Composition, form of production and packaging
The tablets covered with a film cover of light yellow color, capsular, biconcave, with engraving "Рў5" on one side and a logo of the company "Grjunental" - on another; on the cross section the nucleus is almost white.
1 tab.
tramadol hydrochloride 37.5 mg
paracetamol 325 mg
Excipients: microcrystalline cellulose - 26 mg, pregelatinized starch - 6.5 mg, sodium carboxymethyl starch (type A) - 6.5 mg, corn starch - 26 mg, magnesium stearate - 2.5 mg.
Composition of the membrane: hypromellose (hydroxypropylmethylcellulose 6 mPa.s) - 3.69 mg, lactose monohydrate - 1.878 mg, titanium dioxide 2.86 mg, macrogol 6000 0.915 mg, iron dye oxide yellow 0.132 mg, propylene glycol 0.305 mg, talc 1.22 mg .
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
Combined drug with analgesic action.
Tramadol is a synthetic opioid analgesic, an opioid receptor agonist. Activates opioid receptors (mu, delta, kappa) on the pre- and postsynaptic membranes of the afferent fibers of the nociceptive system in the brain and GI tract. Has an effect on the brain and spinal cord: promotes the discovery of K + - and Ca 2+ -channels, causes hyperpolarization of membranes and inhibits pain impulses. Strengthens the action of sedatives.
Paracetamol is an analgetic-antipyretic. It blocks cyclooxygenase in the central nervous system, affecting the centers of pain and thermoregulation. Does not cause irritation of the mucous membrane of the stomach and intestines, does not affect the water-salt metabolism, since it does not affect the synthesis of prostaglandins in peripheral tissues.
Paracetamol provides a rapid onset of analgesic effect, while tramadol - prolongation of analgesia. The synergism of the analgesic effect of the two components reduces the risk of side effects.
PHARMACOKINETICS
Suction
After ingestion, the active components are quickly and almost completely absorbed from the digestive tract. The absorption of tramadol is slower than paracetamol.
C max paracetamol in blood plasma is achieved within 1 h and does not change when combined with tramadol. The bioavailability of tramadol is approximately 75%, with repeated application increases to 90%.
Distribution
The binding with plasma proteins of tramadol is about 20%, V d is about 0.9 l / kg. A relatively small part (up to 20%) of paracetamol binds to plasma proteins.
Metabolism
Tramadol is metabolized in the liver by N- and O-demethylation, followed by conjugation with glucuronic acid. 11 metabolites have been identified, of which mono-O-desmethyltramadol (M 1 ) has pharmacological activity.
Paracetamol is metabolized predominantly in the liver.
Excretion
The mean T 1/2 of the metabolite of tramadol is 4.7-5.1 hours, T 1/2 of paracetamol is 2-3 hours.
Tramadol (about 30%) and its metabolites (about 60%) are excreted mainly with urine. Paracetamol and its conjugates are also excreted in the urine.
INDICATIONS
- pain syndrome of moderate and strong intensity of various etiology (including inflammatory, traumatic, vascular origin);
- Anesthesia for painful diagnostic or therapeutic procedures.
DOSING MODE
The dosage regimen and duration of treatment are set individually, depending on the severity of the pain syndrome and the sensitivity of the patient. Do not prescribe the drug over a time-justified from a therapeutic point of view.
For adults and children older than 14 years, the initial single dose is 1-2 tablets, the interval between doses of single doses is not less than 6 hours. The maximum daily dose is 8 tablets. (300 mg of tramadol and 2.6 g of paracetamol).
Tablets should be taken regardless of food intake, swallowing whole, not breaking and not chewing, squeezed with liquid. If the patient forgot to take another pill, then the next dose should not be doubled.
In elderly patients (aged 75 years and older), there is no need to correct a single dose. However, in connection with the possibility of delayed induction, the interval between single-dose doses may be increased.
In patients with impaired renal function (QA 30-10 ml / min), the interval between doses of single doses should be at least 12 hours. Since tramadol is very slowly excreted during hemodialysis or haemofiltration, postdialysis to maintain analgesic activity is usually not required.
With a moderate violation of liver function, the interval between doses should be increased. With severe violations of liver function, the drug should not be used.
SIDE EFFECT
Allergic reactions: urticaria, itching, angioedema.
From the side of the central nervous system and peripheral nervous system: dizziness, headache, weakness, increased fatigue, inhibition, paradoxical stimulation of the central nervous system (nervousness, agitation, anxiety, tremor, muscle spasms, euphoria, emotional lability, hallucinations), drowsiness, sleep disturbance, confusion , impaired coordination of motion, convulsions of the central genesis (with the simultaneous administration of antipsychotics), depression, amnesia, cognitive impairment, paresthesia, unsteadiness of gait, impaired siren and taste.
On the part of the digestive system: dry mouth, nausea, vomiting, flatulence, abdominal pain, constipation, diarrhea, difficulty in swallowing, increased activity of liver enzymes (usually without the development of jaundice).
From the cardiovascular system: tachycardia, orthostatic hypotension, fainting, collapse.
From the endocrine system: hypoglycemia up to hypoglycemic coma.
From the urinary system: difficulty urinating, dysuria, urinary retention. At long reception in doses considerably exceeding recommended, - nephrotoxicity (an intersticial nephritis, a papillary necrosis).
From the respiratory system: dyspnoea.
Dermatological reactions: exanthema, bullous rash, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).
On the part of the organs of hematopoiesis: sulfgemoglobinemia. With prolonged admission in doses much higher than recommended - aplastic anemia, pancytopenia, agranulocytosis.
Other: increased sweating, impaired menstrual cycle.
CONTRAINDICATIONS
- acute intoxication with alcohol or drugs depressing the central nervous system (hypnotics, opioid analgesics and psychotropic drugs);
- simultaneous use of MAO inhibitors and a period of 2 weeks after their withdrawal;
- severe hepatic and / or renal failure (CC less than 10 ml / min);
- Epilepsy, uncontrolled therapy;
- drug withdrawal syndrome;
- children's age till 14 years;
- Hypersensitivity to the components of the drug.
With caution should be used in patients in shock, with traumatic brain injury, intracranial hypertension, propensity to convulsive syndrome (with epilepsy controlled therapeutically, Zal'diar is prescribed only for vital reasons), confusion of the unknown etiology, impaired respiratory function, simultaneous use of psychotropic drugs, other central analgesics and local anesthetics, bile duct disease, benign hyperbilirubinemia, viral hepatitis , Deficiency of glucose-6-phosphate dehydrogenase, alcoholic liver disease, alcoholism, drug addiction, with the symptom "acute" abdomen of unknown origin, in elderly patients (older than 75 years).
PREGNANCY AND LACTATION
Do not use Zaldiar during pregnancy and lactation (breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function (QA 30-10 ml / min), the interval between doses of single doses should be at least 12 hours. Since tramadol is very slowly excreted during hemodialysis or haemofiltration, postdialysis to maintain analgesic activity is usually not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With a moderate violation of liver function, the interval between doses should be increased. With severe violations of liver function, the drug should not be used.
SPECIAL INSTRUCTIONS
Patients should be informed of the need for strict adherence to the dosing regimen. During the period of Zaldiar's admission, do not use other drugs containing tramadol or paracetamol, without the appointment of a doctor.
With prolonged uncontrolled use of Zaldiar, symptoms of drug dependence may appear (irritability, phobias, nervousness, sleep disturbances, psychomotor activity, tremor, gastrointestinal discomfort). With a sharp withdrawal of the drug may appear signs of withdrawal syndrome.
Patients who are addicted to abuse or addiction should be treated under close medical supervision for a short period of time.
During the period of treatment, Zaldiar is not allowed to drink alcohol. The risk of liver function disorders increases in patients with alcoholic hepatosis.
During a prolonged use of Zaldiar, a picture of the peripheral blood and the functional state of the liver is needed.
Impact on the ability to drive vehicles and manage mechanisms
During treatment with Zaldiar, one should refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
In the case of an acute overdose of Zaldiar, the symptoms may include signs and symptoms of an overdose of tramadol and / or paracetamol.
Symptoms of an overdose of tramadol: miosis, vomiting, collapse, coma, convulsions, depression of the respiratory center, apnea.
Symptoms of paracetamol overdose: acute - diarrhea, decreased appetite; chronic - cerebral edema, hypocoagulation, development of DIC syndrome, hypoglycemia, metabolic acidosis, arrhythmia, collapse (acute overdose develops 6-14 hours after paracetamol administration, chronic - after 2-4 days if dose is exceeded). Rarely lightning impairment of liver function, which can be complicated by renal failure (renal tubular necrosis) is rare.
Treatment: gastric lavage, intake of enterosorbents (activated charcoal, polyphepan), maintenance of cardiovascular function, ensuring airway patency.
If respiratory depression occurs (like tramadol overdose syndrome), naloxone administration is indicated; seizures can be eliminated by the use of diazepam. Tramadol is minimally excreted from blood serum by hemodialysis or hemofiltration, so carrying out only these measures for overdose therapy is ineffective.
When symptoms of paracetamol overdose appear, the introduction of SH-group donors and glutathione synthesis precursors (methionine - 8-9 hours after an overdose and N-acetylcysteine ​​after 12 hours) is shown. The need for additional measures (further introduction of methionine, intravenous injection of N-acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its administration.
DRUG INTERACTION
When Zaldiar is combined with opioid agonist antagonists (buprenorphine, nalbuphine, pentazocine), the analgesic effect is reduced as a result of competing effects on receptors and there is a risk of withdrawal syndrome, therefore, the use of this combination is not recommended.
When Zaldiar therapy together with other drugs that exert a depressing effect on the central nervous system (for example, hypnotics or tranquilizers), and with the simultaneous administration of ethanol, the side effects characteristic of tramadol may be more pronounced.
Naloxone, being an antagonist of opioid receptors, activates respiration, eliminating the cause of Zaldiar's analgesia.
Inductors of microsomal oxidation (including carbamazepine, phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) reduce the analgesic effect of Zaldiar and its duration.
Inhibitors of microsomal oxidation (including cimetidine) with simultaneous application reduce the risk of hepatotoxic action Zaldiara.
Long-term use of barbiturates reduces the effectiveness of paracetamol.
Long-term combined use of paracetamol and NSAIDs increases the risk of developing nephropathy and renal papillary necrosis, the onset of the terminal stage of renal failure. Simultaneous long-term administration of paracetamol in high doses and salicylates increases the risk of developing kidney or bladder cancer.
The concomitant use of Zaldiar with drugs that lower the threshold of convulsive readiness (eg with selective serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics) may increase the risk of seizures.
Zal'diar with simultaneous application for a long time enhances the effect of indirect anticoagulants (warfarin and other coumarins), which increases the risk of bleeding.
Preparations that inhibit the isoenzyme CYP3A4, such as ketoconazole and erythromycin, can slow the metabolism of tramadol (N-demethylation) and the active O-demethylated metabolite.
Diflunisal increases the concentration of paracetamol in the blood plasma by 50%, and the risk of hepatotoxicity increases.
Quinidine increases the concentration in the blood plasma of tramadol and reduces the concentration of M 1 metabolite due to competitive inhibition of the CYP2D6 isoenzyme.
The rate of absorption of paracetamol can be increased with simultaneous administration of metoclopramide or domperidone and reduced with simultaneous administration of colestyramine.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
