Instructions Artrocol solution for injection 100 mg/ml ampoule 2 ml No. 5
Composition
active ingredient: ketoprofen;
1 ampoule (2 ml) of solution contains 100 mg of ketoprofen;
Excipients: propylene glycol, ethanol 96%, benzyl alcohol, sodium hydroxide, sodium hydroxide or hydrochloric acid solution, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: clear, colorless or slightly yellowish solution.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ketoprofen. ATX code M01A E03.
Pharmacological properties
Pharmacodynamics
Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic effects.
During inflammation, ketoprofen inhibits the synthesis of prostaglandins and leukotrienes, inhibiting the activity of cyclooxygenase and partially lipoxygenase. It also inhibits the synthesis of bradykinin and stabilizes lysosomal membranes.
It has a central and peripheral analgesic effect and eliminates the symptoms of inflammatory and degenerative diseases of the musculoskeletal system.
In women, ketoprofen reduces the symptoms of primary dysmenorrhea due to inhibition of prostaglandin synthesis.
Pharmacokinetics
Absorption.
In most patients, after intramuscular administration, ketoprofen is detected in the blood plasma within 15 minutes, and the maximum concentration in the blood plasma is reached after 2 hours. The average concentration of ketoprofen in the blood plasma is 26.4 + 5.4 μg / ml 4-5 minutes after intravenous infusion or intramuscular administration. The bioavailability of ketoprofen in the form of a solution for injection is linearly dependent on the dose and is 90%.
Distribution.
The degree of protein binding is 99%. The volume of distribution is 0.1–0.2 l/kg. 3 hours after the administration of 100 mg of ketoprofen, its concentration in blood plasma is approximately 3 μg/ml, and the concentration in synovial fluid is 1.5 μg/ml. Although the concentration of ketoprofen in synovial fluid is somewhat lower than in blood plasma, it is more stable (after 9 hours, the concentration of ketoprofen in blood plasma is 0.3 μg/ml, and in synovial fluid - 0.8 μg/ml), so pain syndrome and joint stiffness are reduced for a long time. A stable concentration of ketoprofen in blood plasma is achieved within 24 hours after administration. In elderly patients, a stable concentration of ketoprofen in blood plasma is achieved after 8.7 hours and is 6.3 μg/ml. Cumulation of ketoprofen in tissues is not observed.
After intramuscular administration of ketoprofen at a dose of 100 mg, its concentration in blood plasma and cerebrospinal fluid was detected after 15 minutes. The maximum concentration in blood plasma was reached within 2 hours (1.3 μg/ml).
Metabolism.
Ketoprofen is extensively metabolized in the liver by microsomal enzymes and is excreted from the body as a conjugate with glucuronic acid.
Breeding.
The half-life is 2 hours. Up to 80% of the administered dose of ketoprofen is excreted in the urine, usually (more than 90%) in the form of glucuronide, approximately 10% in the feces.
Special categories of patients.
Patients with renal impairment.
In patients with impaired renal function, the elimination of ketoprofen is slowed down, the half-life increases by 1 hour.
Patients with impaired liver function.
In patients with impaired liver function, ketoprofen may accumulate in tissues.
Elderly patients.
In elderly patients, the metabolism and excretion of ketoprofen are slowed down, but this is of clinical significance only in cases of impaired renal function.
Indication
Joint diseases: rheumatoid arthritis; seronegative spondyloarthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis); gout, pseudogout; osteoarthritis; extra-articular rheumatism (tendinitis, bursitis, capsulitis of the shoulder joint).
Pain syndrome: lumbago, post-traumatic pain in joints, muscles; postoperative pain; pain with tumor metastases to the bones; algodysmenorrhea.
Contraindication
Hypersensitivity to the active substance and/or to other excipients of the medicinal product.
History of allergic conditions, such as bronchospasm, asthma attacks, urticaria, angioedema, acute rhinitis, after taking acetylsalicylic acid or other NSAIDs.
History of chronic dyspepsia.
Gastric or duodenal ulcer in the acute stage or a history of gastrointestinal bleeding, ulcers or perforation.
Cerebrovascular or other bleeding.
Tendency to hemorrhage; hemorrhagic diathesis.
Hemostatic disorders or concomitant use of anticoagulants.
Severe heart failure.
Severe liver dysfunction.
Severe renal dysfunction.
History of bronchial asthma and rhinitis.
Treatment of perioperative pain during coronary artery bypass graft surgery.
Interaction with other medicinal products and other types of interactions
The simultaneous use of ketoprofen with the following agents is not recommended.
Concomitant use of ketoprofen with such agents increases the risk of ulcers and gastrointestinal bleeding.
Anticoagulants (heparin, vitamin K antagonists (e.g. warfarin), thrombin inhibitors (e.g. dabigatran), direct factor Xa inhibitors (e.g. apixaban, rivaroxaban, edoxaban), platelet aggregation inhibitors (e.g. ticlopidine, clopidogrel)).
Concomitant use of ketoprofen with such agents increases the risk of bleeding. If such a combination cannot be avoided, close medical supervision is necessary.
Agents that bind to proteins (e.g. anticoagulants, sulfonamides, hydantoins).
When used simultaneously with such agents, dose adjustment may be necessary to prevent increased levels of these drugs due to competition for binding to blood plasma proteins.
Lithium.
Concomitant use with ketoprofen increases the risk of increased plasma lithium levels, up to toxic levels due to decreased renal lithium excretion. If concomitant use cannot be avoided, this indicator should be monitored at the beginning of treatment, during dose changes and after discontinuation of NSAIDs.
Methotrexate (when used in doses exceeding 15 mg/week).
With simultaneous use with ketoprofen, the risk of hematological toxicity of methotrexate increases due to a decrease in its renal clearance against the background of NSAID therapy. At least 12 hours should elapse between the end or start of treatment with ketoprofen and treatment with methotrexate.
Thrombolytic agents.
Concomitant use of ketoprofen with such agents may increase the risk of bleeding.
Selective serotonin reuptake inhibitors (SSRIs).
Concomitant use of ketoprofen with such agents may increase the risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").
Corticosteroids.
Concomitant use of ketoprofen with such agents increases the risk of gastrointestinal ulcers or bleeding.
Caution should be exercised when using ketoprofen with the following agents.
Diuretics.
Concomitant use of ketoprofen with such agents increases the risk of decreased renal blood flow due to prostaglandin inhibition, especially in the presence of dehydration. In the case of concomitant use of these agents, adequate hydration of the patient and monitoring of renal function at the beginning of treatment are recommended (see section "Special instructions").
ACE inhibitors and angiotensin II receptor antagonists.
With the simultaneous use of ketoprofen with such agents, the development of acute renal failure is possible in patients at risk (elderly age, dehydration, combination therapy with diuretics, impaired renal function) due to a decrease in the glomerular filtration rate (suppression of the function of vasodilator prostaglandins by NSAIDs).
Low-dose methotrexate (≤15 mg/week).
When used simultaneously with ketoprofen, the risk of hematological toxicity of methotrexate increases (reduced renal clearance of methotrexate). In the first weeks of simultaneous use, it is necessary to monitor the complete blood count weekly. In case of impaired renal function, as well as in elderly patients, careful monitoring of changes (even minor) in renal function is recommended.
Tenofovir.
When used simultaneously with ketoprofen, the risk of renal toxicity increases.
Nicorandil.
Concomitant use with ketoprofen increases the risk of serious complications, such as gastrointestinal ulcers accompanied by perforations and bleeding (see section "Special warnings and precautions for use").
Cardiac glycosides.
No pharmacokinetic interaction between ketoprofen and digoxin has been observed. However, concomitant use of these agents should be undertaken with caution, especially in patients with renal insufficiency, as NSAIDs may cause renal dysfunction and reduce renal clearance of cardiac glycosides.
Pentoxifylline.
When used simultaneously with ketoprofen, the risk of bleeding increases. In the case of simultaneous use of these drugs, monitoring of the blood coagulation system is necessary.
The need for concomitant use of ketoprofen with the following agents should be carefully considered.
Antihypertensive drugs (beta-blockers, ACE inhibitors, diuretics).
When used simultaneously with ketoprofen, the effectiveness of these agents may be reduced (due to inhibition of prostaglandin synthesis).
Cyclosporine, tacrolimus.
Concomitant use of ketoprofen with such agents may increase the risk of additive nephrotoxicity, especially in elderly patients.
Probenecid.
With simultaneous use with probenecid, a significant decrease in the clearance of ketoprofen from blood plasma is possible.
Mifepristone.
When used simultaneously with NSAIDs, the effect of mifepristone is reduced. NSAIDs, including ketoprofen, should be used 8–12 days after the end of mifepristone treatment.
Oral antidiabetic, antiepileptic drugs (phenytoin).
When used simultaneously with ketoprofen, the effect of these drugs is enhanced.
Some drugs, such as potassium salts, diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, trimethoprim can cause hyperkalemia.
The development of hyperkalemia may depend on the presence of additional factors. The risk of hyperkalemia increases with the simultaneous use of the above-mentioned drugs with ketoprofen.
Risk due to the use of antiplatelet drugs.
A number of drugs cause interactions due to the effect of inhibiting platelet aggregation. These include acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, ticlopidine, clopidogrel, tirofiban, eptifibatide, abciximab, iloprost.
Application features
Side effects of ketoprofen can be minimized by using the lowest effective dose for the shortest time necessary to control symptoms.
The drug should be used with caution in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), SSRIs or antiplatelet agents such as acetylsalicylic acid, and nicorandil (see section “Interaction with other medicinal products and other forms of interaction”).
Concomitant use of the drug with other NSAIDs, including selective COX-2 inhibitors, should be avoided.
Cases of gastrointestinal bleeding, ulceration or perforation (sometimes fatal) have been reported with all NSAIDs at various stages of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disease.
According to epidemiological data, ketoprofen may be associated with an increased risk of serious gastrointestinal adverse reactions compared to some other NSAIDs, especially at high doses (see section "Contraindications").
The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose, in patients with a history of ulcer, especially complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. In this case, treatment should be started with the lowest possible dose of ketoprofen. For such patients and patients taking low-dose acetylsalicylic acid or other agents that increase the risk of adverse reactions from the digestive tract, combination therapy with protective drugs, such as misoprostol or proton pump inhibitors, should be considered (see below and section "Interaction with other medicinal products and other forms of interaction").
Patients, especially the elderly, who have a history of adverse reactions from the digestive tract, should notify their doctor of all unusual symptoms related to the digestive system (in particular, gastrointestinal bleeding), especially in the initial stages of treatment.
In case of gastrointestinal bleeding, the drug should be discontinued. Bleeding and perforation may develop suddenly without prior symptoms.
Elderly patients have a higher incidence of adverse reactions to NSAIDs, including gastrointestinal bleeding and perforation, which can be fatal.
The drug should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as there is a risk of their exacerbation (see section "Adverse reactions").
Serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and Lyell's syndrome, have been reported very rarely with the use of NSAIDs (see section 4.8). Patients are at greatest risk of developing these reactions at the start of treatment. In most patients, they occurred within the first month of treatment. If skin rash, signs of mucosal involvement or other symptoms of hypersensitivity occur, the drug should be discontinued.
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and over a long period) may increase the risk of arterial thrombosis (e.g. myocardial infarction or stroke). There is insufficient data to exclude such a risk with ketoprofen.
At the beginning of the use of the drug, it is recommended to monitor renal function in elderly patients, patients with heart failure, cirrhosis of the liver, nephritis, chronic renal failure and patients taking diuretics. In such patients, when using ketoprofen, a decrease in renal blood flow is possible due to inhibition of the vasodilatory effect of renal prostaglandins, which can lead to decompensation of renal function.
Patients with arterial hypertension and/or mild to moderate heart failure require close medical supervision, as fluid retention in the tissues and edema have been observed during treatment with NSAIDs.
Patients with uncontrolled arterial hypertension, chronic heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should use the drug only after careful examination. Before starting long-term use of the drug, patients with risk factors such as hyperlipidemia, diabetes mellitus or smoking should also undergo a careful examination.
Ketorolac may mask the symptoms of an infectious disease, which may delay the initiation of appropriate treatment and thereby complicate the course of the disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. In the case of use of the drug for fever or for pain relief in an infection, monitoring of the infectious disease is recommended. In the context of treatment outside a medical institution, the patient should consult a doctor if symptoms persist or worsen.
The use of the drug should be discontinued before major surgical interventions.
In patients with impaired liver function or a history of liver disease, periodic monitoring of transaminase levels is necessary, especially with long-term use of the drug.
Ketoprofen may impair female fertility and is therefore not recommended for use in women attempting to conceive. Women who have difficulty conceiving or are undergoing investigation for infertility should consider discontinuing ketoprofen.
Patients with asthma in combination with chronic rhinitis, chronic sinusitis and/or nasal polyps are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs than other patients. The use of the drug may cause asthma attacks or bronchospasm, especially in patients with allergy to acetylsalicylic acid or NSAIDs.
The drug should be used with caution in patients with hemostasis disorders, hemophilia, von Willebrand disease, severe thrombocytopenia, renal or hepatic insufficiency, as well as in individuals taking anticoagulants (coumarin and heparin derivatives, mainly low molecular weight heparins).
During the use of the drug, careful monitoring of diuresis and renal function is necessary in patients with impaired liver function, in patients receiving diuretics, in hypovolemia due to major surgery, especially in elderly patients.
The relative risk of gastrointestinal bleeding is higher in patients with low body weight. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued immediately.
With prolonged use of the drug, the number of formed blood elements, as well as liver and kidney function should be monitored. If creatinine clearance is below 0.33 ml/s (20 ml/min), the dose of ketoprofen should be adjusted.
For severe pain, the drug can be used simultaneously with morphine by intravenous administration.
Hyperkalemia may develop during the use of ketoprofen, especially in patients with diabetes, renal insufficiency and/or concomitant therapy with drugs that promote hyperkalemia. In such cases, regular monitoring of plasma potassium levels should be performed.
Precautions related to excipients.
Each ampoule of the medicinal product contains 8 vol.% ethanol, i.e. 197.2 mg per dose, which is equivalent to 4 ml of beer or 1.6 ml of wine. The medicinal product may have a negative effect on persons suffering from alcoholism, therefore it should be used with caution in such patients. The ethanol content should be taken into account when using the medicinal product in the 1st and 2nd trimesters of pregnancy, during breastfeeding, in children and patients at risk, for example, with liver diseases, as well as patients with epilepsy.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially sodium-free.
The medicinal product contains 800 mg of propylene glycol in 1 ampoule (2 ml), which corresponds to 400 mg/ml.
The drug contains 40 mg of benzyl alcohol in 1 ampoule, which may cause allergic reactions. In large quantities, it can also accumulate in the body and cause the development of adverse reactions (metabolic acidosis).
Use during pregnancy or breastfeeding
Pregnancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. Epidemiological studies have shown that the use of drugs that inhibit prostaglandin synthesis in early pregnancy increases the risk of miscarriage, fetal heart defects and anterior abdominal wall nonunion. Thus, the absolute risk of developing cardiovascular anomalies increased from <1% to approximately 1.5%. It is believed that the risk of such phenomena increases with increasing dose and duration of therapy. The use of prostaglandin synthesis inhibitors in animals caused an increase in pre- and post-implantation losses and increased embryo-fetal lethality. In addition, in animals treated with prostaglandin synthesis inhibitors during organogenesis, the incidence of fetal malformations, including cardiovascular anomalies, increased.
Use of ketoprofen from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation of the drug. In addition, cases of ductus arteriosus narrowing have been reported following treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment.
The use of the drug in the I-II trimester of pregnancy is possible only in case of extreme necessity. When using ketoprofen to a woman planning a pregnancy, or during the I and II trimesters of pregnancy, the minimum possible dose and duration of therapy should be observed.
Antenatal monitoring for oligohydramnios and narrowing of the ductus arteriosus should be considered in case of exposure to ketoprofen for several days starting from the 20th week of gestation. The drug should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected.
During the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may have the following effects on the fetus:
cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction, which may progress to renal failure with oligohydramnios (see above);
for the pregnant woman and fetus at the end of pregnancy:
possible increase in bleeding duration, decrease in platelet aggregation ability, even when using very low doses;
suppression of uterine contractile function, which can lead to an increase in the duration of labor.
The use of the drug in the third trimester of pregnancy is contraindicated.
Breastfeeding period.
There are no data on the excretion of ketoprofen into breast milk. The drug is not recommended for use during breastfeeding, as the safety of ketoprofen during lactation has not been proven.
Ability to influence reaction speed when driving vehicles or other mechanisms
Until the individual reaction to the drug is determined (dizziness, drowsiness, seizures, and visual disturbances may occur), it is recommended to refrain from driving or operating other mechanisms.
Method of administration and doses
The drug is intended for intravenous and intramuscular administration.
The dosage should be selected individually, depending on the patient's condition and response to treatment.
Intramuscular injection.
The drug should be used in a dose of 100 mg (1 ampoule) 1–2 times a day. The maximum daily dose should not exceed 200 mg.
If necessary, intramuscular administration can be supplemented with the use of oral or rectal forms of ketoprofen.
Intravenous administration.
The drug should be administered as an infusion only in a hospital setting. The infusion should be carried out within 0.5–1 hour, the course of treatment with intravenous administration should not exceed 48 hours. The maximum daily dose is 200 mg.
Intermittent intravenous infusion: 100–200 mg of ketoprofen should be dissolved in 100 ml of 0.9% sodium chloride solution and administered over 0.5–1 hour. The maximum daily dose is 200 mg.
Continuous intravenous infusion: 100–200 mg of ketoprofen dissolved in 500 ml of infusion solution (0.9% sodium chloride solution, lactated Ringer's solution, glucose solution) and administered over 8 hours. The maximum daily dose is 200 mg.
Caution: vials with infusion solution should be wrapped in dark paper or aluminum foil, as ketoprofen is sensitive to light.
Tramadol and ketoprofen should be administered separately, as a precipitate may form when mixed.
The duration of treatment depends on the severity and course of the disease, however, adverse reactions to ketoprofen can be minimized by using the lowest effective dose for the shortest possible time (see section "Special instructions").
To prevent the negative effects of ketoprofen on the mucous membranes of the digestive tract, antacids can be taken simultaneously.
Simultaneous use with other agents.
Ketoprofen can be used together with centrally acting analgesics; it can be mixed with morphine in one vial: 10–20 mg of morphine and 100–200 mg of ketoprofen are dissolved in 500 ml of infusion solution (0.9% sodium chloride solution or lactated Ringer's solution). The maximum daily dose is 200 mg.
Special categories of patients.
Elderly patients are at increased risk of adverse reactions to ketoprofen. After 4 weeks of treatment, the patient should be monitored for gastrointestinal bleeding. It is recommended to start with the lowest dose in order to keep patients on the lowest effective dose.
Patients with renal impairment.
In patients with moderate renal impairment with creatinine clearance less than 0.33 ml/s (20 ml/min), the dose of ketoprofen should be reduced. Ketoprofen is contraindicated in patients with severe renal impairment.
Patients with impaired liver function.
The dose of ketoprofen should be reduced in patients with chronic liver disease and low plasma albumin levels. Ketoprofen is contraindicated in patients with severe hepatic impairment.
Children
The medicine should not be used in children under 18 years of age.
Overdose
Symptoms: headache, drowsiness, nausea, vomiting, epigastric pain, bloody vomiting, diarrhea, black stools, impaired consciousness, respiratory depression, shortness of breath, convulsions, dizziness, arterial hypotension, decreased renal function and renal failure, gastrointestinal bleeding.
Treatment.
In case of overdose, immediate inpatient treatment should be carried out: gastric lavage and administration of activated charcoal. Further therapy is symptomatic. H2-receptor antagonists, proton pump inhibitors and prostaglandins alleviate the dangerous effects of ketoprofen on the digestive tract. There is no specific antidote.
Side effects
Adverse reactions of ketoprofen are classified as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); unknown (frequency cannot be estimated from the available data).
Side effects are usually transient. The most common side effects are gastrointestinal disorders.
From the blood and lymphatic system:
Infrequently - hemorrhagic anemia, hemolysis, purpura, thrombocytopenia, agranulocytosis, leukopenia; unknown - hemolytic anemia.
High doses of ketoprofen may inhibit platelet aggregation, thereby prolonging bleeding time, and cause nosebleeds and hematoma formation.
On the part of the immune system:
Rare: exacerbation of bronchial asthma; unknown: bronchospasm or shortness of breath (especially in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs), angioedema and anaphylaxis, anaphylactic reactions, including shock.
Metabolism and nutrition: unknown - hyponatremia, hyperkalemia (see sections "Special instructions for use" and "Interaction with other medicinal products and other types of interactions").
From the psyche:
often - depression, nervousness, nightmares, drowsiness; rarely - delirium with visual and auditory hallucinations, disorientation, speech disorders, mood changes.
From the nervous system:
infrequently - headache, asthenia, discomfort, fatigue, weakness, drowsiness; rarely - paresthesia; unknown - aseptic meningitis, convulsions, dizziness; there have been isolated reports of cases of pseudotumor cerebri.
On the part of the organs of vision:
often - visual impairment (see section "Special instructions for use"); rarely - blurred vision, conjunctivitis.
On the part of the hearing organs:
often - tinnitus.
From the cardiovascular system:
often - edema; infrequently - heart failure, arterial hypertension; unknown - vasculitis (including leukocytic vasculitis).
Clinical trials and epidemiological data suggest that some NSAIDs (especially at high doses and in long-term use) may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction and stroke). There are insufficient data to exclude such a risk with ketoprofen (see section 4.4).
From the respiratory system, chest organs and mediastinum:
infrequently - hemoptysis, shortness of breath, pharyngitis, rhinitis, bronchospasm (especially in patients with hypersensitivity to acetylsalicylic acid or other NSAIDs), laryngeal edema (signs of anaphylactic reaction); rarely - attacks of bronchial asthma.
From the digestive tract:
very often - dyspepsia; often - nausea, abdominal pain, diarrhea, constipation, flatulence, anorexia, vomiting, stomatitis, gastritis;
not known – colitis, intestinal perforation (as a complication of diverticula), melena, hematemesis, stomatitis, gastric or duodenal ulcer, exacerbation of ulcerative colitis or Crohn's disease, enteropathy with perforation, stenosis, pancreatitis. Peptic ulcers, perforation or gastrointestinal bleeding may occur. Enteropathy may be accompanied by minor bleeding with protein loss. Gastrointestinal discomfort, stomach pain, and in rare cases, colitis have been observed.
There have been reports of a case of rectal perforation in an elderly woman.
Ulceration, hemorrhage, or perforation may develop in 1% of patients after 3–6 months of treatment or in 2–4% of patients after 1 year of treatment with NSAIDs.
From the hepatobiliary system:
unknown - severe liver dysfunction accompanied by jaundice and hepatitis.
Common: skin rash, pruritus; uncommon: alopecia, eczema, purpura-like rash, increased sweating, urticaria, exacerbation of chronic urticaria, exfoliative dermatitis; rare: photosensitivity, photodermatitis; not known: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis.
From the kidneys and urinary tract:
not known - acute renal failure, interstitial nephritis, nephrotic syndrome, acute pyelonephritis, organic kidney damage, acute tubular necrosis, acute papillary necrosis; fluid/sodium retention, hyperkalemia (see sections "Special warnings and precautions for use" and "Interaction with other medicinal products and other types of interactions").
From the reproductive system:
infrequently - menometrorrhagia.
Laboratory indicators:
very often - deviations from the norm of liver transaminase levels (ALT, AST), increased bilirubin levels in blood plasma.
On the part of the body as a whole and reactions at the injection site:
uncommon - burning sensation and/or pain at the injection site, swelling; unknown - injection site reaction known as Nicolau syndrome.
Ketoprofen reduces platelet aggregation, thereby prolonging bleeding time.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions that occur after the registration of a medicinal product is very important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in a place inaccessible to children.
Incompatibility
Tramadol and ketoprofen should not be mixed in the same bottle due to the formation of a precipitate.
Packaging
2 ml of solution in a glass ampoule; 5 ampoules in a contour blister pack; 1 or 2 contour blister packs in a cardboard box.
Vacation category
According to the recipe.
Producer
K.O. Rompharm Company SRL, Romania/SC Rompharm Company SRL, Romania.
Location of the manufacturer and address of its place of business
Otopeni city, Eroilor str. № 1A, 075100, jud. Ilfov, Romania.
Applicant
WORLD MEDICINE LLC, Ukraine/WORLD MEDICINE LLC, Ukraine.
