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

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

SHELL:

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

Description:Oval biconvex tablets, covered with a film coating of white color. On the break the tablets have a white uneven surface.

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

ATX: & nbsp

N.02.A.X.02 Tramadol

Pharmacodynamics:

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.

Opioid synthetic analgesic, which has a 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 effect of sedative drugs (JIC). 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 (CNS). It is a racemic mixture of two enantiomers - dextrorotatory (+) and levorotatory (-), each of which exhibits a different receptor affinity. Tramadol is a selective agonist of the μ-opioid receptors, and selectively inhibits the reverse neuronal seizure of serotonin. Tramadol inhibits the reverse neuronal seizure of norepinephrine. Mono-O-desmethyltramadol (M₁-metabolite) also selectively stimulates μ-opioid receptors.

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 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:

After oral administration tramadol quickly and almost completely absorbed from the gastrointestinal tract. The average bioavailability after oral administration is about 65-68%.Simultaneous food intake does not have a significant effect on the duration and completeness of absorption. The therapeutic concentration is noted approximately 2 hours after the drug intake, reaches a maximum after 4 hours and lasts up to 12 hours.

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

In the liver, about 85% of tramadol is metabolized. by N- and O-demethylation followed by conjugation with glucuronic acid. Identified 11 metabolites, of which mono-O-desmethyltramadol (M₁) has pharmacological activity. In the metabolism of the drug takes part isoenzyme CYP2D6.

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 insufficiency T_1/2 lengthened, with a CK of 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 M₁ decreased in patients with severe cirrhosis of the liver (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, 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.

The delayed release of the active ingredient from the tablet results in its slow, constant intake into the blood plasma and prolonged 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 different etiology (postoperative period, trauma, pain in cancer patients, with diagnostic or therapeutic manipulations).

Contraindications:

- Hypersensitivity to tramadol, other components of 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).

- Severe hepatic or renal insufficiency.

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

- Children up to 14 years.

- Hereditary intolerance to galactose, deficiency of Lappa lactase or glucose-galactose malabsorption syndrome.

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:Safety of use of the drug during pregnancy has not been studied. High doses of tramadol can be unsafe for the fetus and the newborn. therefore tramadol not recommended for use in pregnancy. Tramadol, assigned before or during labor, does not affect the contractility of the uterus. In newborns, there may be a slowing of breathing, which is clinically insignificant. Tramadol is released in very small amounts (about 0.1% of the intravenously administered dose) in human milk. therefore tramadol Do not use while breastfeeding.

Dosing and Administration:

Inside, with a sufficient amount of liquid, regardless of time of ingestion. 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 should be justified. Tramadol retard is recommended for adults and children over 14 years for 1-2 tablets of 100 mg twice daily (morning and evening). The drug should be taken with a 12-hour interval, in the absence of other recommendations of the attending physician. The maximum daily dose is 400 mg (4 tablets).

In patients with renal and / or liver failure, a dose reduction or lengthening of the time interval between doses of the drug is recommended. Patients with creatinine clearance (CK) of less than 30 ml / min or 0.5 ml / s are 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 hepatic insufficiency. Patients over the age of 75 are recommended to reduce the daily dose to 300 mg.

Side effects:

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

- dizziness; often (from> 1/100 to <1/10) - vertigo, headache; infrequently (from> 1/1000 to <1/100) - anxiety, drowsiness, anorexia; rarely (from> 1/10000 to <1/1000)

- paradoxical stimulation of the central nervous system (nervousness, agitation, anxiety, tremors, muscle spasms), hallucinations, euphoria, emotional lability, sleep disturbances, cognitive function, depression, amnesia, impaired motor coordination, seizures of central origin (with concomitant administration of antipsychotic drugs), paresthesia, impaired concentration, gait disturbance, asthenia, weakness, fatigue, lethargy, confusion.

From the digestive system: very often (> 1/10) - nausea; often (from> 1/100 to <1/10) - constipation, vomiting, diarrhea, dry mouth; infrequently (from> 1/1000 to <1/100) - dyspepsia, flatulence, abdominal pain; rarely (from> 1/10000 to <1/1000) - difficulty in swallowing.

From the cardiovascular system: rarely (from> 1/10000 to <1/1000) - vazodilyatatsyi manifestations (tachycardia, orthostatic hypotension, collapse, syncope); arterial hypertension; palpitation.

Allergic reactions: infrequently (from> 1/1000 to <1/100) - skin rash, skin itching; rarely (from> 1/10000 to <1/1000) - angioedema, hives, exanthema, bullous rash.

From the musculoskeletal system: rarely (from> 1/10000 to <1/1000) - increased muscle tone.

From the genitourinary system: infrequently (from> 1/1000 to <1/100) - urinary retention, frequent urination, menstrual irregularity, symptoms of menopause; rarely (from> 1/10000 to <171000) - dysuria, difficulty urinating.

From the sense organs: very rarely (from> 1/10000 to <1/1000) - impaired vision, taste.

From the respiratory system: very rarely (from> 1/10000 to <1/1000) - shortness of breath. Other: often (from> 1/100 to <1/10) - increased sweating; rarely (from> 1/10000 to <1/1000) - weight reduction.

With prolonged use, it is possible to develop drug dependence; with a sharp cancellation is not excluded the development of the syndrome of "cancellation."

Overdose:

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

Treatment: ensuring airway patency, maintaining breathing and cardiovascular activity; Opiate-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:

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

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

Inductors of microsomal oxidation (incl. carbamazepine, barbiturates) increase the metabolism of tramadol, resulting in a decrease in the severity of the analgesic effect and the duration of the action. 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. Naloxone activates breathing, eliminating analgesia after the use of opioid analgesics.

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).Simultaneous use with selective serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, MAO inhibitors, furazolidone and procarbazine may increase the risk of seizures. Quinidine increases the plasma concentration of tramadol and reduces the concentration of mono-O-desmethyltramadol (Ml metabolite) due to competitive inhibition of the isoenzyme CYP2D6.

Caution is necessary for simultaneous appointment with coumarins (for example, warfarin), t. the risk of increasing the international standardized ratio (MHO) is increasing.

Special instructions:

Tramadol retard should be avoided for patients with drug dependence (including dependence on opioids, alcoholism). Do not use for the treatment of the syndrome of "withdrawal" of opioids.

With extended time intervals, Tramadol retard is 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.

Caution should be given to patients with intracranial hypertension (eg, with CCT) or in conditions accompanied by respiratory depression.

Tramadol retard tablets contain lactose, so the drug should not be used in patients with hereditary galactose intolerance, Lappease lactase deficiency, or glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:When using Tramadol retard tablets, it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated, 100 mg.

Packaging:

10 tablets per blister. 3 blisters place a pack of cardboard along with the instruction

on application.

Storage conditions:

Store at a temperature not exceeding 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:

5 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N011326 / 01

Date of registration:10.09.2009

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp16.09.2015

Illustrated instructions

Instructions

Tramadol retard (Tramadol retard)