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

Excipients: propylene glycol 400.0 mg; ethanol 95% (in terms of 100% substance) - 100.0 mg; benzyl alcohol 20.0 mg; sodium hydroxide - up to pH 6.0-7.5; water for injection - up to 1.0 ml.

Description:Transparent colorless or with a slight yellowish tinge liquid.

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. Ketoprofen has anti-inflammatory, analgesic and antipyretic effect. Ketoprofen blocks the action of the enzyme cyclooxygenase-1 and cyclooxygenase-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

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and in blood plasma - 0.3 μg / ml, which means that ketoprofen slower penetrates into the synovial fluid and is slowly withdrawn from it.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 spinal 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 of ketoprofen is 2 hours. Up to 80% of ketoprofen is excreted by the kidneys within 24 hours, mainly (> 90%) in the form of ketoprofen glucuronide, and about 10% through the intestine.

Pharmacokinetics in special clinical cases

In patients with renal insufficiency ketoprofen is displayed more slowly, its half-life is increased by an hour. In patients with hepatic impairment the elimination half-life increases, so that the accumulation of ketoprofen in tissues is possible. Have 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 pain syndrome, incl.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, 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 polyposis nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including 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 (CK) 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;

- smoking;

- elderly age;

- long-term use of NSAIDs, simultaneous administration of anticoagulants (incl. warfarin), antiaggregants (including clopidogrel), oral glucocorticosteroids (including prednisolone), selective inhibitors re-uptake of serotonin (including fluoxetine, paroxetine, citalopram, sertraline) (see below). section "Interaction with other drugs");

- childhood;

- pregnancy and the period of breastfeeding;

- patients from the high-risk group, including those with liver disease and epilepsy, craniocerebral trauma, brain diseases.

Pregnancy and lactation:

Inhibition of prostaglandin synthesis may have an adverse effect on pregnancy and / or embryonic development. Data received during the epidemiological studies using prostaglandin synthesis inhibitors in early pregnancy confirm the increased risk of spontaneous abortion and the formation of heart defects (up to 1.5%) and congenital defects of 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, h. premature closure of the arterial duct and pulmonary hypertension, kidney dysfunction, which can progress to renal failure with the development of malnutrition).

To date, there is no data on the isolation of ketoprofen in breast milk, therefore, if it is necessary to prescribe ketoprofen to a 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 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 a 0.9% solution of sodium chloride, is introduced within 0.5 -1h.

Continuous intravenous infusion: from 100 (to 200) mg (1 - 2 ampoules) of ketoprofen diluted in 500 ml of an 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 the drug can be combined with the use of oral forms (tablets, capsules) or rectal suppositories.

Side effects:

The adverse events presented below are listed according to anatomophysiological classification and frequency of occurrence. Frequency of occurrence is determined by WHO and has the following gradation: Often ≥ 1/10); often (≥ 1/100, < 1/10); infrequently (≥ 1/1000, < 1/100); rarely (≥ 1/10000, < 1/1000); 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: the 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 unknown - convulsions, a violation of taste, emotional lability.

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

Co cardiovascular system: infrequently - tachycardia; frequency unknown - Heart failure, increased blood pressure, vasodilation.

Co of the respiratory system: rarely - exacerbation of bronchial asthma, nosebleeds, laryngeal edema; frequency unknown - bronchospasm (in particular, in patients with hypersensitivity to NSAIDs), rhinitis.

From the gastrointestinal tract: often - nausea, vomiting, dyspepsia, pain in the abdominal area, 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 unknown - gastrointestinal discomfort, pain in the stomach.

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

On the part of 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; rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values of renal function; frequency 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: symptomatic and supportive therapy; the effect of ketoprofen on the gastrointestinal tract can be weakened by means of reducing gastric gland secretion (eg proton pump inhibitors), H2 histamine receptors, prostaglandins, monitoring of 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 NSAIDs (including selective inhibitors of cyclooxygenase-2), salicylates in high doses, due to increase the risk of gastrointestinal bleeding and the appearance of the mucous membrane of the gastrointestinal tract.

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 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 and 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 in 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 ACE inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, elderly patients) may 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, 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 (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. Admission 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 the 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 more often to control blood pressure when using ketoprofen for the treatment of patients suffering from arterial 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 under close medical supervision. Because of the important role prostaglandins in the maintenance of renal blood flow should be particularly careful in the appointment of ketoprofen to patients with cardiac or renal insufficiency, as well as in the treatment of elderly patients taking diuretics and patients who, for whatever reason, there is a decrease in the volume of circulating blood (for example, after surgical intervention). The use of ketoprofen can affect women's fertility, so patients with infertility (incl.passing the examination) is not recommended to use the drug.

In each ampoule of the drug Ketoprofen contains 100 mg of ethanol.

Effect on the ability to drive transp. cf. and fur:During the treatment with ketoprofen, the speed of mental and motor reactions may be reduced, so it is necessary to refrain from driving and doing other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection 50 mg / ml.

Packaging:

2 ml per ampoule of light-protective neutral glass type I with a colored break ring or with a colored dot and a notch or without a kink ring, a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding can additionally be applied to the ampoules.

5 ampoules per circuit cell packaging made of polyvinylchloride film and aluminum foil foil or polymer film or without foil and without film.Or 5 ampoules are placed in a prefabricated form (tray) made of cardboard with cells for laying ampoules.

1, 2 or 10 contour squares or cardboard trays, together with the instruction for use and the ampoule ampoule or ampoule scarifier, or without the ampoule ampoule scraper and ampoule ampoule are placed in a cardboard package.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

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:LP-003883

Date of registration:05.10.2016

Expiration Date:05.10.2021

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

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp05.01.2018

Illustrated instructions

Instructions

Ketoprofen (Ketoprofen)