Mefenaminca

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MeFenamynka® (Mefenamynka)

Composition:

Active substance: mefenamic acid;

1 tablet contains 500 mg of mefenamic acid;

Excipients: lactose monohydrate, sodium lauryl sulfate, povidone, crospovidone, pregelatinized starch, colloidal anhydrous silicon dioxide, microcrystalline cellulose, talc, magnesium stearate, Opadry 200 White.

Medicinal form. Film-coated tablets.

Main physicochemical properties: elongated, biconvex tablets with a score line, coated with a white or almost white film coating.

Pharmacotherapeutic group. Nonsteroidal anti-inflammatory and antirheumatic agents. Fenamates. ATC code M01AG01.

Pharmacological properties.

Pharmacodynamics.

Mefenamic acid is a non-steroidal anti-inflammatory agent. Its 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 response. Mefenamic acid stabilizes cellular protein ultrastructures and membranes, decreases vascular permeability, disrupts oxidative phosphorylation processes, inhibits mucopolysaccharide synthesis, suppresses cell proliferation at the site of inflammation, increases cellular resistance, and stimulates wound healing. Antipyretic properties are associated with the ability to inhibit prostaglandin synthesis and affect the thermoregulatory center.

Mefenamic acid stimulates interferon production.

In the mechanism of analgesic action, in addition to affecting central pain sensitivity mechanisms, a significant role is played by local effects on the inflammatory site and the ability to inhibit the formation of algogenic substances (kinins, histamine, serotonin).

Pharmacokinetics.

After oral administration, mefenamic acid is rapidly and almost completely absorbed from the gastrointestinal tract. Maximum blood concentration is reached within 2–4 hours after intake. Blood levels are proportional to the dose. Steady-state concentration (20 μg/mL) is achieved by day 2 of treatment (1 g four times daily). It is 90% bound to plasma albumin. In the liver, it undergoes metabolism via oxidation, hydrolysis, and glucuronidation to form metabolites. The elimination half-life (T_1/2) is 2–4 hours. It is excreted from the body unchanged and as metabolites primarily through the kidneys (67% of the dose), with feces (20–25%).

Clinical characteristics.

Indications.

Acute viral respiratory infections and influenza.

Mild to moderate pain: muscular, joint, traumatic, dental, headache of various etiologies, postoperative and postpartum pain.

Primary dysmenorrhea. Dysfunctional menorrhagia, including that caused by intrauterine contraceptives, in the absence of pelvic organ pathology.

Inflammatory disorders of the musculoskeletal system: rheumatoid arthritis, rheumatism, ankylosing spondylitis.

Contraindications.

Hypersensitivity to the components of the drug. Bronchospasm, angioedema, allergic rhinitis induced by mefenamic acid, bronchial asthma or urticaria in medical history occurring after administration of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant use of specific COX-2 inhibitors. Active peptic ulcer of the stomach or duodenum, including history of peptic ulcer, inflammatory bowel diseases, blood disorders, severe heart failure, severe impairment of liver or kidney function, gastrointestinal bleeding or perforation caused by NSAIDs. Pain treatment following coronary artery bypass graft (CABG) surgery. Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interactions.

Concomitant use of mefenamic acid with other medicinal products that bind to plasma proteins may require dose adjustment.

Thiamine, pyridoxine hydrochloride, barbiturates, phenothiazine derivatives, narcotic analgesics, caffeine, dimethylaminoethanol (dimebolin): enhanced analgesic effect of the drug.

When mefenamic acid is used concomitantly with methotrexate, the toxic effects of methotrexate are potentiated.

Antihypertensive agents (ACE inhibitors and angiotensin II receptor antagonists): reduced antihypertensive effect, increased risk of renal impairment, particularly in elderly patients. Patients should maintain adequate fluid intake. Renal function should also be assessed at the beginning of treatment and during concomitant therapy.

Acetylsalicylic acid (aspirin): experimental data indicate that concomitant use of mefenamic acid may inhibit the antiplatelet effect of low-dose aspirin and thus may reduce the effectiveness of aspirin in cardiovascular disease prophylaxis. However, due to limitations of these experimental data and uncertainty regarding extrapolation of ex vivo data to clinical situations, definitive conclusions about the impact of mefenamic acid during regular use cannot be drawn.

Diuretics: reduced diuretic effect. Diuretics may increase the nephrotoxic potential of NSAIDs.

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 used within 8–12 days after mifepristone administration—NSAIDs may reduce the efficacy of mifepristone.

Corticosteroids: increased risk of gastrointestinal ulcers and bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): 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. Increased risk of joint hemorrhage and bruising in HIV-positive hemophilia patients receiving zidovudine concurrently.

Lithium preparations: reduced lithium excretion and increased risk of lithium toxicity. Patients receiving mefenamic acid and lithium preparations should be under close medical supervision for early detection of signs of lithium toxicity.

Mefenamic acid enhances the activity of oral anticoagulants; therefore, concomitant use increases the risk of bleeding. Concomitant use of mefenamic acid with oral anticoagulants requires careful monitoring of prothrombin time. NSAIDs should be used with warfarin or heparin with particular caution and under mandatory medical supervision.

Oral hypoglycemic agents: inhibition of sulfonylurea metabolism, prolonged elimination half-life, and increased risk of hypoglycemia.

Concomitant use with other NSAIDs increases anti-inflammatory effect and the likelihood of gastrointestinal adverse effects.

Special precautions for use.

Adverse reactions to mefenamic acid can be minimized by using the lowest effective dose for the shortest duration possible.

Patients undergoing prolonged treatment with mefenamic acid should be under continuous medical supervision for the development of hepatic dysfunction, skin rashes, blood dyscrasias, or diarrhea. If any of these pathological conditions or symptoms occur, treatment should be discontinued immediately.

Prolonged use of the drug for headache treatment may lead to headache worsening. In such cases, treatment should be discontinued and medical advice sought.

Mefenamic acid should be used with caution in patients who are dehydrated due to vomiting, diarrhea, or increased diuresis, and in patients with renal impairment, especially elderly patients.

Elderly patients have an increased frequency of adverse reactions associated with NSAID use, particularly gastrointestinal bleeding and perforation, which may be fatal. The medicinal product should be used at the lowest effective dose for the shortest possible duration. During NSAID therapy, gastrointestinal status should be monitored for possible complications, especially gastrointestinal bleeding. Mefenamic acid should be used cautiously in elderly patients with dehydration and kidney disease. Cases of non-oliguric renal failure and proctocolitis have been reported, primarily in elderly patients who did not discontinue mefenamic acid after the onset of diarrhea.

Administration of mefenamic acid may cause gastrointestinal disorders (e.g., diarrhea). These may occur immediately after drug administration or after prolonged use. If such symptoms occur, the drug should be discontinued.

The medicinal product should be prescribed with caution to patients with acute heart failure, arterial hypertension, or ischemic heart disease.

The medicinal product should be prescribed with caution to patients with epilepsy.

Mefenamic acid should be used cautiously in patients with bronchial asthma (including in medical history), as NSAIDs have been reported to accelerate bronchospasm development in such patients.

The use of NSAIDs may lead to dose-dependent reduction in prostaglandin synthesis and provoke the development of renal failure. Patients at highest risk include those with impaired kidney, liver, or heart function, patients taking diuretics, and elderly patients. Renal function should be monitored in such patients.

Mild disturbances in liver and kidney function may occur during mefenamic acid use. If such disturbances develop, the drug should be discontinued. Patients receiving long-term mefenamic acid treatment should be under medical supervision due to the potential for liver and kidney function impairment.

There are no special recommendations for drug use in patients with mild hepatic or renal impairment.

Clinical and epidemiological data indicate that the use of certain NSAIDs (particularly at high doses and for prolonged periods) may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). There is insufficient data to exclude such risk with mefenamic acid use.

If mefenamic acid use is necessary in patients with cardiovascular or cerebrovascular diseases, medical consultation is required. The recommended dose or treatment duration should not be exceeded during therapy. Treatment with mefenamic acid in patients with uncontrolled arterial hypertension, congestive heart failure, diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be initiated by a physician after careful benefit-risk assessment. Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure require appropriate evaluation and medical advice, as fluid retention and edema have been reported with NSAID use. Long-term treatment with mefenamic acid in patients with cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, or smoking) should only be initiated by a physician after careful benefit-risk assessment.

Mefenamic acid should be used with caution in patients with intracranial hemorrhage or hemorrhagic diathesis due to the ability of NSAIDs to inhibit platelet function.

There have been reports of potentially fatal gastrointestinal bleeding, ulcers, or perforations occurring at any stage of NSAID treatment, regardless of prior warning symptoms or history of severe gastrointestinal disorders. Smoking and alcohol consumption are additional risk factors.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as disease exacerbation may occur. If mefenamic acid use leads to gastrointestinal bleeding or perforation, treatment with the drug must be discontinued.

Elderly patients generally have an increased risk of gastrointestinal adverse effects, particularly gastrointestinal bleeding and perforation, which may be fatal; therefore, treatment should be initiated at the lowest dose.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, a history of peptic ulcer (especially if complicated by bleeding or perforation), and in elderly patients. Patients at risk of gastrointestinal bleeding, such as elderly patients or those concurrently taking low-dose acetylsalicylic acid (aspirin) or other drugs that increase gastrointestinal risk, should consult a physician regarding the possibility of combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors).

Patients with systemic lupus erythematosus or mixed connective tissue diseases have an increased risk of aseptic meningitis.

Mefenamic acid should be prescribed with caution to patients at high risk of serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Mefenamic acid use should be discontinued at the first sign of skin rash, mucosal damage, or any other sign of hypersensitivity.

During long-term use of the drug, blood parameters should be monitored, as mefenamic acid may cause pathological blood changes. If any signs of blood dyscrasia occur, treatment should be discontinued.

Caution should be exercised when co-administering mefenamic acid with other drugs that increase the risk of gastotoxicity or bleeding, such as corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents.

Limited data suggest that drugs inhibiting cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment. Mefenamic acid may impair female fertility and is not recommended for women attempting to conceive. If used in women with symptoms of dysmenorrhea or menorrhagia without therapeutic effect, medical advice should be sought.

Mefenamic acid should be used with caution in patients with slow metabolism mediated by CYP2C9, as well as in patients expected to have slow CYP2C9 metabolism based on metabolism of other CYP2C9 substrates, due to potentially abnormally high plasma levels of mefenamic acid resulting from reduced metabolic clearance.

Important information on excipients.

If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

The medicinal product is not used in women during pregnancy or breastfeeding.

From the 20th week of pregnancy, mefenamic acid use may cause oligohydramnios due to fetal renal dysfunction. This effect may occur soon after treatment initiation and is usually reversible upon discontinuation of treatment.

Therefore, the medicinal product Mefenaminka is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Ability to affect reaction speed when driving or operating machinery.

Caution should be exercised when driving or operating machinery requiring high attention, as the drug may occasionally cause drowsiness, blurred vision, or seizures.

Dosage and Administration.

The medicinal product should be used under the supervision of a physician who determines the dose and duration of treatment. Administer orally. The medicinal product should be taken after food.

For adults and children aged 12 years and older, the dose is 250–500 mg 3–4 times daily. Depending on indications and good tolerability, the daily dose may be increased up to the maximum of 3000 mg. After achieving the therapeutic effect, the dose should be reduced to 1000 mg/day.

For children aged 5 to 12 years: 250 mg 3–4 times daily.

The treatment course for joint diseases may last from 20 days to 2 months or longer. For pain syndrome treatment, the therapy course lasts up to 7 days.

Children.

The medicinal product is contraindicated in children under 5 years of age.

Overdose.

Symptoms: epigastric pain, nausea, vomiting, drowsiness. In severe cases – gastrointestinal bleeding, respiratory depression, arterial hypertension, muscle twitching, coma.

Treatment: no specific antidote is available. Gastric lavage with activated charcoal suspension. Urine alkalization and forced diuresis. Symptomatic therapy. Hemoadsorption and hemodialysis are poorly effective due to the strong binding of mefenamic acid to blood proteins.

Side effects.

Eye disorders: vision disturbances, reversible loss of color vision, eye irritation.

Ear and labyrinth disorders: tinnitus, otalgia.

Respiratory, thoracic and mediastinal disorders: dyspnea, bronchospasm.

Gastrointestinal disorders: 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 hemorrhage, sometimes fatal, particularly in elderly patients, dyspepsia, constipation, diarrhea.

Renal and urinary disorders: dysuria, cystitis. Renal function impairment, albuminuria, hematuria, oliguria or polyuria, renal failure, including papillary necrosis, acute interstitial nephritis, nephrotic syndrome, allergic glomerulonephritis, hyponatremia, hyperkalemia.

Nervous system disorders: somnolence or insomnia, weakness, irritability, excitement, headache, blurred vision, convulsions, optic neuritis, paresthesia, dizziness, nuchal rigidity, fever, disorientation.

Psychiatric disorders: confusion, depression, hallucinations.

Cardiovascular disorders: arterial hypertension, arrhythmia, rarely – congestive heart failure, peripheral edema, syncope, arterial hypotension, palpitations, dyspnea, thrombotic complications (e.g., 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 disorders: hypersensitivity reactions, including skin rash, pruritus, facial swelling, allergic rhinitis, angioneurotic edema, laryngeal edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, urticaria, bullous pemphigoid, photosensitivity, asthma, anaphylaxis.

Skin and subcutaneous tissue disorders: purpura, skin rash, pruritus, erythema multiforme, urticaria, bullous pemphigoid.

Laboratory findings: impaired glucose tolerance in patients with diabetes mellitus, positive reaction in certain tests for mefenamic acid and its metabolites in bile and urine. Increased levels of liver enzymes in blood plasma.

Other: aseptic meningitis, sweating, increased fatigue, malaise, multiple organ failure, hyperthermia.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization of a medicinal product is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister pack; 1 or 2 blister packs in a carton.

Prescription status. Over-the-counter.

Manufacturer. JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's address and place of business.

13 Borispilska Street, Kyiv, 02093, Ukraine.