Pharmadol of the tab. No. 10

Pharmacological properties

Pharmacodynamics. pharmadol — the combined medicament with anti-inflammatory, febrifugal and analgeziruyushchy effect. effect of medicament is defined by its components.

Antipyretic effect of acetylsalicylic acid (ASK) is implemented by

through central nervous system by oppression of synthesis of PGE _{2 prostaglandin} in a hypothalamus in response to effect of endogenous pyrogens. Its analgeziruyushchy efficiency has as peripheral (slowing down of synthesis of prostaglandins in the inflammation center, prevention of a sensitization of pain receptors to mechanical and chemical irritants), and central (action on the centers of a hypothalamus, without oppressing at the same time consciousnesses by hypnotic effect or decrease in a mental threshold of pain) origin.

Anesthetizing and febrifugal effect of paracetamol is caused by oppression of synthesis of prostaglandins and primary influence on the center of thermal control in a hypothalamus. It is much weaker inhibitor of a peripheral system of biosynthesis of prostaglandins which play an important role in inflammation reaction development.

Mechanism of effect of caffeine is caused by oppression of activity of FDE that leads to accumulation of tsAMF. An important link in the mechanism of effect of caffeine is its interaction with purine receptors of a brain. It strengthens analgeziruyushchy action of ASK and paracetamol and accelerates its beginning.

Pharmacokinetics. It was not investigated.

Indication

Weak or moderate pain syndrome (headache, migraine, toothache, neuralgia, arthralgia, primary dysmenorrhea); diseases which are followed by a hyper thermal syndrome.

Use

Pharmadol to apply

inside on 1–2 tablet 2–3 times a day after a meal, to wash down with a large amount of liquid. the maximum daily dose makes 6 tablets in 3 receptions. it is not necessary to take the medicament more than 5 days as anesthetic and more than 3 days — as febrifugal.

Contraindication

Hypersensitivity to medicament components, other derivatives of xanthines (theophylline, theobromine), other salicylates; oh, caused by intake of salicylates or others npvp in the anamnesis; a congenital hyperbilirubinemia, congenital insufficiency glyukozo-6-fosfatdegidrogenazy, blood diseases, a leukopenia, anemia, thrombosis, thrombophlebitis, acute gastrointestinal ulcers, hemorrhagic diathesis, the profound renal failure, the profound liver failure, a serious cardiovascular illness, including disturbance of a heart rhythm, the profound atherosclerosis, a severe form of an ischemic heart disease, the profound heart failure, expressed ag, tendency to an angiospasm; acute pancreatitis, prostatauxe, severe forms of diabetes; conditions of overexcitement, sleep disorder, epilepsy, hyperthyroidism, glaucoma, alcoholism. the period of use of inhibitors of Mao and also the period during 2 weeks after the termination of their use, it is contraindicated to the patients accepting tricyclic antidepressants or blockers of β-adrenoceptors. a combination with a methotrexate in a dosage of ≥15 mg/week.

Side effects

Allergic reactions: skin rashes (usually erythematic, a small tortoiseshell), an itching, a Quincke's disease, a multiformny exudative erythema (including Stephens's syndrome — Johnson), a toxic epidermal necrolysis, not cardiogenic fluid lungs, asthma;

from a digestive tract: dispeptic disorders, including nausea, vomiting, discomfort and pain in epigastriums, heartburn, abdominal pain; inflammation of a digestive tract, erosive cankers of a digestive tract which can cause in isolated cases gastrointestinal hemorrhages and perforation with the corresponding laboratory and clinical manifestations;

from a gepatobiliarny system: increase in activity of liver enzymes, as a rule, without development of jaundice, gepatonekroz (dose-dependent effect);

from an endocrine system: a hypoglycemia, up to a hypoglycemic coma.

from the system of a hemopoiesis: a sulfhemoglobinemia and a methemoglobinemia (cyanosis, short wind, pain in heart), hemolytic anemia, thrombocytopenia, an agranulocytosis, perioperatsionny hemorrhages, hematomas, hemorrhages of bodies of an urinogenital system, nasal hemorrhages, hemorrhages from gums, cerebral hemorrhages; hemorrhages can lead to an acute and chronic posthemorrhagic/iron deficiency anemia (owing to the latent microbleeding) with the corresponding laboratory manifestations and clinical symptoms, such as asthenia, pallor of integuments, hypoperfusion;

from the immune system: a Quincke's disease, an acute anaphylaxis which can be followed by cardiorespiratory insufficiency, reactions of hypersensitivity, rhinitis, congestion of a nose, a bronchospasm;

from a cardiovascular system: short-term AG, tachycardia, arrhythmia;

from central nervous system: dizziness, insomnia, concern, a ring in ears;

from an urinary system: it was reported about a renal failure and development of OPN.

Concomitant use of medicament in the recommended doses with the products containing caffeine can strengthen

side effects caused by caffeine, such as hyperexcitability, alarm, irritability, headache, disturbances from a GIT and a cardiopalmus.

Special instructions

not to use medicament with other means containing paracetamol, ask. not to exceed the specified medicament doses.

Already available diseases of a liver increase risk of damage of a liver paracetamol.

At patients with OH, allergic diseases, hypersensitivity to NPVP the development of allergic reaction or exacerbation of a basic disease is possible

. Drug with care is appointed to elderly people.

during medicament treatment is not recommended to take excessive amount of the drinks containing caffeine (for example coffee, tea). It can cause problems with a dream, a tremor, unpleasant feeling in a chest cavity owing to heartbeat.

during treatment not to take alcoholic beverages.

is Applied with care in the following cases:

• hypersensitivity to analgetic, anti-inflammatory, antirheumatic medicaments and also an allergy to other substances;
• an ulcer of a GIT, including chronic and recurrent, or gastrointestinal bleedings in the anamnesis;
• simultaneous use of anticoagulants;
• a renal failure or disturbance of cardiovascular blood circulation (for example pathology of vessels of a kidney, stagnant heart failure, a hypovolemia, extensive operations, sepsis or severe bleedings) as ASK also increases risk of a renal failure and development of OPN;
• heavy insufficiency glyukozo-6-fosfatdegidrogenazy — ASK can cause hemolysis or hemolytic anemia, especially with risk factors of hemolysis, for example high doses of drug, fever or acute infectious process;
• abnormal liver function.

development of a bronchospasm or attack OH or other hypersensitivity reactions can cause

ASK. Risk factors include OH in the anamnesis, hay fever, polyposes of a nose or a chronic respiratory disease, allergic reactions (for example skin reactions, an itching, urticaria) on other substances in the anamnesis.

Because of the inhibiting effect of ASK concerning aggregation of thrombocytes remaining within several days after reception, use of the medicaments containing ASK increases the probability of strengthening of bleeding at surgeries (including insignificant surgical interventions, for example odontectomy).

At use of ASK in low doses the removal of uric acid can decrease. It can lead to a gout attack at the patients predisposed to it.

should not use the medicaments containing ASK, to children and teenagers from the SARS which is followed by fervescence or without it without having consulted with the doctor. In some viral diseases, especially in flu A, flu B and chicken pox, there is a risk of development of a syndrome of Ray which is very rare, but life-threatening disease demanding urgent medical intervention. The risk can be raised if ASK is applied as the accompanying medicine, however relationship of cause and effect in this case is not proved. If the specified states are followed by constant vomiting, it can be manifestation of a syndrome of Ray.

If symptoms do not disappear, it is necessary to see a doctor.

If the headache becomes a constant, it is necessary to see a doctor.

to the Patients accepting analgetics every day in arthritises of an easy form needs to consult with the doctor. At patients with heavy infections, such as sepsis which are followed by decrease in level of glutathione at intake of paracetamol the risk of developing of a metabolic acidosis increases. Symptoms of a metabolic acidosis is the deep, speeded-up or complicated breath, nausea, vomiting, loss of appetite. It is necessary to see immediately a doctor in case of these symptoms.

Drug contains lactose therefore to patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is impossible to use drug.

Use during pregnancy and feeding by a breast. Not to apply.

Children. Not to use medicament to children because of risk of development of a syndrome of Ray (a hyper pyrexia, a metabolic acidosis, disturbances from nervous system and mentality, vomiting, abnormal liver functions) at a hyperthermia against the background of viral diseases.

Ability to influence speed of response at control of vehicles or work with other mechanisms. In case of developing of dizziness it is necessary to avoid potentially dangerous activity, in particular control of vehicles and/or the performance of work requiring special attention and speed of psychomotor reactions.

Interaction

Contraindicated combinations

Methotrexate: at the combined use with salicylates in a dose of 15 mg/week and more the hematologic toxicity of a methotrexate owing to decrease in renal clearance of a methotrexate by anti-inflammatory agents and its replacement from communication with blood plasma proteins increases therefore such combination is contraindicated.

Barbiturates reduce febrifugal effect of paracetamol.

due to the maintenance of ASK medicament can enhance hypoglycemic effect of oral anti-diabetic drugs.

Combination which should be applied with care

Paracetamol: antidepressants and other stimulators of microsomal oxidation — these medicaments increase producing the hydroxylated active metabolites influencing function of a liver owing to what development of heavy intoxications at small overdoses of medicament is possible. Speed of absorption of paracetamol can increase at simultaneous use with Metoclopramidum and domperidony and decrease at use with holestiraminy. Paracetamol reduces efficiency of diuretics. Coumarin derivatives (warfarin) at prolonged use of paracetamol increase risk of developing bleedings. Under the influence of paracetamol increases by 5 times of T _½ chloramphenicol. Simultaneous use of high doses of paracetamol with an isoniazid increases risk of development of a hepatotoxic syndrome.

Kofein: Cimetidinum, hormonal contraceptives, an isoniazid strengthen effect of caffeine. Caffeine reduces effect of opioid analgetics, anxiolytics, hypnotic medicaments and sedatives, is an antagonist of the anesthetics and other medicaments oppressing central nervous system (competitive antagonist of the medicaments oppressing central nervous system), the competitive antagonist of medicaments of adenosine, ATP. At simultaneous use of caffeine with ergotamine the absorption of ergotamine from a GIT improves, with thyritropic means — the thyroid effect increases. Caffeine reduces concentration of lithium in blood. Caffeine increases effect (improves bioavailability) analgetics-antipyretics, exponentiates effects of derivatives of xanthine, alpha and beta-adrenergic agonists, psychogogic means. Simultaneous use of caffeine with MAO inhibitors can cause dangerous increase in the ABP.

ASK: simultaneous use with uricosuric means, such as benzbromaron, probenetsid, reduces effect of removal of uric acid (because of the competition of removal of uric acid renal tubules). At simultaneous use with digoxin the concentration of the last in blood plasma increases owing to decrease in renal excretion. APF inhibitors in a combination with high doses of ASK cause decrease in filtration in balls owing to inhibition of vazodilatatorny prostaglandins and decrease in hypotensive effect. Selective serotonin reuptake inhibitors — the risk of bleeding from upper parts of a digestive tract because of a possibility of synergy effect increases. At simultaneous use with ASK valproic acid forces out it from communication with blood plasma proteins, increasing toxicity.

Overdose

paracetamol overdose Symptoms

Damage of a liver is possible

at the adults who accepted ≥10 g of paracetamol and at the children who took the medicament in a dose of 150 mg/kg of body weight. Damage of a liver can be shown in 12–48 h after administration of medicament in overdoses. In the first 24 h there can be following symptoms: pallor, nausea, vomiting, anorexia, abdominal pain, gepatonekroz, increase in activity of hepatic transaminases, increase in the prothrombin ratio. In a serious poisoning the liver failure can lead to encephalopathy, a coma and a lethal outcome. OPN with acute necrosis of tubules can be shown by severe lumbar pain, a hamaturia, a proteinuria and to develop even in the absence of severe damage of kidneys. Also pancreatitis was noted. There can be disturbances of metabolism of glucose and a metabolic acidosis. Cardiac arrhythmia was observed. At prolonged use of high doses the developing of aplastic anemia, thrombocytopenia, a pancytopenia, an agranulocytosis, a neutropenia, leukopenia is possible.

At patients with risk factors (long-term treatment by carbamazepine, phenobarbital, Phenytoinum, Primidonum, rifampicin, a St. John's wort or other medicines — inductors of enzymes of a liver, an alcohol abuse; the deficiency of glutathione, for example digestive disturbances, a mucoviscidosis, HIV infection, malnutrition, a cachexia) can lead reception of ≥5 g of paracetamol to damage of a liver.

At reception of high doses from central nervous system — dizziness, psychomotor initiation and disturbance of orientation; from an urinary system — nephrotoxicity (renal colic, interstitial nephrite, papillary necrosis).

Treatment by N-Acetylcysteinum can be carried out by

during 24 h after intake of paracetamol, but the maximum protective effect is gained at its use during 8 h after overdose. The efficiency of antidote sharply decreases after this time.

Symptoms of overdose of ASK

Overdose of salicylates is possible

because of the chronic intoxication which arose owing to long therapy (use of 100 mg/kg/days within more than 2 days can cause toxic effects) and also because of the acute intoxication posing threat of life (overdose) which reasons can be accidental use, in particular children, or unexpected overdose.

Chronic poisoning with salicylates can have the hidden character as its signs nonspecific. The moderate chronic intoxication caused by salicylates or a salitsilizm, meets, as a rule, only after repeated receptions of high doses.

Main symptoms: balance disturbance, dizziness, a ring in ears, deafness, the strengthened sweating, nausea and vomiting, a headache, confusion of consciousness. The specified symptoms can be controlled a dose decline. The ring in ears can be noted at concentration of salicylates in blood plasma 150–300 mkg/ml. Serious side reactions meet at concentration of salicylates in blood plasma of 300 mkg/ml. The significant change of acid-base balance which can differ depending on age of the patient and weight of intoxication testifies to acute intoxication. Weight of a state cannot be defined only on the basis of concentration of salicylates in blood plasma.

symptoms of poisoning with salicylates can include

In view of complex pathophysiological effects:

• intoxication of easy or average degree which can be followed: tachypnea, hyperventilation, respiratory alkalosis (alkalemiya, alkaluria); the strengthened sweating; nausea, vomiting;
• intoxication of average or heavy degree which can be followed: a respiratory alkalosis with a compensatory metabolic acidosis (acidemia, an aciduria); hyper pyrexia; respiratory disturbances: hyperventilation, not cardiogenic fluid lungs, respiratory insufficiency, asphyxia; cardiovascular disturbances: arrhythmia, arterial hypotension, cardiovascular insufficiency; loss of liquid and electrolytes; dehydration, oliguria, renal failure; glucose metabolism disturbance, ketoacidosis; a ring in ears, deafness; gastrointestinal bleeding; hematologic disorders: inhibition of thrombocytes, coagulopathy; neurologic disorders: toxic encephalopathy and oppression of central nervous system with such manifestations as a lethargy, confusion of consciousness, a lump and a spasm.

caffeine overdose Symptoms

High doses of caffeine can cause pain in epigastric area, vomiting, a diuresis, rapid breathing, premature ventricular contraction, tachycardia or cardiac arrhythmia, influence on central nervous system (dizziness, insomnia, nervous excitement, irritability, the heat of passion, uneasiness, a tremor, spasms).

Treatment. Treatment is defined by severity, clinical symptoms and is provided with standard methods. At overdose the emergency medical service is necessary even if symptoms of overdose are absent. Prescribing of methionine orally or Acetylcysteinum in/in can give positive effect during 48 h after overdose. It is necessary to hold also all-supporting events, symptomatic therapy, including use of antagonists of β-adrenoceptors who can eliminate cardiotoxic effects.

Storage conditions

B the place protected from light at a temperature not above 25 °C.