Ketolac

Ukraine
Brand name Ketolac
Form tablets
Active substance / Dosage
ketorolac · 10 mg
Prescription type prescription only
ATC code
M01AB15
Registration number UA/4802/01/01
Manufacturer JSC "Kyiv Vitamin Plant"
Ketolac tablets

Table of Contents

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT KETOLAC (KETOLAC)

Composition:

Active substance: 1 tablet contains ketorolac tromethamine 10 mg;

Excipients: lactose monohydrate; microcrystalline cellulose; potato starch; colloidal anhydrous silicon dioxide; magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, biconvex tablets, white or almost white in color.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents.

ATC code M01AB15.

Pharmacological Properties.

Pharmacodynamics.

Ketorolac tromethamine is an analgesic – a non-narcotic analgesic agent. It is a nonsteroidal anti-inflammatory drug exhibiting strong analgesic and anti-inflammatory effects, as well as 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 respiratory depression. Ketorolac tromethamine does not cause pupillary constriction.

Pharmacokinetics.

Ketorolac tromethamine is rapidly and completely absorbed after oral administration, with peak plasma concentration of 0.87 mg/kg reached within 45 minutes after 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 penetrates poorly into brain tissue. A small amount may be detected in breast milk. In healthy humans, less than 50% of the administered dose is metabolized. Major metabolites include glucuronide conjugates and 4-hydroxy-ketorolac, both 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 accumulation occurs with prolonged use. 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, 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-hydroxymetabolites) is via urine (90%), with the remainder excreted in feces. A high-fat, difficult-to-digest meal reduces the rate but not the extent of absorption, 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 nonsteroidal anti-inflammatory drugs (NSAIDs) or to any component of the medicinal product;
  • History of hypersensitivity reactions such as bronchial asthma, rhinitis, angioneurotic edema, or urticaria 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 or recurrent peptic ulcer/gastrointestinal bleeding (two or more episodes) in exacerbation or in history;
  • Do not use as an analgesic before and during surgical procedures and after 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; also do not use 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 impairment (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;
  • Not to be used in children and adolescents under 16 years of age.

Interaction with other medicinal products and other types of interactions.

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

Do not use simultaneously with ketorolac.

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 prolonged effects of acetylsalicylic acid, platelet function recovers within 24–48 hours after discontinuation of ketorolac.

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

Renal clearance of lithium may be reduced by some drugs that inhibit prostaglandin synthesis, leading to increased plasma lithium concentration. Cases of elevated plasma lithium concentration during ketorolac therapy have been reported.

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

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

When ketorolac is administered concurrently with oxpentifylline, increased tendency to bleeding is observed.

Medicinal products to be used with caution in combination with ketorolac.

As with all NSAIDs, corticosteroids should be used concomitantly with caution due to 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.

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

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

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

The medicinal product should be administered with particular caution in 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 angiotensin receptor blockers (ARBs), there is an increased risk of renal dysfunction (usually reversible), especially in patients with reduced blood volume or elderly patients. In such cases, careful monitoring of renal function is required at the beginning of treatment and periodically during therapy.

Opioid analgesics (e.g., morphine, pethidine) may be used in parallel; ketorolac does not affect 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 resulted in reduced peak plasma concentration of ketorolac and increased 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 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.

It is unlikely that the following medicinal products interact with ketorolac.

Ketorolac did not affect protein binding of digoxin in plasma. In vitro studies at therapeutic salicylate concentrations (300 μg/mL), 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 ketorolac protein binding in plasma. Since ketorolac is a highly protein-bound drug with low plasma concentration, significant displacement of other protein-bound drugs by ketorolac is not expected.

Animal and human studies have not shown 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 drugs.

Hallucinations have been reported with concomitant use of ketorolac and psychotropic drugs (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 therapy 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. These events may occur at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal disorders. The risk of developing severe gastrointestinal bleeding depends on the dosage of the drug. 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. These patients should start treatment with the lowest available dose. This is particularly relevant for 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. Such patients should be warned to report any unusual gastrointestinal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment. For these patients, as well as for those concurrently using low-dose acetylsalicylic acid or other drugs increasing gastrointestinal risk, consideration should be given to combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors). Ketorolac should be used with caution in patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, selective serotonin reuptake inhibitors, or antiplatelet agents like acetylsalicylic acid. NSAIDs, including ketorolac, should be used cautiously in patients with inflammatory bowel disease (Crohn’s disease, ulcerative colitis). NSAIDs, particularly ketorolac, may be associated with an increased risk of gastrointestinal anastomotic dehiscence. Careful medical monitoring and caution are recommended when using ketorolac following gastrointestinal surgery.

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

Hematological effects.

Ketorolac 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 section "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 baseline bleeding time, bleeding duration increased 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.

Skin reactions.

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

The risk of such reactions is higher at the beginning of treatment; these reactions most commonly occur within the first month of therapy. Ketorolac should be discontinued at the first signs of skin rash, mucosal lesions, or any other signs of hypersensitivity (see section "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 of the drug.

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.

Fluid and sodium 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, 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 slightly increase the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Clinical trials and epidemiological data suggest that the use of coxibs and certain NSAIDs (particularly at high doses) is associated with a certain increase in the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Although ketorolac treatment has not demonstrated an increased frequency of such thrombotic complications as myocardial infarction, there is insufficient data to exclude this risk with the use of tromethamine salt of ketorolac.

Cardiovascular, renal, and hepatic disorders.

The drug should be used with caution in 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. Volume depletion should be corrected, and serum urea and creatinine levels, as well as urine output, should be carefully monitored until normovolemia is achieved, as there is a risk of developing renal failure if these recommendations are not followed. In patients undergoing renal dialysis, creatinine clearance was reduced by approximately half compared to normal, and the elimination half-life was prolonged by about threefold. Patients with hepatic impairment due to cirrhosis showed no clinically significant changes in ketorolac clearance or elimination half-life. Mild elevations in one or more liver function tests (ALT [alanine aminotransferase]/AST [aspartate aminotransferase]) may occur. These deviations from normal may be transient, remain unchanged, or progress with continued treatment. If clinical signs and symptoms suggest liver disease or if systemic manifestations are observed, the drug should be discontinued.

Ketorolac should be used with caution in patients with a history of cardiovascular disorders.

Renal effects.

Inhibitors of prostaglandin synthesis (including NSAIDs) have been reported to cause nephrotoxic effects. The drug should be used with caution in patients with renal, cardiac, or hepatic impairment and in those with a history of kidney disease, as NSAID use may lead to worsening renal function due to inhibition of prostaglandin synthesis (see above). Since ketorolac tromethamine and its metabolites are primarily excreted by the kidneys, patients with moderate to severe renal impairment (serum creatinine > 160 µmol/L) should not take ketorolac. Patients with mild renal impairment should receive lower doses of ketorolac (not exceeding 60 mg daily intramuscularly), and renal function should be closely monitored in these patients. As with other drugs inhibiting prostaglandin synthesis, cases of increased serum urea, creatinine, and potassium levels have been reported during ketorolac tromethamine use, which may occur after a single dose. Discontinuation of the drug usually leads to recovery of renal function.

Respiratory function disorders.

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 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 ketorolac tromethamine administration. These reactions may also occur in individuals with angioedema, bronchospasm (e.g., asthma), and nasal polyps. Anaphylactoid reactions, such as anaphylaxis, may develop slowly. Therefore, ketorolac tromethamine is contraindicated in patients with a history of asthma and in patients with complete or partial syndrome of nasal polyps, angioedema, and bronchospasm.

Lactose. The medicinal product contains lactose; therefore, it should not be used in patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Effect on fertility.

The use of ketorolac, like any medicinal product that inhibits cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended for use in women planning to become pregnant. For women who are unable to conceive or undergoing fertility investigations, discontinuation of ketorolac should be considered.

Use during pregnancy or breastfeeding.

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

Therefore, the use of ketorolac tromethamine is contraindicated during pregnancy, labor, and delivery due to the known effects of NSAIDs on the fetal cardiovascular system.

Pregnancy.

The safety of use during pregnancy has not been proven. It has been demonstrated that ketorolac crosses the placental barrier and enters the fetal organism. Therefore, ketorolac tromethamine is contraindicated during pregnancy and labor.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of spontaneous abortion, cardiac malformations, and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. This risk is believed to increase with higher doses and longer duration of therapy. Animal studies have shown that prostaglandin synthesis inhibitors lead to more frequent loss of fertilized ova before implantation and interruption of pregnancy after implantation, as well as an increased risk of embryonic and fetal mortality. Additionally, reports indicate a higher incidence of various malformations, including cardiovascular malformations, in animals treated with a prostaglandin synthesis inhibitor during organogenesis.

From the 20th week of pregnancy, the use of ketorolac tromethamine may cause oligohydramnios due to fetal renal dysfunction. This condition may occur soon after the start of treatment and is usually reversible upon discontinuation of therapy. Furthermore, reports of ductus arteriosus constriction after second-trimester treatment, mostly reversible after discontinuation, have been documented.

Additionally, during pregnancy, all prostaglandin synthesis inhibitors may cause in the fetus:

  • cardiopulmonary toxicity (with premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
  • renal dysfunction, which may progress to renal failure with the development of oligohydramnios (reduced amniotic fluid volume) (see above).

In late pregnancy, these drugs may cause in both mother and newborn:

  • prolonged bleeding time due to antiplatelet effects, which may manifest even with very low doses;
  • inhibition of uterine contractions, potentially leading to delayed or prolonged labor.

Therefore, the use of ketorolac is contraindicated throughout pregnancy.

If a pregnant woman has taken the drug, antenatal monitoring for oligohydramnios following ketorolac exposure may be advisable for several days starting from the 20th week of pregnancy. Ketorolac use should be discontinued.

Breastfeeding.

Ketorolac passes into breast milk in low amounts; therefore, the drug is contraindicated during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Some patients may experience somnolence, dizziness, vertigo, insomnia, increased fatigue, visual disturbances, headache, or depression when using ketorolac. If patients experience these or similar effects, they should not drive or operate machinery.

Method of Administration and Dosage

It is advisable to take tablets during or after a meal.

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 administration) 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 continues after parenteral therapy:

  • 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 up to 4 times daily at intervals of 4 to 6 hours;
  • For patients weighing 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 for adults and 60 mg for elderly patients with impaired renal function or patients weighing less than 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 adverse events. During NSAID therapy, patients should be monitored regularly, and a longer dosing interval is generally recommended, for example, every 6–8 hours.

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 severe poisoning, acute renal failure and liver damage are possible.

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.

Adverse reactions.

Gastrointestinal disorders: peptic ulcer, perforation or gastrointestinal hemorrhage, sometimes fatal (especially in elderly people), nausea, dry mouth, dyspepsia, gastrointestinal pain, abdominal discomfort, spasm or burning in the epigastric region, vomiting with blood, gastritis, esophagitis, diarrhea, belching, constipation, flatulence, feeling of stomach fullness, melena, rectal bleeding, stomatitis, ulcerative stomatitis, vomiting, hemorrhages, 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): cases of 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 may 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, inability to concentrate, 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 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, especially at high doses and for prolonged periods, increases the risk of arterial thromboembolic complications (myocardial infarction or stroke). Although such reactions have not been observed with ketorolac, the possibility of their occurrence cannot be excluded.

Respiratory disorders: dyspnea, asthma, pulmonary edema.

Hepatobiliary disorders: liver function abnormalities, hepatitis, jaundice and liver failure, hepatomegaly, abnormalities in liver function laboratory tests.

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 rash.

Musculoskeletal and connective tissue disorders: myalgia, functional disorders.

Renal and urinary disorders: increased frequency of urination, oliguria, acute renal 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.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach of children.

Packaging.

10 tablets per blister; 1 blister per carton.

Prescription status. Prescription only.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of business activity.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua