle administration for drivers of vehicles and for persons involved in potentially hazardous activities requiring rapid physical and mental reactions.

During treatment with the drug is not recommended to take ethanol. Tramadol has a low potential for dependence development. However, with prolonged use, addiction, physical and mental dependence can develop. In patients with inclinations to drug abuse, or to the development of drug dependence, tramadol treatment should be performed only for short periods of time and under strict medical supervision.

Tramadol is not suitable as a substitute for patients with opioid dependence. Although tramadol is an agonist of opioid receptors, it can not suppress symptoms of morphine withdrawal.

Effect on the ability to drive transp. cf. and fur:Solution for injection 50 mg / ml.

Form release / dosage:By 1 ml or 2 ml in ampoules of colorless glass (type I) with a ring on the neck of the ampoule. For 5 or 10 ampoules together with instructions for use in a cardboard pack.

Packaging:

Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

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

Shelf life:

3 years.

Do not use after the expiry date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N 015374/01

Date of registration:11.08.2009

The owner of the registration certificate:Plethiko Pharmaceuticals Co., Ltd. Plethiko Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

PLETHICO PHARMACEUTICALS, Ltd. India

Representation: & nbspREZLOV ZAO REZLOV ZAO Kazakhstan

Information update date: & nbsp16.09.2015

Illustrated instructions

Instructions

Tramadol-Plekhiko (Tramadol-Plethico)