Instructions for Citramon Maxi tablets No. 20
Composition
active ingredients: paracetamol, caffeine, acetylsalicylic acid;
1 tablet contains: paracetamol 250 mg, caffeine 65 mg, acetylsalicylic acid 250 mg;
excipients: low-substituted hydroxypropylcellulose, anhydrous citric acid, pregelatinized starch, microcrystalline cellulose, stearic acid.
Dosage form
Pills.
Main physicochemical properties: oblong tablets with a biconvex surface, white or almost white in color. Grayish inclusions are allowed.
Pharmacotherapeutic group
Analgesics. Other analgesics and antipyretics. Acetylsalicylic acid, combinations without psycholeptics. ATC code N02B A51.
Pharmacological properties
Pharmacodynamics
The drug has analgesic, antipyretic and anti-inflammatory effects. The components that make up the drug enhance each other's effects.
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 the influence of endogenous pyrogens. The analgesic effect has both peripheral and central origin: peripheral effect - inhibition of prostaglandin synthesis in inflamed tissues; central effect - effect on the hypothalamic centers. Acetylsalicylic acid also reduces platelet aggregation.
Paracetamol has analgesic, antipyretic and very weak anti-inflammatory effects, which are associated with its effect on the thermoregulation center in the hypothalamus and its weak ability to inhibit prostaglandin synthesis in peripheral tissues.
Caffeine stimulates the central nervous system. It also enhances positive conditioned reflexes, stimulates motor activity, weakens the effect of hypnotics and narcotics, and enhances the effect of analgesics and antipyretics.
Pharmacokinetics
Acetylsalicylic acid.
Absorbed rapidly and completely after oral administration. Predominantly hydrolyzed in the gastrointestinal tract, liver and blood to salicylate, which is then metabolized mainly in the liver.
Paracetamol.
After ingestion, absorbed in the gastrointestinal tract, the peak concentration of paracetamol in the blood plasma is observed after 30-120 minutes. Paracetamol is metabolized in the liver and excreted mainly in the urine in the form of glucuronides and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol. The half-life is 1-4 hours. Under normal therapeutic concentrations, the connection with plasma proteins is insignificant, but proportional to the increase in concentrations.
A side hydroxylated metabolite, which is normally formed in the liver in very small amounts and is detoxified mainly by conjugation with hepatic glutathione, can accumulate in paracetamol overdose and cause liver damage.
Caffeine.
The maximum concentration of caffeine is observed between 5 and 90 minutes after taking Citramon Maxi® on an empty stomach. There is no data on its presystemic metabolism. In adults, it is almost completely metabolized in the liver. The elimination rate in adults is individual. The average half-life from blood plasma is 4.9 hours with a range of 1.9-12.2 hours. Caffeine is evenly distributed in all body fluids. The average binding to blood plasma proteins is 35%.
Caffeine is almost completely metabolized by oxidation, demethylation and acetylation and is excreted in the urine. Its main metabolites are 1-methylxanthine, 7-methylxanthine, 1,7-dimethylxanthine (paraxanthine). Among the associated metabolites: 1-methyluracilic acid and 5-acetylamino-6-formylamino-3-methyluracil (AMFU).
There is no cross-interaction of the three active ingredients, as well as an increased risk of interaction with other drugs when using the active ingredients in combination. Due to the combination of the three active ingredients, the content of each of them is set low, which, accordingly, reduces the toxicity of the drug.
Indication
Emergency treatment of headaches and migraine attacks with or without aura.
Contraindication
Hypersensitivity to the components of the drug, hypersensitivity to other xanthine derivatives (theophylline, theobromine), other salicylates; bronchial asthma, urticaria or rhinitis caused by the use of salicylates or other NSAIDs in history; congenital hyperbilirubinemia, severe renal failure or hepatic failure, Gilbert's syndrome, congenital deficiency of glucose-6-phosphate dehydrogenase; blood diseases, hemophilia, hemorrhagic diathesis, hypoprothrombinemia, anemia, leukopenia, increased tendency to bleeding, thrombosis, thrombophlebitis, hemorrhagic diseases; acute gastrointestinal ulcers, gastrointestinal bleeding, surgical interventions accompanied by significant bleeding; severe cardiovascular diseases, including rhythm disturbances, paroxysmal tachycardia, severe atherosclerosis, severe ischemic heart disease, severe heart failure, acute myocardial infarction, severe arterial hypertension, portal hypertension, tendency to vasospasm; states of increased excitement, sleep disorders, old age, alcoholism, glaucoma, hyperthyroidism, acute pancreatitis, prostatic hypertrophy, severe forms of diabetes mellitus.
Use simultaneously with MAO inhibitors, as well as within 2 weeks after their discontinuation. Combination with methotrexate at a dosage of 15 mg/week or more.
Contraindicated in patients taking tricyclic antidepressants or β-blockers.
Interaction with other medicinal products and other types of interactions
Possible types of interactions between active substances.
Acetylsalicylic acid (ASA)
| Use of acetylsalicylic acid in combination with drugs | Possible consequence |
| Other nonsteroidal anti-inflammatory drugs (NSAIDs) | There is an increased risk of gastrointestinal ulcers and bleeding due to synergistic effects. When concomitant use of these agents is necessary, gastroprotectors should be considered if possible. Therefore, the use of this combination is not recommended. |
| Corticosteroids | There is an increased risk of gastrointestinal ulcers and bleeding due to synergistic effects. In patients taking ASA and corticosteroids, especially in the elderly, it is recommended to consider the appropriateness of prescribing gastroprotectors. Systemic glucocorticosteroids reduce the level of salicylates in the blood and increase the risk of overdose after the end of treatment. Therefore, the use of such a combination is not recommended. |
| Oral anticoagulants (e.g., coumarin derivatives) | ASA may enhance the anticoagulant effect. Clinical and laboratory monitoring of bleeding time and prothrombin time is necessary. Therefore, the use of this combination is not recommended. |
| Thrombolytics | There is an increased risk of hemorrhagic complications. In particular, in patients with acute stroke, ASA therapy should not be initiated within the first 24 hours after alteplase administration. Therefore, the use of this combination is not recommended. |
| Heparin | There is an increased risk of hemorrhagic complications. Clinical and laboratory monitoring of bleeding time is necessary. Therefore, the use of this combination is not recommended. |
| Platelet aggregation inhibitors (ticlopidine, clopidogrel, cilostazol) | There is an increased risk of hemorrhagic complications. Clinical and laboratory monitoring of bleeding time is necessary. Therefore, the use of this combination is not recommended. |
| Selective serotonin reuptake inhibitors (SSRIs) | SSRIs, when used concomitantly with ASA, may inhibit coagulation or impair platelet function, leading to hemorrhagic complications in general and gastrointestinal bleeding in particular. Therefore, concomitant use of these agents should be avoided. |
| Digoxin | With simultaneous use, the concentration of digoxin in the blood plasma increases due to a decrease in renal excretion. |
| Phenytoin | Serum levels of phenytoin increase when ASA is administered. Serum levels of phenytoin should be carefully monitored. |
| Valproate | ASA inhibits the metabolism of valproate, and therefore its toxicity may increase. Serum valproate levels should be carefully monitored. |
| Aldosterone antagonists (spironolactone, canrenoate) | ASA may reduce their activity due to inhibition of urinary sodium excretion. Blood pressure should be carefully monitored. |
| Loop diuretics (e.g., furosemide) | ASA may reduce their activity by competition and inhibition of urinary prostaglandins. NSAIDs may cause acute renal failure, especially in dehydrated patients. When diuretics are used concomitantly with ASA, measures should be taken to ensure adequate hydration of the patient and to monitor renal function and blood pressure, especially at the beginning of diuretic therapy. |
| ASA may reduce their activity due to competition and inhibition of urinary prostaglandins. The use of such a combination may lead to acute renal failure in elderly patients and patients with dehydration. At the beginning of therapy, it is recommended to carefully monitor blood pressure and renal function, as well as ensure adequate hydration of the patient. In the case of simultaneous use with verapamil, it is also necessary to monitor bleeding time. |
| Uricosuric agents (e.g., probenecid, sulfinpyrazone) | ASA may reduce their activity by inhibiting tubular resorption, leading to high levels of ASA and uric acid in the blood plasma. |
Methotrexate ≤ 15 mg/week | ASA, like all NSAIDs, reduces the tubular secretion of methotrexate, which increases its plasma concentrations and, consequently, its toxicity. Therefore, concomitant use of NSAIDs is not recommended in patients receiving high doses of methotrexate. The risk of drug interactions between methotrexate and NSAIDs should also be considered in patients receiving low doses of methotrexate, especially in patients with impaired renal function. If combination therapy is necessary, complete blood count, liver and kidney function tests should be monitored, especially during the first days of such therapy. |
| Sulfonylureas and insulin | ASA enhances their hypoglycemic effect, so it may be advisable to slightly reduce the dose of the antidiabetic agent if high doses of salicylates are used. More careful monitoring of blood glucose levels is recommended. |
| Alcohol | There is an increased risk of gastrointestinal bleeding. This combination should be avoided. |
Paracetamol
| Use of paracetamol in combination with drugs | Possible consequence |
| Liver enzyme inducers or substances with potential hepatotoxicity (e.g. alcohol, rifampicin, isoniazid, hypnotics and antiepileptics, including phenobarbital, phenytoin and carbamazepine) | Increased toxicity of paracetamol, which may lead to liver damage, even at doses of paracetamol that are not harmful under other circumstances. In this regard, it is necessary to monitor liver function tests. Concomitant use is not recommended. |
| Chloramphenicol | The risk of increased plasma concentrations of chloramphenicol may increase during therapy with paracetamol. Concomitant use is not recommended. |
| Zidovudine | Against the background of paracetamol therapy, the risk of neutropenia may increase, therefore, it is necessary to monitor the indicators of the hematopoietic system. Simultaneous use is not recommended, except in cases where such use is carried out under the supervision of a physician. |
| Probenecid | Probenecid reduces the clearance of paracetamol, therefore, when used simultaneously with this agent, the dose of paracetamol should be reduced. Concomitant use is not recommended. |
| Oral anticoagulants | Anticoagulant effects are enhanced with repeated use of paracetamol for more than 1 week. Irregular use of paracetamol does not significantly affect coagulation. |
| Propantheline or other agents that slow the evacuation of gastric contents | These agents slow down the absorption of paracetamol. The analgesic effect may be delayed and less pronounced. |
| Metoclopramide or other agents that accelerate the evacuation of gastric contents | These active ingredients accelerate the absorption of paracetamol, increasing its effectiveness and accelerating the onset of the analgesic effect. |
| Cholestyramine | Cholestyramine causes a decrease in the absorption of paracetamol, therefore, if you want to achieve maximum analgesic effect, cholestyramine should be taken no earlier than 1 hour after taking paracetamol. |
Caffeine
| The use of caffeine in combination with drugs | Possible consequence |
| MAO inhibitors | When combined with caffeine, a dangerous increase in blood pressure is possible, so this combination is contraindicated. |
| Sleeping pills (e.g., benzodiazepines, barbiturates, antihistamines) | When used concomitantly, the hypnotic effect may be reduced or the anticonvulsant effect of barbiturates may be suppressed. Therefore, concomitant use is not recommended. If concomitant use of these drugs is necessary, it may be more beneficial to take the combination in the morning. |
| Lithium preparations | Serum lithium levels increase after caffeine withdrawal, as caffeine may increase renal clearance of lithium. Therefore, a reduction in lithium dosage may be necessary during caffeine withdrawal. Therefore, concomitant use is not recommended. |
| Patients with alcohol dependence who are being treated for their dependence with disulfiram should be advised to avoid caffeine to prevent the risk of worsening alcohol withdrawal syndrome due to caffeine-induced cardiovascular and cerebral excitation. |
| Ephedrine-type substances | The use of such a combination may increase the risk of dependence. Therefore, simultaneous use is not recommended. |
| Sympathomimetics or levothyroxine | When using this combination, the tachycardic effect may be more pronounced due to synergistic effects. Therefore, simultaneous use is not recommended. |
| Theophylline | With simultaneous use, the excretion of theophylline may decrease. |
| Quinolone antibacterials (ciprofloxacin, enoxacin, and pipemidic acid), terbinafine, cimetidine, fluvoxamine, and oral contraceptives | Increased half-life of caffeine due to inhibition of the hepatic cytochrome P450 pathway. Therefore, patients with impaired liver function, cardiac arrhythmias, or latent epilepsy should avoid caffeine. |
| Nicotine, phenytoin, and phenylpropanolamine | These substances increase the half-life of caffeine. |
| Clozapine | Caffeine increases serum levels of clozapine, likely due to an interaction mediated by both pharmacokinetic and pharmacodynamic mechanisms. Serum levels of clozapine should be monitored. Therefore, concomitant use is not recommended. |
| Analgesics-antipyretics | Increasing their effect |
Impact on laboratory test results
The use of high doses of acetylsalicylic acid may affect the results of several clinical chemistry laboratory tests. The use of paracetamol may affect the results of uric acid determinations when the analysis is performed using the phosphotungstic acid reagent method and the results of glycemia determinations when the analysis is performed using the glucose oxidase/peroxidase method. Caffeine may antagonize the effect of dipyridamole on myocardial blood flow and thus affect the results of this test. It is recommended to stop taking caffeine 8-12 hours before the start of this test.
Application features
You should consult a doctor before using the medicine.
Do not exceed the indicated doses of the drug. For short-term use.
Do not use the drug with other drugs containing paracetamol or acetylsalicylic acid.
Patients with liver and kidney dysfunction should reduce the dose of the drug or increase the interval between doses. In case of impaired kidney and liver function, the interval between doses should be at least 8 hours.
Since acetylsalicylic acid, like all non-selective non-steroidal anti-inflammatory drugs, causes irritation of the mucous membrane of the digestive tract, the drug should be taken only after meals, washed down with water, alkaline mineral waters, sodium bicarbonate solution (preferably milk).
With prolonged use of the drug, it is necessary to check for the presence of blood in the stool to detect ulcerogenic effects and perform blood tests (effect on platelet aggregation, some anticoagulant activity).
In case of hyperthermia, the drug should be prescribed only if other analgesics and antipyretics are ineffective, as there is a risk of developing Reye's syndrome. If vomiting occurs as a result of using the drug, Reye's syndrome should be suspected.
It should be noted that patients with alcoholic liver disease are at increased risk of hepatotoxicity from paracetamol. Liver disease increases the risk of liver damage from paracetamol. The risk of overdose is higher in patients with non-cirrhotic alcoholic liver disease.
Patients with severe infections such as sepsis, which are accompanied by a decrease in glutathione levels, are at increased risk of metabolic acidosis when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. You should seek immediate medical attention if these symptoms occur.
During surgical operations (including dental), the use of drugs containing acetylsalicylic acid increases the likelihood of bleeding, which is due to the inhibition of platelet aggregation for some time after the use of acetylsalicylic acid. The use of the drug should be discontinued 5-7 days before surgery (to reduce the risk of increased bleeding).
The patient must inform the doctor in advance about taking the drug Citramon Maxi®.
Acetylsalicylic acid, which is part of the drug, even in small doses can reduce the excretion of uric acid from the body, which can cause an acute attack of gout in sensitive patients.
During treatment with the drug, it is not recommended to consume excessive amounts of beverages containing caffeine (e.g. coffee, tea). This may cause sleep disturbances, tremors, feelings of tension, irritability, and an unpleasant feeling behind the chest due to palpitations.
It is necessary to consult a doctor for patients who take analgesics every day for mild arthritis; if the patient uses warfarin or similar drugs that have an anticoagulant effect; when using the drug before starting to take ibuprofen as a painkiller.
It should not be used in case of hypersensitivity to analgesics, anti-inflammatory, antirheumatic drugs, and with caution, with simultaneous use of anticoagulants, in patients with circulatory disorders (e.g. renal vascular pathology, congestive heart failure, hypovolemia, extensive surgery, sepsis or severe bleeding), since acetylsalicylic acid also increases the risk of renal dysfunction and acute renal failure. Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation.
The drug may affect the results of laboratory tests for blood glucose and uric acid.
It is not recommended to use the drug without consulting a doctor for more than 5 days as an analgesic and more than 3 days as an antipyretic.
Do not drink alcoholic beverages during treatment (increased risk of gastrointestinal bleeding).
If symptoms persist, you should consult a doctor.
If the headache becomes persistent, you should see a doctor.
It is contraindicated for patients with bronchial asthma, with increased bleeding, and with special caution during simultaneous therapy with anticoagulants (coumarin and heparin), with impaired liver function and kidney diseases, as well as with simultaneous anti-inflammatory therapy.
Ability to influence reaction speed when driving vehicles or other mechanisms
Since adverse reactions from the nervous system (dizziness, increased excitability, impaired orientation and attention) are possible, when using the drug, driving and work requiring increased attention and speed of psychomotor reactions should be avoided.
Use during pregnancy or breastfeeding
Do not use the medicine during pregnancy or breastfeeding.
Acetylsalicylic acid has a teratogenic effect; when used during pregnancy in the first trimester, it leads to a developmental defect - cleft palate, in the third trimester - to inhibition of labor activity (inhibition of prostaglandin synthesis), closure of the ductus arteriosus in the fetus, which causes pulmonary vascular hyperplasia and hypertension in the vessels of the small circulation, impaired kidney function with the possible subsequent development of renal failure with oligohydramnios, prolongation of bleeding time, antiplatelet effect, which can occur even after the use of very low doses.
Caffeine increases the risk of spontaneous miscarriage.
The drug passes into breast milk, which increases the risk of bleeding in children due to impaired platelet function.
Method of administration and doses
For headaches:
The usual recommended dose is 1 tablet; an additional 1 tablet may be taken at 4-6 hour intervals. In case of more intense pain, 2 tablets may be taken. If necessary, an additional 2 tablets may be taken at 4-6 hour intervals.
Citramon Maxi® is intended for occasional use. In the treatment of headache, the duration of therapy should be up to 4 days.
For migraine:
When symptoms appear, take 2 tablets. If necessary, it is allowed to take 2 additional tablets with an interval between doses of 4-6 hours.
Citramon Maxi® is intended for occasional use. In the treatment of migraine, the duration of therapy should be up to 3 days.
For both headache and migraine, the maximum daily dose of the drug is 6 tablets (in 3 doses). This drug should not be used for longer or in higher doses than recommended without consulting a doctor.
Take each dose of the medicine with a full glass of water.
Do not take with other medicines containing paracetamol.
Patients with hepatic or renal insufficiency should be aware that although the effect of hepatic and renal disease on the pharmacokinetics of Citramon Maxi® has not been studied, given the mechanism of action of acetylsalicylic acid and paracetamol, hepatic and renal disorders may be exacerbated. For this reason, Citramon Maxi® is contraindicated in patients with severe hepatic or renal insufficiency and should be used with caution in patients with mild to moderate hepatic or renal insufficiency.
Citramon Maxi® should be used with caution in elderly patients, especially those with low body weight.
The drug should not be used in children due to the risk of developing Reye's syndrome (hyperpyrexia, metabolic acidosis, nervous system and mental disorders, vomiting, liver dysfunction) in case of hyperthermia against the background of viral diseases.
Overdose
Symptoms of paracetamol overdose.
Liver damage is possible in adults who have taken 10 g or more of paracetamol, and in children who have taken more than 150 mg/kg of body weight. In patients with risk factors (long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John's wort or other drugs that induce liver enzymes; regular intake of excessive amounts of ethanol; glutathione cachexia (digestive disorders, cystic fibrosis, HIV infection, starvation, cachexia) taking 5 g or more of paracetamol can lead to liver damage.
Symptoms of overdose in the first 24 hours: pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12-48 hours after overdose. Glucose metabolism disorders and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma and be fatal. Acute renal failure with acute tubular necrosis may present with severe lumbar pain, hematuria, proteinuria and may develop even in the absence of severe renal damage. Cardiac arrhythmia and pancreatitis have also been reported.
With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may develop from the hematopoietic system. When taking large doses, dizziness, psychomotor agitation and disorientation may occur from the CNS; from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).
Treatment: In case of overdose, urgent medical attention is required. The patient should be taken to hospital immediately, even if there are no early symptoms of overdose. Symptoms may be limited to nausea and vomiting or may not reflect the severity of the overdose or the risk of organ damage. Treatment with activated charcoal should be considered if an overdose of paracetamol has been taken within 1 hour. The concentration of paracetamol in the blood plasma should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine can be used within 24 hours of paracetamol ingestion, but the maximum protective effect is obtained when it is used within 8 hours of ingestion. The effectiveness of the antidote decreases sharply after this time. If necessary, the patient should be given N-acetylcysteine intravenously according to current recommendations. In the absence of vomiting, oral methionine can be used as a suitable alternative in remote areas outside the hospital. General supportive measures should also be applied.
Symptoms of acetylsalicylic acid overdose.
Salicylate overdose is possible due to chronic intoxication resulting from long-term therapy (administration of more than 100 mg/kg per day for more than 2 days may cause toxic effects), as well as acute intoxication, which is life-threatening (overdose) and may be caused by accidental use by children or an unforeseen overdose.
Chronic salicylate poisoning may be latent, as its symptoms are nonspecific. Moderate chronic salicylate intoxication, or salicylism, usually occurs only after repeated ingestion of large doses. The main symptoms are: balance disorders, dizziness, tinnitus, deafness, increased sweating, nausea and vomiting, headache, confusion. These symptoms can be controlled by reducing the dose. Tinnitus may occur at plasma salicylate concentrations above 150-300 μg/ml. More serious adverse reactions occur at plasma salicylate concentrations above 300 μg/ml. Acute intoxication is indicated by a pronounced change in acid-base balance, which may vary depending on age and severity of intoxication. The severity of the condition cannot be determined solely on the basis of plasma salicylate concentrations.
Treatment: intoxication caused by an overdose of acetylsalicylic acid is determined by the severity, clinical symptoms and is treated by standard methods used in poisoning. All measures taken should be aimed at accelerating the removal of the drug and restoring electrolyte and acid-base balance. Activated charcoal, forced alkaline diuresis should be used. Depending on the state of acid-base balance and electrolyte balance, infusion of electrolyte solutions should be carried out. In severe poisoning, hemodialysis is indicated. With long-term use of high doses, aplastic anemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia, leukopenia are possible. When taking high doses, disorders of the central nervous system may occur (dizziness, psychomotor agitation, impaired orientation and attention, insomnia, tremor, nervousness, anxiety), and nephrotoxicity of the urinary system (renal colic, interstitial nephritis, papillary necrosis). In case of overdose, increased sweating, psychomotor agitation or CNS depression, drowsiness, impaired consciousness, cardiac arrhythmias, tachycardia, extrasystole, tremor, hyperreflexia, and convulsions may occur.
Symptoms of caffeine overdose.
Large doses of caffeine can cause epigastric pain, vomiting, diuresis, rapid breathing, extrasystole, tachycardia or cardiac arrhythmia, effects on the central nervous system (dizziness, insomnia, nervousness, nervous excitement, syndrome of increased neuro-reflex excitability, headache, irritability, state of affect, anxiety, restlessness, tremor, convulsions). Clinically significant symptoms of caffeine overdose are also associated with liver damage by paracetamol.
Treatment. In case of overdose, urgent medical attention is required, even if symptoms of overdose are absent. Administration of methionine orally or acetylcysteine intravenously may have a positive effect within 48 hours after overdose. It is also necessary to apply general supportive measures, symptomatic therapy, including the use of β-adrenoreceptor antagonists, which can eliminate cardiotoxic effects. There is no specific antidote.
Adverse reactions
When using the drug, some patients may experience adverse reactions typical of acetylsalicylic acid, paracetamol, or caffeine drugs.
Most of the adverse reactions listed below are clearly dose-dependent and manifest themselves differently in each individual case.
Possible side effects:
| Often from ≥ 1/100 to < 1/10 | Infrequently from ≥ 1/1000 to < 1/100 | Single from ≥ 1/10000 to < 1/1000 |
| Infections and infestations | | | Pharyngitis |
| From the organs of vision | | | Eye pain; vision impairment |
| From the side of the organs of hearing and vestibular apparatus | | Sensation of noise/ringing in the ears | |
| Respiratory, thoracic and mediastinal disorders | | | Nosebleed; hypoventilation; rhinorrhea |
| Gastrointestinal tract | Nausea; abdominal discomfort | Dry mouth; diarrhea; vomiting | Decreased appetite; eructation; flatulence; dysphagia; oral paresthesia; salivary hypersecretion |
| From the nervous system | Dizziness | Tremor; paraesthesia; headache; feeling restless | Dysgeusia; disturbance in attention; amnesia; coordination disorder; hyperesthesia; sinus headache |
| From the psyche | Nervousness | Insomnia | Anxiety; euphoric mood; tension |
| Cardiovascular system | | Arrhythmia | Hyperemia; peripheral vascular disorders |
| Skin and subcutaneous tissue disorders | | | Hyperhidrosis; itching; urticaria |
| Musculoskeletal and connective tissue disorders | | | Musculoskeletal stiffness; neck pain; back pain; muscle spasms |
| General disorders | | Increased fatigue; | General weakness; chest discomfort |
| Laboratory indicators | | Increased heart rate | |
Data on side effects obtained from post-marketing surveillance (frequency unknown):
From the side of the organs of hearing and vestibular apparatus: disorientation.
On the part of the respiratory system, thoracic organs and mediastinum: rhinitis, nasal congestion, shortness of breath, bronchial asthma, bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.
On the part of the liver and biliary tract: increased activity of liver enzymes, usually without the development of jaundice, hepatonecrosis (dose-dependent effect), transient liver failure with increased levels of liver transaminases.
