INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FASTENAL

Composition:

Active substance: ketoprofen lysine salt;

One dual-chamber sachet contains 80 mg of ketoprofen lysine salt, equivalent to 50 mg of ketoprofen;

Excipients: sorbitol (Neosorb R60) (E 420), sorbitol (Neosorb R30/R60) (E 420), povidone, colloidal anhydrous silicon dioxide, sodium chloride, sodium saccharin, ammonium glycyrrhizinate, peppermint flavor.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: homogeneous powder, white to light yellow.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Ketoprofen.

ATC code M01AE03.

Pharmacological Properties.

Pharmacodynamics.

Ketoprofen lysine salt is the lysine salt of 2-(3-benzoylphenyl)propionic acid with analgesic, anti-inflammatory, and antipyretic effects, belonging to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) (M01 AE).

Ketoprofen lysine salt is more soluble than the acid form of ketoprofen.

The mechanism of action of NSAIDs is related to the reduction of prostaglandin synthesis through inhibition of the enzyme cyclooxygenase. In particular, cyclooxygenase catalyzes the conversion of arachidonic acid into cyclic endoperoxides—PGG2 and PGH2, precursors of prostaglandins PGE1, PGE2, PGF2α, and PGD2, as well as prostacyclin PGI2 and thromboxanes (TxA2 and TxB2). Furthermore, inhibition of prostaglandin synthesis may interfere with other mediators such as kinins, causing an indirect effect that supports the direct action.

Ketoprofen lysine salt exerts pronounced analgesic and anti-inflammatory effects and also demonstrates central analgesic activity.

Ketoprofen lysine salt has antipyretic activity without disrupting normal thermoregulatory processes.

Painful inflammatory processes are eliminated or reduced, promoting joint mobility.

Pharmacokinetics.

Ketoprofen lysine salt is more soluble than the acid form of ketoprofen.

The oral formulation allows administration of the active substance dissolved in water, thereby ensuring rapid increase in its plasma concentration and, consequently, accelerating the attainment of peak concentration.

Clinically, this manifests as faster absorption and more intense analgesic and anti-inflammatory effects.

Pharmacokinetic parameters in children do not differ from those in adults.

With repeated administration, the kinetics remain unchanged and the drug does not accumulate.

Ketoprofen is 95–99% bound to plasma proteins.

High concentrations of ketoprofen have been detected in tonsillar tissue and synovial fluid following systemic administration.

The drug is rapidly eliminated from the body, primarily via the kidneys: 50% of the drug is excreted in urine within 6 hours after systemic administration.

Ketoprofen is extensively metabolized: 60–80% of the administered drug is metabolized and excreted in urine.

Clinical characteristics.

Indications.

Adults: symptomatic treatment of inflammatory conditions associated with pain in rheumatoid arthritis, ankylosing spondylitis, painful osteoarthritis, periarticular rheumatism; post-traumatic inflammation; painful inflammatory conditions in dentistry, otolaryngology, urology, and pulmonology.

Children: symptomatic short-term treatment of inflammatory conditions associated with pain and fever in the following conditions: musculoskeletal disorders, postoperative pain, and otitis.

Contraindications.

Hypersensitivity to the active substance, to other nonsteroidal anti-inflammatory drugs (NSAIDs), or to any of the excipients.
History of hypersensitivity reactions such as bronchospasm, asthma attacks, acute rhinitis, nasal polyps, urticaria, nasal polyps, angioneurotic edema, or other allergic-type reactions to ketoprofen or substances with a similar mechanism of action (e.g., acetylsalicylic acid (ASA) or other NSAIDs). Serious, rarely fatal anaphylactic reactions have been reported in such patients.
Active peptic ulcer/gastrointestinal bleeding, history of gastrointestinal ulcer, perforation (two or more confirmed cases of peptic ulcer or bleeding), or chronic dyspepsia.
History of gastrointestinal bleeding or perforation of the gastrointestinal tract wall associated with the use of NSAIDs, other active bleeding, or hemorrhagic disorders.
Crohn’s disease or ulcerative colitis.
History of bronchial asthma.
Severe heart failure.
Severe hepatic insufficiency (liver cirrhosis, severe hepatitis).
Severe renal insufficiency.
Hemorrhagic diathesis and other coagulation disorders, as well as hemostasis disorders or patients receiving anticoagulant therapy.
Leukopenia and thrombocytopenia.
Gastritis.
Intensive diuretic therapy.
Third trimester of pregnancy.
Children under 6 years of age.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of the following medicinal products is not recommended:

other NSAIDs (including selective cyclooxygenase-2 inhibitors), including salicylates in high doses (≥ 3 g/day): when used concomitantly with NSAIDs, the risk of gastrointestinal bleeding or ulcers increases due to mutual enhancement of effects;
anticoagulants (e.g., heparin and warfarin): NSAIDs enhance the effect of anticoagulants, increasing the risk of bleeding due to inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be carried out under close medical supervision with monitoring of appropriate laboratory parameters;
antiplatelet agents (e.g., ticlopidine and clopidogrel): the risk of gastrointestinal bleeding increases due to inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be carried out under close medical supervision with monitoring of appropriate laboratory parameters;
lithium: there is a risk of increased lithium levels in the blood, potentially leading to toxicity due to reduced renal excretion of lithium. If combination therapy is necessary, lithium plasma levels should be carefully monitored and after discontinuation of NSAID treatment;
methotrexate, when used in high doses, over 15 mg/week: increased risk of hematological toxicity, especially when used in high doses (> 15 mg/week), due to displacement of methotrexate from plasma protein binding and reduced renal clearance. At least 12 hours should elapse between discontinuation or initiation of ketoprofen treatment and methotrexate administration;
hydantoins and sulfonamides: the toxic effect of these substances may be increased.

Concomitant use of the following medicinal products requires caution:

drugs or categories of medicinal products that may promote hyperkalemia: some drugs or categories of medicinal products may promote hyperkalemia, e.g., potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs (NSAIDs), heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim. The occurrence of hyperkalemia may also be influenced by the presence of cofactors. The risk of developing hyperkalemia increases with concomitant use of the above-mentioned drugs;
tenofovir: concomitant use of tenofovir disoproxil fumarate and NSAIDs may increase the risk of renal failure;
corticosteroids: increased risk of gastrointestinal ulcers or bleeding;
diuretics: patients with dehydration, including severe dehydration, and those taking diuretics, are at high risk of developing secondary renal failure due to reduced renal blood flow caused by inhibition of prostaglandins. Patients should be adequately hydrated, and renal function should be monitored after initiation of combination therapy. NSAIDs may reduce the effectiveness of diuretics;
ACE inhibitors and angiotensin II antagonists: in some patients with impaired renal function (e.g., dehydrated patients or elderly patients with impaired renal function), concomitant administration of an ACE inhibitor or angiotensin II antagonist or agents that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure. Therefore, combination therapy should be used with caution, especially in elderly patients. Patients should be adequately hydrated, and renal function should be monitored after initiation of combination therapy;
methotrexate used in low doses, less than 15 mg/week: increased hematotoxicity of methotrexate should be considered due to reduced renal clearance caused by NSAIDs. Blood tests should be performed weekly during the first weeks of combination therapy. More frequent monitoring is required if there are changes in renal function, as well as in elderly patients;
pentoxifylline: increased risk of bleeding. It is important to enhance clinical monitoring and more frequently check coagulation time;
zidovudine: increased risk of hematological toxicity due to reticulocyte effects, accompanied by severe anemia occurring one week after initiation of NSAID treatment. A complete blood count and reticulocyte count should be performed one or two weeks after initiation of NSAID treatment;
sulfonylureas: NSAIDs may enhance the hypoglycemic effect of sulfonylureas by displacing their binding to plasma proteins;
cardiac glycosides: it should be noted that NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase cardiac glycoside levels; however, a pharmacotherapeutic interaction between ketoprofen and active glycosides has not been demonstrated.

Potential interactions should be considered when using the following agents:

antihypertensive agents (beta-blockers, angiotensin-converting enzyme inhibitors, diuretics): NSAIDs may reduce the effect of antihypertensive drugs by inhibiting the synthesis of vasodilatory prostaglandins;
mifepristone: the effectiveness of this contraceptive method may theoretically be reduced due to the anti-prostaglandin properties of NSAIDs, including aspirin (acetylsalicylic acid). Some data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not negatively affect the ability of mifepristone or prostaglandin to affect cervical ripening or uterine contractility and does not reduce the clinical effectiveness of the method of medical termination of pregnancy;
intrauterine contraceptive devices (IUDs): device effectiveness may decrease, thus pregnancy may occur;
thrombolytics: increased risk of bleeding;
probenecid: concomitant use of probenecid may significantly reduce the clearance of ketoprofen in plasma and, consequently, the plasma concentration of ketoprofen may be increased; this interaction occurs due to inhibition of tubular secretion and glucuronidation, requiring dose adjustment of ketoprofen;
antiplatelet agents (ticlopidine and clopidogrel) and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding;
cyclosporine, tacrolimus: risk of nephrotoxic additive effects, especially in elderly patients. Renal function should be monitored during concomitant therapy;
quinolone antibiotics: data obtained from animal studies show that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones concomitantly may be prone to an increased risk of seizures;
phenytoin and sulfonamides: since the degree of binding of ketoprofen to blood proteins is high, a reduction in the dose of phenytoin or sulfonamides may be required if they need to be administered concomitantly with ketoprofen;
gemeprost: reduced efficacy of gemeprost is observed when used concomitantly with NSAIDs;
avoid alcohol consumption.

Special precautions for use.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to relieve symptoms.

Concomitant use of ketoprofen with NSAIDs, including selective COX-2 inhibitors, should be avoided.

Gastrointestinal bleeding, ulceration, and perforation: During treatment with any NSAID, regardless of duration and presence or absence of gastrointestinal symptoms or history of serious gastrointestinal disorders, gastrointestinal bleeding, ulceration, and perforation have been reported, which may potentially result in fatal outcomes.

In elderly patients and those with a history of peptic ulcer, especially if complicated by bleeding or perforation, the risk of developing gastrointestinal bleeding, ulceration, or perforation is significantly increased when higher NSAID doses are used. Such patients should begin treatment with the lowest dose providing therapeutic effect. For these patients, as well as for patients taking low-dose aspirin or other drugs that may increase the risk of gastrointestinal disorders, consideration should be given to concomitant use of protective agents (misoprostol or proton pump inhibitors). Patients who previously experienced adverse gastrointestinal reactions, particularly elderly individuals, should report any unusual abdominal symptoms (particular attention should be paid to the risk of gastrointestinal bleeding), especially in the early stages of treatment. Patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as aspirin, should be closely monitored.

Elderly patients. Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

As with other nonsteroidal anti-inflammatory drugs, in cases of infection, the anti-inflammatory, analgesic, and antipyretic effects of ketoprofen lysine salt may mask signs and symptoms of progression of infectious diseases, such as fever.

Children. Cases of gastrointestinal bleeding, sometimes severe, and ulcer formation have been reported in some pediatric patients receiving ketoprofen lysine salt; therefore, this medication should be administered under strict medical supervision, with the physician determining the appropriate dosage each time.

Gastrointestinal disorders. Patients with current or previous gastrointestinal disorders should be closely monitored for the development of gastrointestinal disturbances, particularly gastrointestinal bleeding.

If gastrointestinal bleeding or ulceration occurs in patients taking ketoprofen lysine salt, treatment should be discontinued.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated.

According to epidemiological data, the use of ketoprofen lysine salt may be associated with a high risk of severe gastrointestinal adverse reactions, typical for other NSAIDs, especially when high doses are used.

Skin reactions.

Very rarely, serious skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been observed with the use of NSAIDs. The highest risk of such reactions occurs at the beginning of treatment. If skin rashes, mucosal lesions, or other signs of hypersensitivity appear, use of ketoprofen lysine salt should be discontinued immediately. To avoid any manifestations of hypersensitivity or photosensitivity, exposure to sunlight should be avoided during treatment.

The use of the medicinal product FASTENAL, 80 mg oral powder, does not affect the efficacy of low-calorie diets and does not interfere with principles of controlled nutrition; this medicinal product can also be prescribed to patients with diabetes.

FASTENAL, 80 mg oral powder, does not contain:

gluten, therefore this medicinal product is not contraindicated in individuals with gluten-sensitive celiac disease;
aspartame, therefore it can be prescribed to patients with phenylketonuria.

Precautions.

Hepatic and renal function disorders.

Treatment with ketoprofen in patients with impaired renal function should be carried out with particular caution, considering that this medicinal product is primarily excreted by the kidneys. Renal function should be carefully monitored at the beginning of treatment in patients with heart failure, cirrhosis, nephrotic syndrome, those taking diuretics, and patients with chronic renal insufficiency, especially in the elderly. In such patients, the use of ketoprofen lysine salt may lead to a reduction in renal blood flow, associated with prostaglandin inhibition, and may result in renal decompensation. Particular attention and a cautious approach are also required in patients undergoing diuretic therapy and in patients with a high likelihood of developing hypovolemia, as this increases the risk of nephrotoxicity.

As with treatment with most NSAIDs, an increase in blood urea nitrogen and creatinine levels is possible.

Like other inhibitors of prostaglandin synthesis, the medicinal product may negatively affect renal function, potentially leading to glomerulonephritis, renal papillary necrosis, nephrosis, and acute renal failure.

In patients with impaired liver function or a history of liver disease, transaminase levels should be continuously monitored, especially during prolonged treatment.

In patients taking NSAIDs, including ketoprofen lysine salt, an increase in one or more liver function tests, as well as a significant increase in ALT or AST, may occur. If these parameters are markedly elevated, treatment should be discontinued. Cases of jaundice and hepatitis have also been reported during treatment with ketoprofen lysine salt.

During prolonged treatment courses, liver and kidney function tests and blood analyses should be monitored.

Elderly patients are more prone to decreased renal, cardiovascular, or hepatic function.

Cardiovascular disorders.

Therapy with ketoprofen lysine salt, as with any NSAID, should be initiated only after careful assessment in patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Such an assessment is also necessary at the beginning of long-term treatment in patients at high risk of cardiovascular disorders (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Patients with a history of mild to moderate arterial hypertension and/or heart failure should start treatment cautiously, and medical consultation is required, as fluid retention and edema have been reported during NSAID therapy.

Clinical trials and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and for prolonged periods) may be associated with a moderate increase in the risk of arterial thrombosis (e.g., myocardial infarction and stroke). There are insufficient data to exclude such a risk for ketoprofen lysine salt.

An increased risk of atrial fibrillation (atrial flutter) associated with NSAID use has been reported.

Hyperkalemia may develop, particularly in patients with diabetes as the underlying condition, renal insufficiency, and/or concomitant therapy with drugs whose active substances promote hyperkalemia.

In such cases, potassium levels should be monitored.

Use with caution in patients with signs of allergy or a history of allergy.

Respiratory disorders.

The use of ketoprofen, as with all other NSAIDs, in the treatment of patients with bronchial asthma or allergic diathesis may provoke an asthmatic attack. Patients with asthma associated with chronic rhinitis, chronic sinusitis, and/or nasal polyps are at higher risk of developing allergy to acetylsalicylic acid and/or NSAIDs in general than the rest of the population.

Administration of this drug may provoke asthma attacks or bronchospasm, shock, and other allergic phenomena, especially in patients allergic to acetylsalicylic acid or NSAIDs. Due to the interaction of the drug with arachidonic acid metabolites, bronchospasm, possibly shock reactions, and other allergic phenomena may develop in asthmatics and predisposed individuals.

Visual disturbances. Treatment should be discontinued in case of visual disturbances, such as blurred vision.

Ketoprofen lysine salt should be prescribed with caution to patients suffering from hematological disorders, systemic lupus erythematosus, or mixed connective tissue diseases.

Masking symptoms of underlying infections: FASTENAL, 80 mg oral powder, may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby complicating the course of the disease. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. If FASTENAL, 80 mg oral powder, is used for fever or pain relief during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Important information about certain excipients.

The medicinal product contains sorbitol; therefore, patients with rare hereditary fructose intolerance should not take this medicinal product. If a patient has intolerance to certain sugars, they should consult a physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

Ketoprofen should be avoided during the first and second trimesters of pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development; therefore, ketoprofen lysine salt should not be taken during pregnancy.

Epidemiological data suggest an increased risk of miscarriage and congenital heart defects and abdominal wall defects after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of congenital heart defects increased from less than 1% to nearly 1.5%. It is assumed that this risk increases with higher doses and longer duration of treatment. Animal studies have shown that prostaglandin synthesis inhibitors lead to increased pre- and post-implantation losses and embryonic/fetal death. In addition, an increased incidence of various developmental abnormalities, including cardiovascular, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, the use of the medicinal product FASTENAL may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation of therapy. In addition, cases of arterial duct constriction after treatment during the second trimester of pregnancy have been reported, most of which resolved after discontinuation of treatment. Therefore, ketoprofen lysine salt should be prescribed during the first and second trimesters of pregnancy only if clearly necessary.

In women planning pregnancy or during the first or second trimester of pregnancy, the dose of ketoprofen lysine salt should be as low as possible and the duration of treatment as short as possible. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to FASTENAL for several days, starting from the 20th gestational week. Treatment with FASTENAL should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus, causing:

cardio-pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
renal dysfunction, which may progress to renal failure in the presence of oligohydramnios (see above).

Near the end of pregnancy, prostaglandin synthesis inhibitors in the mother and newborn may lead to:

possible prolongation of bleeding time and antiplatelet effect, even at very low doses;
inhibition of uterine contractions, which may lead to delayed or prolonged labor.

Use of the drug before delivery may cause changes in hemodynamics of the fetal pulmonary circulation with serious consequences for the respiratory system.

Therefore, the medicinal product is contraindicated during the third trimester of pregnancy.

Breastfeeding.

There is no information available on the passage of ketoprofen into breast milk. Ketoprofen is not recommended during breastfeeding.

Fertility.

Use of ketoprofen lysine salt, as with any other medicinal product that inhibits prostaglandin and cyclooxygenase synthesis, may impair female fertility; therefore, it is not recommended for use in women attempting to conceive.

For women experiencing difficulty conceiving or undergoing infertility investigations, use of ketoprofen lysine salt should be discontinued.

Ability to influence reaction rate when driving or operating machinery.

Patients should be aware of the possible occurrence of somnolence, dizziness, or seizures and must avoid driving or performing tasks requiring high concentration if these symptoms occur.

Dosage and Administration.

Adults: one 80 mg sachet (full dose), dissolved in 100 mL of water, stirred, and taken orally three times daily during meals.

The maximum daily dose is 200 mg of ketoprofen, corresponding to 320 mg of ketoprofen lysine salt. Before initiating treatment with a daily dose of 200 mg ketoprofen, the potential risks and expected benefits should be carefully evaluated; the use of higher doses is not recommended.

Children 6–14 years of age: contents of ½ dual-chamber sachet, 40 mg (half dose), dissolved in 100 mL of water, stirred, and taken orally three times daily during meals.

Use in children under 6 years of age is contraindicated.

Elderly patients: dosage should be carefully determined by the physician, who must assess the possibility of dose reduction as indicated below.

Patients with hepatic impairment: treatment should be initiated with the lowest daily dose.

Patients with mild or moderate renal impairment: the initial dose should be reduced, and maintenance therapy should be conducted using the lowest effective dose. Dose adjustment may be performed individually only after good tolerability of the drug has been established. Monitor diuresis and renal function.

The medicinal product must not be administered to patients with severe hepatic or renal dysfunction.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.

Instructions for use of the sachet: to obtain half a dose (40 mg), open the sachet along the line marked "half dose". To obtain a full dose (80 mg), open the sachet along the line marked "full dose". Dissolve the contents of one sachet or half a sachet in 100 mL of water and stir.

Children.

The product must not be administered to children under 6 years of age.

Overdose.

Cases of overdose with doses exceeding 2.5 g of ketoprofen lysine salt have been reported. In most cases, observed symptoms were benign and limited to lethargy, somnolence, nausea, vomiting, and epigastric pain. Symptoms of overdose may also include central nervous system disorders such as headache, dizziness, confusion, and loss of consciousness, as well as abdominal pain, nausea, and vomiting. Hypotension, respiratory depression, and cyanosis may also occur.

There is no specific antidote for overdose with ketoprofen lysine salt. In case of suspected severe overdose, gastric lavage is recommended, along with supportive or symptomatic treatment to correct fluid deficits. Renal function should be monitored, and acidosis, if present, should be corrected.

In cases of renal impairment, the drug can be removed from systemic circulation by hemodialysis.

Side effects

Experience with oral medicinal products containing lysine salt of ketoprofen indicates that adverse reactions are very rare.

Based on patient evaluations, considering the number of packages used and the number of spontaneous reports, fewer than one patient per 100,000 experienced adverse reactions. In most cases, symptoms resolved and did not recur after discontinuation of the drug; in some cases, resolution occurred after specific treatment.

Information on the adverse reactions listed below was collected during the use of lysine salt of ketoprofen in adults.

Adverse reactions are classified by frequency: 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 (cannot be estimated based on available data).

Infections and infestations: frequency unknown – aseptic meningitis, lymphangitis.

Blood and lymphatic system disorders: rare – anemia due to bleeding; frequency unknown – thrombocytopenia, agranulocytosis, medullary aplasia, hemolytic anemia, leukocytosis, lymphangitis, purpura, thrombocytopenic purpura, and leukopenia.

Immune system disorders: frequency unknown – anaphylactic reactions (including anaphylactic shock), hypersensitivity.

Metabolism and nutrition disorders: frequency unknown – hyperkalemia, hyponatremia.

Psychiatric disorders: frequency unknown – depression, confusion, mood changes, excitement, insomnia; one case of anxiety, visual hallucinations, increased excitability, and behavioral changes was reported in a child who received a dose twice the recommended amount; symptoms resolved within 1–2 days.

Nervous system disorders: uncommon – headache, dizziness, somnolence, vertigo; rare – paresthesia; very rare – dyskinesia, chills, fainting, dizziness; frequency unknown – convulsions, ageusia, dysgeusia; one case of tremor and hyperkinesia was reported in an elderly patient who was simultaneously receiving a quinolone antibiotic.

Eye disorders: rare – blurred vision; frequency unknown – periorbital edema.

Ear and labyrinth disorders: rare – tinnitus.

Cardiac disorders: frequency unknown – heart failure, atrial fibrillation, palpitations, tachycardia.

Vascular disorders: frequency unknown – hypertension, vasodilation; very rare – arterial hypotension; cases of vasculitis and skin redness have been reported in exceptional cases. Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially at high doses and for prolonged periods) may be associated with a small increase in the risk of arterial thrombosis (e.g., myocardial infarction or stroke).

Respiratory, thoracic and mediastinal disorders: rare – asthma; very rare – laryngeal edema; frequency unknown – bronchospasm (particularly in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnea, laryngospasm. One case of acute respiratory failure with fatal outcome was reported in an asthmatic patient and in a patient with known aspirin hypersensitivity. Adverse reactions were generally severe in patients with allergic reactions, particularly those suffering from asthma or known hypersensitivity to NSAIDs.

Gastrointestinal disorders: the most frequently observed adverse drug reactions are gastrointestinal events; gastric ulceration, perforation, and gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. Common – nausea, vomiting, dyspepsia, abdominal pain; uncommon – constipation, diarrhea, flatulence, gastritis, abdominal discomfort; rare – ulcerative stomatitis, gastric ulcer, colitis; frequency unknown – exacerbation of colitis and Crohn’s disease, gastrointestinal bleeding and perforation (sometimes with fatal outcome, especially in elderly patients), gastric ulcer, duodenal ulcer, heartburn, oral mucosal edema, pancreatitis, melena, hematemesis, hyperchlorhydria, stomach pain, erosive gastritis, tongue edema.

Hepatobiliary disorders: rare – hepatitis, increased transaminase levels, increased serum bilirubin due to hepatic dysfunction, jaundice.

Skin and subcutaneous tissue disorders: uncommon – pruritus, rash; frequency unknown – photosensitivity, alopecia, urticaria, angioneurotic edema, bullous dermatitis including Stevens-Johnson syndrome, Lyell’s syndrome, and toxic epidermal necrolysis, erythema, exanthema, contact eczema, maculopapular rash, purpura, acute generalized exanthematous pustulosis, dermatitis.

Renal and urinary disorders: very rare – hematuria; frequency unknown – acute renal failure, tubulointerstitial nephritis, nephritis or nephrotic syndrome, glomerular nephritis, water/sodium retention with possible development of edema, acute tubular necrosis, renal papillary necrosis, oliguria, signs of impaired kidney function, dysuria.

General disorders and administration site conditions: uncommon – edema, fatigue, peripheral edema, chills; very rare – asthenia, facial swelling; frequency unknown – allergic and anaphylactic reactions, anaphylactic shock, oral cavity edema. Isolated cases of loss of consciousness have been reported.

Laboratory abnormalities: rare – weight gain.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions. No special storage conditions are required for this medicinal product. Keep out of reach of children!

Packaging. 2 g of medicinal product, equivalent to 80 mg of lysine salt of ketoprofen, in a dual-compartment sachet made of paper/aluminum/polyethylene. 30 dual-compartment sachets with the instruction for medical use are packaged in a cardboard box.

Prescription status. Prescription only.

Manufacturer/Applicant. SPECIAL PRODUCTS LINE S.P.A., Italy / UAB "MRA", Republic of Lithuania.

Address of manufacturer and location of its place of business / address of applicant.

Via Fratta Rotonda Vado Largo, 1, Anagni (FR), 03012, Italy / Totoriu St. 20-9, LT-01121, Vilnius, Republic of Lithuania.

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