Ketoprofen
Undesirable drug combinations
The combined use of ketoprofen with other NSAIDs (including selective cyclooxygenase-2 inhibitors), salicylates in high doses is not recommended, due to the increased risk of gastrointestinal bleeding and ulceration of the gastrointestinal mucosa.
Simultaneous use with anticoagulants (heparin, warfarin), antiplatelet agents (ticlopidine, clopidogrel) increases the risk of bleeding. If the use of such a combination is unavoidable, the patient's condition should be carefully monitored.
When used simultaneously with lithium preparations, it is possible to increase the concentration of lithium in the blood plasma up to toxic values. The concentration of lithium in the blood plasma should be carefully monitored and the dose of lithium preparations should be promptly adjusted during and after treatment with NSAIDs.
Increases the hematological toxicity of methotrexate, especially when used in high doses (more than 15 mg per week). The time interval between stopping or starting therapy with ketoprofen and taking methotrexate should be at least 12 hours. Combinations to use with caution
During therapy with ketoprofen, patients taking diuretics, especially when dehydration develops, have a higher risk of developing renal failure due to a decrease in renal blood flow caused by inhibition of prostaglandin synthesis. Before starting to use ketoprofen in such patients, rehydration measures should be carried out. After starting treatment, it is necessary to monitor kidney function.
Combined use of the drug with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, elderly patients) can lead to worsening deterioration of renal function, incl. to the development of acute renal failure.
During the first weeks of simultaneous use of ketoprofen and methotrexate at a dose not exceeding 15 mg per week, blood tests should be monitored weekly. In elderly patients or if there are any signs of renal impairment, the study should be performed more frequently.
Combinations to take into account
Ketoprofen may weaken the effect of antihypertensive drugs (beta blockers, ACE inhibitors, diuretics).
Concomitant use with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding.
Concomitant use with thrombolytics increases the risk of bleeding.
Concomitant use with potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus and trimethoprim increases the risk of developing hyperkalemia.
When used simultaneously with cyclosporine and tacrolimus, there may be a risk of additive nephrotoxicity, especially in elderly patients.
The use of several antiplatelet drugs (tirofiban, eptifibatide, abciximab, iloprost) increases the risk of bleeding.
Increases the plasma concentration of cardiac glycosides, slow calcium channel blockers, cyclosporine, methotrexate and digoxin.
Ketoprofen may enhance the effect of oral hypoglycemic and some anticonvulsants (phenytoin).
Concomitant use with probenecid significantly reduces the plasma clearance of ketoprofen.
Nonsteroidal anti-inflammatory drugs may reduce the effectiveness of mifepristone. Taking NSAIDs should be started no earlier than 8-12 days after stopping mifepristone.
Pharmaceutically incompatible with tramadol solution due to precipitation.
Ketoprofen, 5 pcs., 2 ml, 50 mg/ml, solution for intravenous and intramuscular administration
Definition of categories of frequency of undesirable effects (according to WHO): very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥ 1/10,000, <1/1000) and very rarely (<1/10,000); frequency unknown (the incidence of adverse events cannot be determined based on available data).
From the hematopoietic and lymphatic systems: rarely - hemorrhagic anemia, hemolytic anemia, leukopenia; frequency unknown - agranulocytosis, thrombocytopenia, impaired bone marrow hematopoiesis.
From the immune system: frequency unknown - anaphylactic reactions (including anaphylactic shock).
From the nervous system: often - insomnia, depression, asthenia; infrequently - headache, dizziness, drowsiness; rarely - paresthesia, confusion or loss of consciousness, peripheral polyneuropathy; frequency unknown - convulsions, taste disturbances, emotional lability.
From the senses: rarely - blurred vision, tinnitus, conjunctivitis, dry mucous membrane of the eye, pain in the eyes, hearing loss; frequency unknown - optic neuritis.
From the cardiovascular system: infrequently - tachycardia; frequency unknown - heart failure, arterial hypertension, vasodilation.
From the respiratory system: rarely - exacerbation of bronchial asthma, nosebleeds, laryngeal edema; frequency unknown - bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.
From the digestive system: often - nausea, vomiting, dyspepsia, abdominal pain NSAID gastropathy; uncommon - constipation, diarrhea, bloating, gastritis; rarely - peptic ulcer, stomatitis; very rarely - exacerbation of UC Crohn's disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of the gastrointestinal tract; frequency unknown - gastrointestinal discomfort, stomach pain.
From the liver and biliary tract: rarely - hepatitis, increased activity of liver enzymes and bilirubin concentration.
From the skin: infrequently - skin rash, itching; frequency unknown - photosensitivity, alopecia, urticaria, exacerbation of chronic urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, purpura.
From the urinary system: rarely - cystitis, urethritis, hematuria; very rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values of renal function indicators; frequency unknown - fluid retention in the body and, as a result, weight gain, hyperkalemia.
Other: infrequently - peripheral edema, fatigue; rarely - hemoptysis, menometrorrhagia, shortness of breath, thirst, muscle twitching.
KETOPROFEN
special instructions
You should not combine Ketoprofen with other NSAIDs and/or COX-2 inhibitors.
With long-term use of NSAIDs, it is necessary to periodically evaluate a clinical blood test, monitor kidney and liver function, especially in elderly patients (over 65 years), and conduct a stool test for occult blood.
It is necessary to be careful and monitor blood pressure more often when using the drug Ketoprofen to treat patients with arterial hypertension and cardiovascular diseases that lead to fluid retention in the body. If the condition worsens, you must stop taking the drug.
If visual disturbances occur, use of Ketoprofen should be stopped immediately.
Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. If you notice signs of infection or deterioration in health while using the drug, you should immediately consult a doctor.
In patients simultaneously taking antiplatelet agents, anticoagulants, and glucocorticosteroids, the risk of developing gastrointestinal bleeding and ulceration increases.
If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer), long-term therapy and the use of high doses of Ketoprofen, the patient should be under close medical supervision. If gastrointestinal bleeding or ulcerative lesions occur, use of Ketoprofen should be discontinued. The use of ketoprofen is contraindicated in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), since exacerbation of these diseases is possible. Like other NSAIDs, ketoprofen may inhibit platelet aggregation and increase bleeding time by inhibiting prostaglandin synthesis. In this regard, the use of Ketoprofen in patients simultaneously taking drugs that affect the hemostatic system (for example, warfarin, coumarin derivatives, heparins) is not recommended.
The use of some NSAIDs may be associated with a risk of arterial thrombosis (myocardial infarction, stroke). There is insufficient data to exclude such a risk for ketoprofen.
Like other NSAIDs, ketoprofen can lead to increased concentrations of creatinine and nitrogen in the blood plasma. Like other prostaglandin synthesis inhibitors, Ketoprofen can have a negative effect on the urinary system, which can lead to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure. Due to the important role of prostaglandins in maintaining renal blood flow, special caution should be exercised when using Ketoprofen in the treatment of patients with cardiac or renal failure, as well as elderly patients taking diuretics, and patients who have a decrease in circulating blood volume for any reason. .
The use of Ketoprofen should be discontinued before major surgery.
As with the use of other NSAIDs, during therapy with Ketoprofen, a slight transient increase in the activity of “liver” transaminases may be observed. In case of a significant increase in the corresponding indicators, the use of the drug should be discontinued.
Ketoprofen should be used with caution in patients with uncontrolled arterial hypertension, coronary heart disease, congestive heart failure, peripheral arterial disease and/or cerebrovascular disease. Patients with risk factors for developing cardiovascular diseases (arterial hypertension, dyslipidemia, diabetes mellitus, smoking) should also use Ketoprofen with caution.
Ketoprofen can affect female fertility, so patients with infertility (including those undergoing examination) are not recommended to use the drug.
There is evidence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) with the use of NSAIDs. At the first manifestations of a skin rash, damage to the mucous membranes or other signs of an allergic reaction, you should immediately stop taking Ketoprofen and consult a doctor.
Ketoprofen film-coated tablets 100 mg 20 pcs. in Novosibirsk
Pharmacological action: Inhibits the activity of COX-1 and COX-2, inhibits the synthesis of PG and LT. It has anti-bradykinin activity, stabilizes lysosomal membranes and delays the release of enzymes from them that contribute to tissue destruction during chronic inflammation. Reduces the release of cytokines, inhibits the activity of neutrophils.
The anti-inflammatory effect occurs by the end of 1 week of use. The lysine salt of ketoprofen has equally pronounced anti-inflammatory, analgesic, and antipyretic effects.
In case of articular syndrome, it relieves pain in the joints at rest and during movement, reduces morning stiffness and swelling of the joints, and helps to increase the range of movements.
When taken orally, it is absorbed quickly and quite completely, bioavailability is about 90%. Cmax in the blood is achieved 0.5–2 hours after oral administration, 1.4–4 hours after rectal administration, 15–30 minutes after parenteral administration, and 5–8 hours after application to the skin. When taking retardated forms, the minimum effective concentration is determined after 2–3 hours, Cmax is usually achieved within 6–7 hours. When taken simultaneously with food, the total bioavailability (AUC) does not change, the rate of absorption slows down (for both regular and retardated forms) . Absorption is accompanied by a “first pass” effect through the liver. Binding to blood plasma proteins, mainly albumin - 99%. Equilibrium plasma concentrations are achieved 24 hours after the start of regular use. Easily passes through histohematic barriers and is distributed in tissues and organs. It does not penetrate the BBB in significant quantities. The level of ketoprofen in the synovial fluid is lower than in the blood, but remains within therapeutic limits for a longer time (6–8 hours). Metabolized in the liver by glucuronidation. It is excreted primarily by the kidneys - 80% within 24 hours, mainly in the form of a glucuronic derivative. T1/2 - (2.05±0.58) hours after i.v. administration; 2–4 hours after oral administration in the usual dosage form at a dose of 200 mg; (5.4±2.2) hours after taking the retarded form at a dose of 200 mg. In renal failure, excretion slows down.
Lysine salt of ketoprofen: Tmax after oral administration in the form of granules - 15 minutes, with parenteral administration - 20-30 minutes, with rectal administration - 45-60 minutes. When taken in the form of delayed-release capsules, the effective concentration is achieved within 20–30 minutes and persists for 24 hours.
Therapeutic concentration in synovial fluid persists for 18–20 hours. Metabolized by microsomal liver enzymes. Excreted by the kidneys, 60–80% in the form of glucuronide in 24 hours.
In elderly patients, plasma and renal clearance are reduced, the values of Cmax, AUC and unbound fraction increase with increasing age (more in women than in men).
With cutaneous application, slow transdermal absorption of ketoprofen occurs, which ensures that its concentration in inflamed tissues is maintained within a therapeutic level for a long time. Penetrates well into synovial fluid and connective tissue. Absorption into the systemic circulation is insignificant, bioavailability for gel and spray is about 5%.
When using a solution for topical use (rinse solution) at a dose of 160 mg, Tmax is 1 hour, Cmax value is 350 mg/ml (4% of the concentration obtained by oral administration of 80 mg).
Carcinogenicity, mutagenicity, effect on fertility
Chronic toxicity studies in mice when administered orally (up to 32 mg/kg/day, 96 mg/m2/day, approximately 0.5 MRDC) did not reveal the carcinogenic effect of ketoprofen. In a two-year carcinogenicity study in rats at doses up to 6 mg/kg/day (36 mg/m2/day), no adverse oncogenic effects were detected. Moreover, animals in all groups received drugs for 104 weeks, with the exception of females who received 6 mg/kg/day (36 mg/m2/day) for 81 weeks due to low survival. Survival rate in groups receiving drugs for 104 weeks was 6% compared to the control group.
The mutagenicity of ketoprofen was not detected in the Ames test. When ketoprofen was administered to male rats (up to 9 mg/kg/day, 54 mg/m2/day), no significant effect on reproductive function and fertility was found. In female rats at doses of 6 or 9 mg/kg/day (36 or 54 mg/m2/day), a decrease in the number of implantations was noted.
At high doses, spermatogenesis is disrupted and inhibited in rats and dogs, and testicular weight decreases in dogs and baboon monkeys.
