Tramadol - instructions for use, dose, side effects, contraindications

shell capsule: titanium dioxide -0.67849 mg, dye quinoline yellow [E 104] - 0.183502 mg, dye sunset yellow [E 110] - 0.001862 mg, gelatin - up to 38 mg.

Description:

Hard gelatin capsules No. 4, lid and body opaque, yellow.

The contents of capsules are powder from white to almost white.

Pharmacotherapeutic group:An analgesic with a mixed mechanism of action.

ATX: & nbsp

N.02.A.X.02 Tramadol

Pharmacodynamics:

Tramadol is an opioid synthetic analgesic with central action and action on the spinal cord (it facilitates the discovery of potassium K + and Ca2 + calcium channels, causes hyperpolarization of membranes and inhibits pain impulses), enhances the action of sedatives. 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 (GI tract).

Slows down the destruction of catecholamines, stabilizes their concentration in the central nervous system (CNS).

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

(+)Tramadol is a selective agonist of mu-opioid receptors, and selectively inhibits reverse neuronal seizure of serotonin. (-)Tramadol inhibits the reverse neuronal seizure of norepinephrine.Mono-O-desmethyltramadol (Ml metabolite) also selectively stimulates mu-opioid receptors. The affinity of tramadol for opioid receptors is ten times weaker than that of codeine, and 6000 times weaker than morphine. Expression of analgesic action is 5-10 times weaker than morphine. Analgesic effect is due to a decrease in nociceptive activity and an increase in 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 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 - 90%, bioavailability - 75% when taken orally (increases with repeated use). The time to reach the maximum concentration of TCmax after ingestion of the capsules is 2 hours, the Ml metabolite is 3 hours.Penetrates through blood-brain and placental barriers, 0.1% is excreted in breast milk. The volume of distribution is 306 liters. Connection with plasma proteins - 20%. In the liver, it is metabolized by N- and O-demethylation followed by conjugation with glucuronic acid. 11 metabolites have been identified, of which mono-O-desmethyltramadol (Ml) has pharmacological activity. The half-life (T1 / 2) in the second phase is 6h (tramadol), 7.9 h (mono-O-desmethyltramadol); 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 hours (mono-O-desmethyltramadol), in severe cases -22.3 hours and 36 hours, respectively; with chronic renal failure (creatinine clearance (CK) less than 5 ml / min) - 11 ± 3.2 h (tramadol), 16.9 ± 3 h (mono-O-desmethyltramadol), in severe cases - 19.5 h and 43.2 h respectively. It is excreted by the kidneys (25-35% unchanged) the average cumulative index of renal excretion - 94%. About 7% is excreted by hemodialysis.

Indications:Pain syndrome of moderate and severe intensity of various etiology (including postoperative period, trauma, pain in cancer patients). Anesthesia when performing painful diagnostic or therapeutic manipulations.

Contraindications:

- Hypersensitivity to tramadol or one of the excipients.

- Conditions accompanied by respiratory depression or severe central nervous system depression (alcohol poisoning, hypnotics, narcotic analgesics, psychotropic drugs).

- Severe hepatic and / or renal failure (CC less than 10 mL / min).

- Simultaneous use of monoamine oxidase inhibitors (MAO) (and two weeks after their cancellation).

- In pregnancy and during lactation, use is only possible for life indications, the use should be limited only to one-time administration.

- Risk of suicide, addiction to substance abuse.

- Pharmacoresistant epilepsy.

- Children's age (up to 14 years).

Carefully:

- With caution and under the supervision of a physician, the drug should be used for patients with impaired renal and liver function fuquency, with craniocerebral trauma, with a disturbance of consciousness of various genesis, convulsions, intracranial hypertension, epilepsy, and persons with drug dependence for opioids, alcohol addicts , in patients with a pain in the abdominal cavity of an unknown genesis ("acute" abdomen), with renal failure (CC 10 to 30 ml / min), simultaneous

designation with selective serotonin reuptake inhibitors (some antidepressants and drugs (LC) reduces appetite), tricyclic antidepressants, other tricyclic compounds (e.g., promethazine) protivomigrenoznymi LC (triptans), narcotic analgesics, neuroleptics and others. LC lowering threshold convulsive readiness.

Pregnancy and lactation:

There is still no data on the safety of tramadol when it is used by pregnant women.

Use of the drug during pregnancy and lactation is possible only when the intended benefits to the mother outweighs the potential risk to the fetus and child.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:Tramadol is used according to the doctor's prescription, dosing regimen of the drug is selected individually, depending on the severity of the pain syndrome and the sensitivity of the patient. Duration of treatment is determined individually, do not prescribe the drug beyond the term justified from a therapeutic point of view.

For adults and adolescents, over 14 years - single dose is 50-100 mg. If after a single dose there was no satisfactory analgesia, then after 30-60 minutes you can repeat taking the drug at a dose of 50 mg. In severe pain, 100 mg can be used as the initial dose. If necessary, appoint again, but not earlier than 6-8 hours. The maximum daily dose should not exceed 400 mg.

In elderly patients (aged 75 years and older) in connection with the possibility of delayed excretion, the interval between injections of the drug can be increased in accordance with individual characteristics. The recommended daily dose of 300 mg (6 capsules of 50 mg).

In patients with kidney and liver disease tramadol may last longer (possibly extending T1 / 2). For such patients, the doctor may recommend an increase in the interval between the administration of single doses. With QC less than 30 ml / min and in patients with liver failure 12 hours interval between taking the next dose of the drug is needed.

In case of impaired renal function - The maximum daily dose should not exceed 200 mg (4 capsules of 50 mg). Since hemodialysis removes only 7% of the drug from the plasma, dialysis patients are prescribed regular doses even on dialysis day.

Patients suffering from cirrhosis of the liver are recommended 50 mg every 12 hours (100 mg per day).

Tramadol should not be prescribed for longer than it is therapeutically necessary.

Side effects:

From the central and peripheral nervous system: increased sweating, headache, dizziness, weakness, increased fatigue, inhibition, paradoxical stimulation of the central nervous system (nervous system, agitation, anxiety, tremor, muscle spasms, euphoria, emotional lability, hallucinations), drowsiness, confusion, impaired coordination motion, convulsions of the central genesis (with the simultaneous appointment of antipsychotics - neuroleptics), depression, amnesia, cognitive impairment, paresthesia, unsteadiness of gait. 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 application of high doses of tramadol or with the simultaneous use of drugs that reduce the threshold of convulsive readiness.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, flatulence, abdominal pain, constipation or diarrhea, difficulty in swallowing, in several cases, increased activity of liver enzymes, destructive changes in the liver. From the cardiovascular system (CVS): the manifestation of vasodilation - tachycardia, orthostatic hypotension, fainting, collapse, bradycardia and increased blood pressure.

Allergic reactions: urticaria, itching, exanthema, bullous rash; very rarely - anaphylactic reaction, bronchospasm, worsening of the course of bronchial asthma.

From the side of the urinary system: difficulty urinating, dysuria, urinary retention.

On the part of organs feelings: a violation of visual acuity, sometimes mydriasis, a violation of taste.

From the respiratory system: shortness of breath, respiratory depression, pulmonary edema.

Other: violation of the menstrual cycle.

With prolonged use - the development of drug dependence. With a sharp cancellation - the syndrome of "cancellation": agitation, anxiety, nervousness, sleep disturbance, hyperkinesia, tremor and symptoms from the digestive tract (abdominal pain, diarrhea, nausea).

Overdose:

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

Treatment: airway patency. Maintaining respiration and CAS activities, opioid-like effects can be stopped with naloxone, seizures - with benzodiazepine.

Interaction:Strengthens the effect of drugs (LS), having a depressing effect on the central nervous system, and ethanol, increases the toxicity of digoxin. Inductors of microsomal oxidation (incl. carbamazepine, barbiturates) reduces the severity of the analgesic effect and the duration of the action. Long-term use of opioid analgesics or barbiturates stimulates the development of cross tolerance. Due to the increased risk of seizures, the simultaneous use of carbamazepine and tramadol is not recommended.

Anxiolytics increase the severity of the analgesic effect; the duration of analgesia increases with combination with barbiturates.

Naloxone activates breathing, eliminating analgesia after the use of opioid analgesics.

MAO inhibitors, furazolidone, procarbazine, antipsychotic JIC (neuroleptics) increase the risk of seizures (reduction of the convulsive threshold).

Quinidine increases the plasma concentration of tramadol and reduces the M1 metabolite due to competitive inhibition of the CYP2D6 isoenzyme. Inhibitors of the CYP2D6 isoenzyme (such as fluoxetine, paroxetine and amitriptyline) reduce the metabolism of tramadol.

Selective serotonin reuptake inhibitors, serotonin reuptake inhibitors and norepinephrine, tricyclic antidepressants, MAO inhibitors, antimigrenous drugs (triptans), and LCs that disrupt the metabolism of tramadol (inhibitors of the CYP2D6 and CYP3A4 isoenzymes), when combined with tramadol, can cause serotonin syndrome.

Symptoms of serotonin syndrome: confusion, agitation, hyperthermia, sweating, ataxia, hyperreflexia, myoclonus and diarrhea. The abolition of serotonergic drugs causes a rapid relief of symptoms.

Selective serotonin reuptake inhibitors (some antidepressants and LS that reduce appetite), tricyclic antidepressants, other tricyclic compounds (for example, promethazine), antimigrenous drugs (triptans), narcotic analgesics, MAO inhibitors, neuroleptics, etc. LS, reducing the threshold of convulsive readiness, increase the risk of seizures.

With the simultaneous use of tramadol and indirect anticoagulants of coumarin derivatives (for example, warfarin), careful monitoring of patients is necessary. in some of them, the prothrombin time increases with the development of bleeding and subcutaneous hemorrhage.

The pre- or post-operative use of an anti-emetic agent-antagonist of 5-HTZ-serotonin receptors increased the need for tramadol in patients with postoperative pain syndrome.

Special instructions:Do not use Tramadol for the treatment of the syndrome of "withdrawal" of drugs. With increased time intervals apply Tramadol in elderly patients. Under careful medical supervision and in reduced doses should be used Tramadol against the background of the action of funds for anesthesia, sleeping pills and psychotropic drugs. It is forbidden to use ethanol when treated with Tramadol.

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

When using Tramadol, it is necessary to refrain from driving vehicles and practicing potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Capsules 50 mg.

Packaging:For 10 capsules in PVC / aluminum blister. 2 blisters with instructions for use in a pack of cardboard.

Storage conditions:Store in a dry, protected from light place at a temperature of 15 to 25 ° C.

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

KEEP OUT OF THE PREPARATION FOR THE CHILDREN!

Shelf life:4 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016053 / 02

Date of registration:03.11.2009

The owner of the registration certificate:Hemofarm ADHemofarm AD Serbia

Manufacturer: & nbsp

HEMOFARM, A.D. Serbia

Representation: & nbspHEMOFARM A.D. HEMOFARM A.D. Serbia

Information update date: & nbsp16.09.2015

Illustrated instructions

Instructions

Tramadol (Tramadol)