Ketoprofen (When ATH M01AE03)

When ATH:
M01AE03

Characteristic.

NSAIDs. Ketoprofen is a racemic mixture of enantiomers, wherein the pharmacological activity is associated with the S-enantiomer. White or almost white, fine-grained granular or powder, without smell, not hygroscopic. Practically insoluble in water at 20 °C, slightly soluble in ethanol, xloroforme, acetone, ether, benzene and strong alkalis. Molecular weight 254,28.

Ketoprofen lysine salt: molecular weight 400,47.

Pharmacological action.
Analgesic, pyretic, anti-inflammatory, antiagregatine.

Application.

For systemic use (inside, / m, I /, rectally)

Inflammatory and degenerative diseases of the musculoskeletal system, incl. rheumatoid arthritis, nonspecific spondylitis (ankiloziruyushtiy and psoriaticheskiy spondylitis), podagricheskiy arthritis, pseudogout, osteoarthritis, extra-articular rheumatism (tendinitis, ʙursit, kapsulit). Relief of pain of various origins, incl. Postoperative, posttraumatic pain, işialgija, myalgia, radiculitis, bruises and muscle strains, počečnaâ how, dental pain syndromes, gynecological, Neurological, oncology practice. Symptomatic treatment of acute pain in inflammatory diseases of the musculoskeletal system (only for the / m). Primary dysmenorrhea.

For topical application,:

when applied to the skin - Acute and chronic inflammatory diseases of the musculoskeletal system (rheumatoid arthritis, Spondylitis, arthrosis, osteochondrosis); painful inflammatory or traumatic (incl. sport) joint damage, tendons, ligaments and muscles (incl. arthritis, parasynovitis, Tendinitis, tendosynovyt, ʙursit, muscle injuries, sprains, torn ligaments and tendons muscles, sprains, knee meniscus damage, Kryvosheya, lyumbago), phlebitis, superficial vein thrombophlebitis, limfangit, inflammation of the skin;

as a solution for rinsing - Symptomatic treatment of inflammatory diseases of the oral cavity, pharynx and larynx (incl. sore throat, laringit, pharyngitis, stomatitis, glossitis, gingivitis, periodontitis, parodontoz), analgesia for the treatment or removal of teeth (as an auxiliary drug).

Contraindications.

Hypersensitivity (incl. to other NSAIDs). For systemic use: «Aspirinovaya» asthma, gastric ulcer and duodenal ulcer (exacerbation), yazvennыy colitis (exacerbation), Crohn's disease, diverticulitis, pepticheskaya ulcer, disorders of blood coagulation ('s also in hemophilia), kidney and liver failure, childhood and adolescence up 18 years, pregnancy (III Plus); Rectal (additionally): hemorrhoids, proctitis, proktorragii; for cutaneous application: moist dermatitis, eczema, infected abrasions, violation of the integrity of the skin, Children up to age 6 years.

Ketoprofen is not indicated for the relief of pain during coronary bypass surgery.

Pregnancy and breast-feeding.

Teratogenic effects. In studies in mice when administered at doses up ketoprofen 12 mg / kg / day (36 mg / m²/d) in rats at doses 9 mg / kg / day (54 mg / m²/d), which is roughly equivalent 0,2 MRDC (185 mg / m²/d), There were no teratogenic or embryotoxic effects. In separate studies in rabbits toxic dose for females associated with embryotoxic, but not with teratogenicity. However, reproductive studies in animals do not always predict effects in humans.

Nonteratogenic effects. Since it is known the adverse influence of the, ingibiruyushtih synthesis NG, on the cardiovascular system of the fetus (premature closure of the ductus arteriosus), should be avoided in pregnancy (especially in the later stages).

The ingestion or rectal administration during pregnancy may impair hemodynamics in the newborn, which is accompanied by severe disorders of respiratory function, and the use shortly before delivery may lead to delays.

There are no adequate and well-controlled studies in pregnant women have not held. Pregnancy I and II trimester possible, if the effect of therapy outweighs the potential risk to the fetus, in the III trimester (particularly after 36 Sun) - Contraindicated due to the possible impact on the tone of the uterus.

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Labor and delivery. The effects of ketoprofen on labor and delivery in humans is unknown. Studies in rats have shown, ketoprofen dose 6 mg / kg (36 mg / m²/d), which is roughly equivalent 0,2 MRDC, prolongs pregnancy, if it is used before delivery.

Women, planning pregnancy, should refrain from the use of ketoprofen, tk. against the background of his admission may decrease the likelihood of implantation of the egg.

Unknown, Do ketoprofen penetrates into human breast milk. Rats at doses 9 mg / kg (54 mg / m²/d, about 0,3 MRDC) ketoprofen had no effect on perinatal development. When administered to lactating dogs ketoprofen concentration in milk was 4-5% of plasma concentration. Like other substances, which are excreted into breast milk, Ketoprofen is not recommended for nursing mothers.

Side effects.

Systemic side effects

In clinical trials the following side effects were noted (possibly involving the use of ketoprofen):

From the digestive tract: dyspepsia (11%); 3-9% - Nausea, abdominal pain, diarrhea / constipation, flatulence; >1% - Anorexia, vomiting, stomatitis; <1% - Increased appetite, dry mouth, belching, gastritis, rectal bleeding, ground, occult bleeding, drooling, pepticheskaya ulcer, perforation of the gastrointestinal tract, gematemezis, ulceration of the bowel, liver dysfunction, hepatitis, cholestatic hepatitis, jaundice, hyperdipsia.

From the nervous system and sensory organs: 3-9% - Headache, excitation (incl. insomnia, nervousness, unusual dreams); >1% - Dizziness, CNS depression (incl. drowsiness, malaise), tinnitus, blurred vision; <1% - Amnesia, confusion, migraine, paraesthesia, vertigo, conjunctivitis, sore eyes, hearing loss, retinal hemorrhage and discoloration, taste disturbances.

Cardio-vascular system and blood (hematopoiesis, hemostasis): <1% - Increase in blood pressure, heartbeat, tachycardia, worsening heart failure, Peripheral Vascular Disease, vasodilation, hypocoagulation, agranulocytosis, anemia, gemoliz, thrombocytopenia.

From the respiratory system: >1% - Dyspnoea, hemoptysis, nose bleed, pharyngitis, rhinitis, bronchospasm, laryngeal edema.

With the genitourinary system: 3-9% - Renal dysfunction (swelling, increase in blood urea nitrogen); >1% - The signs and symptoms of the urinary tract irritation; <1% - Menometrorrhagia, hematuria, renal failure, interstitial nephritis, nephrotic syndrome.

For the skin: >1% - Rashes, alopecia, eczema, prurit, hives, bullous rash, exfoliative dermatitis, photosensitivity, livor, onixolizis, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome.

Other: <1% - Chills, swelling of the face, infection, pain, allergic reactions, anaphylaxis, weight gain, giponatriemiya, myalgia, purpura, increased sweating.

Side effects, occurs with a frequency <1% (a causal relationship to the use of ketoprofen is not installed):

Cardio-vascular system and blood (hematopoiesis, hemostasis): arrhythmia, myocardial infarction.

From the digestive tract: buccal necrosis (oral form), yazvennыy colitis, microvesicular steatosis, pancreatitis, worsening of diabetes.

From the nervous system and sensory organs: disforija, hallucinations, nightmares, personality changes, aseptic meningitis.

Other: septicemia, shock, violation of libido, acute tubulopathy, gynecomastia.

Ketoprofen lysine salt compared to ketoprofen causes less side effects on the gastrointestinal tract (because, that ketoprofen lysine salt has a neutral pH and, respectively, less irritating to the stomach lining).

Local side effects: when applied to the rectum - itching, heaviness in the anorectal area, aggravation of hemorrhoids; when dermal application - allergic skin reactions, photosensitivity, development of systemic side effects (long-term use on large surface of the skin); using a solution for rinsing - sensitization (prolonged use).

Cooperation.

Pharmaceutical incompatible with a solution of tramadol. Reduces the effectiveness of drugs urikozuricheskih, enhances the effect of anticoagulants, antiagregantov, fibrinolitikov, ethanol, side effects gluco- and mineralocorticoid, estrogen; reduces the effectiveness of antihypertensive drugs and diuretics. Joint reception with other NSAIDs, gljukokortikoidami, ethanol, corticotropin may lead to the development of ulcers and gastrointestinal bleeding, an increased risk of renal dysfunction. Co-administration with oral anticoagulants, geparinom, thrombolytics, antiplatelet, cefoperazone, Tsefamandol tsefotetanom and increases the risk of bleeding. It increases the hypoglycemic effect of insulin and oral hypoglycemic drugs (recalculation of the dose needed). Inductors of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites. Co-administration with sodium valproate causes a disturbance of platelet aggregation. It increases concentration of plasma verapamil and nifedipine, lithium preparations, methotrexate. Antacids (incl. aluminum- and magnesium-) did not affect the rate and magnitude of absorption of ketoprofen. Myelotoxic drugs increase the expression gematotoksichnosti.

Overdose.

Symptoms: lethargy, dizziness, nausea, vomiting, epigastric pain - symptoms usually reversible. May experience respiratory distress, coma, convulsions. Rarely - bleeding from the gastrointestinal tract, hypotension / hypertension, acute renal failure.

Treatment: symptomatic and supportive therapy, monitoring of the respiratory and cardiovascular system. The specific antidote is not found. Hemodialysis maloeffyektivyen.

Dosing and Administration.

Inside, / m, I /, rectally, fur gloves, locally. Dose picked individually, depending on the nature of the disease, severity of pain, of the patient. If necessary, the dosage forms can be used in various combinations, wherein the total daily dose may be increased to 300 mg or reduced to 100 mg. At the beginning of treatment daily dose - 300 mg 2-3 reception, maintenance - 150-200 mg / day.

Capsules, tablets, granulate is recommended to take with meals.

Rectal: 1-2 Suppository per day.

/ M: 100 mg 1-2 times a day; after the relief of pain appointed interior and / or rectally.

B /: 100-200 100-150 mg ml 0,9% sodium chloride solution. Infusion of ketoprofen should be carried out only in a hospital.

Fur gloves: 2-4 Times daily gel / cream / spray applied to the skin over the hearth inflammation and gently rubbed; possible imposition of a dry dressing.

Locally (rinse solution): 2-3 Rinses a day.

Lysine salt of ketoprofen: solution for injection: / m or / by 160 mg (2 ml) 13 times per day, electrophoresis solution is applied to the negative pole. Suppozitorii: adults - 160 mg. Babies weighing 15-30 kg - for 30 mg, more 30 kg - 60 mg 2-3 times a day. Granules: adults - 80 mg, Children - 40 g dissolved in 1/2 glass of water and taken orally 2-3 times a day.

Precautions.

Care should be taken to conduct a thorough medical supervision with a history of allergic reactions to the instructions on the drug "aspirin" series, "Aspirin" triad, gastric ulcer and duodenal ulcer, with anemia, alcoholism, tobacco use, alcoholic liver cirrhosis, giperʙiliruʙinemii, hepatic insufficiency, diabetes, degidratacii, sepsis, chronic heart failure, edema, hypertension, blood diseases (incl leukopenia, thrombocytopenia, in violation of blood coagulation), definition, glucose-6-fosfatdegidrogenazы, Stomat; Caution is advised when used externally - with the aggravation of hepatic porphyria, erosive and ulcerative lesions of the gastrointestinal tract, severe violations of liver and kidney function, chronic heart failure, asthma, in children under 12 years.

When referring to a history of allergic reactions to NSAIDs used only in emergency cases.

The risk of cardiovascular events. NSAIDs may cause increased risk of serious cardiovascular complications, incl. myocardial infarction and stroke, that can lead to death, especially with prolonged use. Patients with cardiovascular disease or risk factors for cardiovascular disease risk is particularly high.

The risk of gastrointestinal complications. NSAIDs cause an increased risk of serious side effects from the gastrointestinal tract, including bleeding, ulceration and perforation of the stomach or intestines, which can be fatal, especially with prolonged use. These complications can occur at any time without the use of the symptoms heralding. Elderly patients are at greater risk of serious complications from the gastrointestinal tract.

Admission ketoprofen may mask the symptoms of an infectious disease.

During treatment requires monitoring of peripheral blood and functional state of the liver and kidneys. If you want to determine the 17-ketosteroids drug should be discontinued for 48 h before the test.

Avoid contact with eyes and other mucous membranes forms for cutaneous application; Do not apply to open wounds or damaged skin.

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Cooperation