Instructions for Mefenamic acid film-coated tablets 500 mg No. 10
Composition
active ingredient: mefenamic acid;
1 tablet contains 500 mg of mefenamic acid;
Excipients: lactose monohydrate, sodium lauryl sulfate, povidone, crospovidone, pregelatinized starch, colloidal anhydrous silica, microcrystalline cellulose, talc, magnesium stearate, Opadry 200 white.
Dosage form
Film-coated tablets.
Main physicochemical properties: oblong tablets with a biconvex surface, with a score, coated with a white or almost white coating.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Fenamates. ATX code M01A G01.
Pharmacological properties
Pharmacodynamics
Mefenamic acid is a nonsteroidal anti-inflammatory drug. The mechanism of anti-inflammatory action is due to the ability to inhibit the synthesis of inflammatory mediators (prostaglandins, serotonin, kinins, etc.), reduce the activity of lysosomal enzymes involved in the inflammatory reaction. Mefenamic acid stabilizes protein ultrastructures and cell membranes, reduces vascular permeability, disrupts oxidative phosphorylation processes, inhibits the synthesis of mucopolysaccharides, inhibits cell proliferation in the focus of inflammation, increases cell resistance and stimulates wound healing. Antipyretic properties are associated with the ability to inhibit the synthesis of prostaglandins and affect the thermoregulation center.
Mefenamic acid stimulates the formation of interferon.
In the mechanism of analgesic action, along with the effect on the central mechanisms of pain sensitivity, a significant role is played by the local effect on the focus of inflammation and the ability to inhibit the formation of algogens (kinins, histamine, serotonin).
Pharmacokinetics
After oral administration, mefenamic acid is rapidly and fairly completely absorbed from the gastrointestinal tract. The maximum concentration in the blood is observed 2–4 hours after administration. The level in the blood is proportional to the dose. The equilibrium concentration (20 μg/ml) is determined on the 2nd day of administration (1 g 4 times a day). It is 90% bound to blood albumin. In the liver, it forms metabolites by oxidation, hydrolysis, and glucuronidation. The half-life (T1/2) is 2–4 hours. It is excreted from the body unchanged and in the form of metabolites mainly by the kidneys (67% of the dose), with feces (20–25%).
Indication
Acute respiratory viral infections and influenza.
Low and medium intensity pain: muscular, joint, traumatic, dental, headache of various etiologies, postoperative and postpartum pain.
Primary dysmenorrhea. Dysfunctional menorrhagia, including that caused by the presence of intrauterine contraceptives, in the absence of pelvic organ pathology.
Inflammatory diseases of the musculoskeletal system: rheumatoid arthritis, rheumatism, Bechterew's disease.
Contraindication
Hypersensitivity to the components of the drug. Bronchospasm, angioedema, allergic rhinitis to mefenamic acid, bronchial asthma or urticaria in history, which occurred after the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of specific COX-2 inhibitors. Gastric and duodenal ulcer, including a history, inflammatory bowel diseases, diseases of the blood-forming organs, severe heart failure, severe liver or kidney dysfunction, gastrointestinal bleeding or perforation caused by taking NSAIDs. Treatment of pain after coronary artery bypass grafting surgery.
Interaction with other medicinal products and other types of interactions
Concomitant use of mefenamic acid with other drugs that bind to plasma proteins may require dose adjustment.
Thiamine, pyridoxine hydrochloride, barbiturates, phenothiazine derivatives, narcotic analgesics, caffeine, diphenhydramine: increased analgesic effect of the drug.
The combined use of mefenamic acid and methotrexate increases the toxic effects of methotrexate.
Antihypertensive agents (ACE inhibitors and angiotensin II receptor antagonists): reduced antihypertensive effect, increased risk of renal failure, especially in elderly patients. Patients should be adequately hydrated. Renal function should also be assessed at the beginning of treatment and during concomitant therapy.
Acetylsalicylic acid (aspirin): Experimental data suggest that when used concomitantly, mefenamic acid may inhibit the antiplatelet effect of low-dose aspirin and may therefore reduce the efficacy of aspirin prophylaxis for cardiovascular disease. However, due to the limitations of these experimental data and the uncertainty regarding the extrapolation of ex vivo data to the clinical situation, no firm conclusions can be drawn regarding the effects of mefenamic acid when used routinely.
Diuretics: decreased diuretic effect. Diuretics may increase the nephrotoxicity of NSAIDs.
Cyclosporine: increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be taken for 8–12 days after taking mifepristone – NSAIDs may reduce the effects of mifepristone.
Corticosteroids: increased risk of gastrointestinal ulcers and bleeding.
Antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.
Fluoroquinolones: NSAIDs increase the risk of seizures.
Aminoglycosides: NSAIDs increase the risk of nephrotoxic effects.
Tacrolimus: possible increased risk of nephrotoxic effects.
Zidovudine: NSAIDs increase the risk of hematological toxicity. There is an increased risk of joint hemorrhage and hematoma in HIV-positive hemophiliacs receiving concomitant zidovudine treatment.
Lithium preparations: reduced lithium excretion and increased risk of lithium toxicity. Patients taking mefenamic acid and lithium preparations should be under close medical supervision for timely detection of signs of lithium toxicity.
Mefenamic acid increases the activity of oral anticoagulants, so their simultaneous use increases the risk of bleeding. The simultaneous use of mefenamic acid with oral anticoagulants requires careful monitoring of prothrombin time. NSAIDs with warfarin or heparin should be used with extreme caution and under mandatory medical supervision.
Oral hypoglycemic agents: inhibition of the metabolism of sulfonylurea drugs, prolongation of the half-life and increased risk of hypoglycemia.
Concomitant use with other NSAIDs increases the anti-inflammatory effect and the likelihood of gastrointestinal side effects.
Application features
Adverse reactions to mefenamic acid can be minimized by using the lowest effective dose for the shortest period of time.
During long-term treatment with mefenamic acid, patients should be monitored closely for the development of liver dysfunction, rash, blood dyscrasias, or diarrhea. If any of these symptoms develop, treatment should be discontinued immediately.
Prolonged use of the drug for the treatment of headaches may lead to their intensification. In this case, treatment should be discontinued and a doctor should be consulted.
Mefenamic acid should be used with caution in patients dehydrated by vomiting, diarrhea, or increased diuresis, in patients with renal insufficiency, and especially in elderly patients.
Elderly patients have an increased frequency of adverse reactions associated with the use of NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal. The drug should be used at the lowest effective dose for the shortest possible period of time. During therapy with NSAIDs, it is necessary to monitor the state of the gastrointestinal tract for possible disorders, especially gastrointestinal bleeding. Mefenamic acid should be used with caution in elderly patients with dehydration and renal disease. Cases of non-oliguric renal failure and proctocolitis have been reported, which were recorded mainly in elderly patients who did not stop taking mefenamic acid after the onset of diarrhea.
Taking mefenamic acid may cause gastrointestinal disorders (e.g. diarrhoea). These may occur either immediately after taking the medicine or after long-term use. If such symptoms occur, the medicine should be discontinued.
The drug should be prescribed with caution to patients with acute cardiovascular failure, arterial hypertension, and ischemic heart disease.
The drug should be prescribed with caution to patients with epilepsy.
Mefenamic acid should be used with caution in patients with bronchial asthma (including a history of it), as NSAIDs have been reported to accelerate the development of bronchospasm in such patients.
The use of NSAIDs can lead to a dose-dependent decrease in prostaglandin synthesis and provoke the development of renal failure. The highest risk of developing this reaction is in patients with impaired renal function, liver function, heart failure, patients taking diuretics, and elderly patients. In such patients, renal function should be monitored.
Moderate hepatic and renal dysfunction may occur with mefenamic acid. Patients who develop such dysfunction should discontinue the drug. Patients taking mefenamic acid for a long time should be monitored by a physician due to the possibility of hepatic and renal dysfunction.
Clinical trial data and epidemiological data suggest that the use of some NSAIDs (particularly at high doses and over long periods) may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There is insufficient evidence to exclude such a risk with mefenamic acid.
If necessary, the use of mefenamic acid in patients with cardiovascular and cerebrovascular diseases should consult a doctor. During treatment, the recommended dose or duration of treatment should not be increased. In patients with uncontrolled arterial hypertension, congestive heart failure, diagnosed ischemic heart disease, peripheral artery disease and/or cerebrovascular disease, treatment with mefenamic acid can be prescribed by a doctor only after a careful analysis of the benefit/risk ratio. For patients with a history of arterial hypertension and/or mild to moderate congestive heart failure, it is necessary to conduct an appropriate examination and obtain medical advice, since cases of fluid retention and edema have been reported in connection with the use of NSAIDs. For patients with risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes mellitus, smoking), long-term treatment with mefenamic acid may be prescribed by a physician after a careful analysis of the benefit/risk ratio.
Mefenamic acid should be used with caution in patients with intracranial hemorrhage and hemorrhagic diathesis due to the ability of NSAIDs to suppress platelet function.
There have been reports of cases of potentially fatal gastrointestinal bleeding, ulceration or perforation occurring at any stage of NSAID treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders. Smoking and alcohol consumption are additional risk factors.
NSAIDs should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), as exacerbation of the disease is possible. If the use of mefenamic acid has led to gastrointestinal bleeding or perforation, treatment with the drug should be discontinued.
Elderly patients are generally at increased risk of gastrointestinal side effects, especially gastrointestinal bleeding and perforation, which can be fatal, so treatment should be started at the lowest dosage.
The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose, with a history of ulcer, especially if complicated by bleeding or perforation, and in elderly patients. Patients at risk of gastrointestinal bleeding, such as the elderly, and patients taking concomitant low-dose acetylsalicylic acid (aspirin) or other drugs that may increase the risk for the gastrointestinal tract, should consult a doctor about the possibility of using combination therapy with protective drugs (e.g. misoprostol or proton pump inhibitors).
Patients with systemic lupus erythematosus and mixed connective tissue diseases are at increased risk of aseptic meningitis.
Mefenamic acid should be used with caution in patients at high risk of serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Mefenamic acid should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
With long-term use of the drug, it is necessary to monitor blood parameters, since mefenamic acid can cause pathological changes in the blood. If any dyscrasia occurs, drug therapy should be discontinued.
Caution should be exercised when administering mefenamic acid concomitantly to patients receiving concomitant therapy with medicinal products that increase the risk of gastrotoxicity or bleeding, such as corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors or antiplatelet agents.
There is limited evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This process is reversible after discontinuation of treatment. The use of mefenamic acid may impair female fertility and is not recommended in women attempting to conceive. When used by women with symptoms of dysmenorrhea and menorrhagia and in the absence of a therapeutic effect, a doctor should be consulted.
Important information about excipients.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.
Ability to influence reaction speed when driving vehicles or other mechanisms
Caution should be exercised when driving or operating machinery that requires increased attention, as sometimes the use of the drug can cause drowsiness, blurred vision, and seizures.
Use during pregnancy or breastfeeding
The medicine is not used in women during pregnancy or breastfeeding.
Method of administration and doses
The drug should be used under the supervision of a doctor who determines the dose and duration of treatment. It is administered orally. The drug should be taken after meals.
Adults and children over 12 years of age are prescribed 250–500 mg 3–4 times a day. According to indications and with good tolerability, the daily dose is increased to the maximum – 3000 mg, after achieving a therapeutic effect, the dose is reduced to 1000 mg/day.
Children aged 5 to 12 years - 250 mg 3–4 times a day.
The course of treatment for joint diseases can last from 20 days to 2 months or more. In the treatment of pain syndrome, the course of therapy lasts up to 7 days.
Children
The drug is contraindicated in children under 5 years of age.
Overdose
Symptoms: epigastric pain, nausea, vomiting, drowsiness. In severe cases, gastrointestinal bleeding, respiratory depression, hypertension, twitching of individual muscle groups, coma.
Treatment: no specific antidote. Gastric lavage with a suspension of activated charcoal. Alkalization of urine, forced diuresis. Symptomatic therapy. Hemosorption and hemodialysis are ineffective due to the strong binding of mefenamic acid to blood proteins.
Adverse reactions
On the part of the organs of vision: visual impairment, reversible loss of the ability to distinguish colors, eye irritation.
From the side of the organs of hearing and vestibular apparatus: tinnitus, otalgia.
Respiratory, thoracic and mediastinal disorders: dyspnea, bronchospasm.
Gastrointestinal: epigastric pain, anorexia, heartburn, nausea, flatulence, vomiting, enterocolitis, colitis, exacerbation of colitis and Crohn's disease, gastritis, hepatotoxicity, steatorrhea, cholestatic jaundice, hepatitis, pancreatitis, hepatorenal syndrome, hemorrhagic gastritis, peptic ulcer with or without bleeding. Gastrointestinal bleeding, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients, dyspepsia, constipation, diarrhea.
Renal and urinary disorders: dysuria, cystitis. Renal dysfunction, albuminuria, hematuria, oliguria or polyuria, renal failure, including papillary necrosis, acute interstitial nephritis, nephrotic syndrome, allergic glomerulonephritis, hyponatremia, hyperkalemia.
From the nervous system: drowsiness or insomnia, weakness, irritability, agitation, headache, blurred vision, seizures, optic neuritis, paresthesia, dizziness, rigidity of the occipital muscles, fever, loss of orientation.
On the part of the psyche: confusion, depression, hallucinations.
Cardiovascular system: arterial hypertension, arrhythmia, rarely - congestive heart failure, peripheral edema, syncope, arterial hypotension, palpitations, shortness of breath, thrombotic complications (for example, myocardial infarction or stroke).
Blood and lymphatic system disorders: aplastic anemia, autoimmune hemolytic anemia, prolonged bleeding time, eosinophilia, leukopenia, thrombocytopenia, decreased hematocrit, thrombocytopenic purpura, agranulocytosis, neutropenia, pancytopenia, bone marrow hypoplasia.
Immune system: hypersensitivity reactions, including skin rash, skin itching, facial edema, allergic rhinitis, angioedema, laryngeal edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, urticaria, bullous pemphigus, photosensitivity, asthma, anaphylaxis.
Skin and subcutaneous tissue disorders: purpura, skin rash, pruritus, erythema multiforme, urticaria, bullous pemphigus.
Laboratory indicators: impaired glucose tolerance in patients with diabetes mellitus, positive reaction in some tests for the presence of mefenamic acid and its metabolites in bile and urine. Increased levels of liver enzymes in blood plasma.
Others: aseptic meningitis, sweating, fatigue, malaise, multiple organ failure, hyperthermia.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a contour blister pack, 1 contour blister pack in a pack.
Vacation category
Without a prescription.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
