Ketoprofen - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate - 60.0 mg; corn starch - 44.2 mg; talc - 8.0 mg; povidone 5.0 mg; magnesium stearate - 1.6 mg; silicon dioxide colloidal - 1.2 mg;

film sheath: dry film-coating mixture containing hypromellose (60%), talc (20%), titanium dioxide (10.66%), macrogol 4000 (polyethylene glycol 4000) (9%), aluminum dye based on indigo carmine dye (0.34 %) - 7.0 mg.

Description:

Round biconvex tablets, covered with a film coating of blue color. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID)

ATX: & nbsp

M.02.A.A.10 Ketoprofen

Pharmacodynamics:

Ketoprofen has an anti-inflammatory, analgesic and antipyretic effect.

Ketoprofen blocks the action of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) and partially lipoxygenase,which leads to suppression of the synthesis of prostaglandins (including the central nervous system (CNS), most likely in the hypothalamus), causes significant inhibition of neutrophil activity in patients with rheumatoid arthritis.

Ketoprofen stabilizes liposomal membranes in vitro and in vivo, at high concentrations in vitro Suppresses the synthesis of bradykinin and leukotrienes.

Ketoprofen does not adversely affect the condition of the articular cartilage. Anti-inflammatory effect occurs by the end of the first week of admission.

Pharmacokinetics:

Suction

Ketoprofen is easily absorbed from the gastrointestinal tract (GIT), bioavailability is 90%. Connection with blood plasma proteins - 99%. When administered 100 mg of ketoprofen, the maximum concentration (C_ma_x) in blood plasma (10,4mkg / ml) is achieved after 1 hour 22 minutes.

Distribution

Ketoprofen 99% binds to blood plasma proteins, mainly with the albumin fraction. The volume of distribution is 0.1 l / kg. Ketoprofen penetrates into the synovial fluid and reaches there a concentration equal to 30% of the concentration in the blood plasma. The concentration of ketoprofen in the synovial fluid is stable (lasts up to 30 hours),as a result of which the pain syndrome and joint stiffness are reduced for a long time. Plasma clearance of ketoprofen is approximately 0.08 l / kg / h.

Metabolism and excretion

Ketoprofen undergoes intensive metabolism under the action of microsomal liver enzymes, the half-life period (T1 / 2) is less than 2 hours. There are no active metabolites of ketoprofen. Ketoprofen binds to glucuronic acid and is excreted from the body in the form of glucuronide by the kidneys (60-80%) for 24 hours.

It does not possess cumulative properties, due to fast and fairly complete excretion.

Pharmacokinetics in specific patient groups

Patients with impaired renal function

In patients with severe renal insufficiency, most of the ketoprofen is excreted through the intestine. When taking high doses, the liver clearance also increases. Through the intestine, up to 40% of ketoprofen is excreted.

In patients with renal insufficiency, the clearance of ketoprofen is reduced, but dosage adjustment is required only in the case of severe renal failure.

Patients with impaired hepatic function

In patients with severe hepatic insufficiency, the plasma concentration of ketoprofen is doubled (probably,due to a high level of unbound active ketoprofen due to hypoalbuminemia); such patients need to prescribe the drug in the minimum therapeutic dose.

Elderly patients

In elderly patients, metabolism and excretion of ketoprofen are slower, which is of clinical importance only for patients with severe renal failure.

Indications:

Symptomatic therapy of painful and inflammatory processes of various origin, including:

- inflammatory and degenerative diseases of the musculoskeletal system:

- rheumatoid arthritis;

- seronegative arthritis: ankylosing spondylitis - Bechterew's disease, psoriatic arthritis, reactive arthritis (Reiter's syndrome);

- gouty arthritis;

- osteoarthritis;

- tendonitis, bursitis, myalgia, neuralgia, sciatica;

- pain syndrome, including mild, moderate and severe:

- headache;

- toothache;

- post-traumatic and postoperative pain syndrome;

- pain syndrome in cancer;

- otitis;

- algodismenorea.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:

- Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates and other NSAIDs;

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history);

- rhinitis or urticaria in history caused by the use of acetylsalicylic acid or other NSAIDs;

- peptic ulcer of the stomach or duodenum in the stage of exacerbation;

- ulcerative colitis, Crohn's disease;

- hemophilia and other bleeding disorders;

- children's age (up to 15 years);

- severe degree of hepatic insufficiency;

- severe renal insufficiency (creatinine clearance (CK) less than 30 ml / min);

- Decompensated heart failure;

- Postoperative period after aorto-coronary bypass;

- gastrointestinal, cerebrovascular and other bleeding (or suspicion of bleeding);

- progressive kidney disease, diverticulitis, active liver disease, inflammatory bowel disease, confirmed hyperkalemia; lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

- chronic dyspepsia;

- III trimester of pregnancy;

- the period of breastfeeding.

Carefully:

Anemia, history of bronchial asthma, clinically expressed cardiovascular, cerebrovascular diseases and peripheral arterial diseases, dyslipidemia, progressive liver disease, hepatic insufficiency, hyperbilirubinemia, alcoholic cirrhosis, renal failure (Q30-60 ml / min), chronic heart failure , arterial hypertension, blood diseases, dehydration, diabetes mellitus, anamnestic data on the development of gastrointestinal ulceration, the presence of infection Helicobacter pylori, severe somatic diseases, sepsis, edema, stomatitis, advanced age, smoking, concomitant anticoagulant therapy (eg, warfarin), antiplatelet agents (eg, acetylsalicylic acid), oral glucocorticosteroids (eg, prednisolone), selective serotonin reuptake inhibitors (eg, sertraline), long-term use of NSAIDs; elderly patients taking diuretics; patients with a decrease in the volume of circulating blood.

Pregnancy and lactation:

Pregnancy

Inhibition of prostaglandin synthesis may have an adverse effect on the course of pregnancy and / or on embryonic development. Data from epidemiological studies using prostaglandin synthesis inhibitors in early pregnancy confirm the increased risk of spontaneous abortion and the formation of heart defects (about 1-1.5%).

The use of the drug by pregnant women in I and II trimesters of pregnancy is possible only if the expected effect of therapy exceeds the potential risk to the fetus.

Contraindicated drug use Ketoprofen in pregnant women in the third trimester of pregnancy because of the possible effect on the tone of the uterus and / or premature closure of the arterial duct, the possible increase in bleeding time, the development of malnutrition and kidney failure.

Breastfeeding period

If it is necessary to use the drug, breastfeeding should be discontinued.

Fertility

NSAIDs can affect fertility and are not recommended for use by women planning a pregnancy.

Dosing and Administration:

Inside.The tablet should be swallowed whole during or after a meal, washed down with water or milk (the volume of the liquid is not less than 100 ml).

Usually, the drug is prescribed for adults and children older than 15 years.

Inflammatory and degenerative diseases of the musculoskeletal system 1 tablet (100 mg) 2 times a day.

Pain syndrome, including weak, moderate and pronounced 1 tablet (100 mg) 2 times a day.

Elderly patients

Older patients should take the drug Ketoprofen, starting with the minimum recommended dose.

The maximum daily dose of ketoprofen is 200 mg.

Do not exceed the maximum daily dose of the drug.

In order to reduce the risk of developing adverse events from the gastrointestinal tract, patients with risk factors are encouraged to simultaneously prescribe the intake of proton pump inhibitors.

Side effects:

Classification of the incidence of adverse events according to recommendations

World Health Organization (WHO):

very often ≥ 1/10;

often from ≥ 1/100 to <1/10;

infrequently from ≥ 1/1000 to <1/100;

rarely from ≥ 1/10000 to <1/1000;

very rarely <1/10000, including individual messages;

the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

Violations of the blood and lymphatic system:

rarely - agranulocytosis, anemia, hemorrhagic anemia, thrombocytopenia, leukopenia. High doses of ketoprofen can inhibit platelet aggregation, thus prolonging the bleeding time, and cause nasal bleeding and hematoma formation.

Immune system disorders:

infrequently - the reactivity of the respiratory system, including bronchial asthma and its aggravation; bronchospasm or dyspnea (especially in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs);

very rarely - angioedema and anaphylaxis.

Disturbances from the nervous system:

infrequently - headache, dizziness, drowsiness, insomnia, agitation, nervousness, depression, asthenia;

rarely - confusion or loss of consciousness, forgetfulness, memory impairment, migraine, peripheral neuropathy, dizziness.

Visual impairment:

rarely - blurred vision, conjunctivitis, dry eye mucosa, eye pain, conjunctival hyperemia.

Hearing disorders and labyrinthine disorders:

rarely - noise in the ears, hearing loss, vertigo.

Heart Disease:

frequency unknown - heart failure;

rarely - tachycardia.

Vascular disorders:

infrequently - increased blood pressure;

frequency is unknown - vasodilation.

Disturbances from the respiratory system, chest and mediastinal organs:

infrequently - hemoptysis, dyspnea, pharyngitis, rhinitis, bronchospasm (in particular, in patients with hypersensitivity to NSAIDs), laryngeal edema (signs of anaphylactic reaction);

rarely - exacerbation of bronchial asthma.

Disorders from the gastrointestinal tract:

often - NSAIDs-gastropathy, abdominal pain, dyspepsia (nausea, vomiting, heartburn, flatulence, decreased appetite, diarrhea);

infrequently - stomatitis;

rarely - erosive and ulcerative lesions;

very rarely - bleeding and perforation of the gastrointestinal tract, a change in taste.

Disturbances from the liver and bile ducts:

rarely - hepatitis, increased activity of "liver" transaminases, increased bilirubin concentration.

Disturbances from the skin and subcutaneous tissues:

often - skin rash (including erythematous urticaria), itching;

rarely - exfoliative dermatitis;

frequency unknown - bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract:

infrequently - edematous syndrome;

rarely - cystitis, urethritis, renal dysfunction, interstitial nephritis, nephrotic syndrome; very rarely - hematuria.

Other:

infrequently - swelling, increased sweating;

rarely - epistaxis, myalgia, muscle twitching, shortness of breath, thirst, photosensitivity, with prolonged use in large doses - vaginal bleeding.

Overdose:

Possible Symptoms

As with other NSAIDs, with an overdose of ketoprofen, nausea, vomiting, abdominal pain, vomiting with blood, melena, impaired consciousness, respiratory depression, seizures, impaired renal function, and kidney failure may occur.

In case of overdosage, gastric lavage and the use of activated charcoal are indicated.

Treatment

Symptomatic. The effect of ketoprofen on the gastrointestinal tract can be weakened with the help of drugs that reduce the secretion of the glands of the stomach (for example, proton pump inhibitors) and prostaglandins.

Interaction:

Ketoprofen can weaken the effect of uricosuric medicines, diuretics and antihypertensives and increase the effect of hypoglycemic drugs for ingestion and some anticonvulsants (phenytoin). Joint use with other NSAIDs, salicylates, glucocorticosteroids, ethanol increases the risk of developing unwanted effects from the gastrointestinal tract. Simultaneous use with anticoagulants (heparin, warfarin), thrombolytics, antiplatelet agents (ticlopidine, clopidogrel), Pentoxifylline increases the risk of bleeding.

Simultaneous application with potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, NSAIDs, low-molecular heparins, cyclosporine, tacrolimus and trimethoprim increases the risk of hyperkalemia.

Ketoprofen increases the concentration in the blood plasma of cardiac glycosides, blockers of "slow" calcium channels, lithium preparations, cyclosporine, methotrexate and digoxin.

Ketoprofen increases the toxicity of methotrexate and the nephrotoxicity of cyclosporine.Simultaneous application with probenecid significantly reduces the clearance of ketoprofen in the blood plasma.

Combined use with glucocorticosteroids and other NSAIDs (including selective inhibitors of COX-2) increases the likelihood of side effects (in particular, on the part of the gastrointestinal tract).

NSAIDs can reduce the effect of mifepristone. Admission of NSAIDs should be started no earlier than 8-12 days after the withdrawal of mifepristone.

Special instructions:

Do not combine the drug intake Ketoprofen with the administration of other NSAIDs and / or COX-2 inhibitors.

With prolonged use of NSAIDs, it is necessary to periodically evaluate the clinical analysis of blood, monitor kidney and liver function, in particular, in elderly patients (over 65 years old), conduct fecal occult blood test.

Care must be taken to control blood pressure more often when using the drug Ketoprofen for the treatment of patients with arterial hypertension, cardiovascular diseases, which lead to fluid retention in the body. In case of worsening, it is necessary to stop taking the drug.

If there is a violation of the sight, the applicationpreparation Ketoprofen should be stopped immediately.

Like others NSAIDs, ketoprofen can mask symptoms Infectious-inflammatory diseases. In case of signs of infection or deterioration of well-being on the background of the use of the drug, immediately consult a doctor.

In patients, simultaneously taking antiplatelet agents, anticoagulants, glucocorticosteroids, the risk of developing gastrointestinal bleeding, ulceration increases.

In the presence of an anamnesis contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer disease), prolonged therapy and the use of high doses of the drug Ketoprofen the patient must be under close medical supervision. In the event of gastrointestinal bleeding or ulcerative lesions, the use of the drug Ketoprofen should be discontinued. The use of ketoprofen is contraindicated in patients with gastrointestinal ailments in history (ulcerative colitis, Crohn's disease), as possible exacerbation of these diseases. Like other NSAIDs, ketoprofen can inhibit platelet aggregation and increase bleeding time by inhibiting the synthesis of prostaglandins. In this regard, the use of Ketoprofen in patients who simultaneously take drugs that affect the hemostasis system (for example, warfarin, coumarin derivatives, heparins) is not recommended.

The use of certain NSAIDs may be associated with a risk of developing arterial thrombosis (myocardial infarction, stroke). Data to exclude such a risk for ketoprofen is not enough.

Like other NSAIDs, ketoprofen can lead to an increase in the concentration of creatinine and nitrogen in the blood plasma. Like other inhibitors of prostaglandin synthesis, 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. Because of the important role of prostaglandins in maintaining renal blood flow, caution should be exercised when using the drug Ketoprofen in the treatment of patients with cardiac or renal insufficiency, as well as elderly patients taking diuretics, and patients who for any reason have a decrease in the volume of circulating blood.

Application of the drug Ketoprofen must be discontinued before a large surgical intervention.

As with the use of other NSAIDs, against the background of Ketoprofen therapy there may be a slight transient increase in the activity of "liver" transaminases. In case of a significant increase in the relevant indicators, the drug should be discontinued.

A drug Ketoprofen should be used with caution in patients with uncontrolled hypertension, ischemic heart disease, congestive heart failure, peripheral arterial disease and / or cerebrovascular disease. Patients with risk factors for the development of cardiovascular diseases (hypertension, dyslipidemia, diabetes, smoking) should also be used Ketoprofen carefully.

Ketoprofen may affect female fertility, so patients with infertility (including undergoing examination) are not recommended to use the drug.

There are data on the occurrence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) in the application of NSAIDs.At the first manifestations of skin rashes, lesions of mucous membranes or other signs of an allergic reaction, it is necessary to immediately stop taking the drug Ketoprofen and see a doctor.

Effect on the ability to drive transp. cf. and fur:

Data on the negative effects of ketoprofen in recommended doses on the ability to drive or work with mechanisms are not present. At the same time, patients who have drowsiness, dizziness, or other unpleasant sensations on the part of the nervous system, including visual impairment, should refrain from driving and practicing potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 100 mg.

Packaging:

5, 10, 15 or 20 tablets in a contoured cell pack of a polyvinylchloride or polyvinylchloride / polyvinylidene chloride film and aluminum foil.

20, 40 or 60 tablets in a can of high-density polyethylene.

4 contour cell packs of 5 tablets, 2, 4 or 6 contour cell packs of 10 tablets,4 contourcell packs of 15 tablets, 1, 2 or 3 contourcell packs of 20 tablets or one pot together with instructions for use in a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004615

Date of registration:25.12.2017

Expiration Date:25.12.2022

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp24.01.2018

Illustrated instructions

Instructions

Ketoprofen (Ketoprofen)