Ketorolac-pharmak

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KETOROLAC-FARMAK (Ketorolac-Farmak)

Composition:

Active substance: ketorolac tromethamine;

One film-coated tablet contains ketorolac tromethamine 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-shaped, biconvex film-coated tablets.

Pharmacotherapeutic group. Drugs affecting the musculoskeletal system. Anti-inflammatory and antirheumatic agents.

Non-steroidal anti-inflammatory and antirheumatic agents. Acetic acid derivatives and related compounds. Ketorolac. ATC code M01AB15.

Pharmacological Properties

Pharmacodynamics

Ketorolac tromethamine belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs). Its action is primarily based on inhibition of prostaglandin synthesis, particularly PGE2 and PGF2α.

In preclinical pharmacological studies, ketorolac demonstrated analgesic activity 350 times stronger than that of acetylsalicylic acid in mice in the phenylquinone-induced pain inhibition test, and 800 times more potent than acetylsalicylic acid in rats with pain induced by flexion of the tibiotarsal joint in arthritic rats.

Ketorolac also showed anti-inflammatory activity (more potent than phenylbutazone) and antipyretic activity (more potent than acetylsalicylic acid).

Ketorolac was found to be 37 times more active than acetylsalicylic acid in inhibiting collagen-induced platelet aggregation in humans.

Ketorolac has no effect on the central nervous system; its effects on the cardiovascular and respiratory systems are minimal.

Clinical studies have shown that the analgesic activity of ketorolac at a dose of 10 mg is not inferior to that of 650 mg acetylsalicylic acid; 600 mg and 1000 mg paracetamol; combination of 600 mg and 1000 mg paracetamol with 60 mg codeine; 400 mg glafenine; 400 mg ibuprofen; and 50 mg diclofenac.

Analgesic effect begins within 1 hour after oral administration; maximum analgesic effect is achieved within 2–3 hours.

The duration of analgesic action averages 4–6 hours.

Ketorolac has no morphine-like effects, does not cause respiratory depression, and the incidence of central nervous system side effects (drowsiness) is significantly lower compared to morphine.

Pharmacokinetics

Absorption: Ketorolac tromethamine is rapidly and completely absorbed after oral administration, reaching peak plasma concentration of 0.87 mg/kg within 35 minutes after a single 10 mg dose.

The pharmacokinetics of ketorolac in humans are linear, both after single and multiple doses; steady-state plasma concentrations are achieved within one day with dosing every 6 hours.

The elimination half-life from plasma averages 5.4 hours. In elderly individuals (mean age 72 years), it is 6.2 hours.

Administration of antacids does not affect ketorolac absorption.

Distribution: 99% of ketorolac in plasma is protein-bound.

Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin, and tolbutamide do not alter the protein binding of ketorolac.

Volume of distribution is 0.11 L/kg.

Biotransformation: Ketorolac is metabolized in the liver; the main metabolites are para-hydroxylated derivatives (12%) and glucuronides (75%), which are inactive.

Excretion: The primary route of elimination of ketorolac and its metabolites is renal—via urine, with the remainder excreted in feces.

Renal clearance of ketorolac is 0.35–0.55 mL/min/kg.

Clinical characteristics

Indications

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

Maximum duration of treatment — 5 days.

Contraindications

Ketorolac-Farmak is not intended for the treatment of mild or chronic pain.

Contraindications for use of the medicinal product:

• Hypersensitivity to ketorolac or to any other components of the medicinal product;
  • Do not use in patients with hypersensitivity to ketorolac or other NSAIDs, or in patients in whom acetylsalicylic acid or other prostaglandin synthesis inhibitors induce allergic reactions (due to the possibility of severe anaphylactic reactions);
  • Active peptic ulcer or gastrointestinal bleeding, history of ulceration or perforation;
  • Previous, suspected, or active cerebrovascular hemorrhage;
  • Hemorrhagic diathesis;
  • Complete or partial syndrome of nasal polyps, Quincke's edema, or bronchospasm;
  • Concomitant treatment with other nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, probenecid, lithium salts, or pentoxifylline (see section "Interaction with other medicinal products and other types of interactions");
  • Severe heart failure;
  • History of hemorrhagic stroke, current or suspected;
  • Bronchial asthma;
  • Do not use in patients with moderate to severe renal impairment (serum creatinine level above 442 µmol/L) or in patients at risk of developing renal failure due to hypovolemia or dehydration;
  • Liver cirrhosis or severe hepatitis;
  • Tendency to bleeding;
  • Coagulation disorders;
  • Do not use in patients receiving anticoagulant therapy;
  • Hypovolemia, dehydration;
  • Do not use in patients undergoing intensive diuretic therapy;
  • Do not use for prophylactic analgesia before surgery or during the operation, as it increases the risk of bleeding due to inhibition of platelet aggregation and prolonged bleeding time;
  • Do not use in patients with suspected or confirmed cerebrovascular hemorrhage due to platelet function inhibition by ketorolac;
  • Do not use in patients who have undergone surgical procedures with high risk of bleeding or incomplete hemostasis, and in individuals with high risk of bleeding;
  • The medicinal product is contraindicated during the third trimester of pregnancy, childbirth, and during breastfeeding (see section "Use during pregnancy or lactation");
• Do not use in children and adolescents under 16 years of age.

Interaction with other medicinal products and other types of interactions

Concomitant use of Ketorolac-Farmak and other NSAIDs should be avoided.

When used concomitantly with corticosteroids, the risk of developing ulcers or gastrointestinal bleeding increases (see section "Special precautions for use").

NSAIDs may enhance the effect of anticoagulants such as warfarin. Ketorolac inhibits platelet aggregation, reduces thromboxane concentration, and prolongs bleeding time. Unlike the prolonged effect of acetylsalicylic acid, platelet function returns to normal within 24–48 hours after discontinuation of ketorolac.

The risk of gastrointestinal bleeding increases with concomitant use of antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) together with NSAIDs (see section "Special precautions for use").

In patients already taking acetylsalicylic acid (ASA) or other NSAIDs, the risk of serious adverse reactions associated with NSAIDs increases.

Concomitant use of ketorolac with pentoxifylline increases the tendency to bleeding.

When ketorolac is used concomitantly with probenecid, reduced plasma clearance and volume of distribution of ketorolac, increased plasma concentration, and prolonged elimination half-life have been reported.

Some drugs that inhibit prostaglandin synthesis are known to reduce methotrexate clearance and thus may increase its toxicity.

It has also been established that some prostaglandin synthesis inhibitors inhibit renal clearance of lithium, leading to increased plasma lithium concentrations. During ketorolac therapy, cases of increased plasma lithium concentrations have been observed.

Ketorolac tromethamine does not affect digoxin protein binding.
In vitro studies have shown that at therapeutic salicylate concentrations (300 µg/mL), protein binding of ketorolac decreases from approximately 99.2% to 97.5%, corresponding to a potential twofold increase in plasma concentration of unbound ketorolac.

Therapeutic concentrations of drugs such as digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin, and tolbutamide do not alter the protein binding of ketorolac tromethamine.

Although studies do not indicate significant interaction between ketorolac and warfarin or heparin, concomitant use of ketorolac with agents affecting hemostasis — particularly with therapeutic doses of anticoagulants (warfarin), prophylactic low doses of heparin (2,500–5,000 units every 12 hours), and dextrans — may increase the risk of bleeding.

NSAIDs may reduce the effectiveness of diuretics and antihypertensive agents.
The risk of developing acute renal failure, which is usually reversible, may increase in some patients with impaired renal function (e.g., dehydrated patients or elderly patients) when angiotensin-converting enzyme inhibitors (ACE inhibitors) and/or angiotensin II receptor antagonists are used concomitantly with NSAIDs. Therefore, such combinations should be used with caution, especially in elderly patients. Adequate dose titration and hydration of the patient, as well as monitoring of renal function at the start of combination therapy and periodically thereafter, are required.

Ketorolac reduces the need for concomitant opioid analgesics in postoperative pain management.

Oral administration of ketorolac tablets after consumption of fatty food resulted in delayed and reduced peak concentration of ketorolac by approximately 1 hour.
Antacids did not affect the extent of absorption.

Special precautions for use

Ketorolac should not be considered a conventional analgesic and must be used under strict medical supervision.

Ketorolac should not be used for the treatment of mild or chronic pain.

Epidemiological data indicate that ketorolac is associated with a higher risk of gastrointestinal toxicity compared to other NSAIDs, especially when used outside approved indications and/or for prolonged durations (see sections "Indications", "Contraindications", "Dosage and administration").

Concomitant use of ketorolac with NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided.

To minimize the risk of adverse effects, ketorolac therapy should be administered for the shortest duration possible and at the lowest effective dose required to control pain.

Prior to initiating ketorolac therapy, it is essential to confirm that the patient has not previously experienced hypersensitivity reactions to ketorolac, acetylsalicylic acid, or other NSAIDs.

Effect on fertility

Use of ketorolac, like any drug that inhibits cyclooxygenase/prostaglandin synthesis, may reduce fertility and is not recommended for women attempting to conceive. For women with infertility or undergoing fertility investigations, consideration should be given to discontinuing ketorolac.

Elderly patients

Particular caution is required in elderly or debilitated patients, as the frequency of certain adverse effects may be higher than in younger patients.

An increased incidence of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, has been observed in elderly patients, which may be fatal (see section "Dosage and administration").

In elderly patients, an increased elimination half-life of ketorolac and a corresponding decrease in clearance may also occur. Therefore, in addition to reducing the total daily dose, an extended dosing interval may be necessary.

Gastrointestinal tract effects

Ketorolac-Farmak may cause gastrointestinal irritation, ulcers, and bleeding in patients, regardless of prior gastrointestinal pathology. Patients with known or active inflammatory gastrointestinal disorders should be treated only under close medical supervision. The frequency of these effects increases with higher doses and longer treatment duration.

Ketorolac-Farmak must not be used concomitantly with other NSAIDs.

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

Gastrointestinal ulcer, bleeding, and perforation

Cases of gastrointestinal bleeding, ulceration, or perforation, sometimes fatal, have been reported with NSAID use, including ketorolac. These complications may occur at any time during treatment, without warning symptoms or prior history of severe gastrointestinal disorders.

An increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, has been observed in elderly patients, which may be fatal. Debilitated patients are less responsive to treatment of ulcers and bleeding than others. Most fatal cases related to gastrointestinal complications associated with NSAID use have occurred in elderly and/or debilitated patients.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, including ketorolac, and in patients with a history of peptic ulcer, especially complicated by bleeding or perforation, and in elderly patients. The risk of clinically significant bleeding is dose-dependent. In such cases, patients should initiate treatment with the lowest available dose. For these patients, as well as for those concurrently using low-dose acetylsalicylic acid or other drugs increasing gastrointestinal risk, combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) may be considered (see section "Interaction with other medicinal products and other forms of interaction").

NSAIDs should be used cautiously in patients with a history of inflammatory gastrointestinal disorders (Crohn’s disease, ulcerative colitis), as their condition may worsen (see section "Adverse reactions").

Patients with prior gastrointestinal disorders, particularly elderly patients, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.

If gastrointestinal bleeding or ulceration occurs in patients receiving Ketorolac-Farmak, treatment should be discontinued.

Ketorolac-Farmak should be used with caution in patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

The frequency and severity of gastrointestinal complications, as with other NSAIDs, may increase with higher doses and longer duration of ketorolac use. The risk of severe gastrointestinal bleeding is dose-dependent, particularly in elderly patients receiving a mean daily dose of ketorolac exceeding 60 mg/day via injection. A history of peptic ulcer increases the likelihood of severe gastrointestinal complications during ketorolac therapy.

Respiratory function effects

Due to its effect on arachidonic acid metabolism, the medicinal product may induce bronchospasm attacks and other pseudoallergic reactions or shock in patients with asthma or hypersensitivity.

Anaphylactic reactions

Anaphylactic/anaphylactoid reactions (including anaphylaxis, bronchospasm, flushing, rash, hypotension, laryngeal edema, and angioneurotic edema) have occurred in patients regardless of prior hypersensitivity to any other NSAID, acetylsalicylic acid, or trometamol ketorolac. These reactions may also occur in individuals with a history of angioneurotic edema, bronchospastic reactivity (e.g., asthma), or nasal polyps. Anaphylactoid reactions such as anaphylaxis may be fatal. Therefore, trometamol ketorolac should be used with caution in patients with a history of asthma and in patients with complete or partial aspirin triad (nasal polyps, angioneurotic edema, and bronchospasm).

Cardiovascular and cerebrovascular effects

Fluid retention and edema have been reported in patients with hypertension and/or congestive heart failure when using NSAIDs; therefore, such patients require appropriate information and close monitoring.

Clinical trials and epidemiological data suggest that use of selective COX-2 inhibitors and certain NSAIDs (particularly at high doses) is associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Although ketorolac use has not demonstrated an increased incidence of thrombotic events such as myocardial infarction, available data are insufficient to exclude this risk.

Initiation of ketorolac therapy in patients with uncontrolled hypertension, congestive heart failure, chronic ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should occur only after careful risk assessment. Such assessment should also be performed before initiating treatment in patients with cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).

Renal effects

Ketorolac, like other NSAIDs, should be used with caution in patients with impaired renal function or a history of kidney disease, as ketorolac is a potent inhibitor of prostaglandin synthesis and may cause nephrotoxicity, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure.

Caution is advised, as renal toxicity has been observed with ketorolac and other NSAIDs in patients with reduced circulating blood volume and/or renal blood flow, where renal prostaglandins play a compensatory role in maintaining renal perfusion.

In such patients, administration of ketorolac or other NSAIDs may dose-dependently reduce renal prostaglandin production and lead to decompensation or renal failure. Patients at greatest risk include those with impaired renal function, renal hypoperfusion states, kidney disease, hypovolemia, heart failure, hepatic dysfunction, liver cirrhosis or severe hepatitis, patients taking diuretics, and the elderly.

Following discontinuation of ketorolac or other NSAIDs, renal function typically returns to baseline levels.

Patients with impaired renal function

Since ketorolac and its metabolites are primarily excreted by the kidneys, caution is required when administering ketorolac to patients with impaired renal function. Specifically, ketorolac is contraindicated in patients with serum creatinine levels above 442 µmol/L.

Ketorolac-Farmak is contraindicated during intensive diuretic therapy.

Fluid and sodium retention in patients with cardiovascular disease and peripheral edema

Fluid retention and edema associated with NSAID therapy have been reported; therefore, ketorolac should be prescribed cautiously to patients with a history of hypertension or heart failure.

Fluid retention, hypertension, and peripheral edema have been observed in some patients receiving NSAIDs, including ketorolac. Therefore, the medicinal product should be used cautiously in patients with heart failure, hypertension, or similar conditions.

Patients with impaired hepatic function

In patients with hepatic impairment due to liver cirrhosis, no clinically significant changes in ketorolac clearance or elimination half-life have been observed. Minor elevations in one or more liver function tests may occur. These deviations may be transient, remain unchanged, or progress with continued therapy. Significant elevations in serum transaminases—alanine aminotransferase (ALT) or aspartate aminotransferase (AST)—more than three times the upper limit of normal were reported in less than 1% of patients in controlled clinical trials.

If clinical signs or persistent symptoms indicating liver disease develop, or if systemic reactions to Ketorolac-Farmak occur, the drug should be discontinued.

Hematological effects

Ketorolac inhibits platelet aggregation and prolongs bleeding time.

Ketorolac-Farmak should not be prescribed to patients with coagulation disorders.

Although studies do not indicate a significant interaction between ketorolac and warfarin or heparin, concomitant use of ketorolac with medicinal products affecting hemostasis (including therapeutic doses of anticoagulants such as warfarin, prophylactic low-dose heparin—2500–5000 units every 12 hours—or dextrans) may be associated with an increased risk of bleeding (see section "Contraindications").

Post-marketing reports have documented postoperative hematomas and other signs of wound bleeding associated with perioperative use of ketorolac injection solution.

The potential risk of bleeding should be considered in situations where hemostasis is critical, such as prostatectomy, tonsillectomy, or plastic surgery (see section "Contraindications").

Skin reactions

Serious skin reactions, sometimes fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely reported with NSAIDs (see section "Adverse reactions"). The risk of such reactions is higher at the beginning of treatment. If early signs of skin rash, mucosal lesions, or any other signs of hypersensitivity occur, Ketorolac-Farmak should be discontinued.

Ketorolac should not be used concomitantly with probenecid, as changes in ketorolac pharmacokinetics have been observed with this combination.

Caution is recommended when using ketorolac concomitantly with methotrexate, as some prostaglandin synthesis inhibitors have been shown to reduce methotrexate clearance and may thereby increase its toxicity.

Abuse and dependence

Ketorolac does not cause dependence—no withdrawal syndrome has been reported upon discontinuation of the drug.

Lactose

Ketorolac-Farmak film-coated tablets contain lactose. Patients with known sugar intolerances should consult their physician before taking this medicinal product.

Use during pregnancy or breastfeeding

Pregnancy
Use of Ketorolac-Farmak is contraindicated during the third trimester of pregnancy, labor, and breastfeeding (see section "Contraindications").

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.

Epidemiological studies indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis with use of prostaglandin synthesis inhibitors in early pregnancy.

The absolute risk of congenital heart defects increases from less than 1% to approximately 1.5%. The risk increases with higher doses and longer duration of treatment. In animal studies, prostaglandin synthesis inhibitors have caused increased pre- and post-implantation loss and embryonic-fetal mortality.

Increased incidence of various congenital malformations, including cardiovascular defects, has also been reported in animals administered prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, ketorolac use may cause oligohydramnios due to impaired fetal renal function. This condition may occur soon after starting treatment and is usually reversible upon discontinuation of therapy.

During the second trimester, cases of arterial duct constriction have been reported, which mostly resolve after stopping treatment. Therefore, ketorolac should not be used during the first and second trimesters except in cases of urgent medical need.

If ketorolac is used by a woman planning pregnancy or during the first or second trimester, the lowest effective dose should be used for the shortest possible duration.

If ketorolac is used for several days from the 20th week of pregnancy onward, prenatal monitoring for oligohydramnios and arterial duct constriction should be considered. If oligohydramnios or arterial duct constriction is detected, ketorolac treatment should be discontinued.

During the third trimester, all prostaglandin synthesis inhibitors may cause in the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• impaired renal function (see above).

At the end of pregnancy, these drugs may cause in the mother and newborn:

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

Therefore, ketorolac is contraindicated during the third trimester of pregnancy.

Ketorolac may be used only if necessary during the first two trimesters of pregnancy.
Approximately 10% of ketorolac crosses the placenta.

In women of reproductive age, potential pregnancy should always be ruled out before initiating treatment, and effective contraception should be ensured during therapy.

Labour
Ketorolac is contraindicated during labor because it inhibits prostaglandin synthesis, which may negatively affect fetal circulation and cause serious respiratory disturbances in the newborn. Additionally, it inhibits uterine contractions, potentially delaying labor and increasing the risk of postpartum hemorrhage.

Breastfeeding

Ketorolac and its metabolites have been detected in the fetus and milk of animals.
The drug passes into breast milk in small amounts; therefore, its use is contraindicated during breastfeeding.

Fertility
Use of ketorolac, like any medicinal product that inhibits cyclooxygenase/prostaglandin synthesis, may reduce fertility and is not recommended for women planning pregnancy.

If a woman experiences difficulty conceiving or is undergoing fertility evaluation, consideration should be given to discontinuing ketorolac.

Ability to affect reaction speed when driving or operating machinery

Despite the absence of narcotic effects and central nervous system influence, ketorolac may cause drowsiness.

During ketorolac use, some patients may experience drowsiness, dizziness, vertigo, insomnia, or depression. If patients experience these or similar adverse effects, they should exercise caution when performing tasks requiring concentration.

Particular caution is advised when driving vehicles or operating machinery.

Method of Administration and Dosage

The total duration of treatment should not exceed 5 days.

Adults

The lowest effective dose should be used to control pain and patient response.

The recommended dose for adults is 10 mg (1 film-coated tablet) as needed every 4 or 6 hours, but not more than 40 mg/day.

On the day of switching from parenteral to oral administration, the total daily dose must not exceed 90 mg, considering that the maximum oral dose should not exceed 40 mg.

For patients with body weight less than 50 kg, the dose should be reduced.

Elderly patients (≥ 65 years of age)

For elderly patients, dosage should be determined by the physician, who should consider the possibility of reducing the above-mentioned doses.

Children. Do not use in children under 16 years of age.

Overdose

Symptoms

Individual cases of ketorolac overdose have been associated with abdominal pain, nausea, vomiting, hyperventilation, peptic ulcer and/or erosive gastritis, and impaired kidney function, which resolved after discontinuation of treatment. Gastrointestinal bleeding may occur. Rarely, following NSAID intake, hypertension, acute renal failure, respiratory depression, and coma may develop.

Anaphylactoid reactions, which have been reported following therapeutic use of NSAIDs, may also occur as a result of overdose.

Treatment
In case of NSAID overdose, treatment should be symptomatic and supportive, employing standard safety measures (induction of emesis, gastric lavage, administration of activated charcoal). There are no specific antidotes. Dialysis does not lead to significant removal of ketorolac from the bloodstream.

Side effects

The following adverse reactions have occurred in patients receiving ketorolac. The frequency of these reactions cannot be determined from the available data.

Infections and infestations: aseptic meningitis.

Blood and lymphatic system disorders: thrombocytopenia, purpura, epistaxis.

Immune system disorders: anaphylactoid reactions such as anaphylaxis, sometimes fatal, hypersensitivity reactions such as bronchospasm, vasodilation, flushing, rash, hypotension, laryngeal edema.

Metabolism and nutrition disorders: hyponatremia, hyperkalemia, anorexia.

Psychiatric disorders: thinking abnormalities, depression, insomnia, anxiety, irritability, nervousness, psychotic reactions, abnormal dreams, hallucinations, euphoria, decreased attention span, catatonic states, confusion.

Nervous system disorders: headache, dizziness, seizures, paresthesia, hyperkinesia, taste disturbances.

Eye disorders: vision impairment, visual abnormalities.

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

Cardiac disorders: tachycardia, bradycardia, heart failure.

Edema, hypertension, and heart failure have been reported with the use of NSAIDs.

Vascular disorders: hypertension, vasodilation, hypotension, bruising, erythema, pallor, bleeding from postoperative wounds.

Clinical studies and epidemiological data suggest that the use of coxibs and certain NSAIDs (particularly at high doses and with prolonged treatment) may be associated with a small increase in the risk of arterial thromboembolic events (e.g., myocardial infarction or stroke) (see section "Special precautions"). Although it has not been proven that ketorolac increases the risk of thromboembolic events such as myocardial infarction, there is insufficient data to fully exclude such a risk.

Respiratory disorders: dyspnea, asthma, pulmonary edema.

Gastrointestinal disorders — the most common adverse effects of NSAIDs. Peptic ulcer, ulceration, perforation, or gastrointestinal bleeding may occur, sometimes fatal, particularly in the elderly (see section "Special precautions"). Following administration of ketorolac, the following have been reported: nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain/discomfort, bloating, melena, rectal bleeding, hematemesis, stomatitis, ulcerative stomatitis, esophagitis, belching, gastrointestinal ulcer, pancreatitis, dry mouth, exacerbation of colitis and Crohn’s disease (see section "Special precautions"). Gastritis has been observed rarely.

Hepatobiliary disorders: hepatitis, cholestatic jaundice, liver failure.

Skin and subcutaneous tissue disorders: angioneurotic edema, exfoliative dermatitis, sweating, maculopapular rash, urticaria, pruritus, purpura, bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

Musculoskeletal and connective tissue disorders: myalgia.

Renal and urinary disorders: polyuria, increased frequency of urination, oliguria, acute renal failure, hemolytic uremic syndrome, interstitial nephritis, urinary retention, nephrotic syndrome, flank pain (with or without hematuria, azotemia). As with other drugs that inhibit prostaglandin synthesis, signs of renal impairment such as elevated serum creatinine and potassium levels may occur after a single dose of ketorolac.

Reproductive system disorders: female infertility.

General disorders: asthenia, fever, edema, chest pain, excessive thirst.

Investigations: prolonged bleeding time, increased blood urea nitrogen (BUN), increased creatinine levels, changes in liver function tests.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It allows ongoing monitoring of the benefit-risk ratio of the drug. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of drug 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 in a blister. 1 or 10 blisters per carton.

Prescription category. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.