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

Tramadol is an opioid synthetic analgesic with central action and action on the spinal cord (contributes to the discovery of K + and Ca 2+ 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.

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

It is a racemic mixture of 2 enantiomers - dextrorotatory (+) and left-rotating (-), 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-opinoid receptors.

The 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.

Pharmacokinetics:

Bioavailability - 100% with parenteral administration.

TSmah in blood plasma with intramuscular injection - 45 min, Ml metabolite - 3 hours.

Penetrates through the blood-brain barrier and the placenta, 0.1% excreted in breast milk.

Connection with plasma proteins - 20%.

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

The half-life (T_1/2) for tramadol and its metabolites is 6-7 hours. With renal insufficiency T_1/2 lengthens. In chronic renal failure (creatinine clearance less than 5 ml / min) T_1/2 - 11 ± 3.2 h (tramadol), 16.9 ± 3 h (mono-O-desmethyltramadol), in severe cases - 19.5 h and 43.2 h respectively. When creatinine clearance is 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. Metabolism of tramadol and Ml decreased in patients with severe cirrhosis of the liver (with liver cirrhosis T_1/2 tramadol is 13.3 ± 4.9 h and T1 / 2 Ml - 18.5 ± 9.4 hours, in severe cases - 22.3 hours and 36 hours, respectively), in connection with which the concentration of the drug in the blood plasma increases and T_1/2, so these patients require a reduction in dose and an increase in the time intervals between doses of the drug. In patients older than 75 years, the maximum value of the drug concentration in the blood plasma increases slightly and T_1/2tramadol (7.4 h). In this case, you need to reduce the dose of the drug.

It is excreted by the kidneys (25-35% unchanged), the average cumulative index of renal excretion is 90%.

Indications:Moderate and severe pain syndrome of different etiology (postoperative period, trauma, pain in cancer patients, with diagnostic or therapeutic manipulations).

Contraindications:

Hypersensitivity to the drug and other opioids, conditions,accompanied by respiratory depression or severe central nervous system (CNS) depression (acute intoxication with alcohol, hypnotics and sedatives, narcotic analgesics, antidepressants, anxiolytics, neuroleptics, psychotropic drugs). Simultaneous application of MAO inhibitors (monoamine oxidase) (and two weeks after their cancellation). Severe hepatic and / or renal failure (creatinine clearance less than 10 mL / min).

Pregnancy, lactation, children's age (up to 1 year).

Carefully:Violations of kidney and liver function, craniocerebral trauma (CCT), intracranial hypertension, convulsive syndrome, drug dependence, incl. to opioids, dependence on alcohol, disorders of consciousness of different genesis.

Pregnancy and lactation:

Dosing and Administration:

The drug is used according to the prescription of the doctor, the dosage regimen is selected individually, depending on the severity of the pain syndrome and the sensitivity of the patient. The duration of treatment is determined individually.

Tramadol is intended for intravenous (to inject slowly!), Intramuscularly,subcutaneous and infusion methods of administration.

The usual single dose for intravenous (inject slowly!) Administration is 50 mg of tramadol. If necessary, in case of insufficient effect, after 30-60 minutes a second single dose of 50 mg can be administered. When intravenous drip infusion, the initial dose of 50-100 mg of tramadol is administered intravenously slowly (within 20 minutes), then begin to maintain a drip infusion at a rate of 12 mg of tramadol per hour to the maximum possible daily dose of 400 mg.

The maximum daily dose of the drug should not exceed 400 mg.

Children aged 1 to 14 years parenterally in a dose of 1-2 mg / kg, the maximum daily dose should not exceed 4-8 mg / kg or not more than 400 mg per day,

In patients with renal and / or liver failure, a dose reduction or lengthening of the time interval between doses of the drug is recommended.

In patients with creatinine clearance (CK) of less than 30 ml / min or 0.5 ml / s, a doubling of the time interval between taking the drug is recommended at the beginning of the treatment. In elderly patients (aged 65 to 75 years), the recommendations are the same as for renal and hepatic insufficiency. Patients over the age of 75 are recommended to reduce the daily dose to 300 mg.

Side effects:

From the central and peripheral nervous system: dizziness, headache, weakness, fatigue, inhibition, paradoxical stimulation of the central nervous system (nervousness, agitation, anxiety, tremor, muscle spasms, euphoria, emotional lability, hallucinations), drowsiness, sleep disorders, confusion, impaired coordination of movements, convulsions of the central genesis (with intravenous administration in high doses or with the simultaneous administration of antipsychotic drugs (neurole tics), depression, amnesia, cognitive impairment, paresthesia, unsteady gait, change in appetite.

On the part of the digestive system: dry mouth, nausea, vomiting, flatulence, abdominal pain, constipation or diarrhea, difficulty in swallowing.

From the side of the cardiovascular system: manifestations of vasodilation (tachycardia, orthostatic hypotension, collapse, syncope), arterial hypertension, palpitations.

Allergic reactions: skin rash, skin itching, angioedema, urticaria, extema, bullous rash.

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

From the senses: a violation of sight, taste.

From the respiratory system: dyspnoea.

Other: disorders of the menstrual cycle, increased sweating, weight loss.

With prolonged use - drug dependence. With a sharp reversal of the syndrome "cancellation."

Overdose:

Symptoms: impaired consciousness (including coma), vomiting, collapse, convulsions, lowering blood pressure, tachycardia, narrowing or dilating the pupil, respiratory center depression, apnea.

Treatment: ensuring airway patency, maintaining breathing and cardiovascular activity, opioid-like effects can be stopped with the help of morphine antagonists (naloxone), seizures - drugs of the benzodiazepine group (diazepam). Hemodialysis or hemofiltration is ineffective.

Interaction:

Pharmaceutically incompatible with solutions of diclofenac, indomethacin, phenylbutazone, diazepam, flunitrazepam, nitroglycerin.

Strengthens the effect of drugs that have a depressing effect on the central nervous system (CNS) (alcohol, sleeping pills and sedatives,narcotic analgesics, antidepressants, anxiolytic drugs, neuroleptics, psychotropic drugs).

Inductors of microsomal oxidation (incl. carbamazepine, barbiturates) reduce 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.

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

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

Simultaneous administration of tramadol and selective serotonin reuptake inhibitors, tricyclic antidepressants, furazolidone, procarbazine, monoamine oxidase inhibitors and antipsychotics (antipsychotics) may increase the risk of seizures (lowering convulsive threshold).

Isolated cases of serotonergic syndrome (agitation, fever, sweating, ataxia, hyperreflexia, myoclonus or diarrhea) are described with simultaneous administration of tramadol and serotonergic drugs (eg, antidepressants).

Quinidine increases the plasma concentration of tramadol and reduces the concentration of mono-O-desmethyltramadol (Ml metabolite) through the competitive and inhibition of the CYP2D6 isoenzyme.

Caution is necessary for simultaneous appointment with coumarins (eg, warfaria), because the risk of increasing the international standardized ratio (MHO) is increasing.

Special instructions:

It is necessary to avoid prescribing the drug to patients with drug dependence (including dependence on opioids, alcoholism). Do not use for the treatment of the syndrome of "withdrawal" of opioids.

With increased intervals of time used in elderly patients.

In patients with renal insufficiency (KC less than 30 ml / min or 0.5 ml / s) at the beginning of treatment, a doubling of the time interval between taking the drug is recommended. increases T1 / 2.

In patients with hepatic insufficiency, T1 / 2 lengthening is possible, so a dose reduction or lengthening of the time interval between doses of the drug is recommended.

With caution appoint patients with intracranial hypertension (for example, with CCT) or in conditions accompanied by respiratory depression.

Form release / dosage:Solution for injection 50 mg / ml.

Packaging:

Solution for injection 50 mg / ml in ampoules of 1 ml and 2 ml.

5 ampoules per contour cell packaging made of polyvinylchloride film and aluminum foil.

For 1 or 2 contour packs with instructions for use, a knife or a scarifier ampoule in a pack of cardboard.

By 20, 50 or 100 contour mesh packaging with foil with 20, 50 or 100 instructions for use, respectively, with knives or scarifiers ampoule into boxes of cardboard or in corrugated cardboard boxes (for inpatient).

When packing ampoules with notches, rings or break points, knives or scarifier ampoules do not.

Storage conditions:

In accordance with the rules for storage of potent substances.

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use at the end of the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002951 / 01

Date of registration:31.10.2008

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp18.09.2015

Illustrated instructions

Instructions

Tramadol (Tramadol)