Artrum - 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 inhibits the synthesis of bradykinin and leukotrienes.

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

Pharmacokinetics:

Suction

When intravenous ketoprofen, the average plasma concentration after 5 minutes from the start of the 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 the 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 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and in blood plasma - 0.3 μg / ml, which means that ketoprofen slower penetrates into the synovial fluid and is slowly withdrawn from it.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, 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 of ketoprofen is 2 hours. Up to 80% of 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 is displayed more slowly, its half-life is increased by 1 hour.

In patients with hepatic impairment the elimination half-life increases, so that the accumulation of ketoprofen in tissues is possible.

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

Indications:

Symptomatic therapy of pain syndrome, including inflammatory processes of various origin:

- rheumatoid arthritis;

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

- gout, pseudogout;

- degenerative diseases of the musculoskeletal system, including osteoarthrosis;

- mild, moderate and severe pain syndrome with headache, migraine, tendinitis, bursitis, myalgia, neuralgia, radiculitis;

- post-traumatic and postoperative pain syndrome, including those accompanied by inflammation and fever;

- pain syndrome in cancer;

- 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 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 non-steroidal anti-inflammatory drugs (including in history);

- 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 hepatic impairment;

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

- Decompensated heart failure;

- Postoperative period after coronary artery bypass grafting;

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

- chronic dyspepsia;

- III trimester of pregnancy;

- the period of breastfeeding.

Carefully:

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

- bronchial asthma in history;

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

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

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

- chronic heart failure, arterial hypertension, blood diseases;

- dehydration, diabetes mellitus;

- smoking;

- elderly age;

- long-term use of non-steroidal anti-inflammatory drugs, simultaneous administration of anticoagulants (including warfarin), antiaggregants (including clopidogrel), oral glucocorticosteroids (including prednisolone), selective serotonin reuptake inhibitors (including fluoxetine, paroxetine, citalopram, sertraline) (see section "Interaction with other drugs").

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 (up to 1.5%) and congenital defects in the anterior abdominal wall. The risk increases with increasing dose and duration of treatment.

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.In this case, the minimum effective dose should be applied as short as possible.

Contraindicated in the use of ketoprofen in pregnant women during the third trimester of pregnancy because of the possible development of weakness of the uterine labor, increased bleeding time, antiaggregant effect (even when taken in small doses), as well as effects on the fetus (cardiopulmonary toxicity, including premature closure of the ductus arteriosus and pulmonary hypertension, renal dysfunction, which can progress to renal failure with development of malnutrition).

To date, there is no data on the isolation 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, 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 injection: 100 mg (1 ampoule) 1 - 2 times a day.

Intravenous infusion of ketoprofen should only be performed in a hospital setting. The duration of the 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 to 2 ampoules) of ketoprofen. diluted in 100 ml of a 0.9% solution of sodium chloride, is introduced within 0.5 - 1 hour.

Continuous intravenous infusion: 100 to 200 mg (1-2 ampoules) ketoprofen diluted in 500 ml infusion solution (0.9% sodium chloride solution, lactate-containing Ringer's solution, 5% dextrose solution) is introduced for 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 bottle.

Pharmaceutically incompatible with tramadol solution due to precipitation. Parenteral administration of the drug Arthrum 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 (≥ 100, <1/10),

- infrequently (≥ 1/1000, <1/100),

- rarely (≥ 1/10000, <1/1000),

- very rarely (<1/10000),

- frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of 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 sensations, emotional lability.

From the sense organs:

rarely: blurred vision, tinnitus, conjunctivitis, dry eye mucosa, eye pain, hearing loss;

frequency is 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 non-steroidal anti-inflammatory drugs), rhinitis.

From the gastrointestinal tract:

often: nausea, vomiting, indigestion, pain in the abdomen. 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 bile ducts:

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

From the skin:

infrequently: skin rash, itchy skin;

frequency is unknown: photosensitization, 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;

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; the effect of ketoprofen on the gastrointestinal tract can be weakened by means of reducing gastric gland secretion (for example, proton pump inhibitors) and prostaglandins, monitoring respiratory and cardiovascular activity, no specific antidote is detected, hemodialysis is ineffective.

Interaction:

Undesirable combinations of drugs

It is not recommended to use ketoprofen together with other nonsteroidal anti-inflammatory drugs (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), antiaggregants (ticlopidine, clopidogrel) increases the risk of bleeding. If this combination is unavoidable, the patient's condition should be carefully monitored.

When used simultaneously with lithium preparations it is possible to increase the concentration of lithium in the blood plasma down to toxic values. It is necessary to carefully monitor the concentration of lithium in the blood plasma and timely adjust the dose of lithium drugs during and after treatment with nonsteroidal anti-inflammatory drugs. 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 and taking methotrexate should be at least 12hours.

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 with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, elderly patients) may lead to aggravation 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, weekly blood test should be monitored. 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 weaken the action antihypertensive agents (beta-blockers, angiotensin-converting enzyme inhibitors, diuretics).

Simultaneous application with selective serotonin reuptake inhibitors increases the risk of developing gastrointestinal bleeding.

Simultaneous application with thrombolytics increases the risk of bleeding. Simultaneous application with potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs, 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, oozeosimple) 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. Admission of non-steroidal anti-inflammatory drugs 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 non-steroidal anti-inflammatory drugs, 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), and conduct 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 non-steroidal anti-inflammatory drugs, 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). The use of ketoprofen can affect female 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: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 per contour cell pack of polyvinyl chloride film. 2 contour squares are placed in a pack of cardboard.

10 ampoules per box of cardboard with a loose paper insert of a cardboard.

In each pack, the box is enclosed with instructions for use, an ampoule knife or scarifier. At packing of ampoules with a ring of a break, points and notches the knife ampullum or skarifikator do not put.

Storage conditions:

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 expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000672

Date of registration:28.09.2011 / 24.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp09.10.2017

Illustrated instructions

Instructions

Artrum (Artrum)