Instructions Doloxen film-coated tablets blister pack No. 100
Composition
active ingredients: paracetamol, diclofenac sodium;
1 tablet contains paracetamol 500 mg, diclofenac sodium 50 mg;
Excipients: croscarmellose sodium, microcrystalline cellulose, povidone, methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), methacrylate copolymer dispersion, magnesium stearate, sodium starch glycolate (type A), hydroxypropyl methylcellulose, macrogol 4000, titanium dioxide (E 171), purified talc, dichloromethane, isopropyl alcohol, purified water.
Dosage form
Film-coated tablets.
Main physicochemical properties: capsule-shaped biconvex tablets, film-coated, white or almost white in color, with a dividing line on one side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A B55.
Pharmacological properties
Pharmacodynamics
Doloxen is a combined drug that has a pronounced anti-inflammatory, analgesic and antipyretic effect. The pharmacological activity of the drug is due to the properties of diclofenac and paracetamol, which are part of Doloxen. The main mechanism of action of diclofenac is to inhibit the synthesis of prostaglandins - endogenous substances that play an important role in the genesis of inflammation, pain and fever. Paracetamol belongs to non-steroidal anti-inflammatory drugs (NSAIDs) from the group of para-aminophenol derivatives. The analgesic and antipyretic effects of paracetamol are due to its effect on the hypothalamic centers of the brain.
In rheumatic diseases, the anti-inflammatory and analgesic properties of Doloxen provide a clinical effect characterized by a reduction in the severity of joint pain, morning stiffness and swelling of the joints, as well as an improvement in the function of the latter.
In post-traumatic and postoperative inflammatory phenomena, Doloxen quickly eliminates pain and reduces inflammatory swelling of the postoperative wound.
Doloxen also has an analgesic effect in pain syndrome of non-rheumatic origin, in particular in primary algodysmenorrhea and migraine attacks.
Pharmacokinetics
After internal use of Doloxen, diclofenac and paracetamol are rapidly and completely absorbed. Food does not affect the absorption of the drug.
The concentrations of active substances in blood plasma have a linear dependence on the dose of the drug, with maximum levels reached 60–90 minutes after taking Doloxen.
The binding of diclofenac to serum proteins (mainly albumin) reaches 99.7%. The apparent volume of distribution is 0.12–0.17 l/kg. Diclofenac penetrates into the synovial fluid, where its maximum concentration is reached 2–4 hours later than in blood plasma. The half-life from the synovial fluid is 3–6 hours.
Diclofenac is metabolized by glucuronidation of the unchanged molecule and methoxylation, which leads to the formation of several phenolic metabolites, the biological activity of which is significantly inferior to that of the parent substance.
The total systemic plasma clearance of diclofenac is approximately 300 ml/min. The terminal half-life is 1–2 hours. 60% of the administered dose is excreted in the urine as glucuronide conjugates of unchanged diclofenac, the rest in the bile and feces.
Paracetamol is metabolized in the liver and excreted mainly in the urine.
After repeated use of Doloxen, the pharmacokinetic parameters of the active substances do not change. Provided that the recommended intervals between administrations are observed, cumulation of the drug is not observed.
Indication
Acute pain (muscular, headache, dental, localized in the spine), in non-articular rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, acute attacks of gout, primary dysmenorrhea, adnexitis, pharyngotonsillitis, otitis. Post-traumatic and postoperative pain syndrome.
Contraindication
Hypersensitivity to diclofenac, paracetamol or any other component of the drug.
Acute stomach or intestinal ulcer; gastrointestinal bleeding or perforation.
Active peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (two or more separate episodes of diagnosed ulceration or bleeding).
Liver failure.
Kidney failure.
Established congestive heart failure [functional class II–IV according to the NYHA (New York Heart Association) classification], ischemic heart disease, peripheral artery disease, cerebrovascular disease.
Contraindicated in patients who develop attacks of bronchial asthma ("aspirin asthma"), angioedema, urticaria or acute rhinitis, nasal polyps and other allergic symptoms in response to the use of diclofenac, paracetamol, acetylsalicylic acid, ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs).
The patient has a history of gastrointestinal bleeding or perforation associated with the use of nonsteroidal anti-inflammatory drugs.
Severe heart failure (functional class III–IV).
Hematopoietic disorders of unknown origin.
Leukopenia.
Moderate and severe anemia.
Glucose-6-phosphate dehydrogenase deficiency.
Inflammatory bowel disease (Crohn's disease or ulcerative colitis).
Alcoholism.
Do not use for the treatment of postoperative pain after coronary artery bypass graft surgery (or use of a cardiopulmonary bypass machine).
The drug is contraindicated during pregnancy or breastfeeding.
Interaction with other medicinal products and other types of interactions
Diclofenac
Lithium, digoxin. The drug may increase plasma concentrations of lithium and digoxin. Monitoring of plasma lithium and digoxin is recommended.
Diuretics and antihypertensives. The drug, like other NSAIDs, when used concomitantly with diuretics or antihypertensive drugs, such as beta-blockers of calcium channels, angiotensin-converting enzyme (ACE) inhibitors, may reduce their antihypertensive effect. Therefore, the combination of such drugs should be prescribed with caution, and patients (especially the elderly) should periodically monitor blood pressure. Patients should drink enough water, and after starting and after stopping concomitant therapy, renal function should be periodically monitored, in particular when using diuretics and ACE inhibitors due to an increased risk of nephrotoxicity.
Drugs causing hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may cause an increase in serum potassium levels, which should be monitored.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. Concomitant use of diclofenac and other NSAIDs or corticosteroids may increase the incidence of gastrointestinal adverse events. Concomitant use of the drug with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to the lack of any evidence of a possible benefit from synergistic action. Like other NSAIDs, diclofenac in high doses may transiently inhibit platelet aggregation.
Anticoagulants and antiplatelet agents: Regular concomitant use of diclofenac with anticoagulants, especially warfarin and other coumarins, and antiplatelet agents increases the risk of bleeding.
Although clinical studies have not shown that diclofenac affects the effectiveness of anticoagulants, there is evidence of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly. Therefore, careful monitoring of patients receiving diclofenac and anticoagulants is recommended and, if necessary, adjustment of the anticoagulant dosage.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant use of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Antidiabetic drugs. With simultaneous use of the drug and antidiabetic drugs, the effectiveness of the latter does not change. However, there are individual reports of the development in such cases of both hypoglycemia and hyperglycemia, which necessitated the need to change the dose of hypoglycemic drugs during use of the drug. Therefore, during therapy with the drug Doloxen, blood glucose levels should be monitored. There are also individual cases of metabolic acidosis with simultaneous use of antidiabetic drugs with diclofenac, especially in patients with pre-existing renal dysfunction.
Phenytoin: When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to the expected increase in phenytoin exposure.
Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. NSAIDs, including diclofenac, should be administered with caution if administered less than 24 hours before methotrexate, as methotrexate blood levels may increase and methotrexate toxicity may be potentiated. Cases of serious toxicity have been reported when methotrexate and NSAIDs, including diclofenac, were administered within 24 hours of each other. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
Drugs that induce drug-metabolizing enzymes: Drugs that induce enzymes, such as rifampicin, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum), are theoretically capable of reducing diclofenac plasma concentrations.
Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4-6 hours after administration of colestipol/cholestyramine.
Cyclosporine: The effect of NSAIDs on prostaglandin synthesis in the kidneys may enhance the nephrotoxicity of cyclosporine, so the drug should be prescribed in lower doses than when prescribing cyclosporine to patients.
Potent CYP2C9 inhibitors: Caution is recommended when administering diclofenac concomitantly with potent CYP2C9 inhibitors (e.g. voriconazole) as there may be a significant increase in maximum plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.
CYP2C9 inducers: Caution is required when diclofenac is co-administered with CYP2C9 inducers (e.g. rifampicin) as significant reductions in plasma concentrations and exposure to diclofenac are possible.
Tacrolimus: There is an increased risk of nephrotoxicity when NSAIDs are administered concomitantly with tacrolimus. This may be mediated through the mechanism of renal prostaglandin inhibition by both the NSAID and the calcineurin inhibitor, and therefore diclofenac should be used at lower doses than in patients not receiving tacrolimus.
Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, decrease glomerular filtration rate (GFR), and increase plasma glycoside concentrations.
Mifepristone: NSAIDs should not be used for 8–12 days after taking mifepristone, as NSAIDs may reduce its effect.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant use of NSAIDs and SSRIs increases the risk of gastrointestinal bleeding.
Probenecid: Medicines containing probenecid may delay the elimination of diclofenac.
Paracetamol
The rate of absorption of paracetamol may be increased by metoclopramide and domperidone and decreased by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by long-term regular daily use of paracetamol, with an increased risk of bleeding. Intermittent use has no significant effect.
Barbiturates reduce the antipyretic effect of paracetamol
Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate the activity of liver microsomal enzymes, may enhance the toxic effect of paracetamol on the liver due to an increase in the degree of conversion of the drug to hepatotoxic metabolites. With the simultaneous use of paracetamol with hepatotoxic agents, the toxic effect of drugs on the liver increases.
Simultaneous use of high doses of paracetamol with isoniazid, rifampicin increases the risk of developing hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics.
Simultaneous administration of paracetamol and ethanol increases the risk of developing hepatotoxic effects and acute pancreatitis.
Do not use simultaneously with alcohol.
Barbiturates, rifampicin, salicylamide, antiepileptic drugs, carbamazepine, phenytoin, ethanol, phenylbutazone, tricyclic antidepressants and other microsomal oxidation stimulants - these drugs increase the production of hydroxylated active metabolites that affect liver function, causing the possibility of developing severe intoxications with small overdoses of the drug.
Paracetamol may reduce the bioavailability of lamotrigine, reducing its effect, probably due to induction of its metabolism in the liver.
The risk of developing neutropenia increases with the simultaneous use of paracetamol and zidovudine.
Microsomal oxidation inhibitors (cimetidine) – reduce the risk of hepatotoxic effects of Doloxen.
Metoclopramide and domperidone – increase the absorption of paracetamol.
Long-term simultaneous use of the drug with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs may lead to kidney damage.
Coumarin derivatives (warfarin) – long-term use of paracetamol increases the risk of bleeding. Taking single doses does not have a significant effect.
Cholestyramine – reduces the absorption of paracetamol.
Under the influence of paracetamol, the elimination time of chloramphenicol increases 5 times.
Probenecid affects the concentration of paracetamol in blood plasma and its excretion.
Application features
The medicine contains paracetamol, so it should not be used together with other medicines containing paracetamol and used, for example, to reduce fever, treat pain, flu and cold symptoms or insomnia. Simultaneous use with other medicines containing paracetamol may lead to overdose. Overdose of paracetamol can cause liver failure, which may lead to the need for a liver transplant or to death.
If you have liver or kidney disease, you should consult a doctor before using the medicine.
It should be borne in mind that patients with liver disease are at increased risk of hepatotoxicity of paracetamol; the drug may affect the results of laboratory tests for blood glucose and uric acid. Patients taking daily analgesics for mild arthritis should consult a doctor before using paracetamol.
Patients with reduced glutathione levels, such as those with severe infections such as sepsis, 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 medical attention immediately if you experience these symptoms.
If symptoms persist, you should consult a doctor.
If the headache becomes persistent, you should see a doctor.
Before using the drug, it is necessary to consult a doctor if the patient is using warfarin or similar drugs that have an anticoagulant effect.
Do not exceed the indicated doses.
Gastrointestinal ulcers, bleeding or perforation can occur at any time during treatment with NSAIDs, regardless of COX-2 selectivity, even in the absence of warning symptoms. To minimize this risk, the lowest effective dose should be used for the shortest duration.
There is an increased risk of thrombotic cardiovascular and cerebrovascular complications with certain selective COX-2 inhibitors. It is not known whether this risk is directly related to the COX-1/COX-2 selectivity of the individual NSAIDs. There are currently no data available on long-term treatment with the maximum dose of diclofenac, the possibility of a similar increased risk cannot be excluded. Until such data become available, a careful risk-benefit assessment should be made regarding the use of diclofenac in patients with clinically proven coronary heart disease, cerebrovascular disorders, peripheral arterial occlusive disease or significant risk factors (e.g. arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). In this regard, the lowest effective dose should be used for the shortest possible period of treatment.
Renal effects of NSAIDs include fluid retention with oedema and/or hypertension. Diclofenac should therefore be used with caution in patients with cardiac dysfunction and other conditions leading to fluid retention. Caution is also required in patients receiving concomitant diuretics or ACE inhibitors or who are at increased risk of hypovolaemia. The effects are generally more severe in the elderly. If gastrointestinal bleeding or ulceration occurs during treatment with NSAIDs, the drug should be discontinued. Caution should be exercised in patients over 65 years of age, taking into account the recommendations for this patient group. In particular, the lowest effective dose is recommended for elderly patients with frail health and patients with low body weight.
Allergic reactions, including anaphylactic/anaphylactoid reactions, may occur with diclofenac, as with other NSAIDs, even without prior exposure to diclofenac. Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that may cause myocardial infarction. Symptoms of such reactions may include chest pain associated with an allergic reaction to diclofenac.
Serious skin reactions, some of which have been fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including diclofenac. The risk of these reactions is highest at the beginning of therapy, and the development of these reactions is noted in most cases in the 1st month of treatment. The drug should be discontinued at the first appearance of skin rash, mucosal ulceration or any other signs of hypersensitivity. Due to its pharmacodynamic properties, the drug, like other NSAIDs, may mask the signs and symptoms of infection.
It is necessary to consult a doctor regarding the possibility of using the drug in patients with impaired kidney and liver function.
It should be taken into account that patients with liver disease have an increased risk of hepatotoxic effects of paracetamol.
Alcoholic beverages should not be consumed during treatment. Paracetamol may be toxic to the liver at doses greater than 6–8 g per day, but adverse effects on the liver may occur at much lower doses in the case of alcohol, liver enzyme inducers, or other substances that have a toxic effect on the liver; this effect is also higher in patients with non-cirrhotic alcoholic liver disease. Long-term alcohol consumption significantly increases the risk of developing hepatotoxic effects of paracetamol. Regular liver function tests are recommended in patients with impaired liver function, as well as in those taking large doses of paracetamol for a long time.
Before using the drug, the patient should consult a doctor if he is taking warfarin or similar drugs that have an anticoagulant effect. Restrictions on the use of the drug in such patients are primarily due to the content of paracetamol.
When treating with oral anticoagulants with simultaneous administration of large doses of paracetamol, monitoring of prothrombin time is necessary.
Cases of liver dysfunction/hepatic failure have been reported in patients with reduced glutathione levels, such as those with severe wasting, anorexia, low body mass index, chronic alcoholism or sepsis. Patients with reduced glutathione levels are at increased risk of metabolic acidosis when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid or labored breathing, nausea, vomiting, loss of appetite. You should seek medical attention immediately if these symptoms occur.
Reservation
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible time necessary to control (relieve) symptoms.
Concomitant use of the medicinal product with systemic NSAIDs such as selective COX-2 inhibitors should be avoided due to the lack of any evidence of a synergistic effect and due to potential additive side effects.
Caution is required in elderly patients. In particular, it is recommended to use the lowest effective dose in frail elderly patients or those with low body weight.
History of bronchial asthma
Patients with bronchial asthma, seasonal allergic rhinitis, nasal mucosal edema (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially those associated with allergic rhinitis-like symptoms) are more likely to experience reactions to NSAIDs, such as exacerbation of bronchial asthma (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Special precautions (emergency medical attention) are therefore recommended. This also applies to patients with allergic reactions (e.g. rash, itching or urticaria) to other substances. Drugs that inhibit prostaglandin synthetase activity, in particular diclofenac sodium and other NSAIDs, may precipitate bronchospasm in patients with bronchial asthma or a history of bronchial asthma.
Effects on the digestive tract
Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and can occur at any time during treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal events, have been reported with NSAIDs, including diclofenac. These events are usually more serious in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients taking diclofenac, the drug should be discontinued.
When using NSAIDs, including diclofenac, patients with symptoms suggestive of gastrointestinal (GI) disorders or a history of gastric or intestinal ulcer, bleeding or perforation require medical supervision and special caution. The risk of gastrointestinal bleeding increases with increasing dose, as well as in patients with a history of ulcer, especially complicated by bleeding or perforation, and in elderly patients.
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
To reduce the risk of such gastrointestinal toxicity in patients with a history of ulcer, especially if complicated by haemorrhage or perforation, and in the elderly, treatment should be initiated and maintained at the lowest effective dose.
For such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid (ASA) or other drugs that are likely to increase the risk of adverse effects on the TT, combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered. Patients with a history of gastrointestinal toxicity, especially the elderly, should be informed of any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant drugs that increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants such as warfarin, antithrombotic agents such as acetylsalicylic acid or selective serotonin reuptake inhibitors.
Close medical supervision and special caution are required in patients with ulcerative colitis or Crohn's disease, as these conditions may be exacerbated. The use of NSAIDs, including diclofenac, is associated with an increased risk of gastrointestinal anastomotic bleeding. Close medical supervision and caution are recommended when prescribing diclofenac after gastrointestinal surgery.
Effect on the liver
During long-term treatment with the drug, regular monitoring of liver function and liver enzyme levels should be prescribed as a precautionary measure. If liver function abnormalities persist or worsen and if clinical signs or symptoms that may be associated with progressive liver disease or if other manifestations are observed (e.g. eosinophilia, rash), the drug should be discontinued.
Diseases such as hepatitis may occur without prodromal symptoms. Caution is required when the drug is used in patients with hepatic porphyria, due to the possibility of provoking an attack.
Effects on the kidneys
Long-term treatment with high doses of NSAIDs, including diclofenac, often (1-10%) leads to edema and hypertension. Particular attention should be paid to patients with impaired cardiac or renal function, a history of hypertension, elderly patients, patients receiving concomitant therapy with diuretics or drugs that significantly affect renal function, as well as patients with a significant decrease in extracellular fluid volume for any reason, for example, before or after major surgery. In such cases, monitoring of renal function is recommended. Discontinuation of therapy usually leads to a return to the state that was before treatment.
Effects on the skin
Serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including diclofenac. The highest risk of these reactions is observed at the beginning of therapy, in most cases during the first month of treatment.
The use of diclofenac should be discontinued at the first appearance of skin rashes, mucosal lesions, or any other signs of hypersensitivity.
SLE and mixed connective tissue diseases
Patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases are at increased risk of developing aseptic meningitis.
Cardiovascular and cerebrovascular effects
Patients with congestive heart failure (NYHA functional class I) and patients with significant risk factors for cardiovascular complications (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) should be treated with diclofenac only after careful evaluation.
Appropriate monitoring and advice is required for patients with a history of hypertension and/or moderate congestive heart failure, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.
Clinical trial data and epidemiological data indicate that the use of diclofenac, especially in high doses (150 mg/day) and with long-term treatment, somewhat increases the risk of arterial thrombotic complications (e.g. myocardial infarction or stroke).
Since the cardiovascular risks of diclofenac increase with increasing dose and duration of treatment, it should be used for the shortest possible period and at the lowest effective dose.
The patient's need for symptomatic relief and response to therapy should be reassessed periodically.
Patients should be advised to monitor for symptoms of serious arterial thromboembolic events (chest pain, shortness of breath, weakness, speech disorders) and to seek medical advice immediately if they experience such events.
Effect on hematological parameters
The medicine is recommended for short-term treatment only.
With prolonged use of this drug, as with other NSAIDs, monitoring of complete blood counts is recommended.
Like other NSAIDs, the drug may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis or hematological disorders should be carefully monitored.
Do not exceed the indicated doses.
It should be noted that patients with alcoholic non-cirrhotic liver disease are at increased risk of hepatotoxic effects of paracetamol; the drug may affect the results of laboratory tests for blood glucose and uric acid.
Do not take the drug simultaneously with other drugs containing paracetamol or diclofenac.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience visual disturbances, dizziness, vertigo, drowsiness, or other central nervous system disorders during treatment with the drug should refrain from driving or operating other mechanisms.
Use during pregnancy or breastfeeding
A large amount of data on pregnant women do not indicate malformative and feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero are inconclusive. The drug is contraindicated during pregnancy or breastfeeding.
Diclofenac may affect female fertility and is therefore not recommended in women attempting to conceive. Discontinuation of the drug should be considered in women who are unable to conceive or in women undergoing investigation for infertility.
Method of administration and doses
The dose is determined by the doctor for each patient individually, depending on the patient's age, the nature and course of the disease, individual tolerance and therapeutic effectiveness of the drug.
Adults and children over 14 years old – 1 tablet 2–3 times a day after meals.
The duration of treatment is no more than 5–7 days and depends on the course of the disease.
The maximum daily dose of the drug for adults and children over 14 years of age is no more than 3 tablets.
Children
The drug is contraindicated in children under 14 years of age.
Overdose
Diclofenac
There is no typical clinical picture characteristic of an overdose of diclofenac. Overdose can cause vomiting, gastrointestinal bleeding, diarrhea, dizziness, tinnitus and convulsions. Acute renal failure and liver damage are possible in case of severe intoxication.
Paracetamol
Liver damage may occur 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 use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort or other drugs that induce liver enzymes, alcohol abuse, insufficiency of the glutathione system, for example, malnutrition, AIDS, starvation, cystic fibrosis, cachexia), taking 5 g or more of paracetamol can lead to liver damage.
Overdose symptoms in the first 24 hours: pallor, nausea, vomiting, anorexia, and abdominal pain. Liver damage may appear 12-48 hours after an overdose. Disorders of glucose metabolism and metabolic acidosis may occur. With severe poisoning, liver failure can progress to encephalopathy, hemorrhage, hypoglycemia, which can lead to death. Acute renal failure with acute tubular necrosis can be manifested by severe pain in the lower back, hematuria, proteinuria and can develop even in the absence of severe liver damage. Cardiac arrhythmia and pancreatitis were also noted.
With long-term use of the drug in large doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may develop from the hematopoietic organs. When taking large doses from the side of the nervous system - dizziness, psychomotor excitement and disorientation; from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis) from the digestive system - hepatonecrosis.
Treatment: urgent measures of supportive and symptomatic therapy.
If an excessive dose was taken within 1 hour, the feasibility of using activated charcoal should be considered. The concentration of paracetamol in the blood plasma should be measured 4 hours or later after administration (earlier concentrations are considered unreliable). Treatment with N-acetylcysteine can be used within 24 hours after taking the drug, but the maximum protective effect can be obtained when it is used within 8 hours after taking it. The effectiveness of the antidote decreases sharply after this time. If necessary, N-acetylcysteine is administered intravenously to the patient according to the established list of doses. In case
