Ketoprofen-Solofarm solution 50mg/ml 2ml ampoules, 10pcs

Composition

>1 ml of the drug contains: Active ingredient: Ketoprofen 50 mgsupport Substances: Propylene glycol 400 mgethanol 95% 100 mg (in terms of anhydrous substance)Benzyl alcohol 20 mg Sodium hydroxide solution 10 M to pH 6.0-7.5 Water for injection up to 1 ml

Pharmacological action

Pharmacodynamics : Ketoprofen is a non-steroidal anti-inflammatory drug. Ketoprofen has anti-inflammatory, analgesic and antipyretic effects. Ketoprofen blocks the action of cyclooxygenase 1 and 2 (COX-1 and COX-2) and, partially, lipoxygenase, which leads to suppression of prostaglandin synthesis (including in the central nervous system, most likely in the hypothalamus). It stabilizes liposomal membranes in vitro and in vivo, and at high concentrations in vitro ketoprofen suppresses the synthesis of bradykinin and leukotrienes. Ketoprofen does not have a negative effect on the condition of articular cartilage. Pharmacokinetics: Absorption With intravenous use of ketoprofen, the average plasma concentration 5 minutes after the start of the infusion and up to 4 minutes after its termination is 26.4 ± 5.4 mcg / ml. Bioavailability is 90%. With a single intramuscular injection of 100 mg of ketoprofen, the drug is detected in blood plasma 15 minutes after the start of the infusion, and the peak concentration (1.3 mcg/ml) is reached after 2 hours. The bioavailability of the drug increases linearly with increasing dose. Distribution Ketoprofen is 99% bound to plasma proteins, mainly the albumin fraction. The volume of distribution in tissues is 0.1-0.2 l / kg. Ketoprofen penetrates the synovial fluid, and with intravenous use of 100 mg after 3 hours, its concentration reaches 1.5 mcg/ml, which is 50% of the concentration in blood plasma (about 3 mcg/ml). After 9 hours, the synovial fluid concentration is 0.8 mcg / ml, and in blood plasma-0.3 mcg / ml, which means that ketoprofen penetrates more slowly into the synovial fluid and is more slowly removed from it. Steady-state plasma concentrations of ketoprofen are detected even 24 hours after its use. After a single intramuscular injection of 100 mg of ketoprofen, the drug is detected in the cerebrospinal fluid, as well as in the blood serum, after 15 minutes. Metabolism Ketoprofen undergoes intensive metabolism with the participation of microsomal liver enzymes. It binds to glucuronic acid and is eliminated from the body in the form of glucuronide. There are no active metabolites of ketoprofen. Elimination The half-life (T 1/2) of ketoprofen is 2 hours. Up to 80% of ketoprofen is excreted by the kidneys within 24 hours, mainly (> 90%) in the form of ketoprofen glucuronide, and about 10% – through the intestine. In patients with renal insufficiency, ketoprofen is excreted more slowly, its T 1/2 increases by 1 h. In patients with hepatic insufficiency, T 1/2 increases, so it is possible to accumulate ketoprofen in the tissues. In elderly patients, ketoprofen metabolism and elimination are slower, which is of clinical significance only for patients with severe renal insufficiency.

Indications

Symptomatic treatment of pain syndrome, including inflammatory processes of various origins: rheumatoid arthritis; seronegative arthritis: ankylosing spondylitis (Ankylosing spondylitis), psoriatic arthritis, reactive arthritis (Reiter’s syndrome); gout, pseudogout; degenerative diseases of the musculoskeletal system, including osteoarthritis; mild, moderate and severe pain syndrome in headaches, migraines, tendinitis, bursitis, myalgia, neuralgia, sciatica; post-traumatic and postoperative pain syndrome, including those accompanied by inflammation and fever; pain syndrome in oncological diseases; algodismenorrhea. The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

Use during pregnancy and lactation

Inhibition of prostaglandin synthesis may have undesirable effects on pregnancy and / or embryonic development. Data obtained during epidemiological studies with the use of prostaglandin synthesis inhibitors in early pregnancy confirm an increased risk of spontaneous abortion and the formation of heart defects (up to 1.5%) and birth defects of the anterior abdominal wall. The risk increases with increasing dose and duration of treatment. Prescribe the drug to pregnant women in the first and second trimesters of pregnancy is possible only if the potential benefit to the mother exceeds the potential risk to the fetus. In this case, it is necessary to apply the minimum effective dose in the shortest possible course. The use of ketoprofen is contraindicated in pregnant women during the third trimester of pregnancy due to the possible development of uterine labor weakness, increased bleeding time, antiplatelet effect (even when taken in small doses), as well as the effect on the fetus (cardiopulmonary toxicity, including premature closure of the arterial duct and pulmonary hypertension, kidney dysfunction, which can progress to renal failure with the development of lack of water). To date, there are no data on the excretion of ketoprofen in breast milk, so if it is necessary to prescribe ketoprofen during breastfeeding, the question of stopping it should be decided.

Recommendations for use

Intravenously, intramuscularly. To reduce the frequency of adverse reactions, it is recommended to use the minimum effective dose of the drug. The maximum daily dose is 200 mg. It is necessary to carefully evaluate the ratio of expected benefit and risk before starting ketoprofen at a dose of 200 mg / day. Intramuscular use: 100 mg (1 ampoule) 1-2 times a day. Intravenous infusion of ketoprofen should only be performed in a hospital setting. The duration of the infusion should be from 0.5 to 1 hour. The intravenous method of use should be used for no more than 48 hours. Short-term intravenous infusion: from 100 (to 200) mg (1-2 ampoules) ketoprofen, diluted in 100 ml of 0.9% sodium chloride solution, is administered within 0.5-1 h. Long-term intravenous infusion: from 100 (to 200) mg (1-2 ampoules) ketoprofen diluted in 500 ml of an infusion solution (0.9% sodium chloride solution, lactate-containing Ringer’s solution,5% dextrose solution) is administered within 8 hours; repeated use is possible after 8 hours. The maximum daily dose is 200 mg. Ketoprofen can be combined with centrally acting analgesics; it can be mixed with opioids (for example, morphine) in a single bottle, pharmacologically incompatible with tramadol solution due to precipitation. Parenteral use of the drug can be combined with the use of oral forms (tablets, capsules) or rectal suppositories

Contraindications

Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other nonsteroidal anti-inflammatory drugs (NSAIDs);complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis);acute gastric or duodenal ulcer;ulcerative colitis, Crohn’s disease; hemophilia and other blood clotting disorders;children (under 15 years of age);severe hepatic insufficiency;severe renal insufficiency: severe renal insufficiency (creatinine clearance less than 30 ml/min), confirmed hyperkalemia, progressive kidney diseases; decompensated heart failure;postoperative period after coronary artery bypass grafting;gastrointestinal, cerebrovascular and other bleeding (or suspected bleeding); chronic dyspepsia; third trimester of pregnancy;breast-feeding period.

Side effects

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: : very common (≥ 1/10), common (≥ 1/100, < 1/10), infrequent (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), and very rare (From the hematopoietic and lymphatic system Rarely: hemorrhagic anemia, hemolytic anemia, leukopenia. Frequency unknown: agranulocytosis, thrombocytopenia, bone marrow dysfunction. Immune system disorders 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: seizures, taste disturbances, emotional lability. From the sensory organs Rarely: blurred vision, tinnitus, conjunctivitis, dry eye mucosa, eye pain, hearing loss. Frequency unknown: optic neuritis. From the cardiovascular system Infrequently: tachycardia. Frequency unknown: heart failure, high blood pressure, 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 gastrointestinal tract (GIT) Often: nausea, vomiting, dyspepsia, abdominal pain, NSAIDs-gastropathy. Infrequently: constipation, diarrhea, bloating, gastritis. Rare: peptic ulcer, stomatitis. Very rare: exacerbation of ulcerative colitis, 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. Skin disorders Infrequently: skin rash, pruritus. 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 rare: acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values of renal function indicators. Frequency unknown: fluid retention in the body and resulting weight gain, hyperkalemia. Other Infrequently: peripheral edema, fatigue. Rarely: hemoptysis, menometrorrhagia, shortness of breath, thirst, muscle twitching.

Interaction

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. Concomitant 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 concomitantly with lithium preparations, it is possible to increase the concentration of lithium in 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 adjusted in a timely manner during and after NSAID treatment. 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 ketoprofen therapy and taking methotrexate should be at least 12 hours. Combinations that should be used with caution During ketoprofen therapy, patients taking diuretics, especially if 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 the use of ketoprofen in such patients, rehydration measures should be taken. After starting treatment, kidney function should be monitored. Concomitant use of the drug with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, elderly patients) may lead to an aggravation of the deterioration of renal function, including the development of acute renal failure. During the first weeks of concomitant use of ketoprofen and methotrexate at a dose not exceeding 15 mg/week, a blood test should be monitored weekly. In elderly patients or if there are any signs of impaired renal function, the study should be performed more often. Combinations to take into account Ketoprofen may weaken the effect of antihypertensive agents (beta-blockers, angiotensin-converting enzyme 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 hyperkalemia. Concomitant use with cyclosporine, tacrolimus may lead to the risk of developing an additive nephrotoxic effect, especially in elderly patients. The use of several antiplatelet drugs (tirofiban, eptifibaride, abciximab, iloprost) increases the risk of bleeding. Increases blood plasma concentrations of cardiac glycosides, slow calcium channel blockers, cyclosporine, methotrexate, and digoxin. Ketoprofen may enhance the effects of oral hypoglycemic and some anticonvulsants (phenytoin). Concomitant use with probenecid significantly reduces the clearance of ketoprofen in blood plasma. Nonsteroidal anti-inflammatory drugs may reduce the effectiveness of mifepristone. NSAIDs should be started no earlier than 8-12 days after mifepristone is discontinued. Pharmacologically incompatible with tramadol solution due to precipitation.

Overdose

An overdose of ketoprofen may cause headache, nausea, vomiting, abdominal pain, vomiting with blood, melena, impaired consciousness, respiratory depression, convulsions, impaired renal function and kidney failure. In case of overdose, gastric lavage and the use of activated charcoal are indicated. Treatment-symptomatic and supportive therapy; the effect of ketoprofen on the gastrointestinal tract can be reduced by means of agents that reduce the secretion of gastric glands (for example, proton pump inhibitors) and prostaglandins; monitoring of respiratory and cardiovascular activity; no specific antidote was found, hemodialysis is ineffective.

Special instructions

With prolonged use of NSAIDs, it is necessary to periodically evaluate the clinical blood test, as well as monitor the function of the kidneys and liver, especially in elderly patients (over 65 years), and conduct a fecal occult blood test. It is necessary to exercise caution and monitor blood pressure more often when using ketoprofen for the treatment of patients suffering from arterial hypertension, cardiovascular diseases that lead to fluid retention in the body. If visual disturbances occur, treatment should be stopped immediately. Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. In case of signs of infection or deterioration of health during the use of the drug, you should immediately consult a doctor. If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer disease), long-term therapy and the use of high dosages of ketoprofen, the patient should be under close medical supervision. Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing ketoprofen to patients with cardiac or renal insufficiency, as well as in the treatment of elderly patients taking diuretics, and patients who for any reason have a decrease in the volume of circulating blood (for example, after surgery). The use of ketoprofen may affect female fertility, so patients with infertility (including those undergoing examination) are not recommended to use the drug.

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf life

3 years

Active ingredient

Ketoprofen

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion