Tilda film-coated tablets strip No. 200

Instructions for Tilda film-coated tablets strip No. 200

Composition

active ingredients:
1 tablet contains: 500 mg paracetamol, 50 mg diclofenac sodium, 250 mg chlorzoxazone;
excipients: corn starch, purified talc, magnesium stearate, colloidal anhydrous silicon dioxide;
film coating: hypromellose, polyethylene glycol 6000, purified talc, titanium dioxide (E 171), quinoline yellow dye (E 104).

Medical form

Film-coated tablets.

Main physicochemical properties: yellow film-coated tablets, elongated, biconvex, with a score on one side and smooth on the other side.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs. Diclofenac, combinations. ATC code M01A B55.

Pharmacological properties

Pharmacodynamics

Tilda® is a combination drug that has a muscle relaxant and analgesic effect.

Paracetamol has analgesic, antipyretic and moderately pronounced anti-inflammatory effects. Paracetamol inhibits cyclooxygenase mainly in the central nervous system, affecting the centers of pain and thermoregulation. The analgesic effect is based on the ability to inhibit the synthesis of prostaglandins due to inhibition of the enzyme cyclooxygenase.

Diclofenac has a pronounced anti-inflammatory, analgesic and moderate antipyretic effect. The mechanism of action is associated with the inhibition of the activity of cyclooxygenase - the main enzyme of arachidonic acid metabolism, which is the precursor of prostaglandins, which play a major role in the pathogenesis of inflammation, pain and fever. The analgesic effect is due to two mechanisms: peripheral (indirectly, by inhibiting the synthesis of prostaglandins) and central (by inhibiting the synthesis of prostaglandins in the central and peripheral nervous system). Diclofenac, by blocking the synthesis of prostaglandins, relieves or significantly reduces the symptoms of inflammation. Diclofenac reduces the prostaglandin-induced increased sensitivity of nerve endings to mechanical irritation and biologically active substances formed in the focus of inflammation; helps to reduce body temperature. Reduces the concentration of prostaglandins in menstrual blood and the intensity of pain in primary dysmenorrhea. Diclofenac helps to increase the range of motion in affected joints, reduce pain at rest and during movement. In vitro, diclofenac at a concentration equivalent to that achieved in human tissues during treatment does not inhibit the biosynthesis of cartilage proteoglycans. Inhibits platelet aggregation. In traumatic and postoperative pain, the drug reduces pain at rest and during movement, as well as swelling during inflammation. A persistent effect is observed after 1–2 weeks of treatment.

Chlorzoxazone has a muscle relaxant effect, blocks multisynaptic reflexes at the spinal cord level, which are involved in the onset and maintenance of skeletal muscle spasm of various etiologies. Chlorzoxazone in combination with paracetamol causes a muscle relaxant and analgesic effect.

The drug Tilda does not have a sedative effect.

Pharmacokinetics

Diclofenac is rapidly absorbed into the blood - the maximum concentration in the blood plasma is reached after 1-2 hours. Binding to blood plasma proteins is over 99%. It penetrates well into tissues and synovial fluid, where its concentration increases slowly, after 4 hours it reaches higher values than in the blood plasma. Food can slow down the rate of absorption, without affecting the completeness of absorption. Bioavailability is about 5%.

The half-life from blood plasma is 1–2 hours, from synovial fluid – 3–6 hours. About 35% is excreted in the form of metabolites with feces; about 65% is metabolized in the liver and excreted by the kidneys in the form of inactive derivatives, about 1% – in unchanged form.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 30–60 minutes. The half-life is 1–4 hours. It is evenly distributed throughout all body fluids. Plasma protein binding is variable. Paracetamol is metabolized in the liver and excreted mainly by the kidneys in the form of conjugated metabolites.

Chlorzoxazone is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations are reached after 1–2 hours. Metabolized in the liver, mainly to form conjugates with sulfates and glucuronates and to a lesser extent by oxidation to form cysteine and mercaptopuric acid. Excreted in the urine mainly as metabolites and only 5% of the dose is excreted unchanged. The half-life is 1–4 hours.

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 the active substances or to any other components of the medicinal product.

History of gastrointestinal bleeding or perforation associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).

Active peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (two or more separate episodes of established ulceration or bleeding).

Liver failure.

Kidney failure.

Congestive heart failure (functional class II–IV according to the NYHA classification - New York Heart Association).

High risk of developing postoperative bleeding, blood clotting disorders, hemostasis disorders, hematopoietic disorders, or cerebrovascular bleeding.

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 non-steroidal anti-inflammatory drugs (NSAIDs).

Blood diseases, hematopoietic disorders of unknown origin, leukopenia.

Severe anemia.

Congenital hyperbilirubinemia.

Glucose-6-phosphate dehydrogenase deficiency.

Inflammatory bowel disease (Crohn's disease or ulcerative colitis).

Do not use for the treatment of perioperative pain in coronary artery bypass grafting (or when using a cardiopulmonary bypass machine).

Coronary heart disease in patients with angina pectoris who have had a myocardial infarction.

Cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks.

Peripheral artery disease.

Alcoholism.

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.

Concomitant use of diclofenac, as with other NSAIDs, with diuretics and antihypertensive agents [e.g. β-blockers, angiotensin-converting enzyme (ACE) inhibitors] may lead to a reduction in their antihypertensive effect by inhibiting the synthesis of vasodilator prostaglandins. Therefore, such a combination should be used with caution and patients, especially the elderly, should be closely monitored for blood pressure. Patients should be adequately hydrated and monitoring of renal function is recommended after initiation of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity.

Drugs that cause hyperkalemia.

Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may be associated with increases in serum potassium levels, therefore patients should be monitored more frequently.

Simultaneous use of the drug Tilda® leads to a decrease in the effect of furosemide and antihypertensive drugs.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids.

Concomitant administration with nonsteroidal anti-inflammatory drugs, glucocorticosteroids increases the frequency of adverse events from the gastrointestinal tract, including gastrointestinal bleeding or ulcers. 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.

Anticoagulants and antiplatelet agents.

Regular concomitant use of the drug with anticoagulants, especially warfarin and other coumarins, and antiplatelet drugs may lead to an increased risk of bleeding. Therefore, in the case of such a combination of drugs, close and regular observation of patients is recommended and careful monitoring of such patients is recommended to ensure that no changes in the dosage of anticoagulants are necessary. Like other non-steroidal anti-inflammatory drugs, diclofenac in high doses may temporarily inhibit platelet aggregation.

Selective serotonin reuptake inhibitors (SSRIs).

Concomitant use of systemic NSAIDs and SSRIs increases the risk of gastrointestinal bleeding.

Antidiabetic drugs.

When using the drug simultaneously with antidiabetic drugs, the effectiveness of the latter does not change. However, there are isolated reports of the development of both hypoglycemia and hyperglycemia in such cases, which necessitated the need to change the dose of sugar-lowering drugs during the use of the drug. Therefore, blood glucose levels should be monitored during therapy.

Methotrexate.

Diclofenac may inhibit the clearance of methotrexate in the renal tubules, leading to increased methotrexate levels.

Caution should be exercised when NSAIDs are administered less than 24 hours before or after methotrexate, as this may increase the blood concentration of methotrexate and increase its toxicity. There are reports of serious toxicity when the interval between the administration of methotrexate and NSAIDs, including diclofenac, was within 24 hours. This interaction is mediated by the accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.

The effect of diclofenac, like other NSAIDs, on prostaglandin synthesis in the kidneys may enhance the nephrotoxicity of cyclosporine; therefore, diclofenac should be used in lower doses than for patients not taking cyclosporine.

Tacrolimus.

When NSAIDs are used with tacrolimus, there may be an increased risk of nephrotoxicity, which may be mediated through the renal antiprostaglandin effects of the NSAIDs and the calcineurin inhibitor.

Antibacterial quinolones.

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 using phenytoin simultaneously with diclofenac, it is recommended to monitor the concentration of phenytoin in the blood plasma due to the expected increase in the exposure of phenytoin.

Cholestipol and cholestyramine.

These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least one hour before or 4-6 hours after colestipol/cholestyramine.

Cardiac glycosides.

Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce GFR, and increase plasma glycoside levels.

Mifepristone.

NSAIDs should not be used for 8–12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.

Potent CYP2C9 inhibitors.

Caution should be exercised when co-administering diclofenac with potent CYP2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in maximum plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.

Drugs that stimulate enzymes that metabolize drugs.

Enzyme-inducing drugs, such as rifampicin, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum), etc., are theoretically capable of reducing diclofenac plasma concentrations.

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.

Do not use simultaneously with alcohol.

Impact on laboratory tests

The use of paracetamol may affect the results of blood glucose tests performed by the glucose oxidase-peroxidase method. The use of paracetamol may affect blood uric acid tests performed by the phosphate-tungsten method. The rate of absorption of paracetamol may be reduced by cholestyramine.

Chlorzoxazone.

The effect of chlorzoxazone is enhanced by ethanol and other agents that have a depressing effect on the central nervous system.

Prescribe with caution together with phenytoin, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants, because there is a risk of intoxication. Simultaneous use with diuretics reduces the effectiveness of the latter, so it is necessary to take the drugs with an interval of several hours. Simultaneous use of chlorzoxazone with disulfiram leads to a decrease in the plasma clearance of chlorzoxazone by 85%, resulting in a doubling of the peak plasma concentration of chlorzoxazone and an extension of its half-life on average from 0.92 h to 5.1 h. With the simultaneous use of chlorzoxazone and isoniazid in slow acetylators, a decrease in the clearance of chlorzoxazone by 56% is noted, which is accompanied by an increase in the sedative effect, headache and nausea. Two days after discontinuation of concomitant use of chlorzoxazone and isoniazid, a reversal reaction occurs, with chlorzoxazone clearance increasing by 56% compared to baseline. Similar, but less pronounced, effects were also observed in rapid acetylators, in whom chlorzoxazone pharmacokinetic parameters returned to baseline values within two days.

Application features

For diclofenac.

To minimize undesirable effects, treatment should be initiated at the lowest effective dose and continued for the shortest time necessary to control symptoms.

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.

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 lead to myocardial infarction. Symptoms of this reaction syndrome may include chest pain resulting from an allergic reaction to diclofenac.

Due to its pharmacodynamic properties, diclofenac may mask the signs and symptoms of infection.

Effect on the digestive tract.

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 previous history of serious gastrointestinal events, have been reported with all NSAIDs, including diclofenac. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
The use of NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic leakage. Caution and close medical supervision are recommended when using diclofenac after gastrointestinal surgery.

As with other NSAIDs, including diclofenac, medical supervision and special caution are required in patients presenting with symptoms suggestive of gastrointestinal (GI) disorders. The risk of GI bleeding, ulceration or perforation increases with increasing dose of NSAIDs, including diclofenac.

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, treatment should be initiated and maintained at the lowest effective dose. For such patients, as well as those requiring concomitant use of medicinal products containing low doses of acetylsalicylic acid (ASA/aspirin) or other medicinal products likely to increase the risk of gastrointestinal adverse effects, combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered. Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant medicinal products that may 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.

Close medical supervision is required when diclofenac is prescribed to patients with impaired liver function, as their condition may worsen.

As with other NSAIDs, including diclofenac, the level of one or more liver enzymes may increase.
During long-term treatment with the drug, regular monitoring of liver function and liver enzyme levels is 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 if the drug is used in patients with hepatic porphyria, due to the possibility of provoking an attack.

Effect on the kidneys.

Since cases of fluid retention and edema have been reported with NSAIDs, including diclofenac, special 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

Patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects.

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.

Clinical trial data and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and with long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Diclofenac is not recommended for patients with uncontrolled arterial hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease; if necessary, use is possible only after a careful risk/benefit assessment and only at a dosage of no more than 100 mg per day.

A similar assessment should be performed before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g., hypertension, hyperlipidemia, diabetes mellitus, and patients who smoke).

Patients should be informed of the possibility of serious antithrombotic events (chest pain, shortness of breath, weakness, speech disorders) that may occur at any time. In this case, a doctor should be consulted immediately.

Effect on hematological parameters.

With prolonged use of this drug, as with other NSAIDs, monitoring of complete blood counts is recommended.

Diclofenac may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis or hematological disorders should be carefully monitored.

History of asthma.

Patients with 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 asthma (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Therefore, special precautions (emergency medical attention) are recommended for such patients. This also applies to patients with allergic reactions to other substances, such as 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.

For paracetamol.

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.

Patients who take analgesics every day for mild arthritis should consult a doctor. In patients with severe infections such as sepsis, which are accompanied by a decrease in glutathione levels, the risk of metabolic acidosis is increased when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. You should consult a doctor immediately if these symptoms occur.

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 noted that patients with alcoholic 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 exceed the indicated doses.

Do not take the drug with other products containing paracetamol.

If symptoms persist, consult a doctor.

For chlorzoxazone.

Should not be administered to patients with impaired liver function and should be discontinued if signs of hepatotoxicity appear. Patients who develop symptoms such as fever, rash, jaundice, dark urine, loss of appetite, nausea, vomiting after administration should consult a doctor. Should not be administered to patients with porphyria.

Like other NSAIDs, the drug may temporarily inhibit platelet aggregation. Patients with impaired hemostasis 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 simultaneously with other products containing paracetamol or diclofenac.

Do not drink alcohol during use.

Excipients.

The medicine contains quinoline yellow dye (E 104), which may cause allergic reactions.

Use during pregnancy or breastfeeding

Fertility in women.

Diclofenac may impair female fertility and is not recommended in women attempting to conceive. In women who may have difficulty conceiving or who are undergoing investigation of infertility, discontinuation of the drug should be considered.

Ability to influence reaction speed when driving vehicles or other mechanisms

Patients who experience visual disturbances, dizziness, drowsiness, or other central nervous system disorders during treatment with the drug should refrain from driving or operating other mechanisms.

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 tolerability and therapeutic efficacy of the drug. The drug should be used in the lowest effective doses for the shortest time, taking into account the treatment goals for each individual patient.

Adults and children over 14 years of age should take 1 tablet 2–3 times a day after meals.

Do not chew the tablets, drink them with a sufficient amount of water (0.5–1 glass).

The interval between doses is at least 4 hours.

The duration of the treatment course is no more than 5–7 days and depends on the dynamics of the symptoms.

The maximum daily dose of the drug for adults and children over 14 years of age is 3 tablets.

The maximum period of use without consulting a doctor is 3 days.

Children.

The drug is contraindicated in children under 14 years of age.

Overdose

Diclofenac.

Symptoms.

There is no typical clinical picture of diclofenac overdose. Overdose may cause symptoms such as 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 cases of severe intoxication.

Treatment.

Treatment of acute poisoning with NSAIDs, including diclofenac, consists of supportive and symptomatic therapy. This applies to 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 can 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.

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; deficiency of the glutathione system, e.g. malnutrition, AIDS, starvation, cystic fibrosis, cachexia), taking 5 g or more of paracetamol may lead to liver damage. Symptoms of overdose in the first 24 hours: pallor of the skin, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12-48 hours after overdose. Disorders of glucose metabolism and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and 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 arrhythmia and pancreatitis have also been reported. With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop from the hematopoietic system. When taking large doses, from the nervous system: dizziness, psychomotor agitation, 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 the overdose has been taken within 1 hour, activated charcoal should be considered. Plasma paracetamol concentrations should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). N-acetylcysteine treatment can be used up to 24 hours after ingestion, but maximum protection is obtained when administered within 8 hours of ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, administer N-acetylcysteine intravenously to the patient according to the established dose schedule. 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 NSAIDs, as the active substances of the drug are highly bound to plasma proteins and are extensively metabolised.

Chlorzoxazone.

Overdose of chlorzoxazone may cause gastrointestinal upset, drowsiness, dizziness, headache, malaise, lethargy followed by marked loss of muscle tone, hypotension, and respiratory depression. There have been isolated cases of coma following overdose of chlorzoxazone, one of which was after intravenous flumazenil. Occasionally, fatal hepatotoxicity and one case of torticollis have been reported following overdose of chlorzoxazone.

Treatment.

Urgent supportive and symptomatic treatment. Gastric lavage and administration of activated charcoal. 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 NSAIDs, as the active substances of the drug are highly bound to plasma proteins and are extensively metabolised.

Adverse reactions

Gastrointestinal: nausea, vomiting, diarrhea, epigastric pain, heartburn, anorexia, increased activity of hepatic transaminases, dyspepsia, abdominal pain, flatulence, gastritis; gastrointestinal bleeding, bleeding and perforation, sometimes fatal, especially in elderly patients; vomiting with blood, hemorrhagic diarrhea, melena, gastric or intestinal ulcer, accompanied or not accompanied by bleeding or perforation (sometimes fatal, especially in elderly patients), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation; stomatitis, including ulcerative stomatitis, glossitis; impaired function of the esophagus, diaphragmatic stenosis of the intestine; pancreatitis.

From the nervous system: sensory disturbances, headache, dizziness, drowsiness, fatigue, agitation, paresthesias, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, cerebrovascular disorders, stroke, visual disturbances, blurred vision, general malaise.

On the part of the psyche: hallucinations, disorientation, depression, memory impairment, sleep disorders, nightmares, insomnia, irritability, anxiety, feelings of fear, psychotic disorders, confusion, psychomotor agitation.

From the organs of vision: visual disturbances, blurred vision, diplopia, optic neuritis.

From the auditory system: vertigo, tinnitus, noise