Instructions for Bol-ran tablets blister No. 100
Composition
active ingredients: paracetamol, diclofenac sodium;
1 tablet contains: paracetamol 500 mg, diclofenac sodium 50 mg;
Excipients: corn starch, microcrystalline cellulose, sodium starch glycolate (type A), croscarmellose sodium, povidone, magnesium stearate, colloidal anhydrous silicon dioxide.
Dosage form
Pills.
Main physicochemical properties: white, round, flat tablets with a score line on one side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A B55.
Pharmacological properties
Pharmacodynamics.
Bol-Ran® 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 the drug.
Diclofenac sodium has a pronounced anti-inflammatory and analgesic, as well as a moderate antipyretic effect. Paracetamol has a pronounced analgesic, minor antipyretic and anti-inflammatory effect. The mechanism of action is associated with inhibition of prostaglandin synthesis.
Pharmacokinetics.
After oral administration, the drug is 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 administration.
The binding of diclofenac to serum proteins (mainly albumin) reaches 99.7%. The expected 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.
The metabolism of diclofenac occurs 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 the drug, the pharmacokinetic parameters of the active substances do not change. Provided that the recommended intervals between taking the tablets are observed, cumulation of the drug is not observed.
Indication
Acute pain (muscular, headache, dental, localized in the spine), pain 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 of the other ingredients of the product. Acute gastric or intestinal ulcer; gastrointestinal bleeding or perforation. Inflammatory bowel disease (Crohn's disease or ulcerative colitis). History of gastrointestinal bleeding or perforation associated with the use of nonsteroidal anti-inflammatory drugs. Active ulcer/bleeding or history of recurrent ulcer/bleeding (two or more separate episodes of established ulcer or bleeding). Last trimester of pregnancy. Severe hepatic impairment (Child-Pugh class C, cirrhosis or ascites). Renal impairment (creatinine clearance < 30 ml/min). Severe heart failure (III–IV degree according to the functional classification of the New York Heart Association of chronic heart failure (NYHA)), congestive heart failure (NYHA II–IV), decompensated heart failure, pronounced increase in blood pressure, organic diseases of the cardiovascular system, including severe atherosclerosis, severe hypertension, acute myocardial infarction, paroxysmal tachycardia, hyperthyroidism. Acute pancreatitis. Severe forms of diabetes mellitus. Glaucoma. 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 ibuprofen, diclofenac, paracetamol, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs). Ischemic heart disease in patients with angina pectoris, myocardial infarction. Cerebrovascular disease in patients with stroke or transient ischemic attacks. Hematopoietic disorders of unknown origin. Blood diseases, leukopenia, severe anemia. States of increased excitement, sleep disorders, epilepsy. Peripheral artery disease. Congenital hyperbilirubinemia. Glucose-6-phosphate dehydrogenase deficiency. Alcoholism. Treatment of postoperative pain in coronary artery bypass grafting (or the use of artificial blood circulation).
Interaction with other medicinal products and other types of interactions
Lithium, digoxin. The drug may increase plasma concentrations of lithium and digoxin. Monitoring of plasma lithium and digoxin levels 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 by inhibiting the synthesis of vasodilator prostaglandins. Therefore, the combination of such drugs should be prescribed with caution, and patients (especially the elderly) should periodically check their 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 use of potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may lead to an increase in serum potassium levels, therefore serum potassium levels should be monitored in patients receiving such drugs.
Anticoagulants and antiplatelet agents. Concomitant use of the drug with anticoagulants, especially warfarin and other coumarins, and antiplatelet agents increases the risk of bleeding. Although clinical studies do not indicate an effect of diclofenac on the activity of anticoagulants, there is evidence of an increased risk of bleeding in patients taking diclofenac and anticoagulants simultaneously. Careful monitoring of the condition of such patients is recommended to ensure that the dosage of anticoagulants does not require correction. Like other non-steroidal anti-inflammatory drugs, diclofenac in high doses may temporarily inhibit platelet aggregation.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. Concomitant use of the drug and other NSAIDs or corticosteroids increases the risk of gastrointestinal bleeding or ulceration. The simultaneous use of two or more NSAIDs should be avoided.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant use of systemic NSAIDs and SSRIs increases the risk of gastrointestinal bleeding.
Antidiabetic drugs. Diclofenac, when used together with oral antidiabetic drugs, did not change their therapeutic effect. However, there are isolated reports of the development in such cases of both hypoglycemia and hyperglycemia, which necessitated the need to change the dose of sugar-lowering drugs during the use of the drug. Therefore, during therapy with the drug, blood glucose levels should be monitored.
There are also isolated reports of metabolic acidosis with concomitant use with diclofenac, especially in patients with pre-existing renal impairment.
Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. Caution should be exercised when NSAIDs, including diclofenac, are administered less than 24 hours before or after methotrexate, as this may increase the blood concentration of methotrexate and increase its toxicity. Serious toxicity has been reported when the interval between administration of methotrexate and NSAIDs, including diclofenac, was within 24 hours. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
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.
Tacrolimus: The use of NSAIDs with tacrolimus increases the risk of nephrotoxicity, which may be mediated through the renal antiprostaglandin effects of the NSAID and the calcineurin inhibitor.
Quinolone antibacterial agents. Convulsions may occur in patients receiving concomitant quinolones and NSAIDs. This may occur in patients with or without a history of epilepsy and seizures. Therefore, caution should be exercised when considering the use of quinolones in patients already receiving NSAIDs.
Phenytoin: When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to the expected increase in phenytoin exposure.
Drugs that induce drug-metabolizing enzymes. Drugs that induce enzymes, such as rifampicin, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum), etc., are theoretically capable of reducing diclofenac plasma concentrations.
Colestipol and cholestyramine. Co-administration of the drug with colestipol or cholestyramine reduces the absorption of diclofenac by approximately 30% and 60%, respectively. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4-6 hours after colestipol/cholestyramine.
Mifepristone: NSAIDs should not be used for 8–12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.
CYP2C9 inhibitors: Caution is advised when co-administering diclofenac with CYP2C9 inhibitors (e.g. voriconazole). This may lead to a significant increase in maximum plasma concentrations and increased effects of diclofenac.
CYP2C9 inducers: Caution is required when co-administering diclofenac with CYP2C9 inducers (e.g. rifampicin). This may lead to a significant decrease in plasma concentrations and a weakening of the effect 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 daily use of paracetamol, with an increased risk of bleeding. Intermittent administration has no significant effect.
Barbiturates reduce the antipyretic effect of paracetamol.
Simultaneous use of paracetamol with chloramphenicol increases the concentration of the latter in blood plasma.
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.
Do not use simultaneously with alcohol.
Application features
General precautions for the use of systemic NSAIDs
Gastrointestinal ulcers, bleeding or perforation may occur at any time during treatment with NSAIDs, regardless of cyclooxygenase-2 (COX-2) selectivity, even in the absence of warning symptoms. To minimize this risk, as well as the risk of other adverse reactions, treatment should be initiated at the lowest effective dose and for the shortest duration possible.
The concomitant use of Bol-Ran® 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. There is an increased risk of thrombotic cardiovascular and cerebrovascular complications when used 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, therefore the risk-benefit ratio of diclofenac should be carefully weighed in patients with clinically proven ischemic heart disease, cerebrovascular disorders, occlusive peripheral arterial disease or significant risk factors (e.g. arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). Diclofenac should be prescribed to patients with significant risk factors for cardiovascular events only after careful clinical evaluation. Since the cardiovascular risks of diclofenac may increase with increasing dose and duration of treatment, it should be used for the shortest possible period and at the lowest effective dose. The response to therapy and the patient's need for diclofenac to relieve symptoms should be reviewed periodically.
Do not use simultaneously with other products containing diclofenac.
This medicine contains paracetamol and should not be used with other medicines containing paracetamol, e.g. to reduce fever, treat pain, treat flu and cold symptoms or insomnia. Taking it with other medicines containing paracetamol may lead to an overdose. Overdose of paracetamol can cause liver failure, which may require a liver transplant or be fatal.
The consequences are usually more serious in elderly patients.
If patients develop gastrointestinal bleeding or ulcers, the use of Bol-Ran® should be discontinued.
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 difficult breathing, nausea, vomiting, loss of appetite. You should seek medical attention immediately if these symptoms occur. If symptoms persist, you should seek medical attention.
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.
Caution is required in patients over 65 years of age. 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, swelling of the nasal mucosa (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 asthma (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Special precautions (emergency medical attention) are therefore recommended for such patients. This also applies to patients with allergic reactions to other substances (e.g. rash, itching or urticaria).
Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can provoke the development of bronchospasm when used in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.
Effects on the digestive tract
As with all NSAIDs, whether selective for COX-2 or not, including diclofenac, cases of gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and can occur at any time during treatment with or without warning symptoms or a history of serious gastrointestinal events, have been reported. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
As with all NSAIDs, including diclofenac, close medical supervision and special caution are required in patients with symptoms suggestive of gastrointestinal (GI) disorders or a history of gastric or intestinal ulcer, bleeding or perforation. The risk of gastrointestinal bleeding increases with increasing dose and is also higher in patients with a history of ulcer, especially complicated by bleeding or perforation. Elderly patients are more likely to experience adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal. To reduce the risk of such gastrointestinal toxicity, 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/aspirin) or other drugs that increase the risk of gastrointestinal adverse reactions, 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 report 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 (e.g. warfarin), antithrombotic agents (e.g. ASA) or selective serotonin reuptake inhibitors.
Effect on the liver
It should be noted that patients with liver disease are at increased risk of hepatotoxic effects of paracetamol. Before using the drug, you should consult a doctor.
Close medical supervision is required when the drug is prescribed to patients with impaired liver function, as their condition may worsen.
As with other NSAIDs, including diclofenac, elevations of one or more liver enzymes may occur. Elevated enzyme levels usually resolve after discontinuation of the drug.
During long-term treatment with the drug, monitoring of liver function and liver enzyme levels is prescribed as a precautionary measure. If liver function abnormalities persist or worsen and if clinical symptoms may be associated with progressive liver disease or if other manifestations are observed (e.g. eosinophilia, rash), the drug should be discontinued.
In addition to elevated liver enzymes, severe liver reactions, including jaundice and fulminant hepatitis, hepatic necrosis and hepatic failure, which in some cases resulted in death, have been observed rarely.
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
Renal effects of NSAIDs, including diclofenac, commonly (1-10%) include fluid retention with oedema and/or hypertension. Therefore, diclofenac should be used with caution in patients with cardiac dysfunction and other conditions leading to fluid retention, especially in patients with impaired cardiac or renal function, a history of hypertension, the elderly, patients receiving concomitant therapy with diuretics, ACE inhibitors or drugs that significantly affect renal function, patients at increased risk of hypovolaemia, and patients with a significant decrease in extracellular fluid volume for any reason, e.g. before or after major surgery. In such cases, monitoring of renal function is recommended. Discontinuation of therapy usually results in a return to pre-treatment status.
Effects on the skin
Serious skin reactions, some of which have been fatal, have been reported very rarely 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. In rare cases, as with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac. Due to its pharmacodynamic properties, the drug, like other NSAIDs, may mask the symptoms of infection.
Systemic lupus erythematosus and mixed connective tissue diseases
Patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases are at increased risk of aseptic meningitis.
Cardiovascular and cerebrovascular effects
Treatment with Bol-Ran® is generally not recommended for patients with diagnosed cardiovascular diseases (heart failure, ischemic heart disease, peripheral artery disease) or uncontrolled arterial hypertension.
Diclofenac should only be prescribed to patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) after careful clinical evaluation and only at doses up to 100 mg per day for a maximum of 4 weeks. Since the cardiovascular risks of diclofenac may 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 diclofenac to relieve symptoms and the response to therapy should be reviewed periodically, especially if treatment is continued for more than 4 weeks.
For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and advice is necessary, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.
Bol-Ran® should be used with caution in patients taking concomitant diuretics or ACE inhibitors, or who are at increased risk of hypovolemia.
Available evidence suggests that the use of diclofenac, especially at high doses (150 mg/day) and with long-term treatment, slightly increases the risk of arterial thrombotic complications (e.g. myocardial infarction or stroke).
The drug is contraindicated in patients with uncontrolled hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.
Patients should be informed that serious antithrombotic symptoms (chest pain, shortness of breath, weakness, speech disorders) may occur at any time and that they should seek immediate medical attention.
Effect on hematological parameters
With prolonged use of this drug, as with other NSAIDs, a complete blood count 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.
Diclofenac, which is part of the drug, may negatively affect female fertility, therefore it is not recommended for use in patients who are trying to become pregnant or undergoing infertility research.
It should be taken into account that patients with alcoholic non-cirrhotic liver damage have an increased risk of hepatotoxic effects of paracetamol. The drug may affect the results of laboratory tests for blood glucose and uric acid.
Do not exceed the indicated doses.
Use during pregnancy or breastfeeding
The drug is contraindicated during pregnancy or breastfeeding.
If the drug is used by a woman who is trying to become pregnant, the dose should be as low as possible and the duration of treatment as short as possible.
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 while using Bol-Ran® should refrain from driving or operating other machinery.
Method of administration and doses
The dose and duration of treatment are determined by the doctor for each patient individually, depending on the patient's age, the nature and course of the disease, individual tolerability and therapeutic efficacy of the drug. The drug should be used in the lowest effective doses for the shortest period of time, taking into account the treatment goals for each individual patient.
Adults and children over 14 years of age – 1 tablet 2–3 times a day after meals, the interval between doses is at least 4 hours. It is recommended to take the tablets without chewing, with half a glass of water. Do not exceed the recommended dose.
The duration of treatment should be minimal and not exceed 5–7 days. The maximum period of use without consulting a doctor is 3 days.
The maximum daily dose of the drug for adults and children over 14 years of age is 3 tablets.
Do not take with other medicines containing diclofenac or paracetamol.
Children
The drug is contraindicated in children under 14 years of age.
Overdose
Diclofenac.
There is no typical clinical picture of diclofenac overdose. Overdose may cause headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, agitation, coma, drowsiness, tinnitus, and convulsions. Acute renal failure and liver damage are possible in severe intoxication.
Treatment.
Treatment of acute poisoning with NSAIDs, including diclofenac, consists of supportive and symptomatic therapy. This applies to the treatment of manifestations such as arterial hypotension, renal failure, convulsions, gastrointestinal disorders, respiratory depression. It is unlikely that such specific therapeutic measures as forced diuresis, dialysis or hemoperfusion will be effective in removing NSAIDs, including diclofenac, since the active substances of these drugs are largely bound to blood proteins and undergo intensive metabolism. Activated charcoal may be used after ingestion of potentially toxic doses, and gastric decontamination (e.g., induction of vomiting, gastric lavage) after ingestion of potentially life-threatening doses.
Paracetamol.
Overdose of paracetamol may cause liver failure, which may require liver transplantation or be fatal. Acute pancreatitis has been observed, usually with liver dysfunction and hepatotoxicity.
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, phenobarbitone, phenytoin, primidone, rifampicin, St. John's wort or other drugs that induce liver enzymes; alcohol abuse; insufficiency of the glutathione system, such as malnutrition, HIV infection, starvation, cystic fibrosis, cachexia), taking 5 g or more of paracetamol may lead to liver damage.
In case of overdose, urgent medical attention is required. Treatment should be started immediately. The patient should be taken to a hospital, even if there are no early symptoms of overdose.
Symptoms of overdose in the first 24 hours: pallor, nausea, vomiting, loss of appetite, abdominal pain. Experience shows that symptoms of liver damage may become apparent 12–48 hours after overdose and usually reach a maximum after 4–6 days. Glucose metabolism disorders and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma and lead to death. Acute renal failure with acute tubular necrosis may manifest as severe pain in the lumbar region, hematuria, proteinuria and develop even in the absence of severe liver damage. Cardiac arrhythmias have also been noted.
With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may develop from the hematopoietic system. When taking high doses, the following reactions may occur: from the central nervous system - dizziness, psychomotor agitation and disorientation; from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis); from the digestive system - hepatonecrosis.
Symptoms of overdose may be limited to nausea and vomiting or may not reflect the severity of the overdose or the risk of organ damage. Immediate medical attention is necessary in case of overdose, even if symptoms of overdose are not observed. If overdose is confirmed or even suspected, the patient should be taken to the nearest medical facility where emergency medical care and qualified treatment can be provided. This should be done even if symptoms of overdose are absent, because of the risk of delayed liver 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 occurs 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 intravenous N-acetylcysteine according to current dosing recommendations. In the absence of vomiting, oral methionine may be used as a suitable alternative in remote areas outside the hospital.
Supportive and symptomatic treatment is indicated for complications such as hypotension, renal failure, convulsions, gastrointestinal disturbances and respiratory depression. Forced diuresis, haemodialysis or haemoperfusion are unlikely to be effective in removing non-steroidal anti-inflammatory drugs (NSAIDs) because the active substances of the drug are highly bound to plasma proteins and are extensively metabolised.
Adverse reactions
From the blood and lymphatic system: thrombocytopenia, neutropenia, leukopenia, anemia, including aplastic anemia, hemolytic anemia (especially for patients with glucose-6-phosphate dehydrogenase deficiency), sulfhemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, heart pain), agranulocytosis, pancytopenia, bruising or bleeding.
Immune system disorders: hypersensitivity reactions (including skin hypersensitivity reactions), anaphylactic/anaphylactoid reactions, including hypotension and anaphylactic shock; angioedema (including facial swelling).
Skin and subcutaneous tissue disorders: skin rash, erythema, mucous membrane rash, urticaria, blistering rash, bullous rash, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic dermatitis, hair loss, photosensitivity reactions, purpura, allergic purpura, pruritus.
Mental disorders: disorientation, depression, nightmares, irritability, anxiety, feelings of fear, psychotic disorders, confusion, psychomotor agitation.
From the nervous system: headache, dizziness, drowsiness, fatigue, paresthesia, sleep disturbances, insomnia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, cerebral circulation disorders, stroke, hallucinations, sensory disturbances, general malaise.
From the organs of vision: visual disturbances, blurred vision, diplopia, optic neuritis.
From the side of the organs of hearing and labyrinth: vertigo, tinnitus, tinnitus, hearing disorders.
Cardiovascular system: palpitations, tachycardia, shortness of breath, pain in the heart area, heart failure, myocardial infarction, hypertension, hypotension, hypertensive crisis, vasculitis.
Respiratory system: bronchial asthma (including shortness of breath), bronchospasm (especially in patients sensitive to aspirin and other NSAIDs), chest pain, pneumonitis.
From the digestive tract: nausea, vomiting, diarrhea (including hemorrhagic diarrhea), dyspepsia, abdominal pain, including epigastric pain, flatulence, anorexia; gastritis, erosive-ulcerative lesions of the digestive tract
