Ketonal Forte 100 mg 20 tablets

Description Light blue, round, biconvex tablets, film-coated. Composition Each tablet contains 100 mg of ketoprofen. Excipients: Tablet core: magnesium stearate, colloidal anhydrous silica, povidone, corn starch, purified talc, lactose monohydrate, hypromellose E464, macrogol 400, indigotine E132, titanium dioxide E171, purified talc, carnauba wax. Pharmacotherapeutic group: Non-steroidal anti-inflammatory and anti-rheumatic drugs. ATC code: M01AE03. See blog: Ketonal - Forms and Ways of Use Pharmacological Properties Pharmacodynamics Ketoprofen – the active substance of the drug – inhibits the synthesis of prostaglandins and leukotrienes, blocks the enzyme cyclooxygenase (cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)), which catalyzes the synthesis of prostaglandins in the metabolism of arachidonic acid. Ketoprofen stabilizes lysosomal membranes in vitro and in vivo, and at high concentrations inhibits leukotriene synthesis in vitro and has antibradykinin activity in vivo. The mechanism of the antipyretic effect of ketoprofen is unknown. It is possible that ketoprofen inhibits prostaglandin synthesis in the central nervous system (most likely in the hypothalamus). In some women, ketoprofen reduces the symptoms of primary dysmenorrhea, possibly by suppressing prostaglandin synthesis and/or efficacy. Pharmacokinetics Ketoprofen is well absorbed from the gastrointestinal tract. After oral administration of 100 mg of ketoprofen, its peak plasma concentration (10.4 mcg/mL) is reached in 1 hour and 22 minutes. The bioavailability of ketoprofen after oral administration of 50 mg is 90% and increases linearly with increasing doses. Ketoprofen is a racemic mixture, but the pharmacokinetics of the two enantiomers are similar. 99% of ketoprofen is bound to plasma proteins, mainly to the albumin fraction. The volume of distribution in tissues is 0.1-0.2 L/kg. Ketoprofen penetrates into synovial fluid. Three hours after administration of 100 mg of ketoprofen, its concentration in plasma is approximately 3 mcg/mL, and the concentration in synovial fluid is 1.5 mcg/mL. After nine hours, its concentration in plasma is approximately 0.3 mcg/mL, and the concentration in synovial fluid is 0.8 mcg/mL. This means that ketoprofen penetrates slowly into the synovial fluid and is also slowly eliminated from it, while its plasma concentration continues to decrease. If ketoprofen is taken with food, absorption is slowed and plasma concentration is slightly reduced, but bioavailability remains unchanged. After oral administration of 50 mg of ketoprofen four times a day with meals, a peak concentration of 3.9 mcg/mL was reached in 1.5 hours, compared to 2.0 mcg/mL two hours after administration on an empty stomach. Steady-state concentrations of ketoprofen are reached within 24 hours of administration. The concentration of sustained-release ketoprofen is stable after the first dose. In elderly patients, steady-state concentration was reached in 8.7 hours and was 6.3 mcg/mL. Ketoprofen is extensively metabolized by hepatic microsomal enzymes. It is conjugated with glucuronic acid and excreted from the body in this form. After oral administration, its plasma clearance is 1.16 mL/min/kg. Due to rapid metabolism, its biological half-life is only two hours. Up to 80% of ketoprofen is excreted in the urine, mainly (more than 90%) as ketoprofen glucuronide, and about 10% is excreted in the feces. Special patient groups With liver damage: In patients with liver insufficiency, likely due to hypoalbuminemia (free biologically active ketoprofen), the concentration of ketoprofen is almost doubled, requiring the administration of the minimum daily dose that provides an adequate therapeutic effect. With kidney damage: In patients with kidney insufficiency, ketoprofen clearance is reduced. Therefore, dose reduction is required in severe kidney insufficiency. Indications for use Ketonal Forte is a non-steroidal anti-rheumatic drug with anti-inflammatory, analgesic, and antipyretic effects. It is used to relieve pain in various painful syndromes and to treat inflammatory, degenerative, and metabolic rheumatic diseases. Indications for use Pain: - Post-traumatic; - Post-operative; - Painful menstruation; - Pain in patients with bone metastases from cancer. Rheumatic diseases: - Rheumatoid arthritis; - Ankylosing spondylitis, psoriatic arthritis, reactive arthritis; - Gout, pseudogout; - Osteoarthritis; - Extra-articular rheumatism (tendinitis, bursitis, shoulder joint capsulitis). Contraindications - Hypersensitivity to ketoprofen or any of the excipients of the preparation; - History of rhinitis, bronchospasm, bronchial asthma, urticaria, or allergic-type reactions after the use of ketoprofen or similarly acting substances, such as other non-steroidal anti-inflammatory drugs (NSAIDs) or salicylates (e.g., acetylsalicylic acid); severe (in rare cases fatal) anaphylactic reactions have been described in such patients (see "Side Effects"); - Severe heart failure; - Pain treatment during the perioperative period of coronary artery bypass grafting (CABG); - History of chronic dyspepsia; - Peptic ulcer in the acute phase, as well as a history of gastrointestinal bleeding, ulceration, or perforation; - Predisposition to bleeding; - Severe renal impairment; - Severe hepatic impairment; - Last trimester of pregnancy (see "Pregnancy and Lactation"); - Children under 15 years of age. Special warnings and precautions Avoid concomitant use of the drug with NSAIDs, including selective COX-2 inhibitors. Elderly patients are more likely to experience adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see "Dosage and Administration"). Bleeding, ulceration, and perforation of the gastrointestinal tract: Gastrointestinal bleeding, ulceration, or perforation, which can be fatal, have been reported with all NSAIDs and can occur at any time during treatment, with or without prior symptoms or a history of severe gastrointestinal diseases. Ketonal Forte intake may be associated with a high risk of severe gastrointestinal toxicity, characteristic of some other NSAIDs, especially at high doses (see also "Dosage and Administration" and "Contraindications"). The risk of developing gastrointestinal bleeding, ulceration, or perforation increases with increasing doses of NSAIDs, in patients with a history of peptic ulcer disease, especially complicated by bleeding or perforation (see "Contraindications"), as well as in elderly patients. Treatment of these patients should be initiated with the lowest available dose. For these patients, as well as for patients taking low doses of acetylsalicylic acid or other drugs with a high risk of gastrointestinal complications concurrently, combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) should be considered (see below "Interactions with other medicinal products and other forms of interaction"). Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment. Special caution is required when co-administered with drugs that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid (see "Interactions with other medicinal products and other forms of interaction"). If gastrointestinal bleeding or ulceration occurs during Ketonal Forte treatment, the drug should be discontinued. NSAIDs should be prescribed with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as they may experience exacerbations of these diseases (see "Side Effects"). Cardiovascular and cerebrovascular effects: Patients with a history of hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and consultation, as reports of fluid retention and edema have been associated with NSAID use. The use of some NSAIDs (especially at high doses and with prolonged treatment) may be associated with an increased risk of arterial thrombosis (e.g., myocardial infarction or stroke) (see "Special warnings and precautions"). Data on ketoprofen are insufficient to rule out such a risk. For patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, Ketonal Forte treatment should only be carried out after careful assessment of benefit and risk. Such an approach is necessary for patients with risk factors for cardiovascular disease (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking) before initiating long-term treatment. Patients with bronchial asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyposis are more likely to experience allergic reactions after taking acetylsalicylic acid and/or NSAIDs than other patients. The administration of Ketonal Forte may trigger an asthma attack or bronchospasm, especially in patients with allergies to acetylsalicylic acid or NSAIDs (see "Contraindications"). Patients with heart failure, cirrhosis, and nephrotoxic syndrome, as well as patients taking diuretics and patients with chronic kidney insufficiency, especially the elderly, should have their renal function carefully monitored at the beginning of treatment. For such patients, the administration of Ketonal Forte, by suppressing prostaglandin synthesis, can lead to a decrease in renal blood flow and cause decompensation of renal function. Patients with abnormal liver function test results or a history of liver disease should have their serum transaminase levels periodically monitored, especially during long-term therapy. Rare cases of jaundice and hepatitis have been reported with ketoprofen intake. If visual disturbances such as blurred vision occur, treatment should be discontinued. The drug should be prescribed with caution to individuals with alcohol dependence. Extremely rare severe skin reactions (some of them fatal) have been reported with the use of NSAIDs, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis (see "Side Effects"). The highest risk of developing these reactions occurs at the beginning of the treatment course; in most cases, reactions appear within the first month of treatment. Ketonal Forte should be discontinued at the first sign of rash, mucosal lesions, or other signs of hypersensitivity. Ketonal Forte may mask the signs and symptoms of infectious diseases, such as fever. Before extensive surgical interventions, the drug must be discontinued. The use of Ketonal Forte may reduce fertility, so it is not recommended for women planning pregnancy. Women who have difficulty conceiving or are undergoing infertility investigations should consider discontinuing Ketonal Forte. Ketonal Forte tablets contain lactose. Therefore, they cannot be taken by patients with hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption. Pregnancy and lactation Suppression of prostaglandin synthesis can negatively affect pregnancy and/or embryonic/fetal development. The drug should not be prescribed during the first and second trimesters of pregnancy unless absolutely necessary. If Ketonal Forte is used by a woman who is trying to conceive or is in the first or second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. The use of Ketonal Forte is contraindicated in the third trimester of pregnancy. Data on the penetration of the drug into breast milk are not available. The use of Ketonal Forte is not recommended for breastfeeding mothers. Effects on ability to drive and use machines The drug can cause CNS side effects such as dizziness, drowsiness, or seizures; in such cases, do not drive or operate machinery. Dosage and administration For oral administration. Tablets should be taken during or after meals, with at least 100 mL of water or milk. Adverse effects can be minimized if the drug is taken at the lowest effective dose necessary to control symptoms for the shortest possible duration. Recommended dose Adults and children over 15 years of age: The usual dose for the treatment of rheumatic diseases is 1 tablet (100 mg) no more than twice daily. Ketonal Forte can be combined with Ketonal suppositories. For example, one tablet of Ketonal Forte (100 mg) in the morning and one suppository of Ketonal (100 mg) in the evening. The maximum daily dose of ketoprofen is 200 mg. Before starting treatment with a dose of 200 mg per day, the potential risks and benefits should be carefully weighed. Higher doses are not recommended (see also "Special warnings and precautions"). Antacids can be taken concurrently, which reduce the likelihood of adverse effects of Ketonal Forte on the digestive system. Elderly: Adverse reactions in elderly patients may have more severe consequences. If NSAID intake is necessary, the lowest dose is prescribed, and the patient is monitored for gastrointestinal bleeding for 4 weeks from the start of NSAID treatment. Children: The drug is contraindicated in children under 15 years of age (see "Contraindications"). Side effects Reports of edema, hypertension, and heart failure are associated with treatment with non-selective NSAIDs. In case of severe side effects, treatment should be discontinued. Adverse reactions are distributed by organ system classes, frequency of occurrence, and descending severity: Very common (≥ 1/10); Common (≥1/100, <1/10); Uncommon (≥1/1,000, <1/100); Rare (≥ 1/10,000, <1/1,000); Very rare (<1/10,000); Frequency not known (frequency cannot be estimated from available data). Blood and lymphatic system disorders - Rare: post-hemorrhagic anemia; - Frequency not known: agranulocytosis, thrombocytopenia, bone marrow failure. Immune system disorders - Frequency not known: anaphylactic reactions (including shock). Psychiatric disorders - Frequency not known: mood changes. Nervous system disorders - Uncommon: headache, dizziness, drowsiness; - Rare: paresthesia; - Frequency not known: convulsions, dysgeusia. Eye disorders - Rare: blurred vision (see "Special warnings and precautions"). Ear and labyrinth disorders - Rare: tinnitus. Cardiac disorders - Frequency not known: heart failure. Vascular disorders - Frequency not known: hypertension, vasodilation. Respiratory, thoracic, and mediastinal disorders - Rare: bronchial asthma; - Frequency not known: bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis. Gastrointestinal disorders - Common: dyspepsia, nausea, abdominal pain, vomiting; - Uncommon: constipation, diarrhea, flatulence, gastritis; - Rare: stomatitis, peptic ulcer; - Frequency not known: exacerbation of ulcerative colitis or Crohn's disease, gastrointestinal bleeding and perforation, melena, hematemesis. The most common adverse reactions include reactions of the gastrointestinal tract. Peptic ulcers, perforations, and bleeding in the gastrointestinal tract may develop, which are sometimes, especially in elderly patients, may be fatal (see "Special warnings and precautions"). Hepato-biliary disorders - Rare: hepatitis, elevated transaminases, elevated serum bilirubin due to hepatitis. Skin and subcutaneous tissue disorders - Uncommon: rash, itching; - Frequency not known: photosensitivity reactions, alopecia, urticaria, angioedema, bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Renal and urinary disorders - Frequency not known: acute renal failure, tubulointerstitial nephritis, nephrotic syndrome, abnormalities in renal function test results. General disorders and administration site conditions - Uncommon: edema; - Frequency not known: fatigue. Laboratory and instrumental data - Rare: weight gain. Data indicate that the use of some non-selective NSAIDs (especially at high doses and for prolonged periods) may be associated with an increased risk of arterial thrombosis (e.g., myocardial infarction or stroke) (see "Special warnings and precautions"). Overdose Cases of ketoprofen overdose up to 2.5 g have been reported. In most cases, the symptoms were benign and limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain. There is no specific antidote for ketoprofen overdose. In case of suspected significant overdose, gastric lavage and symptomatic and supportive therapy to prevent dehydration are recommended. Diuresis should also be monitored and acidosis corrected (if it develops). Hemodialysis may be effective in removing the circulating drug from the blood in case of renal failure. Interactions with other medicinal products and other forms of interaction Combinations of drugs that are not recommended - Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates: High risk of developing ulcers and bleeding in the gastrointestinal tract. Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors (e.g., ticlopidine, clopidogrel): High risk of bleeding (see "Special warnings and precautions"). If co-administration is necessary, careful medical supervision is required. Lithium: Risk of increased plasma lithium levels, which can sometimes reach toxic levels due to decreased renal excretion of lithium. If necessary, plasma lithium concentrations should be carefully monitored and lithium doses adjusted during and after NSAID treatment. Methotrexate at doses exceeding 15 mg/week: High risk of methotrexate hematotoxicity, especially if used at high doses (>15 mg/week), likely due to displacement of methotrexate from protein binding and decreased renal clearance. Combinations requiring caution - Diuretics: Patients taking diuretics, especially those with dehydration, are at high risk of renal insufficiency due to decreased renal blood flow as a result of prostaglandin synthesis inhibition. For such patients, adequate fluid intake is necessary before starting co-administration, and renal function should be monitored at the beginning of treatment (see "Special warnings and precautions"). Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists: In patients with impaired renal function (e.g., patients with dehydration or the elderly), co-administration of ACE inhibitors or angiotensin II receptor antagonists and cyclooxygenase-inhibiting drugs may lead to further deterioration of renal function, including possible acute renal failure. - Methotrexate at low doses of 15 mg/week: In the first weeks of combination therapy, a complete blood count should be monitored weekly. In the presence of any renal impairment and in elderly patients, monitoring should be more frequent. - Corticosteroids: High risk of developing ulcers or bleeding in the gastrointestinal tract (see "Special warnings and precautions"). - Pentoxifylline: Increases the risk of bleeding. Clinical monitoring and bleeding time control are more frequently required. Combinations that require consideration - Antihypertensive drugs (beta-blockers, ACE inhibitors, diuretics): Ketoprofen reduces the effect of antihypertensive drugs (inhibition of vasodilator prostaglandin synthesis). - Thrombolytics: High risk of bleeding. - Selective serotonin reuptake inhibitors: High risk of gastrointestinal bleeding (see "Special warnings and precautions"). - Probenecid: Co-administration with probenecid may significantly reduce the plasma clearance of ketoprofen. Combinations for which information is also necessary to take into account - Cyclosporine, tacrolimus: Risk of additive nephrotoxic effect, especially in elderly patients. Dosage form 20 tablets in a vial contained in a carton. Storage conditions Keep out of reach of children. Store at a temperature not exceeding 25°C. Store in the original packaging. Shelf life 5 years. Do not use after the expiry date indicated on the packaging. Dispensing conditions Prescription only.