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

Ketoprofen blocks the action of the enzyme cyclooxygenase 1 and 2 (COX-1 and COX-2) and, in part, lipoxygenase, which leads to suppression of the synthesis of prostaglandins (including 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

With intravenous administration of ketoprofen, the average 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%.

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 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 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, and in blood plasma - 0.3 μg / ml, which means that ketoprofen slower penetrates into the synovial fluid and is slowly withdrawn from it.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 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 (T1/2) 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 output slower, its T1/2 increases by 1 hour.

In patients with hepatic impairment T1/2 increases, therefore, 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, incl. inflammatory processes of various origins: rheumatoid arthritis; seronegative arthritis: ankylosing spondylitis (Bechterew's disease), psoriatic arthritis,reactive arthritis (Reiter's syndrome); gout, pseudogout; degenerative diseases of the musculoskeletal system, incl. osteoarthritis; mild, moderate and severe pain syndrome with headache, migraine, tendinitis, bursitis, myalgia, neuralgia, radiculitis; Post-traumatic and postoperative pain syndrome, incl. 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 (NSAIDs); complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis); 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 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), antiplatelet agents (incl.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 a drug to pregnant women in I and II trimesters of pregnancy is possible only if the potential benefit to the mother exceeds the potential risk to the fetus. In this case, the minimum effective dose should be applied as short a course 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,(even with 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 it is necessary to prescribe ketoprofen during breastfeeding, the question of its cessation 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 of ketoprofen should only be performed 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 0.9% sodium chloride solution, is introduced within 0.5-1 hour.

Continuous intravenous infusion: from 100 (to 200) mg (1-2 ampoules) of ketoprofen diluted in 500 ml of the infusion solution (0.9% solution of sodium chloride, 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 vial, is pharmaceutically incompatible with tramadol solution due to precipitation.

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

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); 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.

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

From the immune system

The frequency is 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 sensations, 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.

The frequency is unknown: bronchospasm (in particular, in patients with hypersensitivity to NSAIDs), rhinitis.

From the gastrointestinal tract (GIT)

Often: nausea, vomiting, dyspepsia, abdominal pain, NSAIDs-gastropathy.

Infrequent: 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.

The frequency is 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, rash, exacerbation of chronic urticaria, angioneurotic edema, erythema, bullous rashes, 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 indicators.

The 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:

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 with the help of drugs that reduce the secretion of the glands of the stomach (for example, proton pump inhibitors) and prostaglandins; monitoring of respiratory and cardiovascular activity; There is no specific antidote, hemodialysis is 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 angiotensin-converting enzyme (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, 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, 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 is necessary to periodically evaluate the clinical analysis of blood and to control the function of the kidneys and liver, especially in elderly patients (65 years), to conduct fecal occult blood. Care should be taken more frequently monitor blood pressure during application of ketoprofen to treat patients suffering from hypertension, cardiovascular diseases, which result in fluid retention. 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.

In the presence of an anamnesis contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer),prolonged therapy and the use of high doses of ketoprofen, the patient should be under close medical supervision.

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 any reason have a decrease in circulating blood volume 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 per ampoule of dark glass. 5 or 10 vials in blisters of polyvinyl chloride or polyethylene terephthalate film with a polymer film or lacquered aluminum foil or a polymer film without an aluminum foil and lacquer or in the form of cardboard with cells for stacking ampoules.

On 1 contour acheikova packing or the form from a cardboard with 10 ampoules or 2 contour cellular packings or forms from a cardboard with 5 ampoules together with the instruction on application and skarifikatorom ampulnym or without a scarifier ampullum in a pack from a cardboard.

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:LP-004570

Date of registration:06.12.2017

Expiration Date:06.12.2022

The owner of the registration certificate:GROTEKS, LLC GROTEKS, LLC Russia

Manufacturer: & nbsp

GROTEKS, LLC Russia

Information update date: & nbsp18.12.2017

Illustrated instructions

Instructions

Ketoprofen-SOLOfarm (Ketoprofen-SOLOpharm)