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

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 in the central nervous system, most likely in the hypothalamus).

Stabilizes in vitro and in vivo liposomal membranes, at high concentrations in vitro ketoprofen Suppresses the synthesis of bradykinin and leukotrienes. Ketoprofen does not adversely affect the condition of the articular cartilage.

Pharmacokinetics:

Suction

Ketoprofen is easily absorbed from the gastrointestinal tract when ingested. After oral administration of ketoprofen capsules prolonged action 200 mg maximum concentrations in blood plasma C_mOh from 3.1 to 3.4 ± 1.2 mg / l are achieved within 5 hours.

Bioavailability of the drug is 90%. Eating does not affect the overall bioavailability of ketoprofen, but decreases the rate of absorption.

Distribution

Ketoprofen by 99% is associated with 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 50% 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 action microsomal enzymes of the liver, the half-life 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. 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 result of this 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;

- osteoarthrosis;

- pain syndrome: mild, moderate and severe with headache, migraine, tendenitis, bursitis, myalgia, neuralgia, radiculitis, post-traumatic and postoperative pain syndrome, including inflammation and fever, pain syndrome in cancer, algodismenorea, inflammatory processes organs of the small pelvis, including adnexitis.

Contraindications:

- Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other non-steroidal anti-inflammatory drugs;

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

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

- nonspecific ulcerative colitis, Crohn's disease;

- hemophilia and other disorders of blood coagulability;

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

- severe hepatic impairment;

- severe renal failure: severe renal failure (creatinine clearance less than 30 ml / min), confirmed hyperkalemia, progressive kidney disease;

uncompensated heart failure;

- Postoperative period after aortocoronary shunting;

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

- chronic dyspepsia;

- III trimester of pregnancy;

lactation period.

Carefully:

- Peptic ulcer in the anamnesis, presence of an infection Helicobacter pylori;

- history of bronchial asthma;

- clinically expressed cardiovascular, cerebrovascular diseases and diseases of peripheral arteries;

- dyslipidemia, hepatic insufficiency, hyperbilirubinemia, alcoholic cirrhosis of the liver;

- chronic renal failure (CK 30-60 ml / min);

- chronic heart failure, arterial hypertension, blood diseases;

- Dehydration, diabetes mellitus;

- Smoking;

- elderly age;

- long-term use of NSAIDs, simultaneous administration of anticoagulants (including warfarin), antiaggregants (incl.clopidogrel), oral glucocorticosteroids (including prednisolone), selective serotonin reuptake inhibitors (including fluoxetine, paroxetine, citalopram, sertraline).

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%).

Prescribe the drug to pregnant women in the I and II trimesters of pregnancy is possible only if the benefits for the mother justify 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,therefore, if it is necessary to prescribe ketoprofen to the nursing mother, the question of stopping breastfeeding should be resolved.

Dosing and Administration:

Intravenous, intramuscular.

To reduce the incidence 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 to the initiation of ketoprofen administration at a dose of 200 mg / day.

Intramuscular administration: on 100 mg (1 ampoule) 1-2 times a day.

Intravenous infusion introduction ketoprofen should be administered only in a hospital setting. The duration of infusion should be from 0.5 to 1 hour. Intravenous route of administration should be applied no more than 48 hours.

Short intravenous infusion: from 100 (to 200) mg (1 - 2 ampoules) of ketoprofen diluted in 100 ml of a 0.9% solution of sodium chloride, is administered within 0.5-1 h.

Continuous intravenous infusion: from 100 (to 200) mg (1-2 ampoules) of ketoprofen diluted in 500 ml of infusion solution (0.9% solution of sodium chloride, lactate containing Ringer's solution, 5% dextrose solution), administered within 8 hours; it is possible to re-introduce after 8 hours. The maximum daily dose is 200 mg.

Ketoprofen can be combined with analgesics of central action; it can be mixed with opioids (for example, morphine) in one vial, is pharmaceutically incompatible with tramadol solution due to precipitation.

Parenteral administration of Ketonal® can be combined with the use of oral forms (tablets, capsules) or rectal suppositories.

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).

From the hemopoietic system and lymphatic system: rarely - hemorrhagic anemia, hemolytic anemia, leukopenia; frequency unknown - agranulocytosis, thrombocytopenia, impaired bone marrow function.

From the immune system: frequency unknown - anaphylactic reactions (including anaphylactic shock).

From the nervous system: often - insomnia, depression, asthenia; infrequent headache, dizziness, drowsiness; rarely - paresthesia, confusion or loss of consciousness,peripheral polyneuropathy; the frequency is unknown - convulsions, a violation of taste, emotional lability.

From the sense organs: rarely - blurred vision, tinnitus, conjunctivitis, dry eye mucosa, eye pain, hearing loss; frequency unknown - optic neuritis.

From the side of the cardiovascular system: infrequently - tachycardia; the frequency is unknown - heart failure, increased 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: often - nausea, vomiting, dyspepsia, abdominal pain, NSAIDs-gastropathy; infrequently - constipation, diarrhea, bloating, gastritis; rarely: peptic ulcer, stomatitis; very rarely: exacerbation of ulcerative colitis, Crohn's disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of the organs of the gastrointestinal tract; frequency unknown - gastrointestinal discomfort, pain in the stomach.

From the liver and bile ducts: rarely - hepatitis, increased activity of "hepatic" enzymes and bilirubin.

From the skin: infrequently - skin rash, itchy skin; 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; frequency is unknown - fluid retention in the body and as a result, weight gain, hyperkalemia.

Other: infrequently - peripheral edema, fatigue; rarely - hemoptysis, menometrorrhagia, dyspnea, thirst, muscle twitching.

Overdose:

In case of an overdose of ketoprofen, headache, 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 and supportive therapy; ketoprofen effect on the gastrointestinal tract can be reduced by means of reducing the secretion of gastric glands (e.g., proton pump inhibitors) and prostaglandins, monitoring of respiratory and cardiovascular activity, it has been detected a specific antidote, hemodialysis ineffective.

Interaction:

Undesirable combinations of drugs

Not recommended for the combined use of ketoprofen with other NSAIDs (including selective COX-2 inhibitors), salicylates in high doses, due to 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 this combination is unavoidable, the patient's condition should be carefully monitored.

With simultaneous use with lithium preparations, an increase in the concentration of lithium in the blood plasma is possible up to toxic values.The concentration of lithium in the blood plasma should be carefully monitored and the dose of lithium drugs should be adjusted in a timely manner during and after treatment with NSAIDs.

Increases hematological toxicity of methotrexate, especially when used in high doses (more than 15 mg per week). The interval between stopping or starting therapy with ketoprofen and taking methotrexate should be at least 12 hours.

Combinations that must be used with caution

On the background of therapy with ketoprofen, patients taking diuretics, especially with the development of dehydration, have a higher risk of developing renal failure due to decreased renal blood flow caused by inhibition of prostaglandin synthesis. Before starting the use of ketoprofen in these patients should be rehydration measures. After the start of treatment, it is necessary to monitor the kidney function.

Joint use of the drug with ACE inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, elderly patients) can lead to worsening of renal function impairment, including the development of acute renal failure.

During the first weeks of simultaneous use of ketoprofen and methotrexate in a dose not exceeding 15 mg / week, the 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 that need to be taken into account

Ketoprofen can reduce the effect of antihypertensive agents (beta-blockers, angiotensin-converting enzyme inhibitors, diuretics).

Simultaneous use with selective serotonin reuptake inhibitors (SSRIs) increases the risk of developing gastrointestinal bleeding.

Simultaneous use with thrombolytics increases the risk of bleeding.

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

When used simultaneously with cyclosporine, tacrolimus, the risk of developing additive nephrotoxic action is possible, especially in elderly patients.

The use of several antiplatelet agents (tirofiban, eptifimbarid, abciximab, iloprost) increases the risk of bleeding.

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

Ketoprofen can enhance the effect of oral hypoglycemic and some anticonvulsants (phenytoin).

Simultaneous application with probenecid significantly reduces the clearance of ketoprofen in the blood plasma.

Non-steroidal anti-inflammatory drugs can reduce the effectiveness of mifepristone. Admission of NSAIDs should be started no earlier than 8-12 days after the withdrawal of mifepristone.

Pharmaceutically incompatible with tramadol solution due to precipitation.

Special instructions:

With prolonged use of NSAIDs, it is necessary to periodically evaluate the clinical analysis of the blood, as well as monitor kidney and liver function, especially in elderly patients (over 65 years old), and conduct occult blood feces analysis. Care must be taken to control blood pressure more often when ketoprofen is used to treat patients,suffering from hypertension, cardiovascular diseases, which 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 there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer disease), prolonged therapy and 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 in prescribing ketoprofen to patients with cardiac or renal insufficiency, and also in the treatment of elderly patients taking diuretics and patients who, for whatever reason, experience a decrease in the volume of circulating blood (for example, after surgery).

Use of ketoprofen can affect female fertility, so patients with infertility (including passing examination) is not recommended to apply the preparation.

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

During the period of application of the drug, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:

Solution for intravenous and intramuscular injection 50 mg / ml.

Packaging:

2 ml of the drug is placed in ampoules of dark glass I of hydrolytic class with a red breaking point. On the top of the ampoule, the ring is yellow. The label is attached to the ampoule.

5 or 10 ampoules are placed in a transparent open blister or in a transparent blister covered with a white polymer film.

For 2 or 5 blisters (5 ampoules) are placed in a cardboard box together with instructions for medical use.

Five blisters (10 ampoules) are placed in a cardboard box together with instructions for medical use (for hospitals).

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013942 / 01

Date of registration:22.01.2008

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

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp23.09.2014

Illustrated instructions

Instructions

Ketonal (Ketonal)