Majezik-sanovel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MAJEZIK–sanovel (MAJEZIK–sanovel)

Composition:

Active substance: flurbiprofen;

One film-coated tablet contains flurbiprofen 100 mg;

Excipients: lactose monohydrate; microcrystalline cellulose; sodium croscarmellose; hydroxypropyl cellulose; magnesium stearate; colloidal anhydrous silicon dioxide;

Coating: Opadry II Blue OY-L-20906 (lactose monohydrate; hydroxypropyl methylcellulose; titanium dioxide (E 171); polyethylene glycol 4000; FD&C Blue No. 2 (indigo carmine) (E 132)).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: elongated, biconvex film-coated tablets of blue color, with a score line on both sides.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents.
Propionic acid derivatives. Flurbiprofen. ATC code M01AE09.

Pharmacological Properties

Pharmacodynamics

Flurbiprofen is a nonsteroidal anti-inflammatory drug with analgesic properties. Its mechanism of action is associated with pronounced inhibition of prostaglandin synthesis through suppression of the enzyme cyclooxygenase (COX-1 and COX-2), leading to reduced inflammation, hyperemia, edema, and pain relief.

Pharmacokinetics

Absorption: After oral administration, flurbiprofen is rapidly and almost completely absorbed from the gastrointestinal tract. Maximum plasma concentration is reached approximately 1.5 hours after a single dose. Food intake does not affect the drug's bioavailability. The average elimination half-life is 6 hours.

Metabolism: Plasma protein binding exceeds 99%. Flurbiprofen is almost completely metabolized. The drug is primarily excreted in urine, mainly in free and conjugated form (20%) and as hydroxylated metabolites (50%).

Clinical characteristics.

Indications.

• Acute musculoskeletal pain, signs and symptoms of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gouty arthritis.
• Dysmenorrhea.

Contraindications.

• Hypersensitivity to flurbiprofen or any component of the drug.
• Hypersensitivity to flurbiprofen, ibuprofen, acetylsalicylic acid, or other nonsteroidal anti-inflammatory drugs (NSAIDs), manifested as asthma, acute rhinitis, angioneurotic edema, urticaria, or other allergic reactions.
• History of or active peptic ulcer or gastrointestinal bleeding (two or more distinct episodes of ulcer exacerbation or bleeding).
• Treatment of perioperative pain in coronary artery bypass graft (CABG) surgery.
• Cerebrovascular and other hemorrhages.
• Inflammatory bowel diseases.
• Concomitant use with other NSAIDs.
• Severe heart failure, renal failure, hepatic failure.
• Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of flurbiprofen should be avoided with:

Acetylsalicylic acid, unless low-dose acetylsalicylic acid (not exceeding 75 mg per day) has been prescribed by a physician, as this may increase the risk of adverse reactions;

Other NSAIDs, including ibuprofen and selective cyclooxygenase-2 (COX-2) inhibitors, as this may increase the risk of adverse effects.

Flurbiprofen should be used with caution in combination with the following drugs:

Anticoagulants. Nonsteroidal anti-inflammatory drugs may enhance the therapeutic effect of anticoagulants such as warfarin. The interaction between warfarin and NSAIDs increases the risk of serious gastrointestinal bleeding.

Beta-blockers. Flurbiprofen reduces the antihypertensive effect of propranolol, but not of atenolol.

ACE inhibitors and diuretics. Nonsteroidal anti-inflammatory drugs may reduce the therapeutic efficacy of these agents. There is a potential increased risk of nephrotoxicity.

Corticosteroids may increase the risk of gastrointestinal adverse reactions.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): may increase the risk of gastrointestinal bleeding.

Methotrexate and lithium preparations. Data indicate increased plasma levels of these drugs.

Cyclosporines. Some data suggest possible interaction, potentially increasing the risk of nephrotoxicity.

Tacrolimus. Increased risk of nephrotoxicity.

Zidovudine: evidence indicates increased risk of hemarthrosis and hematoma in HIV-infected patients receiving concomitant therapy with zidovudine and ibuprofen.

Quinolone antibiotics may increase the risk of seizures.

Digoxin. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate (GFR), and decrease plasma digoxin levels.

Cimetidine, ranitidine. Do not affect the pharmacokinetics of flurbiprofen, except for a minor systemic effect.

Oral hypoglycemic agents. A slight decrease in plasma glucose concentration has been observed, without causing signs or symptoms of hypoglycemia.

Antacids when administered in elderly individuals: the absorption rate of flurbiprofen is reduced, but there is no effect on the extent of absorption.

Special precautions for use.

Effect of the drug on the gastrointestinal tract.

Patients with a history of peptic ulcer, gastrointestinal bleeding, or perforation are at increased risk of developing complications of the upper gastrointestinal tract.

Effect of the drug on cardiovascular function, hypertension, and edema.

Due to the risk of edema and fluid retention, the drug should be used with caution in patients with heart failure, a history of arterial hypertension, or those who previously experienced edema for any reason. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of serious thrombotic complications, myocardial infarction, and stroke, which can be fatal.

Hemorrhagic complications (bleeding).

Flurbiprofen at a dose of 200 mg per day may prolong bleeding; therefore, the drug should be prescribed with caution to patients at risk of bleeding.

Effect of the drug on kidney and liver function.

The drug should be used with caution in patients with liver or kidney disease. Patients who have been using NSAIDs long-term and have liver or kidney disease should be carefully monitored and require close medical supervision during treatment. If signs of liver dysfunction or abnormal liver function tests occur, the drug should be discontinued.

In elderly patients, the frequency of adverse reactions caused by NSAIDs increases, particularly gastrointestinal bleeding or perforation, which may be fatal.

Bronchospasm may occur in patients with bronchial asthma or allergic conditions currently or with a history of bronchospasm.

Concomitant use of flurbiprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, is not recommended.

Systemic lupus erythematosus and systemic connective tissue diseases – increased risk of aseptic meningitis.

Effect on the cardiovascular and cerebrovascular systems: initiation of treatment with flurbiprofen-containing drugs should be done cautiously (after consultation with a physician) in patients who have experienced elevated blood pressure or edema during NSAID therapy.

Epidemiological data suggest that high-dose NSAID use (2400 mg daily) and prolonged treatment may lead to a small increase in the risk of thrombotic complications (e.g., myocardial infarction or stroke).

Worsening of female reproductive function: the drug may inhibit cyclooxygenase/prostaglandin synthesis and impair female fertility due to effects on ovulation. This effect is reversible.

Gastrointestinal complications may lead to fatal outcomes during treatment, regardless of the presence or absence of gastrointestinal symptoms or a history of serious cardiovascular events.

High NSAID doses and a history of peptic ulcer disease increase the risk of gastrointestinal adverse reactions. During treatment in such cases, the lowest effective dose of the drug should be used.

Patients with a history of gastrointestinal disorders, particularly elderly individuals, should be informed about any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.

The drug should be used with caution in patients receiving concomitant therapy with medications that may increase the risk of peptic ulcer or bleeding, including oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid.

Serious skin reactions, which may be fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely. The highest risk of these reactions occurs early in treatment, with most cases manifesting within the first month of therapy.

Patients should discontinue flurbiprofen treatment at the first sign of rash, mucosal lesions, or other signs of hypersensitivity.

This drug should not be used in patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Masking symptoms of underlying infections.

Epidemiological studies indicate that systemic nonsteroidal anti-inflammatory drugs (NSAIDs) may mask symptoms of infection, potentially delaying appropriate treatment and thereby worsening the course of infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. If MAZESIK-Sanovel is used while a patient is suffering from fever or pain associated with infection, monitoring for the progression of infection is recommended.

Use during pregnancy or breastfeeding.

Starting from the 20th week of pregnancy, use of MAZESIK-Sanovel may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation of therapy. Additionally, there have been reports of arterial duct constriction following second-trimester treatment, most of which resolved after treatment cessation. Therefore, flurbiprofen should not be prescribed during the first and second trimesters of pregnancy unless clearly necessary. If MAZESIK-Sanovel is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of flurbiprofen exposure, starting from the 20th gestational week. Treatment with MAZESIK-Sanovel should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose risks:

Risks to the fetus:

• Cardio-pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• Renal dysfunction (see above);

Risks to the mother at the end of pregnancy and to the newborn:

• Possible prolonged bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• Inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, MAZESIK-Sanovel is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Flurbiprofen should also not be used during breastfeeding.

The concentration of flurbiprofen in breast milk and plasma that may reach the infant is approximately 0.10 mg of flurbiprofen per day when the mother uses flurbiprofen at a dose of 200 mg/day. A decision whether to discontinue breastfeeding or to discontinue the prostaglandin-inhibiting drug should be made, taking into account the importance of the medication for the mother.

Fertility

NSAID use may delay follicular rupture or prevent ovarian follicle rupture, potentially leading to infertility. In women experiencing conception difficulties or undergoing fertility investigations, discontinuation of flurbiprofen should be considered.

Ability to influence reaction speed when driving vehicles or operating machinery.

Studies on the effect of the drug on the ability to drive vehicles or operate complex machinery have not been conducted. However, patients who experience dizziness or drowsiness after taking the drug should refrain from driving vehicles or operating potentially hazardous machinery.

Dosage and Administration

The drug should be taken orally at a dose of 50–100 mg 2–3 times daily.

The recommended daily dose is 150–200 mg.

If necessary, the recommended daily dose may be increased up to 300 mg.

For dysmenorrhea: initially administer 100 mg, followed by 50 mg or 100 mg every 4 or 6 hours. The maximum recommended daily dose should not exceed 300 mg.

Tablets should be taken after meals.

The duration of treatment is determined individually by the physician in each specific case.

The lowest effective dose for the shortest duration necessary to relieve symptoms should be used (see section "Special Instructions").

Children

The drug must not be used in children.

Overdose

Symptoms of overdose: diarrhea, tinnitus, headache, and gastrointestinal bleeding may occur. In more severe poisoning, toxic effects on the central nervous system may develop, such as drowsiness, occasionally excitement, as well as disorientation or coma. Muscle spasms may sometimes be observed in patients. In severe poisoning, metabolic acidosis may occur, and prothrombin time may be prolonged due to effects on blood clotting factors. Acute renal failure and liver damage may also occur. In patients with bronchial asthma, exacerbation of the disease may be observed.

Treatment: treatment may be symptomatic and supportive, including airway management and monitoring of cardiac function and vital signs until a stable condition is achieved. Oral administration of activated charcoal is recommended if the patient presents within 1 hour after ingestion of a potentially toxic amount of the drug. For frequent or prolonged muscle spasms, treatment should include intravenous administration of diazepam or lorazepam. Bronchodilators should be used in cases of bronchial asthma.

Side effects.

The adverse reactions listed below were observed during short-term use of flurbiprofen. The frequency of adverse reactions is defined as follows: very common (> 1/10), common (> 1/100 to <1/10), uncommon (> 1/1000 to <1/100), rare (> 1/10000 to <1/1000), very rare (<1/10000), not known (cannot be estimated from the available data).

When used at recommended doses, transient, mild adverse effects may develop.

Gastrointestinal disorders: common – dyspepsia, constipation, nausea, vomiting, diarrhea, NSAID-induced gastropathy, abdominal pain, liver function abnormalities; with prolonged use – ulcerative stomatitis, gastrointestinal bleeding. Exacerbation of ulcerative colitis and Crohn’s disease; uncommon – bloody diarrhea, esophageal disorders, gastritis, hematemesis, peptic ulcer, stomatitis, gastrointestinal ulcers; rare – in elderly patients, the frequency of adverse reactions increases, especially gastrointestinal bleeding or perforations, which may be fatal.

Gastrointestinal complications may lead to fatal outcomes during treatment, with or without symptoms of worsening or with a history of serious cardiovascular events.

Higher NSAID doses and a history of peptic ulcer disease increase the risk of gastrointestinal adverse reactions.

Cardiovascular system disorders: uncommon – heart failure; rare – myocardial infarction, tachycardia.

Blood and lymphatic system disorders: rare – agranulocytosis, leukopenia, anemia (including hemolytic and aplastic anemia), pancytopenia; uncommon – iron deficiency anemia. Initial symptoms include high fever, sore throat, oral ulcers, flu-like symptoms, severe fatigue, unexplained bleeding and bruising, rash, purpura; frequency not known – inhibition of blood platelet aggregation, thrombocytopenia, neutropenia.

Vascular disorders: uncommon – vasodilation, hypertension.

Nervous system disorders: common – headache, dizziness, somnolence, asthenia, depression, amnesia, tremor; uncommon – ataxia, cerebrovascular ischemia, paresthesia, parosmia.

Psychiatric disorders: common – nervousness, anxiety, insomnia; uncommon – confusion.

Renal and urinary system disorders: uncommon – hematuria, renal failure; rare – tubulointerstitial nephritis, glomerulonephritis, renal papillary necrosis, edema.

Hepatobiliary disorders: uncommon – hepatitis, liver function abnormalities.

Allergic reactions: very common – skin rash; common – pruritus, urticaria, bronchospasm, photosensitivity, Quincke’s edema, anaphylactic shock, angioneurotic edema, eczema.

Bronchospasm may occur in patients with bronchial asthma or current or past history of allergic diseases.

Infections and infestations: common – rhinitis, urinary tract infections.

Respiratory, thoracic and mediastinal disorders: common – asthma, epistaxis, bronchospasm.

Reproductive system disorders: impaired fertility in women. The drug may inhibit cyclooxygenase/prostaglandin synthesis and thereby impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Skin and subcutaneous tissue disorders: serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have occurred very rarely. The highest risk of these reactions occurs at the beginning of treatment, with most initial manifestations appearing within the first month of therapy.

Musculoskeletal disorders: common – convulsions.

Immune system disorders: in patients with autoimmune disorders (such as systemic lupus erythematosus, connective tissue diseases), isolated cases of aseptic meningitis symptoms have been observed during NSAID treatment, including nuchal rigidity, headache, nausea, vomiting, high fever, or disorientation; frequency not known – anaphylaxis.

Eye disorders: cases of visual disturbances, such as blurred vision and/or impaired vision, have been reported with the use of flurbiprofen or other nonsteroidal anti-inflammatory drugs. Regular ophthalmological examinations are recommended during treatment.

Metabolism and nutrition disorders: common – weight changes; uncommon – hyperuricemia, fluid retention.

Other: hearing loss, vertigo, increased sweating, aseptic meningitis (isolated cases reported). Optic neuritis, oral paresthesia, depression, hallucinations, tinnitus, dizziness, malaise, fatigue, somnolence, melena, sensation of warmth or tingling in the mouth when sucking the lozenge; hepatitis, cholestasis, interstitial nephritis, insomnia, nephrotic syndrome.

The use of nonsteroidal anti-inflammatory drugs (especially at high doses of 2400 mg daily) and long-term use may lead to a slight increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Laboratory findings: elevated liver enzymes, decreased hemoglobin and hematocrit levels. Since gastrointestinal disorders and bleeding may occur without any symptoms, regular monitoring is recommended. Patients on long-term treatment should periodically undergo complete blood count and biochemical blood tests.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 5 tablets per blister; 1, 2, or 6 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer: Sanovel Ilac Sanayi ve Ticaret A.S.

Manufacturer's address and place of business.
Balaban Quarter, Cihanger Sokagi, No: 10, Silivri, Istanbul 34580, Turkey.