Instructions Upsarin Upsa 500 mg effervescent tablets 500 mg strip No. 16
Composition
active ingredient: acetylsalicylic acid;
1 tablet contains acetylsalicylic acid 500 mg;
excipients: sodium bicarbonate, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium carbonate, aspartame (E 951), povidone (K30), crospovidone, orange flavoring.
Dosage form
Effervescent tablets.
Main physicochemical properties: flat white tablets with beveled edges, with a score, soluble in water with the formation of an effervescent reaction.
Pharmacotherapeutic group
Analgesics and antipyretics. ATX code N02B A01.
Pharmacological properties
Pharmacodynamics
It has analgesic, anti-inflammatory, antipyretic effects. Acetylsalicylic acid, due to irreversible inhibition of the cyclooxygenase enzyme (COX), inhibits the biosynthesis of prostaglandins. In the focus of inflammation, it reduces capillary permeability, reduces the activity of hyaluronidase, limits the energy supply of the inflammatory process by inhibiting the formation of ATP. Reduces the excitation of thermoregulation and pain centers. In addition, acetylsalicylic acid inhibits platelet aggregation by blocking the synthesis of thromboxane A2 by platelets.
The drug is available in the form of effervescent tablets with buffering properties, which reduces the irritating effect of acetylsalicylic acid on the mucous membrane of the gastrointestinal tract.
Pharmacokinetics
Effervescent soluble tablets of the drug are absorbed faster than regular tablets. The maximum concentration of acetylsalicylic acid in the blood plasma is observed 15-40 minutes after administration. The bioavailability of acetylsalicylic acid varies depending on the dose: it is approximately 60% when used less than 500 mg and 90% when used more than 1 g due to the saturation of the hydrolysis process in the liver. Acetylsalicylic acid is rapidly hydrolyzed to form salicylic acid, which also has pharmacological activity. Acetylsalicylic acid and salicylic acid are rapidly distributed throughout all body tissues. These acids penetrate the placental barrier and also enter breast milk. Salicylic acid is intensively bound to blood plasma proteins (90%). The half-life of acetylsalicylic acid from blood plasma is 15-20 minutes, and salicylic acid is 2-4 hours.
Acetylsalicylic acid is metabolized mainly in the liver and excreted mainly in the urine in the form of salicylic, salicyluric, gentesic acids and glucuronides.
Indication
For symptomatic treatment of headache, toothache; muscle and joint pain; back pain.
For symptomatic relief of pain and fever in colds.
Contraindication
Individual hypersensitivity to acetylsalicylic acid, other salicylates or any component of the drug; phenylketonuria, since the drug contains aspartame; metabolic or respiratory alkalosis, hypocalcemia, decreased acidity of gastric juice, since the drug contains sodium bicarbonate and anhydrous citric acid; bronchial asthma caused by the use of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs; exacerbation of gastric and duodenal ulcers; congenital (hemophilia) or acquired hemorrhagic diseases; increased risk of bleeding; severe liver failure; severe renal failure; severe heart failure resistant to treatment; simultaneous use with methotrexate in doses exceeding 20 mg/week; simultaneous use of high doses of the drug with indirect anticoagulants, especially in the treatment of rheumatic diseases; III trimester of pregnancy.
Interaction with other medicinal products and other types of interactions
Acetylsalicylic acid increases the plasma concentration of digoxin due to reduced renal excretion, the use of high doses of acetylsalicylic acid enhances the effect of hypoglycemic drugs due to its hypoglycemic effect and displacement of sulfonylureas from plasma protein binding, and acetylsalicylic acid enhances the effect of some anticonvulsants, such as valproic acid and phenytoin; enhances the toxicity of valproic acid due to displacement from the protein-bound state, when used simultaneously with alcohol, it increases damage to the gastrointestinal mucosa and increases the duration of bleeding due to an additive effect.
Acetylsalicylic acid, like other nonsteroidal anti-inflammatory drugs, as well as ticlopidine, clopidogrel, trofiban, can have an antiplatelet effect on platelets. The simultaneous use of various drugs that inhibit platelet aggregation may increase the risk of hemorrhagic phenomena.
Concomitant use with heparin or other anticoagulants requires constant monitoring of patients.
Drugs containing sodium bicarbonate increase the renal clearance of acid-containing compounds, such as salicylates and barbiturates, tetracyclines (especially doxycycline), and lithium.
Increased urinary alkalinity increases the half-life of alkaline drugs such as sympathomimetics and may cause toxic effects due to decreased urinary excretion of ephedrine, amphetamines, flecainide, and mecamylamine.
Interactions of citric acid: citrate salts increase the absorption of aluminum from the gastrointestinal tract, especially in patients with impaired renal function.
Contraindicated combinations.
Oral anticoagulants. In combination with anti-inflammatory (≥ 1 g/dose and or ≥ 3 g/day) or analgesic or antipyretic doses (≥ 500 mg/dose and or < 3 g/day) of acetylsalicylic acid, anticoagulants are displaced from plasma protein binding. Increased risk of bleeding, especially in patients with a history of gastric or duodenal ulcer.
Methotrexate in doses exceeding 20 mg/week. In combination with anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid, the hematological toxicity of methotrexate increases (reduction in renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).
Undesirable combinations.
Acetazolamide. In combination with high doses of acetylsalicylic acid, the frequency of side effects increases, especially metabolic acidosis, due to a decrease in the elimination of acetylsalicylic acid due to the interaction with acetazolamide.
Anagrelide: Increased risk of bleeding.
Oral anticoagulants. In combination with analgesic or antipyretic or antiplatelet doses (from 50 to 375 mg/day) of acetylsalicylic acid, the risk of bleeding increases, therefore it is necessary to monitor blood coagulation parameters and especially the duration of bleeding.
Other non-steroidal anti-inflammatory drugs. In combination with anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid, the risk of gastric and duodenal ulcers and gastrointestinal bleeding increases.
Clopidogrel (except for the approved indications for this combination in patients with acute coronary syndrome). Increased risk of bleeding due to antiplatelet effects on platelets.
Glucocorticoids (except for hormone replacement therapy with hydrocortisone). In combination with anti-inflammatory doses of acetylsalicylic acid, the risk of bleeding increases.
Heparins. In combination with anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid, the risk of bleeding increases (inhibition of platelet function and damage to the gastrointestinal mucosa).
Pemetrexed: In combination with anti-inflammatory doses of acetylsalicylic acid in patients with mild to moderate renal impairment, the risk of pemetrexed toxicity is increased due to a decrease in its renal clearance.
Ticagrelor (except for the approved indications for this combination in acute coronary syndromes). Increased risk of bleeding due to antiplatelet effects on platelets.
Ticlopidine: Increased risk of bleeding due to antiplatelet effect on platelets.
Uricosuric agents (benzbromarone, probenecid). Reduction of the uricosuric effect due to competition for the excretion of uric acid in the renal tubules.
Combinations requiring caution.
Antidiabetic agents (insulins). With the simultaneous use of high doses of acetylsalicylic acid and oral antidiabetic drugs from the group of sulfonylurea derivatives or insulin, the hypoglycemic effect of the latter is enhanced due to the hypoglycemic effect of acetylsalicylic acid and the displacement of sulfonylurea bound to blood plasma proteins.
Clopidogrel (except for the approved indications for this combination in patients with acute coronary syndrome). Increased risk of bleeding due to antiplatelet effects on platelets.
Diuretics and angiotensin-converting enzyme inhibitors. In combination with anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid, the development of acute renal failure in dehydrated patients is possible (reduction in glomerular filtration due to inhibition of prostaglandin synthesis, in addition, the hypotensive effect is reduced).
Systemic glucocorticosteroids (except hydrocortisone), which are used for replacement therapy in Addison's disease, during the period of corticosteroid treatment reduce the level of salicylates in the blood and increase the risk of overdose after the end of treatment (corticosteroids enhance the excretion of salicylates).
When methotrexate is used in doses ≤ 20 mg/week in combination with anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid, the hematological toxicity of methotrexate increases (reduction in renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).
Pemetrexed: In patients with normal renal function, there is a risk of increased toxicity of pemetrexed due to reduced renal clearance.
Ticagrelor (for the approved indications for this combination in acute coronary syndromes). Increased risk of bleeding due to antiplatelet effects on platelets.
Drugs acting locally in the gastrointestinal tract, antacids and activated charcoal. Decreased absorption of acetylsalicylic acid in the gastrointestinal tract. It is recommended to take such drugs separately from acetylsalicylic acid with an interval of at least 2 hours.
Combinations to consider.
Oral anticoagulants. In combination with antiplatelet doses of acetylsalicylic acid, the risk of bleeding increases, especially in patients with a history of gastric or duodenal ulcer.
Other nonsteroidal anti-inflammatory drugs. In combination with antiplatelet doses of acetylsalicylic acid, the risk of gastric and duodenal ulcers increases.
Deferasirox. In combination with anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid, the risk of gastric ulcers and gastrointestinal bleeding increases.
Glucocorticoids (except for hormone replacement therapy with hydrocortisone). In combination with analgesic or antipyretic doses of acetylsalicylic acid, the risk of bleeding increases.
Heparins in therapeutic doses/elderly patients. In combination with anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid, the risk of bleeding increases due to inhibition of platelet function and the negative effect of acetylsalicylic acid on the gastrointestinal mucosa.
Heparins when used in prophylactic doses. The simultaneous use of drugs that act on different links of hemostasis increases the risk of bleeding. Therefore, when using a combination of heparins in prophylactic doses with acetylsalicylic acid in patients under 65 years of age, regardless of its dose, the need for clinical and, possibly, biological monitoring should be taken into account.
Selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline). Increased risk of bleeding.
Thrombolytics: Increased risk of bleeding.
Intrauterine devices. Risk of reduced contraceptive effect.
Gastrointestinal local agents: oxides and hydroxides of magnesium, aluminum, calcium salts. Increased renal excretion of salicylates due to alkalinization of urine.
Application features
Acetylsalicylic acid should be used with special caution in the following cases: individual hypersensitivity to other analgesic, anti-inflammatory, antirheumatic drugs and the presence of other types of allergies; history of gastric or duodenal ulcer, as well as gastrointestinal bleeding; concomitant treatment with anticoagulants; impaired renal function or renal failure; circulatory disorders (e.g. renal vascular disease, congestive heart failure, decreased circulating blood volume, massive surgical interventions, sepsis or significant blood loss), since acetylsalicylic acid may further increase the risk of kidney damage and cause acute renal failure; impaired liver function.
During surgical interventions (including dental), the use of medicines containing acetylsalicylic acid may increase the likelihood of bleeding due to inhibition of platelet aggregation for some time after the use of acetylsalicylic acid.
Acetylsalicylic acid can provoke bronchospasm and cause asthma attacks or other hypersensitivity reactions. Risk factors include a history of asthma, hay fever, nasal polyps or chronic respiratory diseases. This also applies to patients who have shown allergic reactions (such as skin reactions, itching, urticaria) to other substances. To prevent overdose, it should be ensured that other medicines that the patient is taking do not contain acetylsalicylic acid.
Caution should be exercised when prescribing the drug to patients who use hypoglycemic agents (regular monitoring of blood sugar levels is required), glucocorticoids, antihypertensive agents, diuretics (it is necessary to ensure sufficient hydration of the patient and monitoring of kidney function), antacids that are not absorbed and contain magnesium and/or aluminum hydroxide (they should be used no earlier than 2 hours after using the drug).
Patients on a sodium-free diet should remember that 1 tablet of the drug contains 388.5 mg of sodium.
When using low doses of acetylsalicylic acid, uric acid excretion may be reduced. This may lead to a gout attack in patients with reduced uric acid excretion.
This medication should be used with caution in patients with congestive heart failure and a history of edema, as well as in patients with arterial hypertension, eclampsia, and algosteronism, since the drug contains anhydrous citric acid.
Ability to influence reaction speed when driving vehicles or other mechanisms
Does not affect.
Use during pregnancy or breastfeeding
During the first and second trimesters of pregnancy, medicinal products containing acetylsalicylic acid should not be prescribed, except in cases of extreme necessity. If medicinal products containing acetylsalicylic acid are used by women planning a pregnancy, as well as during the first and second trimesters of pregnancy, their doses should be as low and the course of treatment as short as possible. The use of salicylates in the first trimester of pregnancy has been associated with an increased risk of congenital malformations (cleft palate, heart defects, gastroschisis) in some retrospective epidemiological studies. According to preliminary estimates, with long-term use of the drug, it is not recommended to use acetylsalicylic acid in a dose exceeding 150 mg/day.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Available epidemiological data indicate a risk of miscarriage and foetal malformations after the use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with increasing dose and duration of therapy. According to the available data, the association between the use of acetylsalicylic acid and an increased risk of miscarriage has not been confirmed. Animal studies indicate reproductive toxicity.
Acetylsalicylic acid is contraindicated during the third trimester of pregnancy.
In the third trimester of pregnancy, the use of salicylates in high doses (more than 500 mg/day) can lead to miscarriage and weakening of labor contractions, as well as cardiopulmonary toxicity (premature closure of the ductus arteriosus and development of pulmonary hypertension) or impaired renal function in the fetus, which can progress to renal failure with a decrease in the amount of amniotic fluid.
Prostaglandin synthesis inhibitors used in late pregnancy may cause increased bleeding time and antiplatelet effects in the mother and fetus, which may occur even at very low doses.
The use of acetylsalicylic acid in large doses shortly before delivery can lead to intracranial bleeding, especially in premature babies.
Therefore, except in extremely special cases due to cardiological or obstetric medical indications with the use of special monitoring, the use of acetylsalicylic acid during the third trimester of pregnancy is contraindicated.
Acetylsalicylic acid passes into breast milk, so it is not advisable to use the drug during breastfeeding.
There are no data on the effect of acetylsalicylic acid on fertility.
Method of administration and doses
Dissolve the tablet in a glass of water immediately before use.
Adults and children over 15 years of age (with a body weight of over 50 kg).
Usually take 1 effervescent tablet of 500 mg, if necessary, repeated use is possible after 4 hours. In case of more intense pain or hyperthermia, 2 tablets can be used at the same time, but repeated use should be no earlier than after 4 hours, with this dosage regimen, no more than 6 effervescent tablets should be taken per day. Systematic administration will help to avoid fluctuations in temperature reaction.
The maximum daily dose is 3 g, i.e. 6 effervescent tablets per day.
Elderly patients.
The maximum daily dose is 2 g, i.e. 4 effervescent tablets per day.
For patients with concomitant liver or kidney dysfunction, it is necessary to reduce the dose of the drug or increase the interval between applications.
Application period.
The patient should be aware that without consulting a doctor, acetylsalicylic acid can be used for no more than 3 days to treat a hyperthermic reaction and no more than 5 days to treat pain.
Children
The drug should be used in children over 15 years of age. Medicines containing acetylsalicylic acid should not be used in children with acute respiratory viral infections (ARI), which are accompanied or not accompanied by an increase in body temperature. With some viral diseases, especially influenza A, influenza B and chickenpox, there is a risk of developing Reye's syndrome, which is a very rare but life-threatening disease that requires urgent medical intervention. The risk may be increased if acetylsalicylic acid is used as a concomitant medicine, but a causal relationship in this case has not been proven. If these conditions are accompanied by prolonged vomiting, this may be a sign of Reye's syndrome.
Overdose
Salicylate toxicity can result from intoxication due to prolonged use of therapeutic doses or acute intoxication (using >100 mg/kg/day for more than two days), which is potentially life-threatening.
Chronic salicylate poisoning may be asymptomatic or have no specific symptoms. Moderate salicylate intoxication, or salicylism, usually develops only after repeated use of high doses.
Symptoms: balance disorders, dizziness, tinnitus, deafness, sweating, nausea, vomiting, headache and depression of consciousness. These symptoms can be controlled by reducing the dose. Alkalemia and alkaluria may also be observed. Tinnitus may occur at plasma concentrations of 150 to 300 μg/ml. More severe side effects occur at concentrations above 300 μg/ml. Increased respiratory rate, hyperventilation, respiratory alkalosis may also be observed. In moderate to severe intoxication, respiratory alkalosis with compensatory metabolic acidosis may develop, as well as hyperpyrexia, non-cardiogenic pulmonary edema up to respiratory arrest, asphyxia; arrhythmia, ECG changes, arterial hypotension up to cardiogenic shock; dehydration, acidemia, aciduria, oliguria up to renal failure, impaired glucose metabolism, ketosis; gastrointestinal bleeding; hematological changes – from platelet suppression to coagulopathies; from the nervous system – toxic encephalopathy and CNS depression, manifested as drowsiness, depression of consciousness up to the development of coma and seizures.
A feature of acute poisoning is a severe disturbance of acid-base balance, which may vary according to age and severity of intoxication.
The most common sign in children is metabolic acidosis. The severity of poisoning cannot be assessed using plasma concentration data alone. Absorption of acetylsalicylic acid may be delayed due to inhibition of gastric emptying, formation of gastric calculi, or use of enteric-coated drugs. Emergency care for acetylsalicylic acid poisoning is determined by the severity, stage, and clinical symptoms and follows standard emergency care for poisoning. Primary measures should be aimed at accelerating the elimination of the drug and restoring electrolyte and acid-base balance.
The following symptoms and laboratory changes may occur as a result of the complex pathophysiological effects of salicylate poisoning.
Symptoms.
Mild to moderate intoxication: tachypnea, hyperventilation, respiratory alkalosis, sweating, nausea, vomiting. Laboratory data: alkalosis, alkaline urine reaction.
Emergency care: gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis.
Severe poisoning: respiratory alkalosis with compensatory metabolic acidosis, hyperpyrexia, tinnitus, deafness. Tinnitus may occur at plasma concentrations of 150 to 300 μg/mL. More severe side effects occur at concentrations above 300 μg/mL.
Respiratory system: from hyperventilation, non-cardiogenic pulmonary edema to respiratory arrest and asphyxia, laboratory data - alkalosis, alkaline urine reaction.
Cardiovascular system: from cardiac arrhythmias, arterial hypotension to cardiac arrest. Fluid and electrolyte loss: dehydration, oliguria, renal failure. Laboratory data - hypokalemia, hypernatremia, hyponatremia, renal dysfunction.
Impaired glucose metabolism, ketosis, is manifested in laboratory tests as hyperkalemia, hypoglycemia (especially in children), and increased levels of ketone bodies.
Gastrointestinal tract: gastrointestinal bleeding.
Changes in the blood system: from inhibition of platelet function to coagulopathies. Laboratory data - prolongation of prothrombin time, hypoprothrombinemia.
Neurological disorders: toxic encephalopathy and CNS depression – from lethargy, depression of consciousness to coma and seizures.
Emergency care: gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, hemodialysis, and in severe cases, infusion of fluid and electrolytes.
Adverse reactions
Gastrointestinal: Dyspepsia, epigastric pain and abdominal pain; in isolated cases, gastrointestinal inflammation, erosive-ulcerative lesions of the gastrointestinal tract, which in isolated cases may cause gastrointestinal bleeding and perforation with corresponding laboratory and clinical manifestations.
Rarely - transient hepatic failure with increased liver transaminase levels.
Bleeding can lead to acute and chronic posthemorrhagic anemia/iron deficiency anemia (due to so-called occult microbleeding) with corresponding laboratory manifestations and clinical symptoms such as asthenia, pallor of the skin, hypoperfusion.
Hemolysis and the development of hemolytic anemia have been reported in patients with severe glucose-6-phosphate dehydrogenase deficiency.
The risk of bleeding may persist for 4 to 8 days after stopping acetylsalicylic acid. This may increase the risk of bleeding during surgery.
Allergic reactions.
In patients with individual hypersensitivity to salicylates, allergic reactions may develop, including symptoms such as rash, urticaria, edema, itching, rhinitis, and nasal congestion.
In patients with bronchial asthma, an increased frequency of bronchospasm; allergic reactions of mild to moderate severity, potentially affecting the skin, respiratory system, gastrointestinal tract and cardiovascular system, may occur. Severe reactions, including anaphylactic shock and non-cardiogenic pulmonary edema, have been observed very rarely.
Nervous system: Headache, dizziness, tinnitus, and a feeling of hearing loss have been reported, which may be signs of overdose.
On the part of the genitourinary system: Kidney damage and the development of acute renal failure have been reported.
Adverse reactions due to the presence of sodium bicarbonate and citric acid in the composition of the medicinal product.
Gastrointestinal: Belching, flatulence.
Metabolism: Hypokalemia, hypercalcemia, metabolic alkalosis, accompanied by dyspnea, muscle effects (such as weakness, muscle hypertonia, twitching and tetany, especially with hypercalcemia and changes in the nervous system).
Expiration date
3 years.
Storage conditions
Store in the original packaging. Store at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
4 tablets in a strip, 4 strips in a cardboard box.
Vacation category
Without a prescription.
Producer
UPSA SAS.
Location of the manufacturer and its business address
304, Avenue Dr. Jean Bru, 47000 Agen, France.
