Instructions for use Mefenamic acid tablets 500 mg No. 10
Composition
active ingredient: mefenamic acid;
1 tablet contains 500 mg of mefenamic acid;
excipients: microcrystalline cellulose, potato starch, povidone, crospovidone, sodium lauryl sulfate, magnesium stearate, colloidal anhydrous silicon dioxide.
Dosage form
Pills.
Main physicochemical properties: tablets are white or grayish-white with a slightly yellowish or greenish tint, oval in shape, the upper and lower surfaces are convex, with a dividing line on one side.
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 in unchanged form 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.
Due to the risk of cross-sensitivity, mefenamic acid should not be used in patients who have previously experienced hypersensitivity reactions (such as bronchial asthma, bronchospasm, rhinitis, angioedema or urticaria) after taking acetylsalicylic acid (aspirin), ibuprofen or other NSAIDs.
History of upper gastrointestinal bleeding or perforation related to previous NSAID therapy.
Peptic ulcer/bleeding, active or history of, or recurrent disease (two or more separate confirmed episodes of ulceration or bleeding).
Inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis.
Diseases of the blood-forming organs.
Severe heart failure (NYHA III-IV).
Severe liver dysfunction (cirrhosis and ascites).
Severe renal failure (creatinine clearance .
Treatment of pain after coronary artery bypass graft surgery (or use of a cardiopulmonary bypass machine).
Concomitant use of specific COX-2 inhibitors.
Pregnancy or breastfeeding.
Children up to 5 years old.
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.
Antihypertensive agents, including diuretics, ACE inhibitors, angiotensin II receptor antagonists and β-blockers: NSAIDs may reduce the efficacy of diuretics and other antihypertensive agents. In patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), concomitant use of cyclooxygenase inhibitors and ACE inhibitors or angiotensin II antagonists or diuretics may further worsen renal function. There is even a possibility of acute renal failure, which is usually reversible. The possibility of such interactions should be considered in patients taking mefenamic acid concomitantly with these antihypertensive agents. These agents should be administered concomitantly with caution, especially in elderly patients. Patients should be adequately hydrated and consideration should be given to monitoring renal function at the start of concomitant therapy and periodically thereafter.
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.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides.
Cyclosporine: increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be taken for 8–12 days after taking mifepristone, as 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 special caution and under mandatory medical supervision. This applies to both warfarin-type anticoagulants and newer anticoagulants such as apixaban, dabigatran and rivaroxaban.
Oral hypoglycemic agents: inhibition of the metabolism of sulfonylurea drugs, prolongation of the half-life and increased risk of hypoglycemia.
NSAIDs have been reported to interfere with the action of oral antidiabetic agents. Therefore, caution should be exercised when mefenamic acid is used concomitantly with oral antidiabetic agents or insulin.
Concomitant use with other NSAIDs increases the anti-inflammatory effect and the likelihood of gastrointestinal side effects.
Application features
Adverse reactions to the use of mefenamic acid can be minimized by taking 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, especially in elderly patients. Cases of non-oliguric renal insufficiency and proctocolitis have been reported, mainly in elderly patients who did not discontinue mefenamic acid after diarrhea.
The drug should be prescribed with caution to patients with epilepsy.
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 such a 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.
Caution is also required in patients receiving concomitant ACE inhibitors and in individuals at increased risk of hypovolemia. In rare cases, NSAIDs, including mefenamic acid, may cause interstitial nephritis, glomerulitis, papillary necrosis, and nephrotic syndrome. NSAIDs inhibit the synthesis of renal prostaglandins, which are involved in the maintenance of renal perfusion in patients with impaired renal blood flow and volume. In these patients, NSAIDs may precipitate overt renal failure, which usually returns to baseline after discontinuation of the drug. Patients with heart failure, hepatic failure, nephrotic syndrome, or overt renal disease are particularly susceptible to this reaction. These patients should be closely monitored during NSAID therapy.
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.
There are no special recommendations for the use of the drug in cases of moderate liver or kidney dysfunction.
The drug should be prescribed with caution to patients with acute cardiovascular failure, arterial hypertension, and ischemic heart disease.
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 are insufficient data 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. For patients with a history of arterial hypertension and/or mild to moderate congestive heart failure, appropriate examination and advice from a doctor are necessary, 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 arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), long-term treatment with mefenamic acid may be prescribed by a doctor after a careful analysis of the benefit/risk ratio.
The relative increase in risk of cardiovascular events appears to be the same in patients with and without cardiovascular disease or risk factors. However, in terms of absolute incidence, patients with pre-existing cardiovascular disease or risk factors are likely to be at higher risk due to their higher baseline incidence.
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.
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.
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 concomitant use of mefenamic acid with other systemic NSAIDs (including COX-2 inhibitors) should be avoided (see sections "Contraindications" and "Interaction with other medicinal products and other types of interactions").
Mefenamic acid should be used with caution in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as corticosteroids, anticoagulants (including warfarin), SSRIs or antiplatelet agents (including acetylsalicylic acid) (see section "Interaction with other medicinal products and other forms of interaction").
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. Serious skin reactions, some of which have been fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported very rarely with NSAIDs (see section 4.8). Patients are likely to be at greatest risk of developing such reactions at the start of treatment, as most cases occur within the first month of treatment. Mefenamic acid should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Like other NSAIDs, mefenamic acid inhibits platelet aggregation and thereby prolongs bleeding time; this should be taken into account when determining bleeding time. Patients with impaired blood coagulation should be carefully monitored. With long-term use of the drug, it is necessary to monitor blood parameters and kidney function, since mefenamic acid can cause pathological changes in the blood. This is especially true for patients with pre-existing renal dysfunction and elderly patients. If any dyscrasia occurs, drug therapy should be discontinued.
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.
Mefenamic acid should be used with caution in patients who are poor metabolizers of CYP2C9, as well as in patients who are expected to be poor metabolizers of CYP2C9, given the metabolism of other CYP2C9 substrates, as these patients may have abnormally high plasma levels of mefenamic acid due to reduced metabolic clearance.
Important information about excipients
This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
The medicine is not used in women during pregnancy or breastfeeding.
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development. Administration of prostaglandin synthesis inhibitors to animals has been shown to increase pre- and post-implantation losses and embryo-fetal mortality. In addition, animals treated with prostaglandin synthesis inhibitors during organogenesis have been shown to have an increased incidence of various malformations, including cardiovascular anomalies. Epidemiological studies have shown that the use of drugs that inhibit prostaglandin synthesis in early pregnancy increases the risk of spontaneous abortion, cardiac malformations and gastroschisis. The absolute risk of cardiovascular anomalies has increased from less than 1% to approximately 1.5%.
From the 20th week of pregnancy, the use of NSAIDs may cause oligohydramnios due to fetal renal dysfunction. This pathology can occur shortly after the start of treatment and is usually reversible after discontinuation of the drug. In addition, there are reports of narrowing of the ductus arteriosus in the fetus after treatment with NSAIDs in the second trimester of pregnancy, which in most cases resolved after discontinuation of treatment.
The use of any prostaglandin synthesis inhibitor during the third trimester of pregnancy may cause
in the fetus:
‒ development of cardiopulmonary toxicity (with premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
- renal dysfunction, which may progress to renal failure with the development of oligohydramnios (see above);
in the mother and newborn, as well as at the end of pregnancy:
- increased bleeding time, antiplatelet effect, which can be observed even when using the drug in low doses;
- suppression of uterine contractile activity, which leads to delayed development of labor or prolonged labor.
Due to the penetration of mefenamic acid into breast milk and the associated possible side effects for the child, the use of the drug is contraindicated during breastfeeding.
Fertility.
The use of mefenamic acid may impair female fertility and is therefore not recommended in women attempting to conceive. Discontinuation of mefenamic acid should be considered in women who have difficulty conceiving or who are undergoing investigation of infertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Caution should be exercised when driving or operating other machinery that requires increased attention, as sometimes the use of the drug can cause drowsiness, fatigue, blurred vision, and seizures.
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.
Undesirable effects can be minimized by using the lowest effective dose for the shortest period of time necessary to control symptoms.
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, headache, rarely - diarrhea, disorientation, agitation, tinnitus, dizziness, loss of consciousness, hallucinations, sometimes convulsions (mefenamic acid has a tendency to induce tonic-clonic convulsions in case of overdose). In severe cases - gastrointestinal bleeding, respiratory depression, arterial hypertension, twitching of individual muscle groups, coma. In case of significant poisoning, renal and hepatic failure are possible. Fatal consequences are possible.
Treatment: There is no specific antidote. If necessary, symptomatic treatment should be carried out. The use of activated charcoal is advisable if no more than 1 hour has passed after taking an excessive dose of mefenamic acid. For adult patients, gastric lavage may be an alternative within 1 hour after taking a potentially life-threatening dose of mefenamic acid. Adequate diuresis and alkalinization of urine should be ensured. Kidney and liver function should be carefully monitored. The patient's condition should be observed for at least 4 hours after taking a potentially toxic dose of mefenamic acid. Frequent or prolonged convulsions should be stopped by intravenous diazepam. Other measures may be prescribed depending on the clinical condition of the patient. Hemosorption and hemodialysis are ineffective due to the strong binding of mefenamic acid and its metabolites to blood plasma proteins.
Adverse reactions
The most common adverse reactions with mefenamic acid are gastrointestinal disorders. Diarrhea may occur both during the first days of mefenamic acid use and after several months of continuous use. Cases of proctocolitis have been reported in patients who did not discontinue mefenamic acid after diarrhea. If diarrhea occurs, mefenamic acid should be discontinued immediately. In such cases, this drug should not be used again.
On the part of the organs of vision: visual impairment (blurred vision), reversible loss of the ability to distinguish colors, eye irritation.
From the side of the organs of hearing and vestibular apparatus: tinnitus, otalgia, vertigo.
From the respiratory system, chest organs and mediastinum: bronchial asthma, dyspnea, bronchospasm.
Gastrointestinal: epigastric pain, abdominal pain, hematemesis, anorexia, heartburn, nausea, flatulence, vomiting, enterocolitis, colitis, exacerbation of colitis and Crohn's disease, gastritis, hepatotoxicity, liver dysfunction, steatorrhea, cholestatic jaundice, hepatitis, pancreatitis, hepatorenal syndrome, hemorrhagic gastritis, peptic ulcer with or without bleeding, melena, ulcerative stomatitis. Gastrointestinal bleeding or perforation, sometimes fatal, especially in elderly patients, dyspepsia, constipation, diarrhea.
Renal and urinary system: dysuria, cystitis. Renal dysfunction, sodium and fluid retention, albuminuria, hematuria, oliguria or polyuria, renal failure, including papillary necrosis or renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, allergic glomerulonephritis, proteinuria, non-oliguric renal failure (especially with dehydration).
Nervous system: drowsiness or insomnia, weakness, fatigue, irritability, agitation, headache, blurred vision, seizures, optic neuritis, paresthesia, dizziness, fever, disorientation; aseptic meningitis (especially in patients with autoimmune disorders such as systemic lupus erythematosus, mixed connective tissue disease) with symptoms such as occipital muscle stiffness, headache, nausea, vomiting.
Mental: nervousness, confusion, depression, hallucinations.
Cardiovascular system: arterial hypertension, arrhythmia, palpitations, rarely - congestive heart failure, peripheral edema, syncope, arterial hypotension, palpitations, shortness of breath, thrombotic complications (e.g. myocardial infarction or stroke).
Blood and lymphatic system disorders: aplastic anemia, autoimmune hemolytic anemia, prolonged bleeding time, eosinophilia, leukopenia with risk of infection, sepsis or disseminated intravascular coagulation, thrombocytopenia, decreased hematocrit, thrombocytopenic purpura, agranulocytosis, neutropenia, pancytopenia, bone marrow hypoplasia.
Immune system disorders: allergic rhinitis, hypersensitivity reactions (have been reported in association with the use of NSAIDs), which may include: non-specific allergic reactions and anaphylaxis, airway reactivity including asthma, asthma exacerbation, bronchospasm and dyspnoea, or various forms of skin reactions including skin rash, urticaria, pruritus, purpura, angioedema, and less commonly exfoliative and bullous dermatoses (including toxic epidermal necrolysis, erythema multiforme).
Skin and subcutaneous tissue disorders: angioedema, laryngeal edema, facial edema, skin rash, pruritus, erythema multiforme, urticaria, bullous reactions, including toxic epidermal necrolysis (Lyell's syndrome) and Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); increased sweating, bullous pemphigus, photosensitivity.
Laboratory indicators: 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: multiple organ failure, hypothermia (in children).
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
2 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 blister, 1, 2 or 10 blisters in a pack.
Vacation category
Without a prescription: pills #10 (10 × 1), #20 (10 × 2).
By prescription: tablets No. 100 (10 × 10).
Producer
JSC "Lubnypharm".
Location of the manufacturer and address of its place of business
Ukraine, 37500, Poltava region, Lubny, Barvinkova st., 16.
