Acetylsalicylic Acid, Caffeine, Paracetamol

Pharmacological properties

The drug has an analgesic, antipyretic and anti-inflammatory effect. the components of the drug are synergists. the antipyretic effect of acetylsalicylic acid is realized through the central nervous system by inhibiting the synthesis of prostaglandins pgf2 in the hypothalamus in response to exposure to endogenous pyrogens. the analgesic effect has both peripheral and central origin: the peripheral effect is the inhibition of prostaglandin synthesis of inflamed tissues; the central effect is the effect on the centers of the hypothalamus. acetylsalicylic acid also reduces platelet aggregation. paracetamol has an analgesic, antipyretic, and very weak anti-inflammatory effect, due to its effect on the thermoregulation center in the hypothalamus and a weak ability to inhibit prostaglandin synthesis in peripheral tissues. caffeine excites central nervous system. also enhances positive conditioned reflexes, stimulates motor activity, reduces the severity of the effect of sleeping pills and drugs, enhances the effect of analgesics and antipyretics.

Indications

Therapy for mild to moderate pain: headache and toothache, myalgia, arthralgia, neuralgia, primary dysmenorrhea, as well as an antipyretic for diseases accompanied by fever.

Application

Assign to adults 1 tablet 2-3 times a day after meals. the maximum daily dose is 6 tablets (in 3 divided doses). the duration of treatment depends on the course and severity of the disease and should not exceed 5 days as an anesthetic and 3 days as an antipyretic.

Do not exceed recommended dose.

Do not take with other medicines containing paracetamol.

Contraindications

Hypersensitivity to the components of the drug, other xanthine derivatives (theophylline, theobromine), other salicylates; a history of salicylates or other NSAIDs; congenital hyperbilirubinemia, congenital deficiency of glucose-6-phosphate dehydrogenase; blood diseases, leukopenia, anemia; acute gastrointestinal ulcers, hemorrhagic diathesis, severe renal failure, severe liver failure, gilbert syndrome, severe cardiovascular diseases, including rhythm disturbance, severe atherosclerosis, severe coronary heart disease, severe heart failure, severe ag; conditions of increased excitement, sleep disturbances, old age, glaucoma, alcoholism. when using MAO inhibitors, as well as within 2 weeks after the cessation of their use. combination with methotrexate at a dose of ≥15 mg / week.

Side effects

From the cardiovascular system: tachycardia, palpitations, ag.

From the blood and lymphatic systems: anemia, sulfate hemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, pain in the heart), hemolytic anemia, bruising or bleeding, thrombocytopenia, agranulocytosis. Due to the antiplatelet effect on platelets, acetylsalicylic acid can increase the risk of bleeding. Hemorrhages such as intraoperative hemorrhages, hematomas, urogenital bleeding, nosebleeds, gum bleeding, gastrointestinal bleeding, and cerebral hemorrhages were noted.

From the nervous system: headache, dizziness, tremor, paresthesia, a feeling of fear, anxiety, agitation, irritability, sleep disturbance, insomnia, anxiety, general weakness, tinnitus.

From the gastrointestinal tract: dyspeptic syndrome (nausea, vomiting, discomfort and pain in the epigastrium, heartburn, abdominal pain); inflammatory diseases, erosive and ulcerative lesions, which in rare cases can cause gastrointestinal bleeding and perforation with appropriate laboratory and clinical manifestations.

On the part of the skin and subcutaneous tissue: itching, rash on the skin and mucous membranes (usually a generalized rash, erythematous rash, urticaria), angioedema, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyells syndrome).

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

From the immune system: hypersensitivity reactions, including anaphylaxis, anaphylactic shock, rhinitis, nasal congestion.

On the part of the hepatobiliary system: increased activity of liver enzymes, usually without the development of jaundice, hepatonecrosis (dose-dependent effect).

On the part of the respiratory system: bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

Other: bleeding can lead to acute and chronic posthemorrhagic anemia / iron deficiency anemia (due to latent microbleeding) with corresponding laboratory manifestations and clinical symptoms (asthenia, pallor of the skin, hypoperfusion, non-cardiogenic pulmonary edema).

special instructions

Do not use with other agents containing paracetamol, acetylsalicylic acid.

Do not exceed the indicated doses.

The drug should be used with caution with a history of gastrointestinal ulcers, including a history of chronic or recurring ulcer or gastrointestinal bleeding, with the simultaneous use of anticoagulants.

You should consult your doctor about the possibility of using the drug in patients with impaired renal and hepatic function.

It should be borne in mind that in individuals with alcoholic liver damage, the risk of hepatotoxic effects of paracetamol is increased. Concomitant liver diseases increase the risk of liver damage with paracetamol. The risk of overdose is higher in people with non-cirrhotic alcoholic liver diseases.

In patients with severe infections, such as sepsis, which are accompanied by a decrease in glutathione, taking paracetamol increases the risk of metabolic acidosis. Symptoms of metabolic acidosis are deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. Seek medical attention immediately if these symptoms occur.

In surgical operations (including dental), the use of preparations containing acetylsalicylic acid can increase the likelihood of bleeding appearing / intensified due to inhibition of platelet aggregation for some time after the use of acetylsalicylic acid.

With the use of the drug, uric acid excretion may decrease. This can lead to gout in patients with reduced uric acid excretion.

During treatment, it is not recommended to consume an excessive amount of drinks that contain caffeine (e.g. coffee, tea). This can cause sleep disturbances, tremors, a feeling of tension, irritability, discomfort behind the sternum due to an increased heartbeat.

Patients taking analgesics every day for mild arthritis should consult a doctor.

The drug can affect the results of laboratory tests on the content of glucose and uric acid in the blood.

During treatment should refrain from drinking alcoholic beverages.

If symptoms persist, consult a doctor.

If the headache becomes constant, you should consult a doctor.

Keep the drug out of the sight of children and out of the reach of children.

During pregnancy and breastfeeding. Do not use.

Children. The drug is not used in children because of the risk of Reye syndrome (hyperpyrexia, metabolic acidosis, disorders of the nervous system and psyche, vomiting, impaired liver function) with hyperthermia due to viral diseases.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms.In case of dizziness, potentially hazardous activities such as driving a vehicle and / or performing work requiring increased attention and speed of psychomotor reactions should be avoided.

Interactions

Contraindicated combinations

Methotrexate - when combined with salicylates at a dose of ≥15 mg / week, the hematological toxicity of methotrexate increases due to a decrease in renal clearance of methotrexate by anti-inflammatory agents and its displacement from the connection with blood plasma proteins, therefore this combination is contraindicated.

MAO inhibitors - when combined with caffeine, a dangerous increase in blood pressure is possible, therefore this combination is contraindicated.

Combinations to be used with caution

Paracetamol: anticonvulsants (including phenytoin, barbiturates, carbamazepine), antidepressants and other microsomal oxidation stimulants - increase the production of hydroxylated active metabolites that affect liver function, causing severe intoxication with a slight overdose of the drug.

With simultaneous use with hepatotoxic drugs, the toxic effect of drugs on the liver increases. The simultaneous use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

The absorption rate of paracetamol may increase with simultaneous use with metoclopramide and domperidone and may decrease when used with colestyramine. Paracetamol reduces the effectiveness of diuretics. Coumarin derivatives (warfarin) with prolonged use of paracetamol increase the risk of bleeding. Do not use simultaneously with alcohol. Under the influence of paracetamol T_½ chloramphenicol increases 5 times.

Caffeine: cimetidine, hormonal contraceptives, isoniazid enhance the effect of caffeine.

Caffeine reduces the effect of opioid analgesics, anxiolytics, sleeping pills and sedatives, is an antagonist of drugs for anesthesia and other drugs that depress the central nervous system, a competitive antagonist of drugs that depress the central nervous system, a competitive antagonist of adenosine drugs, ATP. With the simultaneous use of caffeine with ergotamine, the absorption of ergotamine in the gastrointestinal tract improves, with thyrotropic drugs, the thyroid effect increases. Caffeine reduces the concentration of lithium in the blood. Caffeine increases the effect (improves bioavailability) of antipyretic analgesics, potentiates the effects of xanthine derivatives, α- and β-adrenergic agonists, and psychostimulants.

Acetylsalicylic acid: simultaneous use with uricosuric agents, such as benzobromarone, probenecid, reduces the effect of uric acid excretion (due to competition of excretion of uric acid by the renal tubules). With simultaneous use with digoxin, the concentration of the latter in blood plasma increases due to a decrease in renal excretion. ACE inhibitors in combination with high doses of acetylsalicylic acid cause a decrease in glomerular filtration due to inhibition of vasodilator prostaglandins and a decrease in the severity of the hypotensive effect.

Selective serotonin reverse inhibitors: increased risk of bleeding from the upper digestive tract due to the possibility of a synergistic effect. With simultaneous use with valproic acid, acetylsalicylic acid displaces it from its connection with blood plasma proteins, increasing toxicity.

The drug enhances the effect of agents that reduce blood coagulation and platelet aggregation, side effects of corticosteroids, sulfonylureas, methotrexate.

Combinations with barbiturates, anticonvulsants, salicylates, rifampicin, and alcohol should be avoided.

Overdose

Symptoms of an overdose of paracetamol.in adults who took paracetamol at a dose of ≥10 g, in children who took the drug at a dose of 150 mg / kg of body weight, liver damage is possible. in patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. Johns wort or other drugs that induce liver enzymes, regular intake of excess ethanol; glutathione cachexia (digestive disorders, cystic fibrosis, HIV infection, hunger, )) intake of ≥5 g of paracetamol can lead to liver damage. in the first 24 hours, the following symptoms may occur: pallor, nausea, vomiting, anorexia, abdominal pain. liver damage can occur 12–48 hours after an overdose. impaired glucose metabolism and metabolic acidosis may occur. with severe poisoning, liver failure can progress to encephalopathy, hemorrhage, hypoglycemia, and to whom it can be fatal. arthritis with acute tubular necrosis can manifest itself as severe lumbar pain, hematuria, proteinuria and develop even in the absence of severe liver damage. cardiac arrhythmia and pancreatitis were also noted.

With prolonged use of the drug in high doses from the hemopoietic organs, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia can develop. When taking the drug in high doses from the central nervous system, dizziness, psychomotor agitation, and disorientation are possible; from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

In case of an overdose, emergency medical care is needed. The patient should be taken to the hospital immediately, even if there are no early symptoms of an overdose. Symptoms may be limited by nausea and vomiting, or may not reflect the severity of an overdose or the risk of organ damage. Activated charcoal treatment should be considered if an excessive dose of paracetamol was taken within 1 hour. The plasma concentration of paracetamol should be measured ≥4 hours after administration (earlier concentrations are unreliable). Treatment with N-acetylcysteine ​​can be applied within 24 hours after taking paracetamol, but the maximum protective effect is obtained when it is used within 8 hours after administration.

The effectiveness of the antidote decreases sharply after this time. If necessary, N-acetylcysteine ​​is administered iv to the patient according to the established list of doses. In the absence of vomiting, methionine can be administered orally as an appropriate alternative in remote areas outside the hospital.

Symptoms of an overdose of acetylsalicylic acid. An overdose of salicylates is possible due to chronic intoxication resulting from prolonged therapy (the use of 100 mg / kg / day for more than 2 days can cause toxic effects), as well as due to acute intoxication, which is life threatening (overdose) and the reasons for which there may be accidental use by children or inadvertent overdose.

Chronic salicylate poisoning can be hidden, since its signs are nonspecific. Moderate chronic intoxication caused by salicylates, or salicylism, is noted, as a rule, only after repeated doses in high doses. The main symptoms: imbalance, dizziness, ringing in the ears, deafness, increased sweating, nausea and vomiting, headache, confusion. These symptoms can be controlled by dose reduction. Tinnitus is possible with a concentration of salicylates in the blood plasma of 150-300 μg / ml. Serious adverse reactions are noted at a concentration of salicylates in blood plasma of 300 μg / ml. Acute intoxication is evidenced by a pronounced change in the acid-base balance, which may differ depending on the age and severity of intoxication.The severity of the condition cannot be determined only on the basis of the concentration of salicylates in blood plasma.

Symptoms of an overdose of caffeine. High doses of caffeine can cause pain in the epigastric region, vomiting, diuresis, rapid breathing, extrasystole, tachycardia or cardiac arrhythmia, effects on the central nervous system (dizziness, insomnia, nervous excitement, irritability, affect state, anxiety, tremor, convulsions).

Treatment. In case of an overdose, emergency medical attention is necessary, even if there are no symptoms of an overdose. The use of methionine orally or acetylcysteine ​​can cause a positive effect within 48 hours after an overdose. It is also necessary to apply generally supportive measures, symptomatic therapy, including the use of beta-adrenergic antagonists, which can eliminate cardiotoxic effects.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.