Ambit

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMBIT® (AMBIT)

Composition:

Active substance: ketorolac trometamol;

One tablet contains ketorolac trometamol 10 mg;

Excipients: microcrystalline cellulose; lactose monohydrate; magnesium stearate;

film coating: hypromellose, titanium dioxide (E 171), macrogol.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white or almost white, round, biconvex tablets with a film coating.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. ATC code M01AB15.

Pharmacological properties.

Pharmacodynamics.

Ketorolac tromethamine is an analgesic agent – a non-narcotic analgesic. It is a nonsteroidal anti-inflammatory drug exhibiting potent analgesic, anti-inflammatory, and mild antipyretic activity. Ketorolac tromethamine inhibits prostaglandin synthesis and is considered a peripherally-acting analgesic. It has no known effect on opioid receptors. In controlled clinical studies, administration of ketorolac tromethamine did not result in any phenomena indicating respiratory depression. Ketorolac tromethamine does not cause miosis.

Pharmacokinetics.

Ketorolac tromethamine is rapidly and completely absorbed after oral administration, reaching a peak plasma concentration of 0.87 mg/kg within 45 minutes following a single 10 mg dose. In healthy volunteers, the mean terminal elimination half-life from plasma is approximately 5.4 hours. In elderly individuals (mean age 72 years), it is 6.2 hours. More than 99% of ketorolac in plasma is protein-bound. Ketorolac poorly penetrates into brain tissue. A negligible amount may be detected in breast milk. In healthy humans, less than 50% of the administered dose is metabolized. Major metabolites include glucuronide conjugate and 4-hydroxy-ketorolac, both of which are pharmacologically inactive. In humans, after single or multiple dosing, the pharmacokinetics of ketorolac are linear. Steady-state plasma concentrations are achieved within 1 day with administration four times daily. No changes were observed with prolonged dosing. In healthy volunteers, the terminal elimination half-life from plasma ranges from 4 to 6 hours (mean 5.4 hours). The plasma elimination half-life increases in patients with renal impairment and in elderly patients. In elderly individuals (mean age 72 years), it is 6.2 hours. After a single intravenous dose, the volume of distribution is 0.25 L/kg, the elimination half-life is 5 hours, and clearance is 0.55 mL/min/kg. The primary route of excretion of ketorolac and its metabolites (conjugates and p-hydroxy metabolites) is via urine (90%), with the remainder excreted in feces. A high-fat, difficult-to-digest meal reduces the rate of absorption but not the extent, whereas antacids do not affect ketorolac absorption.

Clinical characteristics.

Indications.

Short-term treatment of moderate-intensity pain, including postoperative pain.

Maximum duration of treatment – 5 days.

Contraindications.

• Hypersensitivity to ketorolac or to other NSAIDs or to any other component of the medicinal product;
  • hypersensitivity reactions such as bronchial asthma, rhinitis, angioneurotic edema, or urticaria in the medical history induced by acetylsalicylic acid or other NSAIDs (due to the possibility of severe anaphylactic reactions);
  • active or history of gastrointestinal bleeding or perforation associated with NSAID use;
  • active recurrent peptic ulcer/gastrointestinal bleeding (two or more episodes) in the exacerbation phase or in the medical history;
  • should not be used as an analgesic before, during, or after surgery or manipulations on coronary vessels due to inhibition of platelet aggregation, which may cause bleeding;
  • suspected or confirmed cerebrovascular hemorrhage, hemorrhagic diathesis, including coagulation disorders and high risk of bleeding, as well as in the postoperative period if there is a high risk of bleeding or incomplete hemostasis;
  • complete or partial nasal polyp syndrome, Quincke's edema, or bronchospasm;
  • concomitant therapy with other nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase inhibitors), acetylsalicylic acid, warfarin, oxpentifylline, probenecid, or lithium salts, anticoagulants, including low-dose heparin (2500–5000 units every 12 hours);
  • hematopoietic disorders of unknown etiology;
  • severe heart failure;
  • history of bronchial asthma;
  • hepatic or moderate to severe renal insufficiency (serum creatinine level >160 μmol/L);
  • risk of developing renal failure due to reduced fluid volume;
  • hypovolemia, dehydration;
  • the medicinal product is contraindicated during pregnancy, labor, and breastfeeding;
• should not be used in children and adolescents under 16 years of age.

Interaction with other medicinal products and other forms of interaction.

Ketorolac is highly bound to plasma proteins (mean value 99.2%), and the degree of binding depends on concentration.

Ketorolac should not be used simultaneously with the following.

Ketorolac should not be used together with other NSAIDs, including selective cyclooxygenase-2 inhibitors, including in patients receiving acetylsalicylic acid, due to the risk of severe adverse reactions.

Ketorolac inhibits platelet aggregation, reduces thromboxane concentration, and prolongs bleeding time. Unlike the long-term effects of acetylsalicylic acid, platelet function recovers within 24–48 hours after discontinuation of ketorolac.

Anticoagulants. Although studies have not shown a significant interaction between ketorolac and warfarin or heparin, concomitant use of ketorolac and therapies affecting hemostasis, including therapeutic doses of anticoagulants (warfarin), prophylactic low-dose heparin (2500–5000 units every 12 hours), and dextrans may increase the risk of bleeding. Concomitant use with anticoagulants (such as warfarin) is contraindicated.

Inhibition of renal clearance of lithium by some drugs that inhibit prostaglandin synthesis has led to increased plasma lithium concentration. Cases of increased plasma lithium concentration during ketorolac therapy have been reported.

Probenecid should not be administered concomitantly with ketorolac due to reduced plasma clearance and volume of distribution of ketorolac, increased ketorolac plasma concentration, and prolonged elimination half-life.

Nonsteroidal anti-inflammatory drugs should not be used within 8–12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.

If ketorolac is administered concomitantly with oxpentifylline, increased bleeding tendency may occur.

Medicinal products that should be used with caution in combination with ketorolac.

As with all NSAIDs, corticosteroids should be used concomitantly with caution due to an increased risk of gastrointestinal ulcers or bleeding. The risk of gastrointestinal bleeding is increased when NSAIDs are used in combination with antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs).

Concomitant administration of methotrexate is recommended with caution, as some prostaglandin synthesis inhibitors have been reported to reduce methotrexate clearance and thus possibly increase its toxicity.

In healthy individuals with normal blood volume, ketorolac reduces the diuretic effect of furosemide by approximately 20%. Concomitant administration with diuretics may lead to reduced diuretic effect and increased risk of NSAID nephrotoxicity.

Ketorolac should be used with caution when administered concomitantly with cyclosporine due to an increased risk of nephrotoxicity.

There is a risk of nephrotoxicity manifestation when NSAIDs are administered together with tacrolimus.

The drug should be prescribed with particular caution to patients with cardiac decompensation. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides when administered concomitantly with cardiac glycosides.

Ketorolac and other nonsteroidal anti-inflammatory drugs may reduce the effect of antihypertensive agents. When ketorolac is used concomitantly with ACE inhibitors (angiotensin-converting enzyme inhibitors) or ARBs (angiotensin receptor blockers), there is an increased risk of renal function impairment (usually reversible), especially in patients with reduced blood volume or elderly patients. Careful monitoring of renal function at the beginning of treatment and periodically during therapy is required when using such combinations in these patients.

Opioid analgesics (e.g., morphine, pethidine) can be used in parallel; ketorolac does not affect the binding of opioid drugs and does not potentiate respiratory depression or sedative effects caused by opioids. It has been demonstrated that in cases of postoperative pain, concomitant use of ketorolac with opioid analgesics reduces the need for the latter.

Oral administration of ketorolac tablets after a high-fat meal leads to reduced peak plasma concentration of ketorolac and increases the time to peak concentration by approximately 1 hour. Antacids do not affect the extent of absorption.

Patients taking NSAIDs and quinolones have an increased risk of developing seizures.

Concomitant use of NSAIDs with zidovudine increases the risk of hematological toxicity. There is an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia who are treated concomitantly with zidovudine and ibuprofen.

The following medicinal products are unlikely to interact with ketorolac.

Ketorolac did not affect the protein binding of digoxin. In vitro studies indicate that at therapeutic salicylate concentrations (300 μg/mL) and higher, ketorolac binding decreased from approximately 99.2% to 97.5%. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, paracetamol, phenytoin, and tolbutamide did not affect the protein binding of ketorolac. Since ketorolac is a highly potent drug and its plasma concentration is low, it is not expected to significantly displace other drugs bound to plasma proteins.

Studies in animals and humans have provided no evidence that ketorolac tromethamine induces or inhibits liver enzymes capable of metabolizing it or other drugs. Therefore, ketorolac is not expected to alter the pharmacokinetics of other drugs via enzyme induction or inhibition mechanisms.

Antiepileptic drugs.

Isolated cases of seizures have been reported during concomitant use of ketorolac and antiepileptic drugs (phenytoin, carbamazepine).

Psychotropic agents.

Hallucinations have been reported during concomitant use of ketorolac and psychotropic agents (fluoxetine, thiothixene, alprazolam).

Effect on laboratory test results.

Ketorolac inhibits platelet aggregation and may prolong bleeding time.

Special precautions for use.

Epidemiological data suggest that ketorolac may be associated with a higher risk of gastrointestinal toxicity compared to other NSAIDs, especially when used outside the approved indications and/or for prolonged periods.

To minimize the risk of adverse effects, ketorolac treatment should be administered for the shortest possible duration and at the lowest effective dose required to control pain. The maximum duration of treatment should not exceed 5 days.

Gastrointestinal bleeding, ulceration, and perforation.

Gastrointestinal bleeding, ulceration, or perforation, which may be fatal, have been reported during NSAID therapy at any time, with or without preceding symptoms or history of severe gastrointestinal disorders. The risk of developing severe gastrointestinal bleeding is dose-dependent. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher doses of NSAIDs, including ketorolac, particularly in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation, and in elderly patients. The risk of clinically significant bleeding episodes is dose-dependent. Such patients should be initiated on the lowest available dose. This particularly applies to elderly and debilitated patients receiving ketorolac at average daily doses exceeding 60 mg. The majority of fatal cases related to NSAID-associated gastrointestinal adverse reactions have occurred in elderly or debilitated patients. These patients should be warned to report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment. For such patients, as well as for patients concurrently using low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk, consideration should be given to concomitant use of protective agents (e.g., misoprostol or proton pump inhibitors). Ambit® should be used with caution in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents like acetylsalicylic acid. NSAIDs should be used cautiously in patients with inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis).

If gastrointestinal bleeding or ulceration occurs in patients receiving Ambit®, treatment should be discontinued.

NSAIDs, including ketorolac, may be associated with an increased risk of gastrointestinal anastomotic dehiscence. Careful medical monitoring and caution are recommended when using ketorolac after gastrointestinal surgery.

Hematological effects.

Ambit® should not be prescribed to patients with coagulation disorders. Patients receiving anticoagulant therapy may have an increased risk of bleeding when ketorolac is used concomitantly (see "Interaction with other medicinal products and other forms of interaction"). Patients receiving other drugs that may affect hemostasis should be closely monitored when ketorolac is prescribed. In controlled clinical trials, the incidence of significant postoperative bleeding was less than 1%. Ketorolac inhibits platelet aggregation and prolongs bleeding time. In patients with normal bleeding time, bleeding duration was prolonged but remained within the normal range of 2–11 minutes. Unlike the prolonged effect of acetylsalicylic acid, platelet function returns to normal within 24–48 hours after discontinuation of ketorolac. Ketorolac should not be administered to patients who have undergone surgery with a high risk of bleeding or incomplete hemostasis. Caution is advised when definitive hemostasis is critical. Hypovolemia should be corrected before initiating ketorolac therapy.

Cutaneous effects.

Severe skin reactions, sometimes fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely reported with NSAID use (see "Adverse reactions").

The risk of such reactions is higher at the beginning of treatment, with most cases occurring within the first month of therapy. Ambit® should be discontinued at the first signs of skin rash, mucosal lesions, or any other signs of hypersensitivity (see "Adverse reactions").

Increasing the dose of ketorolac tablets above the daily dose of 40 mg does not enhance efficacy but increases the risk of adverse reactions.

Ketorolac does not cause dependence, and no withdrawal syndrome has been observed upon discontinuation.

Systemic lupus erythematosus and mixed connective tissue diseases.

Patients with systemic lupus erythematosus and various mixed connective tissue diseases have an increased risk of developing aseptic meningitis.

Sodium and fluid retention and edema.

Fluid retention, hypertension, and edema have been reported during ketorolac use; therefore, the drug should be used with caution in patients with mild to moderate heart failure, arterial hypertension, or similar conditions.

Cardiovascular and cerebrovascular effects.

Patients with uncontrolled hypertension, congestive heart failure, diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be under medical supervision, as the use of the drug may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Clinical trials and epidemiological data suggest that the use of coxibs and certain NSAIDs (mainly at high doses) may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Although ketorolac treatment has not demonstrated an increased frequency of thrombotic events such as myocardial infarction, data are insufficient to exclude such a risk for trometamol ketorolac.

Cardiovascular, renal, and hepatic disorders.

Exercise caution when prescribing the drug to patients with conditions leading to reduced blood volume and/or renal blood flow, where renal prostaglandins play a supportive role in maintaining renal perfusion. Renal function should be monitored in such patients. Blood volume should be corrected, and serum urea and creatinine levels and urine output should be closely monitored until normovolemia is achieved, as there is a risk of renal failure if these recommendations are not followed. In patients undergoing dialysis, creatinine clearance was reduced by approximately half compared to normal, and the terminal elimination half-life was prolonged by about threefold. Patients with hepatic impairment due to cirrhosis showed no clinically significant changes in ketorolac clearance or terminal elimination half-life. Marginal elevations in one or more liver function tests (ALT/AST) may occur. These deviations from normal may be transient, remain unchanged, or progress with continued treatment. Ambit® should be discontinued if clinical signs and symptoms suggest liver disease or if systemic manifestations are observed.

Ketorolac should be prescribed with caution to patients with a history of cardiovascular disorders.

Renal effects.

Inhibitors of prostaglandin biosynthesis (including NSAIDs) have been reported to exert nephrotoxic effects. Exercise caution when prescribing the drug to patients with impaired renal, cardiac, or hepatic function, or with a history of kidney disease, as NSAID use may worsen renal function due to inhibition of prostaglandin synthesis (see above). Since trometamol ketorolac and its metabolites are primarily excreted via the kidneys, patients with moderate to severe renal impairment (serum creatinine > 160 µmol/L) should not take Ambit®. Patients with mild renal impairment should receive lower doses of ketorolac (not exceeding 60 mg/day intramuscularly), and renal function should be closely monitored in such patients. As with other drugs that inhibit prostaglandin synthesis, cases of increased serum urea, creatinine, and potassium have been reported during trometamol ketorolac use, which may occur after a single dose. Discontinuation of the drug usually leads to recovery of renal function.

Respiratory function impairment.

Caution is required when using the drug in patients with bronchial asthma (or a history of asthma), as NSAIDs have been reported to trigger bronchospasm in such patients.

Anaphylactic reactions.

Anaphylactic/anaphylactoid reactions (including, but not limited to, anaphylaxis, bronchospasm, flushing, rash, hypotension, laryngeal edema, and angioedema) have occurred in patients with hypersensitivity to acetylsalicylic acid or any other NSAID, or with a history of intravenous trometamol ketorolac administration. These reactions may also occur in individuals with angioedema, bronchospasm (e.g., asthma), or adenoids. Anaphylactoid reactions, such as anaphylaxis, may develop slowly. Therefore, trometamol ketorolac is contraindicated in patients with a history of asthma, nasal polyps syndrome (complete or partial), angioedema, and bronchospasm.

Effect on fertility.

The use of ketorolac, like any drug that inhibits cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended for women planning pregnancy. For women who are infertile or undergoing fertility investigations, consideration should be given to discontinuing ketorolac.

Lactose.

This medicinal product contains lactose.

If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicinal product.

Use during pregnancy or breastfeeding.

The safety of ketorolac during pregnancy in humans has not been established. Approximately 10% of ketorolac crosses the placenta.

Due to the known effects of NSAIDs on the fetal cardiovascular system (risk of premature constriction/closure of the ductus arteriosus and pulmonary hypertension), ketorolac is contraindicated during pregnancy, labor, and delivery. The safety of ketorolac use during pregnancy has not been established. No evidence of teratogenicity was observed in rats or rabbits studied at maternally toxic doses of ketorolac. In rats, prolonged gestation and/or delayed delivery were observed. Congenital abnormalities have been reported in humans following NSAID use, although their frequency is very low and no causal relationship has been established. Onset of labor may be delayed and duration prolonged due to inhibition of uterine contractility. The risk of bleeding in both mother and child is increased.

Starting from the 20th week of pregnancy, the use of ketorolac may cause oligohydramnios due to fetal renal dysfunction.

Inhibition of prostaglandin synthesis by NSAIDs in early pregnancy may lead to embryonic/fetal developmental abnormalities; cardiac malformations and gastroschisis, urinary tract disorders leading to oligohydramnios after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformation increases from less than 1% to approximately 1.5%. The risk is considered to increase with dose and duration of therapy.

Epidemiological study data indicate an increased risk of spontaneous abortion (miscarriage).

Ketorolac passes into breast milk in small amounts; therefore, Ambit® is contraindicated during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Some patients may experience drowsiness, dizziness, vertigo, insomnia, increased fatigue, visual disturbances, headache, or depression when using ketorolac. If patients experience any of these or similar effects, they should refrain from driving or operating machinery.

Method of Administration and Dosage

Tablets should preferably be taken during or after meals.

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

The total duration of treatment (parenteral administration followed by oral intake) should not exceed 5 days.

Adults.

The usual recommended dose is 10 mg every 4 or 6 hours. A daily dose exceeding 40 mg is not recommended.

If treatment follows an injectable regimen:

• For patients aged 16 to 64 years, with body weight of at least 50 kg and normal renal function – initially administer 20 mg, followed by 10 mg every time, up to 4 times daily at intervals of 4 to 6 hours;
• For patients with body weight less than 50 kg, elderly patients, or patients with impaired renal function – 10 mg up to 4 times daily at intervals of 4 to 6 hours.

For patients who have received ketorolac parenterally and then switched to oral administration, the combined dose of ketorolac should not exceed 90 mg in adults and 60 mg in elderly patients with impaired renal function or patients with body weight below 50 kg.

Patients should be switched to oral administration of the drug as early as possible.

Elderly Patients.

Elderly patients are at increased risk of developing severe complications, particularly gastrointestinal complications. During treatment with NSAIDs, patients should be monitored regularly. A longer dosing interval, e.g., 6–8 hours, is generally recommended.

Children.

Do not use in children under 16 years of age.

Overdose.

Symptoms: headache, nausea, vomiting, epigastric pain, peptic ulcers, erosive gastritis, gastrointestinal bleeding; hyperventilation, hypertension, rarely diarrhea, disorientation, excitement, coma, drowsiness, dizziness, tinnitus, loss of consciousness, seizures. In cases of severe poisoning, acute renal failure and hepatic damage may occur.

Treatment: gastric lavage, administration of activated charcoal. Adequate diuresis should be maintained. Renal and hepatic functions should be closely monitored. Patients should be observed for at least 4 hours after ingestion of a potentially toxic dose. Frequent or prolonged seizures should be treated by intravenous administration of diazepam. Other measures may be implemented depending on the patient's clinical condition. Treatment is symptomatic. There is no specific antidote. Dialysis does not remove ketorolac from the bloodstream.

Side effects.

Gastrointestinal system: peptic ulcer, gastrointestinal perforation or bleeding, sometimes fatal (especially in elderly patients), nausea, dry mouth, dyspepsia, abdominal pain, discomfort in the abdomen, spasm or burning sensation in the epigastric region, vomiting with blood, gastritis, esophagitis, diarrhea, belching, constipation, flatulence, feeling of stomach fullness, melena, rectal bleeding, stomatitis, ulcerative stomatitis, vomiting, hemorrhage, perforation, pancreatitis, exacerbation of colitis and Crohn's disease.

Blood and lymphatic system disorders: purpura, thrombocytopenia, neutropenia, agranulocytosis, aplastic and hemolytic anemia, eosinophilia.

Immune system disorders (hypersensitivity): hypersensitivity reactions have been reported, including non-specific allergic reactions and anaphylactoid reactions such as anaphylaxis, respiratory tract reactivity including asthma, worsening of asthma, bronchospasm, laryngeal edema or dyspnea, as well as various skin disorders including rashes of different types, pruritus, urticaria, flushing, purpura, angioedema, hypotension, and in isolated cases – exfoliative and bullous dermatitis (including epidermal necrolysis and erythema multiforme).

Such reactions may occur in patients with or without known hypersensitivity to ketorolac or other nonsteroidal anti-inflammatory drugs. They may also occur in individuals with a history of angioedema or bronchospastic reactivity (e.g., asthma and nasal polyps). Anaphylactic reactions can be fatal.

Metabolic and nutritional disorders: hyponatremia, hyperkalemia, anorexia.

Central nervous system and psychiatric disorders: dizziness, headache, hyperkinesia, nervousness, paresthesia, functional disturbances, depression, euphoria, seizures, difficulty concentrating, insomnia, malaise, anxiety, somnolence, increased fatigue, excitement, unusual dreams, confusion, hallucinations, dysgeusia, aseptic meningitis with corresponding symptoms (neck stiffness, headache, nausea, vomiting, fever, or disorientation), psychotic reactions, disturbances in thinking.

Eye disorders: visual disturbances, blurred vision, optic neuritis.

Ear and labyrinth disorders: hearing loss, tinnitus, vertigo.

Cardiovascular system disorders: hot flushes, bradycardia, pallor, arterial hypertension, hypotension, palpitations, chest pain, development of edema, heart failure. Clinical and epidemiological data suggest that the use of certain NSAIDs, particularly at high doses and for prolonged periods, may be associated with an increased risk of arterial thromboembolic complications (myocardial infarction or stroke). Although such reactions have not been observed with ketorolac, the risk of their occurrence cannot be excluded.

Respiratory system disorders: dyspnea, asthma, pulmonary edema.

Hepatobiliary system disorders: liver function abnormalities, hepatitis, jaundice and liver failure, hepatomegaly, disturbances in functional laboratory parameters.

Skin and subcutaneous tissue disorders: pruritus, urticaria, sweating, photosensitivity, Lyell's syndrome, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), exfoliative dermatitis, maculopapular rashes.

Musculoskeletal and connective tissue disorders: myalgia, functional disorders.

Renal and urinary system disorders: increased frequency of urination, oliguria, acute kidney failure, hemolytic uremic syndrome, flank pain (with or without hematuria), elevated serum urea and creatinine levels, interstitial nephritis, urinary retention, nephrotic syndrome, renal failure.

Reproductive system disorders: female infertility.

Other: postoperative wound bleeding, hematoma, epistaxis, prolonged bleeding time, asthenia, malaise, anorexia, weight gain, edema, elevated body temperature, increased thirst.

Reporting suspected adverse reactions

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

Shelf life. 2 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

No special storage conditions required. Keep out of reach of children.

Packaging. 10 tablets per blister. 1 or 10 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.