Pharmacological properties
Pharmacodynamics. Ketoprofen is an NSAID that has analgesic, anti-inflammatory and antipyretic effects.
During 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 has a central and peripheral analgesic effect and eliminates the symptoms of inflammatory and degenerative diseases of the musculoskeletal system.
In women, ketoprofen reduces the severity of symptoms of primary dysmenorrhea due to inhibition of prostaglandin synthesis.
Pharmacokinetics
Absorption. When taken orally, ketoprofen is rapidly absorbed from the gastrointestinal tract. After oral administration of 100 mg, Cmax of ketoprofen in blood plasma (10.4 μg/ml) is reached after ≈1.5 hours. The bioavailability of ketoprofen in oral forms is 90% and is directly proportional to the dose administered.
Ketonal Duo modified-release capsules are a new dosage form that differs from conventional capsules in the way the active substance is released. The capsules contain two types of pellets: standard (white) and coated (yellow). Ketoprofen is released quickly from the white pellets (60% of the total amount) and slowly from the yellow pellets (40% of the total amount), which provides a prolonged effect of the drug.
Food intake does not affect the overall bioavailability of ketoprofen, but reduces the rate of absorption. Fatty food increases the time to reach C max, but does not reduce the bioavailability and C max of ketoprofen in blood plasma. Simultaneous administration of drugs that reduce the acidity of gastric juice does not affect the rate and extent of ketoprofen absorption. After taking Ketonal Duo capsules, C max - 9036.64 ng / ml - is achieved within 1.76 hours.
After taking Ketonal Retard prolonged-release tablets, ketoprofen is rapidly absorbed in the gastrointestinal tract, its C max in blood plasma is reached after 4-6 hours. The bioavailability of ketoprofen is 93% and is directly proportional to the dose used.
After rectal administration of 100 mg of ketoprofen (suppositories), C max in blood plasma (10.4 μg/ml) is reached after 1.05-1.22 hours. The bioavailability of ketoprofen after rectal administration is 71-96%.
Parenteral administration. The average concentration of ketoprofen in blood plasma is 26.4 ± 5.4 μg/ml 4-5 minutes after IV infusion or IM administration. The bioavailability of ketoprofen is 90%.
When applied topically as a cream or gel, the absorption of ketoprofen is insignificant, which determines the local nature of the drug's action and the absence of systemic effects. The bioavailability of ketoprofen when applied topically is about 5%.
After three times application of 70-80 mg of ketoprofen in the form of a cream to the knee surface, C max in blood plasma (0.0182 ± 0.118 μg/ml) is achieved 6 hours after application of the drug.
Distribution. The degree of binding to blood plasma proteins is 99%. The volume of distribution is 0.1-0.2 l/kg of body weight. 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 lower than in blood plasma, it is more stable (maintained for up to 30 hours; with parenteral administration after 9 hours, the concentration of ketoprofen in blood plasma is 0.3 μg/ml, and in synovial fluid - 0.8 μg/ml), 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.
When applied topically, 12 hours after the last application of the cream to the skin of the knee, the following concentrations of ketoprofen are reproduced in the joint tissues: adipose tissue - 4.7 ± 3.87 μg / g, joint membrane - 2.35 ± 2.41 μg / g, synovial fluid - 1.31 ± 0.89 μg / g.
The pharmacokinetics of ketoprofen does not depend on the patient's age. For elderly people, a stable concentration in the blood plasma is achieved after 8.7 hours and is 6.3 μg/ml. Cumulation of ketoprofen in tissues is not observed.
Metabolism and excretion. Ketoprofen is extensively metabolized in the liver by enzymes. It is excreted from the body as a conjugate with glucuronic acid. T ½ is 2 hours. Up to 80% of the administered dose of ketoprofen is excreted in the urine, usually 90% - in the form of glucuronide, ≈10% - with feces.
In patients with renal failure, the elimination of ketoprofen is slowed down, T ½ increases by 1 hour. In patients with hepatic failure, ketoprofen may accumulate in the tissues. In older 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; serologically negative 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; postoperative pain; pain with tumor metastases to the bones; algodysmenorrhea.
Application
Doses are selected individually, depending on the patient's condition and response to treatment.
Ketonal capsules. The recommended dose for adults is 1 capsule 3 times a day.
The recommended dose for rheumatoid arthritis and osteoarthritis is 1 capsule every 6 hours.
The duration of treatment depends on the severity and course of the disease, however, side effects can be minimized by using the minimum effective dose for the shortest possible time.
The maximum daily dose of ketoprofen is 200 mg.
Ketonal capsules can be used in combination with Ketonal suppositories according to the following scheme: 1 capsule in the morning and afternoon and 1 suppository (100 mg) in the evening. When taking different forms of the drug (capsules, tablets, suppositories, solution for injection) in combination, the total daily dose should not exceed 200 mg.
Capsules are taken during meals, washed down with water or milk (at least 100 ml).
To prevent the negative effects of ketoprofen on the mucous membrane of the gastrointestinal tract, after consulting a doctor, you can simultaneously take antacids and proton pump inhibitors.
Elderly patients. Elderly patients are at increased risk of adverse reactions, therefore it is recommended to use the minimum effective dose of ketoprofen. After 4 weeks of treatment, monitoring for gastrointestinal bleeding should be carried out.
Ketonal suppositories. Applied rectally.
Recommended doses for adults and children over 15 years of age: 1 suppository is inserted into the rectum 1-2 times a day.
Ketonal suppositories can be combined with oral forms of Ketonal, for example, 1 capsule (50 mg) in the morning and afternoon and 1 suppository (100 mg) in the evening or 1 tablet (100 mg) in the morning and 1 suppository (100 mg) in the evening.
The duration of treatment depends on the severity and course of the disease, however, side effects can be minimized by using the minimum effective dose for the shortest possible time.
The maximum daily dose of ketoprofen is 200 mg. Before prescribing the maximum dose, the benefit/risk ratio of treatment with high doses should be carefully analyzed.
Elderly patients. Elderly patients are at increased risk of adverse reactions. Monitoring for gastrointestinal bleeding should be performed 4 weeks after initiation of NSAID treatment.
Ketonal solution for injection. Doses are selected individually, depending on the patient's condition and his response to treatment. For parenteral use.
Recommended doses for adults
Intramuscular administration: 1 ampoule (100 mg) of ketoprofen is used 1-2 times a day. If necessary, intramuscular administration can be supplemented with the appointment of oral or rectal forms of Ketonal. The maximum daily dose should not exceed 200 mg.
Intravenous infusion: Ketoprofen infusions are carried out only in a hospital setting. The infusion is carried out for 0.5-1 hour, the course of treatment with intravenous administration is no more than 48 hours. The maximum daily dose is 200 mg.
Intermittent intravenous infusion: 100-200 mg of ketoprofen is dissolved in 100 ml of 0.9% sodium chloride solution and administered over 0.5-1 hour. The maximum daily dose is 200 mg.
Continuous intravenous infusion: 100-200 mg of ketoprofen is dissolved in 500 ml of infusion solution (0.9% sodium chloride solution, lactated Ringer's solution, glucose) and administered over 8 hours. The maximum daily dose is 200 mg.
Ketoprofen can be used simultaneously with centrally acting analgesics; it can be mixed with morphine in one vial: 10-20 mg of morphine and 100-200 mg of ketoprofen are dissolved in 500 ml of infusion solution (0.9% sodium chloride solution or lactated Ringer's solution). The maximum daily dose is 200 mg.
The duration of treatment depends on the severity and course of the disease, however, side effects can be minimized by using the minimum effective dose for the shortest possible time.
To prevent the negative effects of ketoprofen on the mucous membrane of the gastrointestinal tract, antacids can be taken simultaneously.
Caution: vials with infusion solution should be wrapped in dark paper or aluminum foil, as ketoprofen is sensitive to light.
Tramadol and ketoprofen should be administered separately, as a precipitate may form when mixed.
Elderly patients. The risk of adverse reactions is increased in elderly patients. Monitoring for gastrointestinal bleeding should be performed 4 weeks after the start of treatment. It is recommended to start ketoprofen therapy with the minimum dose in order to use the lowest effective dose in patients.
Renal impairment: In patients with moderate renal impairment with creatinine clearance of 0.33 ml/s (20 ml/min), the dose of ketoprofen should be reduced.
The use of ketoprofen is contraindicated in patients with severe renal impairment.
Liver dysfunction: Patients with chronic liver disease and reduced plasma albumin levels should have their ketoprofen dose reduced.
The use of ketoprofen is contraindicated in patients with severe liver dysfunction.
Ketonal gel. For external use.
Apply a thin layer of 3-5 cm of gel to the affected area 1-2 times a day and rub it in gently. The amount of gel depends on the size of the injured area: 5 cm of gel corresponds to 100 mg of ketoprofen, 10 cm - 200 mg of ketoprofen. It is not recommended to use an occlusive dressing.
The duration of treatment is 7-10 days. After applying the gel, wash your hands. Ketonal gel can be used in combination with other dosage forms (capsules, tablets, suppositories). The maximum total daily dose should not exceed 200 mg of ketoprofen, regardless of the dosage form used.
The cream is applied to the skin of the affected area with a thin layer 2 times a day and gently rubbed in. The amount of cream depends on the size of the affected area. The drug is used, as a rule, for no more than 10 days. The cream can be used in combination with other dosage forms (capsules, tablets, suppositories). The maximum total daily dose should not exceed 200 mg of ketoprofen, regardless of the dosage form used.
The use of tightening and airtight bandages is not recommended. Hands should be washed after applying the drug, except in cases of application of the cream directly to the skin of the hands.
Ketonal Duo modified-release capsules.
Doses should be selected individually, depending on the patient's condition and response to treatment.
The recommended dose is 150 mg (1 capsule) per day.
The duration of treatment depends on the severity and course of the disease, however, side effects can be minimized by using the minimum effective dose for the shortest possible time.
When using different forms of the drug (capsules, tablets, suppositories, injection solutions) in combination, the maximum daily dose of ketoprofen should not exceed 200 mg.
Capsules are taken during meals, washed down with water or milk (at least 100 ml).
To prevent the negative effects of ketoprofen on the mucous membrane of the gastrointestinal tract, antacids and proton pump inhibitors can be taken simultaneously after consulting a doctor.
Elderly patients. The risk of adverse reactions is increased in the elderly, and if NSAID therapy is prescribed, it is recommended to use the minimum effective dose of ketoprofen, and 4 weeks after the start of treatment, monitoring for gastrointestinal bleeding should be mandatory.
Tablets Ketonal Forte.
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 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 therapy depends on the severity and course of the disease, however, side effects can be minimized by using the minimum 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.
The tablets are taken during meals, washed down with water. The tablets should be swallowed whole, without chewing.
To prevent the negative effects of ketoprofen on the mucous membrane of the gastrointestinal tract, antacids can be taken simultaneously.
Elderly patients: Elderly patients are at increased risk of adverse reactions. Monitoring for gastrointestinal bleeding should be performed 4 weeks after initiation of treatment.
Ketonal Retard prolonged-release tablets. Doses are selected individually, depending on the patient's condition and his response to treatment. The recommended dose for adults is 1 tablet once a day.
The duration of treatment depends on the severity and course of the disease, however, side effects can be minimized by using the minimum effective dose for the shortest possible time.
When combined administration of different forms of the drug (capsules, tablets, suppositories, solution for injection), the maximum daily dose of ketoprofen should not exceed 200 mg.
Ketonal Retard tablets should be taken after or during meals, with a glass of water or milk. Antacids, proton pump inhibitors should be taken at the same time to alleviate the side effects of ketoprofen on the gastrointestinal tract (after consulting a doctor).
Elderly patients. The risk of adverse reactions is increased in the elderly (it is recommended to use the minimum effective dose). After 4 weeks of treatment, monitoring for gastrointestinal bleeding should be carried out.
Contraindication
Ketoprofen in the form for external use (gel, cream) is contraindicated in the presence of skin manifestations of allergy when using ketoprofen, tiaprofenic acid, fenofibrate, ultraviolet (UV) blockers or perfumes; exposure to sunlight (even diffused light) or UV radiation in a solarium during treatment and for 2 weeks after its termination; the presence of pathological changes on the skin, such as wet dermatoses, skin damage, rash, skin trauma, burns, eczema, acne or infectious processes of the skin and open wounds. Do not apply the drug to airtight dressings.
Ketoprofen is contraindicated in patients with impaired homeostasis or receiving anticoagulant therapy.
Side effects
Classification of side effects by organ system and frequency of occurrence: very common (≥1/10), common (≥1/100, 1/10), uncommon (≥1/1000, 1/100), rare (≥1/10,000, 1/1000), very rare (1/10,000), frequency unknown (cannot be estimated from the available data).
Side effects are usually transient. The most common side effects are gastrointestinal disorders.
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 nosebleeds and hematoma formation.
On the part of the immune system: respiratory system reactivity, including asthma, bronchospasm or shortness of breath (especially in patients with hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs); very rarely - angioedema and anaphylaxis, anaphylactic reactions, including shock.
Mental disorders: often - depression, nervousness, nightmares, drowsiness; rarely - delirium with visual and auditory hallucinations, disorientation, speech disorders, mood changes.
Nervous system: often - headache, asthenia, discomfort, fatigue, weakness, dizziness, paresthesia, vertigo, mood changes, drowsiness; infrequently - convulsions; rarely - speech disorders, dysgeusia; very rarely - pseudotumors of the brain; frequency unknown - depression, confusion, hallucinations, weakness, there are reports of aseptic meningitis (especially in patients with autoimmune diseases such as systemic lupus erythematosus, mixed connective tissue disease, in whom the following symptoms are observed - stiffness of the occipital muscles, nausea, vomiting, fever or loss of orientation).
On the part of the organ of vision: often - visual impairment; very rarely - conjunctivitis, blurred vision; frequency unknown - optic neuritis.
On the part of the organ of hearing: often - tinnitus.
From the cardiovascular system: often - edema; infrequently - 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: infrequently - hemoptysis, shortness of breath, pharyngitis, rhinitis, bronchospasm (especially in patients with hypersensitivity to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs), laryngeal edema (signs of an anaphylactic reaction); rare - attacks of bronchial asthma; frequency unknown - shortness of breath.
From the digestive system: very often - dyspepsia; often - nausea, abdominal pain, diarrhea, constipation, flatulence, anorexia, vomiting, stomatitis; rarely - gastritis, gastric ulcer; very rarely - colitis, intestinal perforation (as a complication of diverticulum), melena, exacerbation of ulcerative colitis or Crohn's disease, enteropathy with perforation, stenosis. Perforation, gastrointestinal bleeding, melena, hematemesis may occur. Enteropathy may be accompanied by mild 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: very rarely - severe liver dysfunction, accompanied by jaundice and hepatitis.
Skin: often - skin rash, itching; infrequently - alopecia, eczema, purpuric rash, increased sweating, urticaria, exacerbation of chronic urticaria, exfoliative dermatitis; rarely - photosensitization, photodermatitis; very rarely - bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative and bullous dermatosis, erythema multiforme, angioedema.
From the urinary system: very rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, acute pyelonephritis, abnormal renal function tests.
From the reproductive system: infrequently - menometrorrhagia.
General disorders: rarely - edema, frequency unknown - taste disturbance.
Injection site reactions: burning sensation and/or pain at the injection site, itching, swelling.
For suppositories - the above-listed reactions at the injection site, rectal bleeding.
Ketoprofen reduces platelet aggregation, thereby prolonging bleeding time.
Special instructions
Patients with BA and chronic rhinitis, chronic sinusitis and/or nasal polyposis are at increased risk of developing allergies to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs. Ketoprofen can cause asthma attacks and bronchospasm in them, especially in individuals with hypersensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.
The use of ketoprofen can cause gastrointestinal bleeding, gastric and/or duodenal ulcers or perforation, which can occur even without prodromal symptoms. Ketoprofen should be prescribed with caution to patients with a history of gastrointestinal disorders. There is a high probability of gastrointestinal bleeding in elderly patients prone to such bleeding, in patients with insufficient body weight, as well as in people with impaired platelet function or taking anticoagulants or platelet aggregation inhibitors. If bleeding or symptoms of gastric and/or duodenal ulcers appear, the drug should be stopped immediately. If mild symptoms appear from the stomach, drugs that neutralize gastric acid or coat the gastric mucosa can be used. These patients should start treatment with a minimum dose. Such patients should be given combination therapy with protective drugs (for example, misoprostol or proton pump inhibitors).
Epidemiological data suggest that ketoprofen may be associated with a high risk of severe gastrointestinal toxicity, as is the case with 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 evidence to exclude such a risk for ketoprofen.
Concomitant use of ketoprofen with NSAIDs, including selective COX-2 inhibitors, should be avoided.
Ketoprofen and other nonsteroidal anti-inflammatory drugs can mask the symptoms of a developing infectious disease.
Ketoprofen should be prescribed with caution to patients with gastrointestinal disorders, closely observing such patients for the appearance of diseases such as gastritis and/or duodenitis, nonspecific ulcerative colitis, and 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 liver disease, in patients receiving diuretics, in hypovolemia due to major surgery, especially in elderly patients.
Ketoprofen should be used with caution in individuals with alcoholism.
The drug should be prescribed with caution to patients who use concomitant medications that may increase the risk of bleeding or ulceration, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, antithrombotic drugs (acetylsalicylic acid).
When using ketoprofen, it is also necessary to carefully monitor patients with increased sensitivity to sunlight or a history of phototoxicity. In the elderly and patients with heart failure or impaired liver function, chronic renal failure and impaired water metabolism (e.g. dehydration as a result of diuretic use, hypovolemia after surgery, etc.), ketoprofen can cause renal dysfunction due to inhibition of prostaglandin synthesis.
In the initial period of treatment in such patients, the amount of diuresis and other indicators of renal function should be carefully monitored. Impairment of their function may cause edema and an increase in the concentration of non-protein nitrogen in the blood serum.
In patients with heart failure, especially the elderly, due to fluid and sodium retention in the body, increased manifestation of adverse reactions may be observed. 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. Before starting long-term treatment, patients with risk factors such as hyperlipidemia, diabetes mellitus or patients who smoke should also undergo a careful examination.
Ketoprofen should be administered with particular caution to the elderly, particularly those with impaired liver or kidney function; the dose of the drug should be reduced in such patients.
Ketoprofen should be administered with particular caution to elderly patients, particularly those with impaired liver or kidney function; the dose of the drug should be reduced in such patients. During long-term treatment with ketoprofen, it is necessary to monitor blood morphology and liver and kidney function.
In rare cases, 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 0.33 ml / s (20 ml / min), the dose of ketoprofen should be adjusted.
The use of the drug must be discontinued before major surgical interventions.
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 investigation for infertility.
Taking the drug in the minimum effective dose for the short 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.
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, T½ is prolonged in proportion to the severity of renal insufficiency.
Patients with hepatic insufficiency: plasma clearance and T½ are unchanged; the amount of unbound drug increases almost twofold.
Ketonal gel (Ketonal cream) is used only externally. If the time of application of the drug in the form of a gel or cream is missed, the dose is doubled when the drug is next applied topically. Despite the fact that systemic side effects of ketoprofen with topical application are practically absent, Ketonal gel (Ketonal cream) should be used with caution in patients with impaired renal, cardiac or hepatic function, a history of ulcer or intestinal inflammation, cerebrovascular bleeding or hemorrhagic diathesis.
Ketonal gel (Ketonal cream) should be used externally only. If the time for applying the gel (cream) is missed, the dose is doubled when next used.
Despite the fact that systemic side effects of ketoprofen with topical application are practically absent, the gel (cream) should be used with caution in patients with impaired renal, cardiac or hepatic function, a history of peptic ulcer or intestinal inflammation, cerebrovascular bleeding or hemorrhagic diathesis.
Ketonal gel (Ketonal cream) should not be applied to mucous membranes, perianal area or genital area, as well as to large areas of skin, under airtight dressings, on the skin around the eyes. Avoid getting the drug in the form of a gel or cream into the eyes. Do not exceed the recommended dose and do not apply Ketonal gel (Ketonal cream) together with other topical agents containing ketoprofen or other nonsteroidal anti-inflammatory drugs on the same areas of skin.
It is necessary to protect the skin areas to which the drug is applied from the sun (including from UV rays in a solarium) during treatment, as well as for 2 weeks after its completion to reduce the risk of photosensitization. The drug should be discontinued immediately if any skin reactions occur, including skin reactions, after simultaneous use with products containing octocrylene (octocrylene is a component of some cosmetic and hygiene products, such as shampoos, after-shave gels, shower gels, lipsticks, creams, including anti-aging, make-up removers, hairsprays to delay their photodegradation).
Hands should be washed thoroughly after each application of the drug in the form of a gel or cream. If Ketonal gel (Ketonal cream) needs to be rubbed into the skin for a long time, surgical gloves should be used.
Local application of large amounts of the drug may provoke the appearance of systemic side effects, including attacks of bronchial asthma and manifestations of hypersensitivity, such as contact dermatitis, urticaria, and bronchospasm.
Do not use Ketonal gel near an open flame because it contains ethanol.
Ketonal, Ketonal Duo and Ketonal Forte capsules contain lactose, therefore they are not prescribed to patients with rare hereditary diseases of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Use during pregnancy and breastfeeding. The safety of ketoprofen during pregnancy has not been established, therefore the use of the drug in the I-II trimester of pregnancy is possible only in case of extreme necessity, if the expected benefit to the mother outweighs the potential risk to the fetus.
The use of ketoprofen in the third trimester of pregnancy is contraindicated.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development. Epidemiological data suggest an increased risk of miscarriage and of heart defects and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of congenital heart defects increased from ≤1% to 1.5%. The risk may increase with increasing dose and duration of therapy. In animals, the use of a prostaglandin synthesis inhibitor has resulted in pre- and post-implantation fetal death and embryo/fetal death. In addition, in animals treated with prostaglandin synthesis inhibitors during pregnancy during the period of organogenesis, an increased incidence of various congenital abnormalities, including cardiovascular disorders, was observed. When prescribing ketoprofen to a woman planning a pregnancy or in the first and second trimesters of pregnancy, the lowest possible dose and duration of therapy should be observed.
In the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may have the following effects on the fetus:
Cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligohydramnios;
A pregnant woman and fetus at the end of pregnancy may be exposed to the following:
Possible increase in bleeding duration, decrease in platelet aggregation, even when using very low doses of the drug; suppression of uterine contractile function, which can lead to an increase in the duration of labor.
Breastfeeding. There are no data on the excretion of ketoprofen into breast milk. Ketoprofen is not recommended for use during breastfeeding, as the safety of ketoprofen during breastfeeding has not been proven.
Children. The drug is not used in children. Ketonal suppositories are not used in children under 15 years of age.
Ability to influence the reaction rate when driving or operating other mechanisms. Until the individual reaction to the drug is determined (dizziness, drowsiness, convulsions and visual disturbances may occur), it is recommended to refrain from driving or operating complex mechanisms.
Interactions
Concomitant use with ketoprofen is not recommended.
The simultaneous use of ketoprofen with other NSAIDs and salicylates, including selective COX-2 inhibitors, anticoagulants (heparin and warfarin), platelet aggregation inhibitors (ticlopidine, clopidogrel), lithium preparations, methotrexate at a dose of 15 mg/week should be avoided. The risk of gastrointestinal bleeding/ulceration increases.
The simultaneous use of Ketonal cream and other topical medications containing ketoprofen or other nonsteroidal anti-inflammatory drugs is not recommended, as this may enhance their effects as well as the adverse reactions caused by them.
Ketoprofen is protein bound; when used simultaneously with other drugs that bind to proteins, such as anticoagulants, sulfonylureas
