Zaldiar

General characteristics. Structure:

Active agents: one tablet, coated, contains a tramadol a hydrochloride of 37,5 mg and paracetamol of 325 mg.

Excipients: cellulose microcrystallic, starch prezhelatinizirovanny, starch of sodium is glikolit, starch corn, the water purified magnesium stearate.

Structure of a cover: опадрай® light yellow (bonds-1-6382-3), wax of karnaubskiya.

Structure опадрай® light yellow (bonds-1-6382-3): gipromeloza, titanium dioxide, polyethylene glycol 400 (macrogoal), dye
Ferrous oxide yellow, polysorbate.

Pharmacological properties:

Pharmacodynamics. Zaldiar is the combined medicine containing трамадол and paracetamol. Tramadol - an opioid synthetic analgetic, possesses soothing action, is an agonist of opiate receptors. Possesses the central action and action on a spinal cord (promotes opening of K+ and Ca2 + - channels, causes hyperpolarization of membranes and slows down carrying out painful impulses), strengthens effect of sedatives. Activates opiate receptors (a mu - delta, a kappa-) on pre-and postsynaptic membranes of afferent fibers. Nociceptive system in a brain and digestive tract. Paracetamol - possesses anesthetic and febrifugal action. Blocks cyclooxygenase in the central nervous system, influencing the centers of pain and thermal control. Does not cause irritation mucous a stomach and intestines, does not exert impact on a water salt metabolism as does not influence synthesis of prostaglandins in peripheral fabrics. Thanks to paracetamol there comes bystry anesthesia while трамадол provides the prolonged effect. A synergism of analgetic effect of two active agents reduces risk of emergence of side effects.

Pharmacokinetics. At intake drug quickly and almost is completely soaked up from a GIT. Absorption of a tramadol happens more slowly, than paracetamol. Tramadol is metabolized in a liver by ы-and about - demethylations with the subsequent conjugation with glucuronic acid. 11 metabolites from which mono - about - desmetiltramadol (m1) has pharmacological activity are revealed. The average time of semi-removal for a metabolite of a tramadol makes 4,7 - 5,1 hours, for paracetamol 2-3 hours. The maximum concentration in a blood plasma of paracetamol is reached within 1 hour, and does not change at combined use with tramadoly. Bioavailability of a tramadol makes about 75%, at repeated use bioavailability increases to 90%. Linkng with proteins of plasma - about 20%, distribution volume - about 0,9 l/kg. Rather small part (to 20%) paracetamol contacts proteins of plasma. Tramadol (about 30%) and his metabolites (about 60%) are brought out of an organism preferential through kidneys. Paracetamol is preferential metabolized in a liver. Paracetamol and its conjugates are emitted with kidneys.

Indications to use:

Pain syndrome (average and strong intensity of various etiology, including inflammatory, traumatic, vascular origin). Anesthesia when holding painful diagnostic or therapeutic actions.

Route of administration and doses:

Zaldiar is applied under observation of the doctor, the mode of dosing and duration of treatment are selected individually depending on expressiveness of a pain syndrome and sensitivity of the patient. It is not necessary to appoint drug over the term, justified from the therapeutic point of view.

For adults and children 14 years the recommended initial single dose are more senior makes 1-2 tab., an interval between administrations of drug - not less than 6 hours. Apply regardless of meal, swallow entirely (it is impossible to break or chew), washing down with liquid. The maximum daily dose - 8 tablets (300 mg of a tramadol and 2,6 g of paracetamol). If the patient forgot to take the next pill, then following is accepted as it is recommended the doctor. Do not accept a double dose to fill the missed administration of drug!

At elderly patients (at the age of 75 years and more) usual doses can be used. However in connection with a possibility of the slowed-down removal, the interval between administrations of drug can be increased.

At patients with a renal failure (clearance of creatinine from 10 to 30 ml/min.), administration of drug has to be carried out at observance of 12-hour intervals between receptions. As трамадол it is very slowly removed when carrying out a hemodialysis or haemo filtering, post-dialysis use for maintenance of analgeziruyushchy action usually is not required. At patients with heavy abnormal liver functions drug is not used. At a moderate abnormal liver function it is necessary to increase an interval between administrations of drug. The risk connected with paracetamol overdose is higher at patients with a disease of a liver of an alcoholic etiology.

Features of use:

Patients have to be informed on need of observance of the mode of dosing and should not use other drugs containing трамадол or paracetamol without consultation of the doctor.

At prolonged uncontrollable use dependence symptoms can appear: irritability, phobias, nervousness, sleep disorders, psikhotomotorny activity, a tremor, discomfort in a stomach or intestines. At the patients having tendency to abuse or emergence of dependence, treatment has to be made under careful medical observation during the short period.

During treatment drug forbids to accept alcohol. The risk of development of injuries of a liver increases at patients with an alcoholic hepatosis. During prolonged treatment control of a picture of peripheral blood and a functional condition of a liver is necessary.

During treatment by drug Zaldiar it is necessary to refrain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Allergic reactions: urticaria, itch, Quincke's edema, dieback, violent rash.

From a nervous system: perspiration, dizziness, a headache, weakness, increased fatigue, block, paradoxical stimulation цнс (nervousness, agitation, uneasiness, a tremor, spasms of muscles, euphoria, emotional lability, hallucinations), drowsiness, a sleep disorder, confusion of consciousness, a lack of coordination of movements, spasms of the central genesis (at co-administration of antipsychotic means), a depression, amnesia, disturbance of cognitive function, paresthesia, instability of gait.

From the alimentary system: dryness in a mouth, nausea, vomiting, a meteorism, abdominal pains, a lock, diarrhea, difficulty when swallowing; increase in activity of "hepatic" enzymes, as a rule, without development of jaundice.

From cardiovascular system: tachycardia, orthostatic hypotension, syncope, collapse.

From endocrine system: a hypoglycemia, up to a hypoglycemic coma.

From an urinary system: difficulty of an urination, dysuria, ischuria. At long reception in the doses considerably exceeding recommended - nephrotoxicity (intersticial nephrite, a papillary necrosis).

From sense bodys: vision disorder, taste.

From respiratory system: дипноэ.

From integuments: multiformny exudative erythema (including Stephens-Johnson's syndrome), toxic epidermal necrolysis (Lyell's disease).

From bodies of a hemopoiesis: sulfhemoglobinemia. At prolonged use in the doses considerably exceeding recommended - aplastic anemia, a pancytopenia, an agranulocytosis.

Others: disturbance of a menstrual cycle. At prolonged use - development of medicinal dependence. At sharp cancellation - a syndrome of "cancellation".

Interaction with other medicines:

Combined use with opioid agonists antagonists (buprenorphine, nalbufiny, pentazocine) is not recommended since the analgetic effect decreases as a result of the competing action on receptors and there is a risk of a syndrome of "cancellation". At therapy by drug together with other medicines which exert the oppressing impact on TsNS (for example, hypnagogues or tranquilizers) and also at a concomitant use of alcohol, the side effects characteristic of a tramadol can be more expressed.

Inductors of a microsomal oxidation (including carbamazepine, Phenytoinum, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) reduce analgetic effect and its duration. Naloxonum activates breath, eliminating an analgesia.

Prolonged use of barbiturates reduces efficiency of paracetamol, and ethanol promotes development of acute pancreatitis.

Long sharing of paracetamol and other non-steroidal anti-inflammatory drugs increases risk of development of a "analgetic" nephropathy and renal papillary necrosis, approach of an end-stage of a renal failure. Simultaneous long purpose of paracetamol in the doses exceeding recommended and salicylates increases risk of development of cancer of kidney or bladder.

Diflunisal increases concentration in a paracetamol blood plasma for 50% - risk of development of a hepatotoxic. The accompanying use with the means lowering an epileptic threshold, for example the selection inhibitors of serotonin reuptake, tricyclic antidepressants, neuroleptics can increase danger of developing of spasms. The drugs inhibiting SURZA4 such as кетоконазол and erythromycin, can slow down metabolism of a tramadol ([1-demet-ilirovaniye) and active O-demetilirovannogo a metabolite. Quinidine increases concentration in a blood plasma of a tramadol and reduces concentration of M of 1 metabolite at the expense of competitive inhibition of SUR206 isoenzyme. Inhibitors of a microsomal oxidation (Cimetidinum) reduce risk of a hepatotoxic action. Speed of absorption can be increased at reception of Metoclopramidum or domperidon and is reduced holestiraminy. Drug at reception strengthens effect of indirect anticoagulants (warfarin and other coumarins) for a long time that increases risk of bleedings.

Contraindications:

Hypersensitivity to active components or excipients of drug;

Acute intoxication the alcohol, drugs oppressing the central nervous system (цнс), somnolent, narcotic analgetics and psychotropic drugs;

Simultaneous use of inhibitors of Mao (and 2 weeks after their cancellation);

Heavy liver and/or renal failure (clearance of creatinine less than 10 ml/min.);

The epilepsy which is not controlled by treatment;

Syndrome of "cancellation" of drugs;

Children's age (up to 14 years).

With care - at patients in state of shock, a craniocereberal injury, intracranial hypertensia, tendency to a convulsive syndrome (at the patients sick with the epilepsy controlled therapeutic drug can be used only according to vital indications), confusion of consciousness of an unknown etiology, disturbance of respiratory function, simultaneous use of psychotropic and other anesthetics of the central action, means of local anesthesia, a disease of the bilious removing ways; high-quality hyperbilirubinemias, a viral hepatitis, deficit glucose - 6-fosfatdegidrogenaza, alcoholic damage of a liver, alcoholism, drug addiction, against the background of pains in an abdominal cavity of not clear genesis (a "acute" stomach), advanced age (75 years are more senior).

Use at pregnancy and a lactation
It is not necessary to apply during pregnancy and during feeding by a breast.

Overdose:

In case of acute overdose of drug Zaldiar, symptoms can include signs and symptoms of overdose of a tramadol and/or paracetamol.

Symptoms of overdose of a tramadol: miosis, vomiting, collapse, coma, spasms, depression of a respiratory center, apnoea.

Paracetamol overdose symptoms: (the acute overdose develops in 6-14 hours after paracetamol reception, chronic - in 2-4 days).

Symptoms of acute overdose: diarrhea, loss of appetite.

Symptoms of chronic overdose: wet brain, hypocoagulation, development of the IDCS, hypoglycemia, metabolic acidosis, arrhythmia, collapse; seldom the abnormal liver function develops immediately and can be complicated by a renal failure (a renal tubular necrosis).

Treatment: Usual measures of the emergency help are applied. The gastric lavage and reception of enterosorbents (absorbent carbon, Polyphepanum) is recommended, to support functions of cardiovascular system, to provide passability of respiratory tracts. For reversibility of respiratory depression as syndrome of overdose of a tramadol, Naloxonum is applied. The spasms developing at toxic dosages can be eliminated with diazepam. Tramadol is minimum brought from serum by a hemodialysis or haemo filtering therefore holding only these actions for therapy of overdose is inefficient.

At emergence of symptoms of overdose by paracetamol: introduction of donators 5H - groups and predecessors of synthesis of glutathione - methionine in 8-9 hours after overdose and M-Acetylcysteinum - in 12 hours. Need for holding additional actions (further administration of methionine, in/in introduction of M-Acetylcysteinum) is defined depending on concentration paracetamol in blood, and also from time which passed after its reception.

Storage conditions:

At a temperature not above 25 °C, in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets, coated in the blister from polypropylene / polypropylene or aluminum polypropylene / foil, aluminum PVC / foil. 1,2,3 or 5 planimetric packagings (blisters) together with the application instruction place in a pack cardboard.