Mefenamic acid
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MEFENAMIC ACID
Composition:
Active substance: mefenamic acid;
1 tablet contains 500 mg of mefenamic acid;
Excipients: microcrystalline cellulose, potato starch, copovidone, crospovidone, sodium lauryl sulfate, magnesium stearate, colloidal anhydrous silicon dioxide.
Pharmaceutical form. Tablets.
Main physicochemical properties: tablets of white or greyish-white color with a slightly yellowish or greenish tint, biconvex, with a score line on one side.
Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Fenamates. ATC code M01A G01.
Pharmacological Properties.
Pharmacodynamics.
Mefenamic acid is a nonsteroidal anti-inflammatory agent. Its anti-inflammatory action is due to its 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 protein ultrastructures and cell membranes, decreases vascular permeability, disrupts oxidative phosphorylation processes, inhibits mucopolysaccharide synthesis, suppresses cell proliferation at the inflammatory site, enhances 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, alongside effects on central pain sensitivity mechanisms, a significant role is played by local action at 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 dose-proportional. Steady-state concentration (20 μg/mL) is achieved by day 2 of treatment (1 g administered four times daily). It is 90% bound to blood albumins. In the liver, metabolites are formed via oxidation, hydrolysis, and glucuronidation. The elimination half-life (T1/2) is 2–4 hours. It is excreted from the body unchanged and as metabolites primarily via the kidneys (67% of the dose), with 20–25% eliminated in feces.
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 contraceptive devices, 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. History of bronchospasm, angioedema (Quincke's edema), rhinitis, bronchial asthma, or urticaria following administration of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant use of specific cyclooxygenase-2 inhibitors. Peptic ulcer disease of the stomach or duodenum (including history), inflammatory bowel diseases, blood disorders, severe heart failure, severe hepatic or renal impairment, gastrointestinal bleeding or perforation caused by NSAID use. Should not be used for pain management following coronary artery bypass graft (CABG) surgery.
Interaction with other medicinal products and other forms of interaction.
Thiamine, pyridoxine hydrochloride, barbiturates, phenothiazine derivatives, narcotic analgesics, caffeine, dimethindene enhance the analgesic effect of the drug.
Concomitant use of mefenamic acid and methotrexate enhances methotrexate toxicity and may increase methotrexate plasma levels.
Probenecid: reduced metabolism, delayed elimination of probenecid from the body.
Antihypertensive agents (angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists): reduced antihypertensive effect, increased risk of renal impairment, especially in elderly patients. Patients should maintain adequate fluid intake. Renal function should be assessed at the beginning of treatment and during concomitant therapy.
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.
Cyclosporines: 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 nephrotoxicity.
Tacrolimus: increased risk of nephrotoxicity.
Zidovudine: NSAIDs increase the risk of hematological toxicity. Increased risk of joint hemorrhage and hematoma in HIV-positive patients with hemophilia receiving zidovudine.
Lithium preparations: reduced lithium excretion and increased risk of lithium toxicity.
Mefenamic acid enhances the activity of oral anticoagulants, thus increasing the risk of bleeding when used concomitantly. Concomitant use of mefenamic acid with oral anticoagulants requires careful monitoring of prothrombin time. Particular caution is required when using NSAIDs with warfarin or heparin—medical supervision is necessary.
Concomitant use with other nonsteroidal anti-inflammatory drugs increases anti-inflammatory effect and the likelihood of gastrointestinal adverse effects.
Special precautions for use.
Mefenamic acid should not be used in patients who have previously experienced hypersensitivity reactions (e.g., asthma, bronchospasm, rhinitis, angioedema, or urticaria).
Long-term treatment with mefenamic acid may be prescribed by a physician to patients with risk factors for cardiovascular and cerebrovascular complications (such as arterial hypertension, ischemic heart disease, or diabetes mellitus) only after careful assessment of the benefit-risk ratio.
The use of NSAIDs (especially at high doses and for prolonged periods) may be associated with a small increased risk of myocardial infarction or stroke.
The medicinal product should be prescribed with caution to patients with epilepsy.
Do not use in dehydrated patients who have lost fluids due to vomiting, diarrhea, or increased urination.
For long-term treatment of headache, consultation with a physician is necessary.
There are no specific recommendations regarding the use of the medicinal product in patients with moderate hepatic or renal impairment.
NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated. If treatment with mefenamic acid results in gastrointestinal bleeding or perforation, 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. Smoking and alcohol consumption are additional risk factors.
Patients with systemic lupus erythematosus and mixed connective tissue diseases have an increased risk of developing 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. Treatment with mefenamic acid should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
During long-term use of the medicinal product, blood parameters should be monitored, as mefenamic acid may cause pathological changes in the blood. If any signs of blood dyscrasias occur, treatment with the drug should be discontinued.
Administration of mefenamic acid may lead to gastrointestinal disturbances (e.g., diarrhea), which may occur either immediately after drug administration or after prolonged use. If such symptoms occur, the use of the medicinal product should be discontinued.
Caution is required when using mefenamic acid in patients receiving concomitant therapy with drugs that increase the risk of bleeding: corticosteroids, anticoagulants (warfarin), and aspirin.
Mefenamic acid may impair female fertility and is not recommended for women attempting to conceive. If used for symptoms of dysmenorrhea and menorrhagia without therapeutic effect, a physician should be consulted.
Use during pregnancy or breastfeeding.
The drug should not be used in pregnant women.
From the 20th week of pregnancy, the use of mefenamic acid may cause oligohydramnios due to fetal renal dysfunction; narrowing of the fetal arterial duct has also been reported.
The use of any prostaglandin synthesis inhibitor during the third trimester of pregnancy may cause
in the fetus:
‒ cardiovascular and pulmonary toxicity (with premature constriction/closure of the arterial duct and pulmonary hypertension);
‒ renal dysfunction, which may progress to renal failure and lead to oligohydramnios (see above);
in the mother and newborn, as well as at the end of pregnancy:
‒ prolonged bleeding time, anti-aggregatory effect, which may occur even with low-dose administration of the drug;
‒ inhibition of uterine contractility, leading to delayed onset of labor or prolonged delivery.
The drug should not be used in women during breastfeeding.
Ability to influence reaction speed when driving or operating machinery.
Caution should be exercised when driving or operating machinery requiring heightened attention, as the use of the medicinal product may occasionally cause drowsiness, blurred vision, or seizures.
Method of Administration and Dosage
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 meals.
For adults and children aged 12 years and older, the recommended dose is 250–500 mg 3–4 times daily. If necessary, 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, the recommended dose is 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 management, the treatment 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, headache, rarely diarrhea, disorientation, excitement, tinnitus, loss of consciousness, and occasionally seizures (mefenamic acid has a tendency to induce tonic-clonic seizures in cases of overdose). In severe cases: gastrointestinal bleeding, respiratory depression, arterial hypertension, muscle twitching, coma. In cases of significant poisoning, renal and hepatic failure may occur.
Treatment: There is no specific antidote. Gastric lavage with activated charcoal suspension. Alkalinization of urine and forced diuresis. Symptomatic therapy. Hemoadsorption and hemodialysis are poorly effective due to the strong binding of mefenamic acid to plasma proteins.
Frequent or prolonged seizures should be treated by intravenous administration of diazepam.
Adverse Reactions
The most common adverse reactions associated with the use of mefenamic acid are gastrointestinal disorders. Diarrhea may occur both during the first days of treatment and after several months of continuous use. In patients who continued taking mefenamic acid after the onset of diarrhea, cases of proctocolitis have been reported. If diarrhea develops, mefenamic acid must be discontinued immediately. The drug should not be used again in such cases.
Eye disorders: Visual disturbances, reversible inability to distinguish colors, eye irritation.
Ear and labyrinth disorders: Tinnitus, ear pain (otalgia), vertigo.
Respiratory system disorders: Dyspnea, bronchospasm.
Gastrointestinal disorders: Epigastric pain, peptic ulcer, abdominal pain, hematemesis, 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, melena, ulcerative stomatitis. Gastrointestinal hemorrhage, perforation, or gastrointestinal bleeding, 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, proteinuria, non-oliguric renal failure (especially in cases of dehydration).
Metabolism and nutrition disorders: Impaired glucose tolerance in patients with diabetes mellitus, hyponatremia, hyperkalemia.
Nervous system disorders: Somnolence or insomnia, weakness, irritability, nervousness, headache, blurred vision, convulsions, optic neuritis, paresthesia, dizziness, nuchal rigidity, fever, disorientation; aseptic meningitis (particularly in patients with autoimmune disorders such as systemic lupus erythematosus or mixed connective tissue disease), with symptoms including nuchal rigidity, headache, nausea, and vomiting.
Psychiatric disorders: Nervousness, confusion, depression, hallucinations.
Cardiovascular system disorders: Arterial hypertension, arrhythmia, palpitations, rarely congestive heart failure, peripheral edema, syncope, arterial hypotension, tachycardia, dyspnea, 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 (reported in association with NSAID use), including non-specific allergic reactions and anaphylaxis, respiratory tract reactivity such as asthma, asthma exacerbation, bronchospasm and dyspnea, or various skin reactions including skin rash, pruritus, facial swelling, allergic rhinitis, angioedema, and less commonly exfoliative and bullous dermatoses, including toxic epidermal necrolysis, erythema multiforme; laryngeal edema, Stevens–Johnson syndrome, urticaria, bullous pemphigoid, photosensitivity, asthma, anaphylaxis.
Skin and subcutaneous tissue disorders: Angioedema, purpura, skin rash, pruritus, urticaria, erythema multiforme, bullous reactions including toxic epidermal necrolysis (Lyell’s syndrome) and Stevens–Johnson syndrome; increased sweating, pemphigus.
Laboratory findings: Impaired glucose tolerance in patients with diabetes mellitus, positive tests for mefenamic acid and its metabolites in bile and urine. Elevated liver enzymes in blood plasma.
Other: Aseptic meningitis, sweating, increased fatigue, malaise, multiple organ failure, hyperthermia, pyrexia.
Shelf life. 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 pack, 2 blisters per carton; 1 blister without secondary packaging.
Prescription status. Over-the-counter (without prescription).
Manufacturer.
Pharmaceutical Company "Farmakos" LLC.
Manufacturer's address and location of operations.
360, Svyato-Pokrovska Street, settlement of Hostomel, Irpin, Kyiv region, 08290, Ukraine
Marketing Authorization Holder.
Pharmaceutical Company "Farmakos" LLC.
Address of the Marketing Authorization Holder.
50-A, Zodchykh Street, Kyiv, 03162, Ukraine