Ketan solution for injection 30 mg/ml ampoule 1 ml No. 10

Instructions Ketanov solution for injection 30 mg/ml ampoule 1 ml No. 10

Composition

active ingredient: 1 ml of solution contains ketorolac trometamol 30 mg;

excipients: sodium chloride, disodium edetate, ethanol 96%, water for injection (sodium hydroxide or diluted hydrochloric acid are added to correct pH).

Dosage form: Solution for injection.

Main physicochemical properties: transparent, colorless or pale yellow solution, free from visible particles.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs.

ATX code M01A B15.

Pharmacological properties

Pharmacodynamics.

Ketorolac trometamol is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits analgesic activity. The mechanism of action of ketorolac (as with other NSAIDs) is not fully understood, but may involve inhibition of prostaglandin synthesis. The biological activity of ketorolac trometamol is associated with the S-form. Ketorolac trometamol does not have sedative or anxiolytic properties.

The biggest difference between high and low doses of ketorolac is the duration of analgesia. An analgesic dose of ketorolac also has an anti-inflammatory effect.

Pharmacokinetics

Ketorolac trometamol is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the analgesic activity being due to the S-form. Ketorolac is rapidly and completely absorbed after intramuscular administration. The mean maximum plasma concentration of 2.2 μg/ml is reached on average 50 minutes after administration of a single 30 mg dose.

Linear pharmacokinetics. In adults, clearance of the racemate is not altered after intramuscular administration of ketorolac trometamol in the recommended dosage range. This indicates that the pharmacokinetics of ketorolac trometamol in adults after single or multiple intramuscular administrations of ketorolac trometamol are linear. At higher recommended doses, there is a proportional increase in concentrations of free and bound racemate.

The drug penetrates poorly through the blood-brain barrier. Ketorolac penetrates the placenta and in small quantities into breast milk. More than 99% of ketorolac in blood plasma is bound to proteins within a wide range of concentrations.

Table of approximate average pharmacokinetic parameters

[mean ± standard deviation (SD)]

Metabolism: Ketorolac trometamol is extensively metabolized in the liver. The products of metabolism are hydroxylated and conjugated forms of the parent drug. The products of metabolism and some of the unchanged drug are excreted in the urine.

Excretion. The primary route of elimination of ketorolac and its metabolites is renal. Approximately 92% of the administered dose is recovered in the urine: 40% as metabolites and 60% as unchanged ketorolac. Approximately 6% of the dose is excreted in the feces. A single-dose study of ketorolac 10 mg (n = 9) demonstrated that the S-enantiomer is eliminated twice as rapidly as the R-enantiomer, and clearance is independent of route of administration. This means that the ratio of S-enantiomer/R-enantiomer plasma concentrations after each dose decreases over time. There is little or no difference between the S- and R-forms in humans. The t½ of the S-enantiomer of ketorolac trometamol is approximately 2.5 hours (SD ± 0.4) and the R-enantiomer is approximately 5 hours (SD ± 1.7).

In other studies, the T½ of the racemate was reported to be 5-6 hours.

Accumulation: Ketorolac trometamol administered intravenously as a bolus every 6 hours for 5 days to healthy volunteers (n = 13) showed no significant difference between days 1 and 5. Trough levels averaged

0.29 μg/mL (SD ± 0.13) on day 1 and 0.55 μg/mL (SD ± 0.23) on day 6. Steady state was reached after the fourth dose. Accumulation of ketorolac trometamol in specific patient groups (elderly patients, children, patients with renal insufficiency or liver disease) has not been studied.

Elderly patients: Based only on data obtained after a single administration, the T½ of racemic ketorolac trometamol was increased from 5 to 7 hours in elderly patients (65–78 years) compared to young healthy volunteers (24–35 years).

Children: Pharmacokinetic data on intramuscular administration of ketorolac trometamol in children are not available.

Renal impairment. Based only on data obtained after a single dose, the mean T½ of ketorolac trometamol in patients with renal impairment is 6-19 hours and depends on the severity of the impairment. There is almost no correlation between creatinine clearance and total clearance of ketorolac trometamol in elderly patients and patients with renal impairment (r = 0.5). In patients with renal disease, the AUC8 of each enantiomer increases by almost 100% compared to healthy volunteers. The volume of distribution is doubled for the S-enantiomer and increases by 1/5 for the R-enantiomer. The increase in the volume of distribution of ketorolac trometamol indicates an increase in the unbound fraction.

Hepatic impairment: T½, AUC8, and Cmax values in 7 patients with liver disease were not significantly different from those in healthy volunteers.

Indication

Short-term relief of moderate to severe postoperative pain.

Contraindication

- Hypersensitivity to the active substance or to any component of the medicinal product, or to other NSAIDs (non-steroidal anti-inflammatory drugs).

- Active peptic ulcer, recent gastrointestinal bleeding or perforation, peptic ulcer disease or history of gastrointestinal bleeding.

- Existing or suspected gastrointestinal bleeding.

- Allergic reactions such as bronchial asthma, rhinitis, angioedema or urticaria caused by the use of acetylsalicylic acid or other NSAIDs in history (due to the possibility of severe anaphylactic reactions).

- History of bronchial asthma.

- Do not use as an analgesic before and during surgery and manipulations on coronary vessels, as it inhibits platelet aggregation and is also contraindicated during surgery due to the increased risk of bleeding.

- Severe heart failure.

- Complete or partial syndrome of nasal polyps, angioedema or bronchospasm.

- Do not use in patients who have had surgery with a high risk of hemorrhage or incomplete hemostasis and in patients receiving anticoagulants, including low-dose heparin (2500 - 5000 units every 12 hours).

- Hepatic or moderate to severe renal failure (serum creatinine level greater than 160 μmol/l).

- Suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, including blood clotting disorders and high risk of bleeding.

- Concomitant treatment with other NSAIDs (including selective cyclooxygenase inhibitors), acetylsalicylic acid, warfarin, pentoxifylline, probenecid or lithium salts.

- Hypovolemia, dehydration with risk of renal failure due to decreased fluid volume.

- Pregnancy, childbirth, labor and breastfeeding.

- Use in children under 16 years of age.

- Epidural or intrathecal administration of the drug is contraindicated.

Interaction with other medicinal products and other types of interactions

Ketorolac is extensively bound to plasma proteins (average 99.2%). Ketorolac trometamol does not alter the pharmacokinetics of other agents through enzyme induction or inhibition.

Cannot be used simultaneously with ketorolac.

Warfarin, Digoxin, Salicylates, and Heparin. Ketorolac trometamol slightly reduced the plasma protein binding of warfarin in vitro and did not alter the plasma protein binding of digoxin. In vitro studies indicate that at therapeutic concentrations of salicylates (300 μg/mL), ketorolac binding was reduced from approximately 99.2% to 97.5%, indicating a potential two-fold increase in unbound ketorolac plasma levels. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin, and tolbutamide do not alter the plasma protein binding of ketorolac trometamol. Concomitant use of ketorolac and prophylactic low-dose heparin (2500–5000 IU every 12 hours) has not been extensively studied but may be associated with an increased risk of bleeding. Ketorolac should not be administered to patients receiving anticoagulants or low-dose heparin.

Antithrombotic agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").

Anticoagulants: Concomitant use with anticoagulants may increase bleeding. Concomitant use with anticoagulants (such as warfarin) is contraindicated.

Other NSAIDs and acetylsalicylic acid. When used with acetylsalicylic acid, the binding of ketorolac to plasma proteins is reduced, although the clearance of free ketorolac is not changed. The clinical significance of this type of interaction is unknown, although, as with other NSAIDs, ketorolac trometamol and acetylsalicylic acid or other NSAIDs should not be administered concomitantly due to the potential for increased adverse events.

Diuretics. In some patients, ketorolac may reduce the natriuretic effect of furosemide and thiazides. During concomitant therapy with NSAIDs, the patient should be closely monitored for signs of renal failure and to ensure the effectiveness of diuretics (see section "Special warnings and precautions for use"). In healthy volunteers with normal blood volume, ketorolac reduces the diuretic effect of furosemide by approximately 20%, therefore, special care should be taken when prescribing ketorolac to patients with cardiac decompensation.

Probenecid: Concomitant use of ketorolac trometamol and probenecid resulted in a decrease in ketorolac clearance and a significant increase in its plasma levels and T½. Therefore, concomitant use of ketorolac trometamol and probenecid is contraindicated.

Oxpentifylline. Not recommended due to increased risk of bleeding.

Lithium. Concomitant use of NSAIDs and lithium preparations is contraindicated because of possible inhibition of renal clearance of lithium, increased plasma lithium concentrations, and lithium toxicity.

Opioid analgesics. The effect of opioid analgesics is enhanced, which allows reducing the dose of the latter for pain relief.

Drugs in combination with ketorolac should be prescribed with caution.

Antithrombotic agents and selective serotonin reuptake inhibitors (SSRIs)

The risk of gastrointestinal bleeding increases (see section "Special warnings and precautions for use").

Thrombolytic agents

Concomitant use with NSAIDs increases the risk of bleeding.

Methotrexate: Concomitant administration should be done with caution. Since NSAIDs may impair renal function, thereby reducing the clearance of methotrexate, its toxicity may be increased.

ACE inhibitors: Concomitant use of angiotensin-converting enzyme (ACE) inhibitors increases the risk of renal dysfunction, particularly in patients with reduced interstitial fluid volume.

NSAIDs may reduce the hypotensive effect of ACE inhibitors. This interaction should be kept in mind when prescribing NSAIDs together with ACE inhibitors.

β-blockers. Ketorolac and other NSAIDs weaken the hypotensive effect of β-blockers.

Angiotensin-II receptor antagonists: Ketorolac and other NSAIDs attenuate the hypotensive effect of angiotensin-II receptor antagonists.

Anticonvulsants: Isolated cases of convulsions have been reported during concomitant use of ketorolac trometamol and anticonvulsants (phenytoin, carbamazepine).

Psychotropic drugs: With the simultaneous use of ketorolac and psychotropic drugs (fluoxetine, thiotexene, alprazolam), hallucinations have been reported.

Corticosteroids: As with all NSAIDs, caution should be exercised when corticosteroids are administered concomitantly due to the increased risk of gastrointestinal bleeding.

Quinolines: Patients taking quinolines are at increased risk of seizures.

Antidiabetic agents: NSAIDs may enhance the effects of sulfonylureas.

Antivirals. 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 treated concomitantly with zidovudine and ibuprofen. Ritonavir may increase the concentration of NSAIDs.

Tacrolimus: NSAIDs increase the risk of nephrotoxicity.

Preparations containing garlic, onions, and ginkgo biloba may enhance the effect of ketorolac and increase the risk of hemorrhagic complications.

Non-polarizing muscle relaxants. No formal studies have been conducted on the concomitant use of ketorolac trometamol and muscle relaxants. NSAIDs may reduce the excretion of baclofen (increasing the risk of toxicity). There was no evidence in animal or human studies that ketorolac tromethamine induces or inhibits hepatic enzymes that are capable of metabolizing it or other drugs. Therefore, ketorolac is not expected to alter the pharmacokinetics of other drugs by enzyme induction or inhibition.

Cyclosporine: As with all NSAIDs, concomitant use of cyclosporine is contraindicated due to the increased risk of nephrotoxicity.

Mifepristone. NSAIDs should not be used for 8-12 days after taking mifepristone, as they may weaken the effects of mifepristone.

Ketorolac does not affect the binding of digoxin to plasma proteins. In vitro studies show that in the case of therapeutic concentrations (300 μg/ml) of salicylates, as well as in the case of higher concentrations, the degree of binding of ketorolac to plasma proteins decreases from 99.2 to 97.5%. Digoxin, warfarin, paracetamol, phenytoin and tolbutamide in therapeutic concentrations do not change the binding of ketorolac to blood proteins. Since ketorolac is a potent drug and its content in plasma is insignificant, it is unlikely that it can significantly displace other drugs from plasma protein binding.

Impact on laboratory test results.

Ketorolac inhibits platelet aggregation and may prolong bleeding time.

When ketorolac is used to relieve postoperative pain, the need for concomitant use of opioid analgesics is reduced.

Application features

The likelihood of side effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. Physicians should be aware that some patients may not experience analgesia until 30 minutes after parenteral administration.

The concomitant use of ketorolac and other NSAIDs, as well as selective cyclooxygenase-2 inhibitors, should be avoided (see section "Contraindications").

Combined use of ketorolac trometamol intramuscularly and orally in adult patients should not exceed 2 days.

When treating patients with cardiac, renal or hepatic insufficiency who are taking diuretics, or patients after surgical intervention with hypovolemia, careful monitoring of diuresis and renal function is necessary.

Use in elderly patients

In elderly patients (over 65 years of age), the use of NSAIDs is more likely to cause undesirable side effects, especially bleeding and perforation of the gastrointestinal tract, including fatal outcomes (see section "Method of administration and dosage").

This increased risk with age is common to all NSAIDs. Compared with younger patients, these patients have a longer plasma half-life and a reduced plasma clearance. Therefore, it is not recommended to prescribe a total daily dose exceeding 60 mg to elderly patients (see section 4.2).

Effects on the digestive tract. Epidemiological data suggest that, compared with some other NSAIDs, the use of ketorolac (especially off-label and/or long-term) may be associated with an increased risk of gastrointestinal disorders. Ketorolac trometamol can cause serious gastrointestinal adverse reactions, such as bleeding, ulceration and perforation of the gastrointestinal tract. These adverse reactions can occur in patients taking ketorolac trometamol at any time after or without warning symptoms and can be fatal. The risk of clinically serious gastrointestinal bleeding is dose-dependent. However, adverse reactions can occur even with short-term therapy. In addition to a history of peptic ulcer disease, especially with bleeding or perforation, predisposing factors include concomitant use of oral corticosteroids, anticoagulants, long-term NSAID therapy, smoking, alcohol consumption, advanced age, and poor general health. In such cases, the need to combine NSAIDs with gastroprotective agents, such as misoprostol or a proton pump inhibitor, should be carefully considered. Most spontaneous reports of gastrointestinal events have been in elderly or debilitated patients, and special care should be taken in the treatment of such patients, and ketorolac should be discontinued if suspected. Patients at risk should be offered alternative therapy that does not include NSAIDs. Patients (especially elderly) with a history of diagnosed gastrointestinal (GI) disorders should report any abdominal symptoms (especially gastrointestinal bleeding). It is important to pay close attention to these symptoms at the beginning of treatment.

If a patient taking ketorolac develops gastrointestinal bleeding or ulceration, the drug should be discontinued.

NSAIDs should be used with caution in patients with a history of Crohn's disease and ulcerative colitis due to the possibility of worsening of the disease.

NSAIDs, including ketorolac, may be associated with an increased risk of gastrointestinal anastomotic rupture. Close medical supervision and caution are recommended when ketorolac is used following gastrointestinal surgery.

Anaphylactic (anaphylactic-like) reactions (such as anaphylaxis, bronchospasm, flushing, rash, hypotension, laryngeal edema, and angioedema) may occur in patients with a history of hypersensitivity to aspirin, other NSAIDs, or intravenous ketorolac, as well as in those without a history of hypersensitivity reactions. Such reactions are more likely to occur in patients with a history of angioedema, bronchospastic reactions (e.g., asthma), or nasal polyps. These anaphylactic reactions may be fatal. Therefore, ketorolac should not be used in such patients with a history of asthma and in patients with complete or partial nasal polyposis syndrome, angioedema, or bronchospasm (see Contraindications).

Hematological effects.

Ketorolac should not be administered to patients with coagulation disorders. Concomitant use of ketorolac trometamol in patients receiving anticoagulant therapy increases the risk of bleeding. Detailed studies of the simultaneous use of ketorolac and prophylactic low-dose heparin (2500–5000 IU every 12 hours) have not been conducted. This regimen may also increase the risk of bleeding. Patients already taking anticoagulants or who require low-dose heparin should not receive ketorolac trometamol. Patients taking other drugs that negatively affect hemostasis should be closely monitored when ketorolac trometamol is administered. Clinical studies have shown that the incidence of postoperative bleeding is less than 1%. Ketorolac inhibits platelet aggregation and prolongs bleeding time. In patients with normal function, bleeding time was increased, but did not exceed the normal range of 2–11 minutes. In contrast to the prolonged effect of acetylsalicylic acid, platelet function returns to normal within 24–48 hours after discontinuation of ketorolac. Ketorolac trometamol should not be used in patients undergoing surgery with a high risk of bleeding or incomplete hemostasis. Caution should be exercised in cases where stable hemostasis is important, such as cosmetic or outpatient surgery, prostate resection or tonsillectomy. Hematomas and other signs of wound bleeding, as well as nosebleeds, have been reported with ketorolac.

When prescribing ketorolac, its similarity to other NSAIDs that inhibit cyclooxygenase and the potential risk of bleeding, especially in elderly patients, should be taken into account. Ketorolac trometamol is not an anesthetic and does not have sedative or anxiolytic properties.

Use in patients with renal impairment (see Contraindications). Like other NSAIDs, ketorolac inhibits prostaglandin synthesis and may have toxic effects on the kidneys (e.g. glomerular nephritis, interstitial nephritis, papillary renal necrosis, nephrotic syndrome, acute renal failure), therefore it should be used with caution in patients with impaired renal function or a history of kidney disease. Patients at risk include patients with impaired renal function, hypovolemia, heart failure, impaired liver function, patients taking diuretics, and elderly patients. Caution should be exercised in patients who may have a disease that may reduce blood volume and/or blood flow in the kidneys, where prostaglandins play an important role in maintaining perfusion. In such patients, the use of NSAIDs may cause dose-dependent inhibition of prostaglandin synthesis and renal failure.

Ketorolac may increase serum urea, creatinine, and potassium levels; abnormalities have been observed even after a single dose. Patients usually recover after discontinuation of NSAID therapy.

Patients with less severe renal impairment should receive lower doses of ketorolac (not more than 60 mg/day, intramuscularly). The renal status of such patients should be closely monitored. Patients should be well hydrated before starting treatment. Insufficient fluid/blood transfusion during surgery with subsequent hypovolemia may cause renal dysfunction, which is exacerbated by the administration of ketorolac. The decrease in extracellular fluid volume should be corrected; careful monitoring of serum urea and creatinine levels and monitoring of urine output is necessary until blood volume is normal.

In patients undergoing hemodialysis, ketorolac clearance was reduced to approximately half the normal rate, and the terminal T½ was increased almost threefold.

To minimize the potential risk of adverse cardiovascular events in patients taking NSAIDs, the lowest effective dose should be used for the shortest possible duration. Ketorolac trometamol should be prescribed to patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease only after careful consideration of the benefits and risks. Ketorolac should also be considered before initiating long-term treatment in patients at risk for cardiovascular disease (e.g., hypertension, hyperlipidemia, diabetes mellitus, and smokers).

Clinical trials and epidemiological data suggest that the use of some NSAIDs, particularly at high doses and over long periods, may be associated with a small increased risk of arterial thromboembolic events such as myocardial infarction or stroke. Such a risk cannot be excluded for ketorolac.

Use in patients with hepatic impairment. Ketorolac trometamol should be administered with caution to patients with hepatic impairment or a history of liver disease. In patients with hepatic impairment due to cirrhosis, ketorolac clearance and terminal half-life are not clinically significantly altered.

One or more liver function tests may be elevated. Significant elevations (greater than three times the upper limit of normal) of serum ALT and AST have been observed in less than 1% of patients. In addition, there have been isolated reports of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, hepatic necrosis and hepatic failure, some of which have been fatal. Ketorolac should be discontinued if clinical signs of liver disease or systemic manifestations (e.g. eosinophilia, rash) develop.

Respiratory system: The patient's condition should be monitored due to the possibility of bronchospasm.

Systemic lupus erythematosus and mixed connective tissue diseases.

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

Dermatological: Serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome and Lyell's syndrome have been reported very rarely in association with the use of NSAIDs. The risk of these reactions is highest at the beginning of treatment, with the first manifestations occurring in most cases within the first month of treatment. Patients should discontinue treatment with the drug at the first appearance of rash, mucosal lesions or other signs of hypersensitivity.

Fluid retention and edema: Fluid retention and edema have been reported with ketorolac, and it should be administered with caution to patients with cardiac decompensation, hypertension, or similar conditions.

This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.

This medicine contains a small amount of ethanol (alcohol) less than 100 mg/dose.

Use during pregnancy or breastfeeding

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

Pregnancy.

Safety during pregnancy has not been proven. It has been proven that ketorolac crosses the placental barrier and also enters the fetus. In this regard, ketorolac trometamol is contraindicated during pregnancy and during labor.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological data indicate an increased risk of spontaneous abortion, cardiac anomalies and gastroschisis after the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac anomalies increased from less than 1% to approximately 1.5%. This risk is believed to increase with increasing dose and duration of therapy. Animal studies have shown that the use of prostaglandin synthesis inhibitors leads to an increased frequency of pre-implantation loss of the fertilized egg and post-implantation abortion, as well as an increased risk of embryo-foetal mortality. In addition, there have been reports of an increased frequency of various anomalies, including cardiovascular anomalies, in animals treated with a prostaglandin synthesis inhibitor during the period of organogenesis.

From the 20th week of pregnancy, the use of ketorolac trometamol may cause oligohydramnios due to fetal renal dysfunction. This pathology can occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of narrowing of the ductus arteriosus after treatment in the second trimester, most of which were reversible after discontinuation of treatment.

Also, during pregnancy, all prostaglandin synthesis inhibitors can cause the fetus to:

- impaired renal function, which may progress to renal failure with the development of oligohydramnios (reduced amniotic fluid) (see above)

At the end of pregnancy, for the mother and newborn, these medications can:

- prolong bleeding time due to antiplatelet action, which may occur even when very low doses are used;

- inhibit uterine contractions, which can lead to delayed labor or prolonged labor.

Therefore, the use of ketorolac is contraindicated throughout pregnancy.

If the pregnant woman does take the drug, prenatal monitoring for oligohydramnios should be considered after exposure to ketorolac for several days, starting from the 20th week of pregnancy. Ketorolac should be discontinued.

Breast-feeding.

Ketorolac passes into breast milk in small amounts, so Ketanov is contraindicated during breastfeeding.

Fertility.

When used with other cyclooxygenase/prostaglandin synthesis inhibitors, the use of ketorolac may impair fertility; it is not recommended in women attempting to conceive. Women who have problems conceiving or are undergoing investigation for infertility should discontinue ketorolac.

Ability to influence reaction speed when driving vehicles or other mechanisms

During the period of treatment, it is necessary to refrain from potentially hazardous activities that require increased attention and speed of psychomotor reactions, due to the possible development of adverse reactions from the nervous system. Some patients during treatment with ketorolac may experience dizziness, fatigue, drowsiness, vertigo, visual impairment, insomnia and depression.

Method of administration and doses

It is recommended to use in a hospital setting.

After intramuscular administration, the analgesic effect is observed after approximately 30 minutes, with maximum analgesia occurring after 1–2 hours. In general, the average duration of analgesia is 4–6 hours. The dose should be adjusted depending on the severity of the pain and the patient's response to treatment. Continuous intramuscular administration of multiple daily doses of ketorolac should not exceed 2 days, since the risk of adverse reactions increases with prolonged use. Experience with long-term use is limited, since the vast majority of patients were transferred to oral administration or after a period of intramuscular administration, patients no longer required analgesic therapy. The risk of side effects can be minimized by using the lowest effective dose for the shortest period of time necessary to control symptoms.

The drug should not be administered epidurally or intraspinally.

Adults. The recommended initial dose of ketorolac trometamol is 10 mg (0.3 ml of the drug) followed by 10-30 mg (0.3-1 ml of the drug) every 4-6 hours (if necessary). In the initial postoperative period, ketorolac trometamol can be administered every 2 hours if necessary. The minimum effective dose should be prescribed. The total daily dose should not exceed 90 mg (3 ml of the drug) for young patients, 60 mg (2 ml of the drug) for elderly patients, patients with renal insufficiency and patients weighing less than 50 kg. The maximum duration of treatment should not exceed 2 days. In patients weighing less than 50 kg, the dose should be reduced.

Concomitant use of opioid analgesics (morphine, pethidine) is possible. Ketorolac does not have a negative effect on opioid receptor binding and does not enhance the respiratory depression or sedative effects of opioid drugs.

For patients receiving parenteral therapy who are transferred to oral ketorolac trometamol (tablets), the total combined daily dose should not exceed 90 mg (60 mg for elderly patients, patients with renal impairment, and patients weighing less than 50 kg). On the day of the change, the dose of the oral component should not exceed 40 mg. Patients should be transferred to the oral formulation as soon as possible.

Elderly patients: Patients aged 65 years and over should be prescribed the lower end of the dosage range. The total daily dose should not exceed 60 mg.

Patients with renal impairment. Ketorolac is contraindicated in moderate to severe renal impairment. For less severe impairment, the dosage should be reduced (not higher than 60 mg/day intramuscularly).

Children

Do not use in children under 16 years of age.

Overdose

Symptoms: lethargy, drowsiness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, hypertension, acute renal failure, respiratory depression and coma, convulsions. Anaphylactoid reactions have been reported.

Single overdoses of ketorolac at different times have resulted in pain