Ketonal - instructions for use, dose, side effects, contraindications

Excipients: magnesium stearate 3.0 mg; silicon dioxide colloid 2.0 mg; Povidone K 25 7.5 mg; cellulose microcrystalline 85.5 mg; hypromellose 42.0 mg.

Description:

White, round, biconvex tablets.

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

ATX: & nbsp

M.02.A.A.10 Ketoprofen

Pharmacodynamics:

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID). Ketoprofen has anti-inflammatory, analgesic and antipyretic effect.

Ketoprofen blocks the action of the enzyme cyclooxygenase 1 and 2 (COX₁ and COX₂) and, in part, lipoxygenase, which leads to suppression of the synthesis of prostaglandins (including the central nervous system (CNS), most likely in the hypothalamus).

Stabilizes in vitro and in vivo liposomal membranes, at high concentrations in vitro ketoprofen inhibits the synthesis of bradykinin and leukotrienes.

Ketoprofen does not adversely affect the condition of the articular cartilage.

Pharmacokinetics:

Absorption

Ketoprofen is easily absorbed from the gastrointestinal tract (GIT), bioavailability is 90%. Connection with blood plasma proteins - 99%. When ingesting 150 mg of ketoprofen, the maximum concentrations (C_mOh) of the drug in the blood plasma (10.4 μg / ml) are reached after 4-6 hours.

Distribution

Ketoprofen is 99% bound 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. Plasma clearance of ketoprofen is approximately 0.08 l / kg / h. Effective concentrations of ketoprofen are determined in the blood even after 24 hours after its administration.

Metabolism and excretion

Ketoprofen undergoes intensive metabolism under the action of microsomal liver enzymes, half-life (T_1/2) is less than 2 hours. Ketoprofen binds to glucuronic acid and is excreted from the body in the form of glucuronide. There are no active metabolites of ketoprofen. Up to 80% ketoprofen is excreted by the kidneys within 24 hours, mainly in the form of ketoprofen glucuronide.

When using the drug in a dosage of 100 mg or more, excretion by the kidneys can be difficult. In patients with severe renal insufficiency most of the drug is secreted through the intestine.

When taking high doses, the liver clearance also increases. Up to 40% of the drug is excreted through the intestine.

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

Have patients with renal insufficiency clearance of ketoprofen is reduced, but correction of doses is required only in the case of severe renal failure.

In elderly patients metabolism and excretion of ketoprofen proceed more slowly, which is of clinical importance only for patients with severe renal insufficiency.

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);

- gout, pseudogout;

- osteoarthritis;

- tendonitis, bursitis, myalgia, neuralgia, sciatica;

- pain syndrome, including mild, moderate and severe:

- post-traumatic and postoperative pain syndrome;

pain syndrome with oncological diseases, etc.

Contraindications:

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

- bronchial asthma, bronchospasm, rhinitis or urticaria in anamnesis caused by taking acetylsalicylic acid or other NSAIDs;

- ulcerative colitis, Crohn's disease; hemophilia and other bleeding disorders;

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

severe hepatic impairment;

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

Decompensated heart failure; Postoperative period after coronary artery bypass grafting;

- Stomach ulcer or duodenal ulcer in the stage of exacerbation;

- gastrointestinal,cerebrovascular and other bleeding (or suspected bleeding);

- chronic dyspepsia;

- III trimester of pregnancy;

lactation period.

Carefully:

Bronchial asthma in history, clinically expressed cardiovascular, cerebrovascular diseases and peripheral arterial diseases, dyslipidemia, progressive liver diseases, hyperbilirubinemia, alcoholic liver cirrhosis, renal failure (KK 30-60 ml / min), hepatic insufficiency, infection Helicobacter pylori, elderly age, chronic heart failure, arterial hypertension, blood diseases, dehydration, diabetes mellitus, anamnestic data on the development of gastrointestinal ulcer, smoking, concomitant anticoagulant therapy (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid), glucocorticosteroids for oral administration (for example, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, sertraline), prolonged use of NSAIDs.

Pregnancy and lactation:

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 heart disease (1-1.5%).

Applying the drug to pregnant women in the I and II trimesters of pregnancy is only possible if the intended benefit to the mother exceeds the possible risk to the fetus.

Contraindicated in the use of ketoprofen in pregnant women during the third trimester of pregnancy because of the possibility of developing weakness in the uterine labor activity and / or premature closure of the arterial duct, a possible increase in bleeding time, lack of hydration and kidney failure.

To date, there is no data on the isolation of ketoprofen in breast milk, so if you need to use ketoprofen in a nursing mother, you should decide whether to stop breastfeeding.

Dosing and Administration:

Inside, the tablet is swallowed whole during or after a meal, washed down with water or milk (the volume of the liquid must be at least 100 ml).

The drug is prescribed for 1 tablet (150 mg) 1 time per day.

The maximum dose of ketoprofen is 200 mg / day.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000) and very rarely (<1/10000); frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

Disturbances from the hematopoiesis and lymphatic system

rarely: hemorrhagic anemia;

frequency unknown: agranulocytosis, thrombocytopenia, impaired bone marrow function.

Immune system disorders

frequency unknown: anaphylactic reactions (including anaphylactic shock).

Disturbances from the nervous system

infrequently: headache, dizziness, drowsiness;

rarely: paresthesia;

the frequency is unknown: convulsions, a violation of taste.

Disorders of the psyche

frequency unknown: emotional lability.

Impaired sensory organs

rarely: blurred vision, tinnitus.

Disorders from the cardiovascular system

frequency unknown: heart failure, increased blood pressure, vasodilation.

Disturbances from the respiratory system

rarely: exacerbation of bronchial asthma;

frequency unknown: bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.

Disorders from the gastrointestinal tract

often: nausea, vomiting, indigestion, pain in the abdomen;

infrequently: constipation, diarrhea, bloating, gastritis;

rarely: peptic ulcer, stomatitis; very rarely: exacerbation of ulcerative colitis or Crohn's disease, gastrointestinal bleeding, perforation.

Disturbances from the liver and bile ducts

rarely: hepatitis, increased activity of "hepatic" transaminases, increased bilirubin concentration.

Disturbances from the skin and subcutaneous tissues

infrequently: skin rash, itchy skin;

frequency unknown: photosensitivity, alopecia, urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract

frequency unknown: acute renal failure, interstitial nephritis, nephritic syndrome, nephrotic syndrome, abnormal values of renal function indicators.

Other

infrequently: swelling;

rarely: weight gain;

frequency unknown: increased fatigue.

Overdose:

As with other NSAIDs, with ketoprofen overdose, 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 is symptomatic; the effect of ketoprofen on the gastrointestinal tract can be weakened with the help of drugs that reduce the secretion of the gland of the stomach (for example, proton pump inhibitors or H blockers₂-gistamine receptors), and prostaglandins.

Interaction:

Ketoprofen can weaken the action diuretics and antihypertensive drugs and strengthen action hypoglycemic drugs for oral administration and some anticonvulsants (phenytoin).

Joint application with other NSAIDs, salicylates, glucocorticosteroids, ethanol increases the risk of development undesirable phenomena from the gastrointestinal tract.

Simultaneous application with anticoagulants (heparin, warfarin), thrombolytic agents, antiplatelet agents (ticlopidine, clopidogrel), pentoxifylline increases the risk of bleeding.

Simultaneous application with salts of potassium, potassium-sparing diuretics, ACE inhibitors, NSAIDs, low-molecular-weight heparins, cyclosporin, tacrolimus and trimethoprim increases the risk of hyperkalemia.

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

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

Combination with glucocorticosteroids and dOther NSAIDs (including selective COX inhibitors₂) increases the likelihood of side effects (in particular, from the gastrointestinal tract).

NSAIDs may decrease effectiveness mifepristone. Admission of NSAIDs should be started no earlier than 8-12 days after the withdrawal of mifepristone.

Special instructions:

Do not combine ketoprofen with other NSAIDs and / or COX inhibitors₂.

With prolonged use of NSAIDs, it is necessary to periodically evaluate a clinical blood test,control the function of the kidneys and liver, especially in elderly patients (over 65 years of age), conduct fecal occult blood test.

It is necessary to be careful and more often to control blood pressure when using ketoprofen for the treatment of patients with arterial hypertension, cardiovascular diseases that lead to fluid retention in the body.

If abnormalities occur on the part of the visual organs, treatment should be stopped immediately.

Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. In case of detection of signs of infection or deterioration of well-being on the background of the use of the drug, you should immediately consult a doctor.

If you have a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer disease), prolonged therapy and the use of high doses of ketoprofen, the patient should be carefully monitored by the doctor.

Because of the important role of prostaglandins in maintaining renal blood flow, caution should be exercised when using ketoprofen in patients with cardiac or renal insufficiency,as well as in the treatment of elderly patients taking diuretics, and patients who, for whatever reason, there is a decrease in the volume of circulating blood. The drug should be discontinued before a large surgical intervention.

The use of ketoprofen can affect women's fertility, so patients with infertility (including undergoing examination) are not recommended to use the drug.

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

Data on the adverse effects of Ketonal ® in the recommended doses on the ability to drive or work with mechanisms are not present. However, patients who have drowsiness, dizziness, or other unpleasant sensations on the part of the nervous system, including visual impairment, should refrain from driving control of vehicles and mechanisms.

Form release / dosage:

Long-acting tablets 150 mg.

Packaging:

Primary packaging: 20 tablets are placed in a bottle of dark glass, ukuporenny screw cap with embedded silica gel;

Secondary packaging: 1 bottle together with instructions for medical use is placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013942 / 03

Date of registration:19.11.2007 / 09.10.2014

Expiration Date:Unlimited

The owner of the registration certificate: Lek dd Lek dd Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp02.01.2018

Illustrated instructions

Instructions

Ketonal (Ketonal)