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

Excipients: propylene glycol 400.0 mg, ethanol 95% - 100.0 mg, benzyl alcohol 20.0 mg, 1 M sodium hydroxide solution to pH 6.5-7.5, water for injection up to 1.0 ml.

Description:

Transparent, colorless or yellowish liquid with a characteristic odor.

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), has anti-inflammatory, analgesic and antipyretic effects associated with inhibition of cyclooxygenase-1 (COX-1) activity and cyclooxygenase-2 (COX-2) regulating the synthesis of prostaglandins (Pg).

Pharmacokinetics:

Suction

When intravenous ketoprofen, the mean plasma concentration after 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%. For a single intramuscular injection 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.

Bioavailability of the drug increases linearly with increasing dose.

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 when intravenous 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, and in blood plasma - 0.3 μg / ml, which means that ketoprofen slower penetrates into the synovial fluid and is slowly withdrawn from it.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 100 mg of ketoprofen the drug is detected in the cerebrospinal fluid, like blood 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) of ketoprofen is 2 hours. Up to 80% ketoprofen is excreted by the kidneys for 24 hours, mostly (> 90%) in the form of ketoprofen glucuronide, and about 10% - through the intestines.

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

Have patients with hepatic insufficiency T_1/2 increases, so possibly accumulation in tissues.

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

Indications:

Inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid, 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, tendonitis, arthralgia, bursitis, sciatica,adnexitis, otitis media, headache and toothache, pain with oncological diseases, post-traumatic and postoperative pain syndrome, accompanied by inflammation.

Algodismenorea.

Contraindications:

Hypersensitivity (including other NSAIDs), a complete or incomplete combination of bronchial asthma, recurrent nose and paranasal sinus and intolerance of acetylsalicylic acid or other NSAIDs (including in anamnesis), peptic ulcer and 12 duodenal ulcer (exacerbation), ulcerative colitis (exacerbation), diverticulitis, peptic ulcer, hemophilia and other disorders of blood coagulation, active gastrointestinal bleeding; severe renal failure (KK less than 30 ml / min), progressive kidney disease, severe hepatic insufficiency or active liver disease, condition after aortocoronary shunting, confirmed hyperkalaemia, inflammatory bowel disease, children (under 18 years), pregnancy (III trimester) , the period of breastfeeding.

Carefully:

Anemia, bronchial asthma, alcoholism, tobacco smoking, alcoholic liver cirrhosis, hyperbilirubinemia,hepatic insufficiency, dehydration, sepsis, chronic heart failure (II-IV functional class by classification NYHA), edema, arterial hypertension, blood diseases (including leukopenia), stomatitis, coronary heart disease, cerebrovascular diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, chronic renal failure (CK 30-60 ml / min) ulcerative lesions of the gastrointestinal tract in an anamnesis, the presence of infection Helicobacter pylori, long-term use of NSAIDs, severe somatic diseases, simultaneous administration of oral glucocorticoid agents (including prednisolone), anticoagulants (including warfarin), antiaggregants (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), advanced age, pregnancy (I, II trimester), systemic lupus erythematosus and other autoimmune diseases of connective tissue.

Pregnancy and lactation:

The use of ketoprofen in the I and II trimesters of pregnancy is possible only if the potential benefit to the mother exceeds the risk to the fetus.

The use of the drug in the third trimester of pregnancy is contraindicated.

If it is necessary to use ketoprofen during breastfeeding, the question of stopping breastfeeding should be resolved.

Dosing and Administration:

Intravenous, intramuscular.

Intramuscularly (IM) - 100 mg (1 ampoule) 1-2 times a day.

Intravenous (intravenously) Infusion introduction should be carried out only in a hospital.

A short intravenous infusion: 100-200 mg (1-2 ampoules) is dissolved in 100 ml of 0.9% sodium chloride solution and injected for 0.5-1 hour; it is possible to re-introduce after 8 hours.

Continuous intravenous infusion: 100-200 mg (1-2 ampoules) is dissolved in 500 ml of the infusion solution (0.9% solution of sodium chloride, Ringer's solution, 5% dextrose solution) and injected for 8 hours; it is possible to re-introduce after 8 hours.

Because of the photosensitivity, a bottle or a plastic bag with an infusion solution of ketoprofen should be wrapped with dark paper or aluminum foil.

The maximum daily dose is 200 mg.

Ketoprofen can be used in combination with analgesics of central action; it can be mixed with morphine in one bottle.

The drug should not be taken more than 2-3 days, if necessary - use other dosage forms.

Side effects:

When assessing the incidence of adverse reactions, the following gradation was used: very often (≥10%), often (≥1%, <10%), infrequently (≥0,1%, <1%), rarely (≥0,01% <0.1%), very rarely (<0.01%), the frequency is unknown (according to available data, it is not possible to estimate the frequency of occurrence).

On the part of the hematopoiesis 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 - depression, insomnia, asthenia; infrequently - 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, dryness of the mucous membrane of the eye, pain in the eyes of hearing loss; frequency unknown - optic neuritis.

From the side of the cardiovascular system: infrequently - tachycardia; frequency unknown - heart failure, arterial hypertension, 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 biliary tract: rarely - hepatitis, increased activity of "liver" enzymes and bilirubin.

From the skin: infrequent - skin rash, itchy skin; frequency unknown - photosensitivity, alopecia, urticaria, exacerbation of chronic urticaria, Quincke's edema, 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: infrequent peripheral edema, fatigue; rarely - hemoptysis, menometrorrhagia, dyspnea, thirst, muscle twitching.

Overdose:

Symptoms: nausea, vomiting, abdominal pain, vomiting with blood, melena, impaired consciousness, respiratory depression, convulsions, impaired hepatic impairment.

In case of an overdose, symptomatic therapy, monitoring of respiratory and cardiovascular activity should be carried out, the use of H blockers₂-gistaminovyh receptors, inhibitors Pg. There is no specific antidote. Hemodialysis is ineffective.

Interaction:

Undesirable combinations of drugs

It is not recommended to use ketoprofen together with other NSAIDs (including selective inhibitors of cyclooxygenase-2), salicylates in high doses,due to increased risk of gastrointestinal bleeding and the appearance of the gastrointestinal mucosa. Simultaneous use with anticoagulants (heparin, warfarin), anti-aggregates (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 a decrease in 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 angiotensin-converting enzyme 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 at a dose not exceeding 15 mg per week, a 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, ACE 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, eptifibatide, 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.The intake 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 blood, as well as monitor kidney and liver function, especially in elderly patients (over 65 years old), to perform occult blood feces analysis.

Careful observation of patients with arterial hypertension and / or congestive heart failure is necessary, since there are reports of the development or enhancement of fluid retention in the body during therapy with ketoprofen.

During treatment with ketoprofen, monitoring of blood pressure is recommended, especially in patients with cardiovascular diseases. Patients with uncontrolled arterial hypertension, acute and severe chronic heart failure, coronary heart disease, peripheral arterial disease and / or cerebrovascular disease should be treated with care with ketoprofen. The use of some non-steroidal anti-inflammatory drugs may be associated with a risk of developing arterial thrombosis (myocardial infarction, stroke).Data to exclude such a risk for ketoprofen is not enough.

If visual disturbances are observed during treatment, treatment should be discontinued.

In patients with asthma, with chronic rhinitis, chronic sinusitis, and / or nasal polyposis, allergic reactions may occur more often than in the rest of the patients.

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.

Care should also be taken in patients with hemostatic disorders, hemophilia, Willebrand-Jurgens disease, severe thrombocytopenia, renal or hepatic insufficiency, and in those patients who take anticoagulants (coumarin and heparin derivatives, especially low molecular weight heparins).At the beginning of the treatment, close monitoring of renal function should be performed in patients with heart failure, cirrhosis and nephrosis in patients taking diuretics in patients with chronic renal failure, especially if the patient is elderly. In such patients, taking ketoprofen can cause a decrease in renal blood flow as a result of inhibition of prostaglandin and lead to renal decompensation.

Treatment with ketoprofen should be discontinued before radical surgery.

Admission ketoprofen can worsen female fertility and is not recommended for women who want to become pregnant.

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 per ampoule of neutral light-protective glass or glass of the first hydrolytic class.

5 ampoules per contour cell pack of polyvinyl chloride film.

1 or 2 contour squares are placed in a pack of cardboard.

10 ampoules are placed in a box of cardboard.

In each pack or box, put the instructions for use and the ampoule scaler.

When using ampoules with an incision, a ring of fracture or a break point, the ampoule scaper is not inserted.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003958

Date of registration:11.11.2016 / 13.09.2017

Expiration Date:11.11.2021

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Representation: & nbspPROMO-MED LLC PROMO-MED LLC Russia

Information update date: & nbsp06.01.2018

Illustrated instructions

Instructions

Ketoprofen (Ketoprofen)