Instructions Ketonal forte film-coated tablets 100 mg blister No. 10
Composition
active ingredient: ketoprofen;
1 tablet contains ketoprofen 100 mg;
excipients: lactose monohydrate, corn starch, povidone, colloidal anhydrous silicon dioxide, talc, magnesium stearate;
shell: hypromellose, polyethylene glycol, indigotine (E 132), titanium dioxide (E 171), talc, carnauba wax.
Dosage form
Film-coated tablets.
Main physicochemical properties: light blue round biconvex tablets, film-coated.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ketoprofen. ATX code M01A E03.
Pharmacological properties
Pharmacodynamics.
Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory and antipyretic effects. In inflammation, ketoprofen inhibits the synthesis of prostaglandins and leukotrienes, inhibiting the activity of cyclooxygenase and partially lipoxygenase, it also inhibits the synthesis of bradykinin and stabilizes lysosomal membranes.
It exhibits a central and peripheral analgesic effect and eliminates the symptoms of inflammatory and degenerative diseases of the musculoskeletal system.
In women, ketoprofen reduces the symptoms of primary dysmenorrhea due to inhibition of prostaglandin synthesis.
Pharmacokinetics.
Absorption. After oral administration, it is rapidly absorbed from the gastrointestinal tract. After a dose of 100 mg, the maximum concentration of ketoprofen in the blood plasma (10.4 μg/ml) is achieved after approximately 1.5 hours. The bioavailability of ketoprofen is 90% and is directly proportional to the dose administered.
Distribution. The degree of protein binding is 99%. The volume of distribution is 0.1-0.2 l/kg. Ketoprofen penetrates into the synovial fluid. 3 hours after the administration of 100 mg of ketoprofen, its concentration in blood plasma is about 3 μg/ml, and the concentration in synovial fluid is 1.5 μg/ml. Although the concentration of ketoprofen in synovial fluid is somewhat lower than in blood plasma, it is more stable (maintained for up to 30 hours), so pain syndrome and joint stiffness are reduced for a long time. A stable concentration of ketoprofen in blood plasma is achieved within 24 hours after taking oral forms. The pharmacokinetics of ketoprofen does not depend on the patient's age. Cumulation of ketoprofen in tissues is not observed.
Metabolism and excretion. Ketoprofen is extensively metabolized in the liver by microsomal enzymes. It is excreted from the body as a conjugate with glucuronic acid. The half-life is 2 hours. Up to 80% of the administered dose of ketoprofen is excreted in the urine, usually (over 90%) in the form of glucuronide, about 10% - with feces.
In patients with impaired renal function, the elimination of ketoprofen is slowed down, the half-life is increased by 1 hour. In patients with impaired liver function, ketoprofen may accumulate in the tissues. In elderly patients, the metabolism and elimination of ketoprofen are slowed down, but this is of clinical significance only in cases of impaired renal function.
Indication
Joint diseases: rheumatoid arthritis; seronegative spondyloarthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis); gout, pseudogout; osteoarthritis; extra-articular rheumatism (tendinitis, bursitis, capsulitis of the shoulder joint).
Pain syndrome: lumbago, post-traumatic pain in joints, muscles; algodysmenorrhea.
Contraindication
Hypersensitivity to ketoprofen or to the excipients of the drug, contraindicated in patients in whom the use of ketoprofen, acetylsalicylic acid or other NSAIDs provokes bronchospasm, asthma attacks, urticaria, angioedema, acute rhinitis or other allergic reactions. Severe heart failure; treatment of perioperative pain during coronary artery bypass grafting; chronic dyspepsia; active phase or relapse of gastric and/or duodenal ulcer; history of gastrointestinal bleeding/perforation/ulcers, cerebrovascular or other bleeding; tendency to hemorrhage; severe liver or kidney dysfunction; history of bronchial asthma and rhinitis; III trimester of pregnancy.
Interaction with other medicinal products and other types of interactions
Risk of hyperkalemia
Some drugs, such as potassium salts, diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, trimethoprim can cause hyperkalemia.
The development of hyperkalemia may depend on the presence of additional factors. The risk of hyperkalemia is increased by concomitant use of the above-mentioned drugs.
Risk due to the use of antiplatelet drugs
Concomitant use of antiplatelet agents increases the risk of bleeding, as does concomitant administration of heparin, oral anticoagulants and thrombolytic agents. In such cases, the patient's clinical condition should be monitored and laboratory tests performed.
It is not recommended to use ketoprofen simultaneously with:
other NSAIDs and salicylates, including selective cyclooxygenase-2 inhibitors;
oral anticoagulants and heparin, which is administered parenterally;
lithium (lithium excretion decreases);
methotrexate (in doses above 15 mg/week); after the use of ketoprofen together with methotrexate (mainly in high doses), severe, sometimes fatal toxicity occurred; toxicity is due to an increase and prolongation of the concentration of methotrexate in the blood;
mifepristone, as its effect may be reduced. Nonsteroidal anti-inflammatory drugs should be taken 8 to 12 days after mifepristone administration.
Ketoprofen should be used with caution simultaneously with:
diuretics, angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, as the risk of renal disorders increases; ketoprofen may reduce the effects of antihypertensives and diuretics; diuretics may increase the risk of nephrotoxicity of NSAIDs;
methotrexate (in doses less than 15 mg/week);
anticoagulants, sulfonamides, hydantoins, as dose adjustment may be required to prevent increased levels of these drugs due to competition for binding to blood plasma proteins;
anticoagulants, such as warfarin, due to increased effect;
oral antidiabetic and antiepileptic drugs (phenytoin) due to increased effect;
cardiac glycosides due to the possibility of exacerbation of heart failure, a decrease in glomerular filtration rate and an increase in the level of glycosides in the blood plasma;
pentoxifylline due to the possibility of an increased risk of bleeding; it is necessary to monitor the state of the blood coagulation system.
When used simultaneously with ketoprofen, special attention should be paid to:
other drugs that inhibit platelet aggregation (ticlopidine, clopidogrel, tirofiban, eptifibatide, abciximab, iloprost), due to increased risk of bleeding; other drugs that cause hyperkalemia (potassium salts, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, other NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, trimethoprim), due to risk of hyperkalemia;
antihypertensive drugs (beta-blockers, ACE inhibitors, diuretics) due to the risk of reducing the effectiveness of these drugs (due to inhibition of prostaglandin synthesis, ketoprofen reduces their antihypertensive effect);
tacrolimus, cyclosporine because the risk of nephrotoxicity increases, especially in elderly patients;
possible decrease in the effectiveness of intrauterine contraceptives;
oral hypoglycemic drugs, as the hypoglycemic effect of the latter may be enhanced;
corticosteroids, as there is an increased risk of gastrointestinal bleeding;
probenecid, since simultaneous use may lead to a significant decrease in the clearance of ketoprofen from blood plasma;
selective serotonin reuptake inhibitors, as there is an increased risk of gastrointestinal bleeding;
pentoxifylline, as it increases the risk of bleeding.
Ketoprofen may reduce glomerular filtration rate and increase serum concentrations of cardiac glycosides.
Aluminum compounds with a neutralizing effect do not reduce the absorption of ketoprofen.
Application features
Patients with bronchial asthma and chronic rhinitis, chronic sinusitis and/or nasal polyposis are at increased risk of developing allergies to acetylsalicylic acid and other NSAIDs. Ketoprofen may cause asthma attacks and bronchospasm in them, especially in individuals with hypersensitivity to acetylsalicylic acid and other NSAIDs.
Epidemiological data suggest that ketoprofen may be associated with a high risk of severe gastrointestinal toxicity, as is the case with some other NSAIDs, particularly at high doses. Clinical trials and epidemiological data also suggest that the use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with an increased risk of arterial thrombosis (e.g. myocardial infarction or stroke). There is insufficient data to exclude such a risk for ketoprofen.
Concomitant use of ketoprofen with NSAIDs including selective cyclooxygenase-2 inhibitors should be avoided.
Ketoprofen and other NSAIDs may mask the symptoms of an infectious disease that is developing. Masking of symptoms of underlying infections: Ketonal Forte may mask the symptoms of an infectious disease, which may lead to a delay in the initiation of appropriate treatment and thereby complicate the course of the disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of chickenpox. When Ketonal Forte is used for fever or to relieve pain in an infection, monitoring for the infectious disease is recommended. In outpatient settings, the patient should consult a doctor if symptoms persist or worsen.
Ketoprofen should be prescribed with caution to patients with gastrointestinal disorders, closely monitoring such patients for the appearance of diseases such as gastritis and/or duodenitis, nonspecific ulcerative colitis, Crohn's disease.
The drug should be used with caution in patients with hemostasis disorders, hemophilia, von Willebrand disease, severe thrombocytopenia, renal or hepatic insufficiency, as well as in individuals taking anticoagulants (coumarin and heparin derivatives, mainly low molecular weight heparins).
Careful monitoring of diuresis and renal function is necessary in patients with hepatic impairment, in patients receiving diuretics, in hypovolemia due to major surgery, especially in elderly patients.
Ketoprofen should be used with caution in individuals suffering from alcoholism.
The drug should be used with caution in patients taking concomitant medications that may increase the risk of bleeding or ulceration, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, and antithrombotic drugs (acetylsalicylic acid).
Patients with a history of hypersensitivity to sunlight or phototoxicity should also be carefully monitored when using ketoprofen. In the elderly and in patients with heart failure or liver dysfunction, chronic renal failure and water metabolism disorders (e.g. dehydration due to diuretic use, hypovolemia after surgery), ketoprofen may cause renal dysfunction due to inhibition of prostaglandin synthesis.
During the initial period of treatment, such patients should be carefully monitored for diuresis and other indicators of renal function. Impaired renal function may cause edema and an increase in serum non-protein nitrogen.
In patients with heart failure, especially the elderly, increased manifestation of adverse reactions may be observed due to fluid and sodium retention in the body. In such patients, cardiac and renal function should be monitored.
Patients with uncontrolled arterial hypertension, chronic heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should only receive ketoprofen after careful monitoring. Patients with risk factors such as hyperlipidemia, diabetes mellitus or smoking should also be carefully examined before starting long-term treatment.
Patients with impaired liver function should be carefully monitored (periodic monitoring of transaminase activity) and the dose of the drug should be individually adjusted.
Ketoprofen should be prescribed with particular caution to the elderly, especially those with impaired liver or kidney function; such patients should reduce the dose of the drug. During long-term treatment with ketoprofen, it is necessary to monitor blood morphology and liver and kidney function.
In isolated cases, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with NSAIDs. The highest risk of such reactions is at the beginning of therapy (in most cases, such reactions occur in the first months of treatment). Ketonal® should be discontinued at the first appearance of skin rash, mucosal lesions or other signs of hypersensitivity.
During long-term treatment with ketoprofen, especially in elderly patients, it is necessary to monitor the blood count, as well as liver and kidney function. If creatinine clearance is below 0.33 ml/s (20 ml/min), the dose of ketoprofen should be adjusted.
Ketoprofen may impair female reproductive function and should not be used by women attempting to conceive. Ketoprofen should be discontinued in women who are unable to conceive or are undergoing infertility evaluation.
Taking the drug in the lowest effective dose for the shortest period necessary to relieve symptoms reduces the risk of side effects and the impact on the gastrointestinal tract and circulatory system.
The use of the drug should be discontinued if visual disturbances, such as blurred vision, occur.
The drug contains lactose, so it is not prescribed to patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Elderly: Ketoprofen absorption is not altered, only the half-life of the drug is prolonged (3 hours) and renal and plasma clearance is reduced. Elderly patients are at increased risk of adverse reactions. After 4 weeks of treatment, monitoring for gastrointestinal bleeding should be performed.
Patients with renal insufficiency: renal and plasma clearance is reduced, and the half-life is prolonged in proportion to the severity of renal insufficiency.
Patients with hepatic insufficiency: plasma clearance and half-life are unchanged; the amount of drug not bound to proteins increases almost twofold.
Use during pregnancy or breastfeeding
In the I and II trimesters of pregnancy, the drug can be prescribed only if the expected benefit to the mother outweighs the potential risk to the fetus, only in the minimum effective dose. The duration of treatment should be as short as possible. Like other NSAIDs, the drug is contraindicated in the last trimester of pregnancy (possible inhibition of uterine contractility and premature closure of the ductus arteriosus in the fetus).
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryo-foetal development. Epidemiological data suggest an increased risk of miscarriage and/or cardiac malformations and gastroschisis following exposure to a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations has been increased from less than 1% to approximately 1.5%.
It is possible that the risk increases with increasing dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation losses and embryo/fetal lethality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis. If the drug is used in women attempting to conceive, or in the first and second trimesters of pregnancy, the dose should be kept as low and the duration of treatment as short as possible.
The use of ketoprofen in the third trimester of pregnancy and during breastfeeding is contraindicated.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus in the following ways:
cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction, which may progress to renal failure with oligohydramnios.
For the mother and newborn, as well as at the end of pregnancy:
possible prolongation of bleeding time, antiplatelet effect, which can be observed even at very low doses;
inhibition of uterine contractions, leading to delayed or prolonged labor.
Breast-feeding
There are no data on the excretion of ketoprofen into human milk. It is not recommended to prescribe ketoprofen to mothers who are breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience visual disturbances, dizziness, seizures, fatigue, drowsiness, or other central nervous system disorders during treatment with the drug should refrain from driving or operating other mechanisms.
Method of administration and doses
Doses should be selected individually, depending on the patient's condition and response to treatment.
The recommended dose for adults is 1 tablet 2 times a day.
The recommended dose for the treatment of rheumatoid arthritis and osteoarthritis is 1 tablet 2 times a day.
The recommended dose for mild to moderate pain and dysmenorrhea is 1 tablet once a day.
The duration of treatment depends on the severity and course of the disease, but side effects can be minimized by using the lowest effective dose for the shortest possible time.
The maximum daily dose of ketoprofen is 200 mg.
Ketonal Forte tablets can be used in combination with Ketonal suppositories according to the following scheme: 1 tablet in the morning and 1 suppository (100 mg) in the evening. When combined administration of different forms of the drug (capsules, tablets, suppositories, solution for injection), the total daily dose should not exceed 200 mg.
To prevent the negative effects of ketoprofen on the mucous membranes of the gastrointestinal tract, antacids can be taken simultaneously.
Children
Do not use the drug in children.
Overdose
Symptoms: tinnitus, disorientation, agitation, suffocation, drowsiness, hypotension or hypertension, gastrointestinal bleeding, nausea, vomiting, epigastric pain, bloody vomit, black stools, impaired consciousness, respiratory depression, convulsions, decreased renal function and renal failure; rarely - coma.
Treatment: gastric lavage, use of activated charcoal. Symptomatic and supportive therapy to compensate for dehydration, control diuresis and correct acidosis, if present. In case of renal failure, hemodialysis should be performed. H2-receptor antagonists, proton pump inhibitors, prostaglandins alleviate the dangerous effects of ketoprofen on the digestive tract. There is no specific antidote.
Adverse reactions
Adverse reactions are listed under headings of frequency: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (< 1/10,000), frequency unknown (cannot be estimated from the available data).
Side effects are usually transient. Gastrointestinal disorders are more common.
From the blood system: infrequently - hemorrhagic anemia, hemolysis, purpura, thrombocytopenia, agranulocytosis, bone marrow failure, frequency unknown - neutropenia.
High doses of ketoprofen may inhibit platelet aggregation, thereby prolonging bleeding time, and cause epistaxis and hematoma formation.
Immune system: respiratory system reactivity, including asthma, exacerbation of asthma, bronchospasm or dyspnea (especially in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs), rare - angioedema and anaphylaxis, hypersensitivity, anaphylactic reaction, including shock.
On the part of the psyche: frequent - nervousness, nightmares, drowsiness; rarely - delirium with visual and auditory hallucinations, disorientation, frequency unknown - mood changes.
Nervous system disorders: common: headache, asthenia, discomfort, fatigue, weakness, dizziness, paresthesia, vertigo, drowsiness; rare: speech disorders, dysgeusia; rare: pseudotumor cerebri; uncommon: convulsions; frequency unknown: depression, confusion, hallucinations, malaise; there have been reports of aseptic meningitis (especially in patients with existing autoimmune diseases such as systemic lupus erythematosus, mixed connective tissue disease) with symptoms such as occipital muscle rigidity, nausea, vomiting, fever, disorientation.
On the part of the organs of vision: frequent - visual impairment; rare - conjunctivitis, blurred vision; frequency unknown - optic neuritis.
On the part of the organs of hearing: frequent - tinnitus.
Cardiovascular system: frequent - edema; infrequent - heart failure, arterial hypertension, vasodilation.
Clinical trials and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term use) may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction and stroke). There are insufficient data to exclude such a risk for ketoprofen.
On the part of the respiratory system: infrequent - hemoptysis, shortness of breath, pharyngitis, rhinitis, bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), laryngeal edema (signs of anaphylactic reaction); rare - asthma attacks; frequency unknown - shortness of breath.
From the digestive tract: very common - dyspepsia; common - nausea, abdominal pain, diarrhea, constipation, flatulence, anorexia, vomiting, stomatitis; rare - gastritis, gastric ulcer; rare - colitis, intestinal perforation (as a complication of diverticulitis), exacerbation of ulcerative colitis or Crohn's disease, enteropathy with perforation, stenosis. Perforation, gastrointestinal bleeding, melena, bloody vomiting may occur. Enteropathy may be accompanied by minor bleeding with protein loss.
There have been reports of a case of rectal perforation in an elderly woman.
Ulceration, hemorrhage, or perforation may develop in 1% of patients after 3-6 months of treatment or in 2-4% of patients after 1 year of treatment with NSAIDs.
On the part of the hepatobiliary system: rare - severe liver dysfunction, accompanied by jaundice, hepatitis.
Skin: frequent - skin rashes; infrequent - alopecia, eczema, purpuric rashes, increased sweating, urticaria, exfoliative dermatitis, itching; rare - photosensitivity, photodermatitis; rare - bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative and bullous dermatosis, erythema multiforme, angioedema.
From the urinary system: rare - acute renal failure, interstitial nephritis, nephrotic syndrome, acute pyelonephritis, abnormal renal function tests.
General disorders: rare - edema; frequency unknown - taste disturbance.
Laboratory parameters: common - weight gain; very common - abnormal liver function tests, increased transaminases, serum bilirubin due to diabetes-related disorders; uncommon - ALT and AST levels significantly increase during NSAID treatment.
Ketoprofen reduces platelet aggregation, thereby prolonging bleeding time.
Expiration date
Tablets in a blister pack – 3 years.
Tablets in a bottle – 5 years.
Storage conditions
Store at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 1 blister in a cardboard box.
20 tablets in a bottle; 1 bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
Lek Pharmaceutical Company Ltd., Slovenia.
Location of the manufacturer and address of its place of business.
Verovškova 57, Ljubljana 1526, Slovenia.
