Ketonal solution for injection 50mg / ml, 2ml No. 5

Symptomatic therapy of pain syndrome, incl. with inflammatory processes of various origins:
Х rheumatoid arthritis;
Х seronegative arthritis: ankylosing spondylitis (ankylosing spondylitis), psoriatic arthritis, reactive arthritis (Reiter's syndrome);
Х gout, pseudogout;
Х degenerative diseases of the musculoskeletal system, incl. osteoarthritis;
Х weak, moderate and severe pain syndrome in case of headache, migraine, tendinitis, bursitis, myalgia, neuralgia, sciatica;
Х post-traumatic and postoperative pain syndrome, including accompanied by inflammation and fever;
Х pain syndrome in cancer;
Х algodismenorrhea.
The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.

Intravenous, intramuscular.
To reduce 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 assess the ratio of the intended benefits and risks before starting ketoprofen at a dose of 200 mg / day.
Intramuscular injection: 100 mg (1 ampoule) 1-2 times a day.
Intravenous infusion of ketoprofen should be carried out only in a hospital setting. The duration of the infusion should be from 0.5 to 1 hour. The intravenous
route of administration should be used 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% solution sodium chloride, is introduced within 0.5-1 hours.
Long-term intravenous infusion: from 100 (to 200) mg (1-2 ampoules) of ketoprofen, diluted in 500 ml of infusion solution (0.9% sodium chloride solution, lactate-containing Ringer's solution, 5% dextrose solution), is administered over 8 hours; re-introduction is possible after 8 hours. The maximum daily dose is 200 mg.
Ketoprofen can be combined with central analgesics; it can be mixed with opioids (eg morphine) in one vial, it is pharmaceutically incompatible with tramadol solution due to precipitation.
Parenteral administration of KetonalЃ can be combined with the use of oral forms (tablets, capsules) or rectal suppositories.

1 amp.

active substance: ketoprofen - 100 mg

excipients: propylene glycol - 800 mg; ethanol - 200 mg; benzyl alcohol - 40 mg; water for injection - up to 2 ml

Х hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other non-steroidal anti-inflammatory drugs (NSAIDs);
Х complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including a history);
Х peptic ulcer of the stomach or duodenum in the acute stage;
Х ulcerative colitis, Crohn's disease;
Х hemophilia and other blood clotting disorders;
Х children's age (up to 15 years old);
Х severe liver failure;
Х severe renal failure: severe renal failure (creatinine clearance (CC) less than 30 ml / min), confirmed hyperkalemia, progressive kidney disease;
Х decompensated heart failure;
Х postoperative period after coronary artery bypass grafting;
Х gastrointestinal, cerebrovascular and other bleeding (or suspected bleeding);
Х chronic dyspepsia;
Х III trimester of pregnancy;
Х the period of breastfeeding.

Carefully

Х history of peptic ulcer disease, presence of Helicobacter pylori infection;
Х history of bronchial asthma;
Х clinically pronounced cardiovascular, cerebrovascular and peripheral arterial diseases;
Х dyslipidemia, liver failure, hyperbilirubinemia, alcoholic cirrhosis of the liver;
Х chronic renal failure (CC 30-60 ml / min);
Х chronic heart failure, arterial hypertension, blood diseases;
Х dehydration, diabetes mellitus;
Х smoking;
Х elderly age;
Х long-term use of NSAIDs, concomitant use of anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), oral glucocorticosteroids (including prednisolone), selective serotonin reuptake inhibitors (including fluoxetine) , paroxetine, citalopram, sertraline) (see section 'Interaction with other medicinal products').

Trade name of the drug:

KetonalЃ.

International non-proprietary name:

ketoprofen.

Dosage form:

solution for intravenous and intramuscular administration.

Composition

1 ampoule contains:
active ingredient: ketoprofen - 100 mg;
excipients: propylene glycol - 800 mg; ethanol - 200 mg; benzyl alcohol - 40 mg; water for injection - up to 2 ml.

Description :

Transparent, colorless or slightly yellowish solution.

Pharmacotherapeutic group:

Non-steroidal anti-inflammatory drug (NSAID).

ATC code : MO1AE03 - ketoprofen.

Pharmacological properties

Pharmacodynamics
Ketoprofen is a non-steroidal anti-inflammatory drug.
Ketoprofen has anti-inflammatory, analgesic and antipyretic effects.
Ketoprofen blocks the action of the enzyme cyclooxygenase 1 and 2 (COX1 and COX2) and, in part, lipoxygenase, which leads to suppression of prostaglandin synthesis (including in the central nervous system, most likely in the hypothalamus).
Stabilizes liposomal membranes in vitro and in vivo; 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
Absorption
When administered intravenouslyof 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 ?g / ml.
Bioavailability is 90%.
With a single intramuscular injection of 100 mg of ketoprofen, the drug is found in the blood plasma 15 minutes after the start of the infusion, and the peak concentration (1.3 ?g / ml) is reached after 2 hours. The bioavailability of the drug increases linearly with increasing dose.
Distribution
Ketoprofen is 99% bound to plasma proteins, mainly to the albumin fraction. The volume of distribution in tissues is 0.1-0.2 l / kg.
Ketoprofen penetrates into the synovial fluid, and when administered intravenously100 mg after 3 hours, its concentration reaches 1.5 ?g / ml, which is 50% of the concentration in blood plasma (about 3 ?g / ml). After 9 hours, the concentration in the synovial fluid is 0.8 ?g / ml, and in the blood plasma - 0.3 ?g / ml, which means that ketoprofen penetrates into the synovial fluid more slowly and is excreted from it more slowly. Stationary plasma concentrations of ketoprofen are determined even 24 hours after its administration.
After a single intramuscular injection of 100 mg of ketoprofen, the drug is found in the cerebrospinal fluid, as well as in the blood serum, after 15 minutes.
Metabolism
Ketoprofen undergoes intensive metabolism with the participation of liver microsomal enzymes. It binds to glucuronic acid and is excreted from the body as glucuronide. There are no active metabolites of ketoprofen.
Withdrawal
The half-life (T1 / 2) 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 intestines.
In patients with renal insufficiency, ketoprofen is excreted more slowly, its T1 / 2 increases by 1 hour.
In patients with hepatic insufficiency, T1 / 2 increases, therefore, the accumulation of ketoprofen in the tissues is possible.
In elderly patients, the metabolism and excretion of ketoprofen are slower, which is of clinical importance only for patients with severe renal failure.

Application during pregnancy and during breastfeeding

Inhibition of prostaglandin synthesis can have an undesirable effect on the course of pregnancy and / or on embryonic development. The data obtained in the course of epidemiological studies with the use of inhibitors of prostaglandin synthesis in early pregnancy confirm an 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 dose and duration of treatment.
It is possible to prescribe the drug to pregnant women in the first and second trimesters of pregnancy only if the benefits to the mother justify the possible risk to the fetus. In this case, it is necessary to apply the minimum effective dose in the shortest possible course.
The use of ketoprofen in pregnant women during the third trimester of pregnancy is contraindicated due to the possible development of weakness in labor of the uterus, an increase in bleeding time, an antiplatelet effect (even when taken in small doses), as well as the effect on the fetus (cardiopulmonary toxicity, incl. including premature closure of the ductus arteriosus and pulmonary hypertension, renal dysfunction, which can progress to renal failure with the development of oligohydramnios).
To date, there are no data on the release of ketoprofen into breast milk, therefore, if it is necessary to prescribe ketoprofen to a nursing mother, the question of stopping breastfeeding should be decided.

Side effect

From the hematopoietic and lymphatic system:
rarely: hemorrhagic anemia, hemolytic anemia, leukopenia;
frequency unknown: agranulocytosis, thrombocytopenia, bone marrow dysfunction.
From the immune system:
frequency 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, impaired taste, emotional lability.
From the senses:
rarely: blurred vision, tinnitus, conjunctivitis, dryness of the mucous membrane of the eye, pain in the eyes, hearing loss;
frequency unknown: optic neuritis.
From the side of the cardiovascular system:
infrequently: tachycardia;
frequency unknown: heart failure, increased blood pressure, vasodilation.
From the respiratory system:
rarely: exacerbation of bronchial asthma, epistaxis, laryngeal edema;
frequency unknown: bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.
From the gastrointestinal tract:
often: nausea, vomiting, dyspepsia, abdominal pain, NSAID gastropathy;
infrequently: constipation, diarrhea, bloating, gastritis;
rarely: peptic ulcer, stomatitis;
very rare: exacerbation of ulcerative colitis, Crohn's disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of the gastrointestinal tract.
frequency unknown: gastrointestinal discomfort, stomach pain.
From the liver and biliary tract:
rarely: hepatitis, increased activity of 'liver' enzymes and bilirubin.
On the part of the skin:
infrequently: skin rash, itching;
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;
very rare: 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, an increase in body weight, hyperkalemia.
Other:
infrequently: peripheral edema, fatigue;
rarely: hemoptysis, menometrorrhagia, shortness of breath, thirst, muscle twitching.

Overdose

In case of an overdose of ketoprofen, headache, nausea, vomiting, abdominal pain, vomiting of blood, melena, impaired consciousness, respiratory depression, convulsions, impaired renal function and renal failure may occur.
In case of an overdose, gastric lavage and the use of activated carbon are indicated. Treatment - symptomatic and supportive therapy; the effect of ketoprofen on the gastrointestinal tract can be weakened by means that reduce the secretion of gastric glands (for example, proton pump inhibitors) and prostaglandins, monitoring of respiratory and cardiovascular activity, no specific antidote has been found, hemodialysis is ineffective.

Interaction with other medicinal products

Undesirable combinations of drugs
The combined use of ketoprofen with other NSAIDs (including selective inhibitors of cyclooxygenase-2), salicylates in high doses is not recommended, due to an 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 the use of such a combination is unavoidable, the patient's condition should be carefully monitored.
With simultaneous use with lithium preparations, it is possible to increase the concentration of lithium in the blood plasma up to toxic values. It is necessary to carefully monitor the concentration of lithium in the blood plasma and promptly adjust the dose of lithium preparations during and after treatment with NSAIDs.
Increases the hematological toxicity of methotrexate, especially when used in high doses (more than 15 mg per week). The time interval between stopping or starting therapy with ketoprofen and taking methotrexate should be at least 12 hours.
Combinations that must be used with caution
During 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 such patients, rehydration measures should be taken. After starting treatment, it is necessary to monitor kidney function.
The combined use of the drug with ACE inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, in elderly patients) can lead to an aggravation of the deterioration of renal function, including the development of acute renal failure.
During the first weeks of the simultaneous use of ketoprofen and methotrexate in a dose not exceeding 15 mg / week, a blood test should be monitored weekly. In elderly patients or if any signs of impaired renal function occur, the study should be performed more often.
Combinations to be taken into account
Ketoprofen can weaken the effect of antihypertensive drugs (beta-blockers, angiotensin-converting enzyme inhibitors, diuretics).
Concomitant use with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding.
Concomitant use with thrombolytics increases the risk of bleeding.
Concomitant use 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.
With simultaneous use with cyclosporine, tacrolimus, the risk of developing an additive nephrotoxic effect is possible, especially in elderly patients.
The use of several antiplatelet drugs (tirofiban, eptifibaride, abciximab, iloprost) increases the risk of bleeding.
Increases the concentration in blood plasma of cardiac glycosides, blockers of 'slow' calcium channels, cyclosporine, methotrexate and digoxin.
Ketoprofen may increase the effect of oral hypoglycemic and some anticonvulsants (phenytoin).
Concomitant use with probenecid significantly reduces the plasma clearance of ketoprofen.
Non-steroidal anti-inflammatory drugs can reduce the effectiveness of mifepristone. NSAIDs should be started no earlier than 8-12 days after discontinuation of mifepristone.
Pharmaceutically incompatible with tramadol solution due to precipitation.

special instructions

With long-term use of NSAIDs, it is necessary to periodically evaluate the clinical blood test, as well as monitor the function of the kidneys and liver, especially in elderly patients (over 65 years old), conduct a fecal occult blood test. Care must be taken and blood pressure should be monitored more often when using ketoprofen to treat patients with arterial hypertension, cardiovascular diseases that lead to fluid retention in the body.
In the event of violations of the organs of vision, 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 health while using the drug, you should immediately consult a doctor.
If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer), long-term therapy and the use of high doses of ketoprofen, the patient should be under close medical supervision.
Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing ketoprofen to patients with heart or renal failure, as well as when treating elderly patients taking diuretics and patients who, for any reason, have a decrease in circulating volume. blood (for example, after surgery). The use of ketoprofen can affect female fertility, therefore, the use of the drug is not recommended for patients with infertility (including those undergoing examination).

Influence on the ability to drive vehicles, mechanisms

During the period of use of the drug, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions, since the drug can cause dizziness and other side effects that may affect these abilities.