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

Ketoprofen is a non-steroidal anti-inflammatory drug, a derivative of propionic acid. Has anti-inflammatory, analgesic and antipyretic effects associated with the suppression of cyclooxygenase (COX1 and COX2) activity regulating the synthesis of prostaglandins (Pg).

Pharmacokinetics:

Suction

With intravenous administration of Ketoprofen, the average plasma concentration 5 minutes from the start of infusion and up to 4 minutes after its termination is 26.4 ± 5.4 μg / ml. Bioavailability is 90%.

With a single intramuscular injection of 100 mg of Ketoprofen, the drug is detected in the blood plasma 15 minutes after the start of the infusion, and a peak concentration (1.3 μg / ml) is achieved after 2 hours. The bioavailability of the drug increases linearly with increasing dosage.

Distribution

Ketoprofen is 99% bound to blood plasma proteins, mainly with the albumin fraction. The volume of distribution in tissues is 0.1-0.2 l / kg.

Ketoprofen penetrates into the synovial fluid, and after intravenous administration of 100 mg after 3 hours its concentration reaches 1.5 μg / ml, which is 50% of the concentration in the blood plasma (about 3 μg / ml). After 9 hours, the concentration in the synovial fluid is 0.8 μg / ml, in blood plasma - 0.3 μg / ml, which means that ketoprofen slower penetrates into the synovial fluid and is slowly withdrawn from it. Stationary plasma concentrations of Ketoprofen are determined even after 24 hours after its administration.

After a single intramuscular injection of 100 mg of Ketoprofen, the drug is detected in the cerebrospinal fluid, as in serum, after 15 minutes.

Metabolism

Ketoprofen undergoes intensive metabolism involving microsomal liver enzymes. It binds to glucuronic acid and is excreted from the body in the form of glucuronide.There are no active metabolites of ketoprofen.

Excretion

The half-life (T_1/2) Ketoprofen is 2 hours. Up to 80% Ketoprofen is excreted by the kidneys within 24 hours, mostly (90%) in the form of ketoprofen glucuronide, and about 10% through the intestine.

In patients with renal insufficiency Ketoprofen output slower, its T_1/2increases by 1 hour.

In patients with hepatic impairment T_1/2 increases, therefore, the accumulation of Ketoprofen in tissues is possible.

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

Indications:

Inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid and psoriatic arthritis, Bechterew's disease (ankylosing spondylitis), gouty arthritis, osteoarthritis. It is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Pain syndrome: myalgia, ossalgia, neuralgia, tendinitis, arthralgia, bursitis, sciatica, adnexitis, otitis media, headache and toothache, with oncological diseases,post-traumatic and post-operative pain, accompanied by inflammation.

Algodismenorea.

Contraindications:

Hypersensitivity to ketoprofen or other components of the drug as well as salicylates and other nonsteroidal anti-inflammatory drugs.

Full or partial combination of asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including history), gastric ulcer and duodenum 12 (exacerbation), ulcerative colitis (exacerbation) Crohn's disease, diverticulitis, peptic ulcer, hemophilia and other coagulation disorders, active gastrointestinal bleeding; severe renal impairment (creatinine clearance less than 30 mL / min), progressive renal disease, severe liver failure or active liver disease, condition after coronary bypass, confirmed hyperkalemia, inflammatory bowel disease, III trimester of pregnancy, lactation, infancy (up 15 years).

Carefully:

Bronchial asthma, tobacco smoking, anemia, alcoholism, alcoholic liver cirrhosis, hyperbilirubinemia, hepatic insufficiency, chronic renal failure (creatinine clearance 30-60 ml / min), dehydration, sepsis, chronic heart failure, edema, arterial hypertension, stomatitis, blood diseases including leukopenia), ischemic heart disease, cerebrovascular diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, peptic ulcer lesions in the anamnesis, peripheral arterial disease infection Helicobacter pylori, severe somatic diseases, long-term use of NSAIDs, simultaneous use of oral glucocorticosteroid agents (including prednisolone), anticoagulants (including warfarin), antiaggregants (including clopidogrel), selective serotonin reuptake inhibitors (in t citalopram, fluoxetine, paroxetine, sertraline), advanced age, systemic lupus erythematosus and other autoimmune connective tissue diseases, chronic heart failure (II-IV functional class by classification NYHA).

Pregnancy and lactation:

Application of the drug Ketoprofen in the III trimester of pregnancy is contraindicated. In I and II trimester of pregnancy, the drug is possible in cases where 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 as short a course and only under the supervision of a doctor.

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

Dosing and Administration:

Intravenous (drip), intramuscularly.

To achieve 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 the start of taking Ketoprofen at a dose of 200 mg / day.

Intramuscular injection

Intramuscularly for 100 mg 1-2 times a day. Ketoprofen injected deeply, slowly into the upper outer square of the buttocks, under strictly aseptic conditions. Subsequent injections are injected alternately into both buttocks.

Intravenous administration

Intravenous infusion of ketoprofen should only be performed in a hospital setting.

Short intravenous infusion: from 100 to 200 mg of Ketoprofen diluted in 100 ml of 0.9% sodium chloride solution and injected for 0.5-1 hour; the administration can be repeated every 8 hours for no more than 48 hours.

Continuous intravenous infusion: from 100 to 200 mg of Ketoprofen is diluted in 500 ml of a solution for infusions (0.9% solution of sodium chloride, lactate-containing Ringer's solution, 5% dextrose solution); is introduced within 8 hours; administration can be repeated every 8 hours, for no more than 24 hours.

Treatment with the drug should not exceed 2-3 days.

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

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

Elderly patients: the minimum effective dose is recommended. Patients should be observed regularly.possibly gastrointestinal bleeding during therapy with NSAIDs.

Patients with renal insufficiency the minimum effective dose is recommended, then adapted depending on renal tolerance.

Due to Ketoprofen is sensitive to light, the vial or infusion bag must be covered with black paper or aluminum foil.

Side effects:

According to the World Health Organization (WHO), unwanted 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), the frequency is unknown (the frequency of occurrence of phenomena can not be determined from the available data).

On the part of the hematopoiesis and lymphatic system:

rarely: hemorrhagic anemia, hemolytic anemia, leukopenia;

frequency is unknown: agranulocytosis, thrombocytopenia, impaired bone function the brain.

From the immune system:

frequency is 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 is unknown: convulsions, a violation of taste, emotional lability.

From the sense organs:

rarely: blurred vision, tinnitus, conjunctivitis, dryness of the eye mucosa, pain in the eyes, hearing loss;

frequency unknown: optic neuritis.

From the side of the cardiovascular system:

infrequently: tachycardia;

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

From the respiratory system:

rarely: exacerbation of bronchial asthma, nosebleeds, laryngeal edema;

frequency is 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;

rarely: exacerbation of ulcerative colitis, Crohn's disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of the organs of the gastrointestinal tract;

frequency is unknown: gastrointestinal discomfort, pain in the stomach.

From the liver and biliary tract:

rarely: hepatitis, increased activity of "hepatic" enzymes and bilirubin.

From the skin:

infrequently: skin rash, itchy skin;

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

From the urinary system:

rarely: cystitis, urethritis, hematuria;

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:

Overdose was detected in doses greater than 2.5 g of Ketoprofen.

Symptoms

Appear in the form of increased dose-dependent side effects: convulsions, a feeling of heaviness in the legs, high blood pressure,ringing in the ears, blurred vision, rash, nausea, vomiting, epigastric pain, diarrhea, gastrointestinal bleeding, headache, dizziness, incoherence (confusion), confusion, drowsiness, convulsions, coma, respiratory depression.

Treatment

Symptomatic is not known specific antidote for Ketoprofen. Conduct appropriate hydration, observe renal clearance and correct acidosis. If necessary, apply hemofiltration.

Interaction:

Undesirable combinations of drugs

Not recommended combined use of ketoprofen with other NSAIDs (including selective inhibitors of cyclooxygenase-2), salicylates in high doses, due to increased risk of gastrointestinal bleeding and ulceration of the gastrointestinal mucosa.

Simultaneous application 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 application with lithium preparations it is possible to increase the concentration of lithium in the blood plasma down 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 hematologic toxicity methotrexate, especially when used in high doses (more than 15 mg per week). The interval between stopping or starting therapy with ketoprofen with taking methotrexate should be at least 12 hours.

Combinations that must be used with caution

Against 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 from ACE inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration,elderly patients) can lead to aggravation of renal function impairment, incl. to 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, weekly blood test should be monitored. In elderly patients or if there are any signs of impaired renal function, you should perform the test more often.

Combinations that need to be taken into account

Ketoprofen can weaken the action gand pototenzivnyh funds (beta-blockers, angiotensin converting enzyme inhibitors, diuretics).

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

Simultaneous application with thrombolytics increases the risk of bleeding.

Simultaneous application 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.

When used simultaneously with cyclosporin, tacrolimus there is a risk of developing additive nephrotoxic action, especially in elderly patients.

Application of several antiplatelet agents (tirofiban, eptifibyrid, abciximab, iloprost) increases the risk of bleeding.

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

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

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

Nonsteroidal anti-inflammatory drugs can reduce the effectiveness mifepristone. The intake of NSAIDs should be started no earlier than 8-12 days after the withdrawal of mifepristone.

Pharmaceutically incompatible with solution tramadol because of precipitation.

Special instructions:

With prolonged use of NSAIDs, it is necessary to periodically evaluate the clinical analysis of blood, as well as monitor kidney and liver function, especially in elderly patients (over 65 years old), to perform occult blood feces analysis.

It is necessary to be careful and to control 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 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, 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 into the ampoules of the light-protective glass.

5 ampoules are placed in a contour cell box made of a polyvinylchloride (PVC) film or a polyethylene terephthalate (PET) film.

For 1 or 2 contour mesh packages together with the instruction for use and the ampoule scarifier are placed in a cardboard pack.

For 5 or 10 ampoules, together with the instructions for use and the ampoule scarifier, are placed in a cardboard box with a corrugated liner.

When using ampoules with a dot or a ring of fracture, the ampoule scaper is not inserted.

Packing for hospitals. For 4, 5 or 10 contour packagings together with instructions for use in an amount equal to the number of contiguous cell packs, put in a pack of cardboard for consumer containers.

For 50 or 100 contour mesh packages, together with instructions for use in an amount equal to the number of contour mesh packages, are placed in a box of corrugated 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:

4 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003911

Date of registration:19.10.2016

Expiration Date:19.10.2021

The owner of the registration certificate:ELLARA, LTD. ELLARA, LTD. Russia

Manufacturer: & nbsp

ELLARA, LTD. Russia

Information update date: & nbsp06.01.2018

Illustrated instructions

Instructions

Ketoprofen (Ketoprofen)