Instructions for Ketorolac-Mikrohim injection solution 3% ampoule 1 ml No. 10
Composition
active ingredient: ketorolac;
1 ml of solution for injection contains ketorolac tromethamine 30 mg;
Excipients: sodium chloride, disodium edetate, ethanol 96%, water for injections, sodium hydroxide.
Dosage form
Solution for injection.
Main physicochemical properties: clear yellowish solution.
Pharmacotherapeutic group
Drugs affecting the musculoskeletal system. Anti-inflammatory and antirheumatic drugs. Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related compounds. Ketorolac. ATC code M01A B15.
Pharmacological properties
Pharmacodynamics.
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug that exhibits analgesic activity. The mechanism of action of ketorolac, like that of other NSAIDs, is not fully understood, but may involve inhibition of prostaglandin synthesis. The biological activity of ketorolac tromethamine is associated with the S-form. Ketorolac tromethamine does not have sedative or anxiolytic properties.
The maximum analgesic effect of ketorolac is achieved within 2–3 hours. This effect is not statistically significantly different within the recommended dosage range. The greatest difference between high and low doses of ketorolac is the duration of analgesia.
Pharmacokinetics.
Ketorolac tromethamine 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 affected after intramuscular administration of ketorolac tromethamine at recommended doses. This indicates that the pharmacokinetics of ketorolac tromethamine in adults after single or multiple intramuscular administrations of the drug are linear. At higher recommended doses, there is a proportional increase in concentrations of the free and bound racemate.
Distribution
The mean apparent volume of distribution (Vβ) of ketorolac tromethamine after complete distribution was approximately 13 liters. This parameter was determined from single-dose data. The racemate ketorolac tromethamine has been shown to be highly bound to plasma proteins (99%). However, plasma concentrations above 10 μg/mL occupy approximately 5% of the albumin binding sites. Thus, the unbound fraction for each enantiomer will be constant over the therapeutic range. However, a decrease in serum albumin will result in an increase in free drug concentrations.
Ketorolac passes into breast milk.
Metabolism
Ketorolac tromethamine 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 half-life of the S-enantiomer of ketorolac tromethamine is approximately 2.5 hours (SD ± 0.4) and the R-enantiomer is 5 hours (SD ± 1.7). Other studies have reported a half-life of the racemate of 5–6 hours.
Accumulation
Ketorolac tromethamine administered intravenously as a bolus every 6 hours for 5 days to healthy volunteers (n = 13) showed no significant difference between Cmax on 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 achieved after the fourth dose. Accumulation of ketorolac tromethamine in specific patient groups (elderly, pediatric, renally impaired, or hepatically impaired) has not been studied.
Pharmacokinetics in specific patient groups
Elderly patients
Based on data obtained after a single administration, the elimination half-life of the racemate ketorolac tromethamine was increased from 5 to 7 hours in elderly patients (65-78 years) compared to young healthy volunteers (24-35 years). There was no significant difference in Cmax between the two groups (elderly patients: 2.52 μg/mL ± 0.77; young patients: 2.99 μg/mL ± 1.03).
Children
Pharmacokinetic data on intramuscular administration of ketorolac tromethamine in children are not available.
Based on data obtained after a single dose, the mean elimination half-life of ketorolac tromethamine in patients with renal impairment is 6-19 hours and depends on the severity of the impairment. There is little correlation between creatinine clearance and total clearance of ketorolac tromethamine in elderly patients and patients with renal impairment (r = 0.5). In patients with renal disease, the AUC∞ of each enantiomer is increased by almost 100% compared to healthy volunteers. The volume of distribution is doubled for the S-enantiomer and increased by 1/5 for the R-enantiomer. The increase in the volume of distribution of ketorolac tromethamine indicates an increase in the unbound fraction.
The AUC∞ ratio of ketorolac enantiomers in healthy volunteers and patients remained similar, indicating non-selective excretion of enantiomers in patients compared to healthy volunteers.
Liver failure
The values of half-life, AUC∞ and Cmax in 7 patients with liver disease were not significantly different from those in healthy volunteers.
Indication
Ketorolac tromethamine is indicated for the short-term (≤ 5 days) treatment of moderate to severe pain requiring opioid-level analgesia, usually in the postoperative period.
Contraindication
- Hypersensitivity to ketorolac or to any other component of the drug;
- patients with active peptic ulcer, recent gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding;
- bronchial asthma, angioedema or urticaria caused by the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (due to the possibility of severe anaphylactic reactions);
- do not use as an analgesic before and during surgery;
- do not use during the postoperative period following coronary artery bypass grafting;
- severe renal failure or risk of renal failure due to fluid volume depletion;
- do not use during labor and delivery (due to the inhibitory effect of ketorolac tromethamine on prostaglandin synthesis, it may negatively affect fetal blood circulation and inhibit uterine contractions, thereby increasing the risk of uterine bleeding);
- suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, including blood clotting disorders and high risk of bleeding (due to the ability to inhibit platelet function);
- simultaneous treatment with other NSAIDs, acetylsalicylic acid (due to the cumulative risk of serious adverse reactions associated with NSAIDs);
- simultaneous use with probenecid;
- simultaneous use with pentoxifylline;
- neuraxial (epidural or intrathecal) administration of the drug (due to alcohol content).
Interaction with other medicinal products and other types of interactions
Ketorolac is extensively bound to plasma proteins (average 99.2%). Ketorolac tromethamine does not alter the pharmacokinetics of other agents through enzyme induction or inhibition.
Warfarin, digoxin, salicylates, and heparin
Ketorolac tromethamine 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 mcg/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 tromethamine.
The effects of warfarin and NSAIDs in general on gastrointestinal bleeding are synergistic, so the risk of serious gastrointestinal bleeding is higher in patients who use both drugs simultaneously than in those who use one.
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, it is not recommended to prescribe ketorolac tromethamine and acetylsalicylic acid simultaneously due to the potential increase in the frequency of adverse events.
Diuretics
Clinical studies and post-marketing experience with ketorolac tromethamine have shown that in some patients it can reduce the natriuretic effect of furosemide and thiazides. This effect is due to the inhibition of prostaglandin synthesis in the kidneys by NSAIDs. During concomitant therapy with NSAIDs, the patient should be carefully observed for signs of renal failure, as well as to ensure the effectiveness of diuretics.
Probenecid
Concomitant use of ketorolac tromethamine and probenecid resulted in a decrease in the clearance and volume of distribution of ketorolac tromethamine and a significant increase in its plasma levels (total AUC increased approximately 3-fold from 5.4 to 17.8 μg/h/mL) and half-life (approximately 2-fold from 6.6 to 15.1 hours). Therefore, concomitant use of ketorolac tromethamine and probenecid is contraindicated.
NSAIDs have been shown to increase plasma lithium levels and decrease renal lithium clearance. The mean trough lithium concentration was increased by 15% and renal clearance was decreased by approximately 20%. This effect is due to the inhibition of prostaglandin synthesis in the kidney by NSAIDs. Patients should be observed closely for signs of lithium toxicity when NSAIDs and lithium are used concomitantly.
Methotrexate
NSAIDs have been reported to competitively inhibit the accumulation of methotrexate in rabbit kidney slices. This suggests that NSAIDs may potentiate the toxicity of methotrexate. Caution should be exercised when NSAIDs and methotrexate are administered concomitantly.
ACE inhibitors/angiotensin II antagonists
Concomitant use of ACE inhibitors and/or angiotensin II antagonists may increase the risk of renal dysfunction, particularly in patients with reduced interstitial fluid volume.
NSAIDs may reduce the hypotensive effect of ACE inhibitors and/or angiotensin II antagonists. This interaction should be borne in mind when NSAIDs are prescribed together with ACE inhibitors and/or angiotensin II antagonists.
Anticonvulsants
Isolated cases of seizures have been reported during concomitant use of ketorolac tromethamine and anticonvulsants (phenytoin, carbamazepine).
Psychotropic drugs
Hallucinations have been reported with the concomitant use of ketorolac and psychotropic drugs (fluoxetine, thiotexene, alprazolam).
Pentoxifylline
Concomitant use of ketorolac tromethamine and pentoxifylline increases the risk of bleeding.
Non-depolarizing muscle relaxants
There have been post-marketing reports of a possible interaction between ketorolac tromethamine and non-depolarizing muscle relaxants resulting in apnea. No formal studies have been conducted on the concomitant use of ketorolac tromethamine and muscle relaxants.
Selective serotonin reuptake inhibitors (SSRIs)
There is an increased risk of gastrointestinal bleeding with concomitant use of SSRIs and NSAIDs. Caution should be exercised when using them concomitantly.
Application features
Combined use of ketorolac tromethamine intramuscularly and orally in adult patients should not exceed 5 days.
Impact on fertility
Women who are unable to become pregnant and are undergoing evaluation for this should discontinue use of ketorolac tromethamine. Women of reduced fertility should avoid use of the drug.
Effects on the digestive tract
Ketorolac tromethamine is contraindicated in patients with active peptic ulcer and/or a history of gastrointestinal bleeding.
Ketorolac tromethamine can cause serious gastrointestinal adverse reactions, including bleeding, ulceration, and perforation of the stomach, small intestine, and colon, which can be fatal. These adverse reactions can occur in patients taking ketorolac tromethamine at any time, with or without warning symptoms.
Only one in five patients taking NSAIDs develop serious upper gastrointestinal symptoms. Minor upper gastrointestinal problems, such as dyspepsia, are common and can also occur at any time during NSAID treatment.
The frequency and severity of gastrointestinal complications increase with increasing dose and duration of treatment with ketorolac tromethamine. It is not recommended to use ketorolac tromethamine for more than 5 days.
However, even short-term therapy is not without risk. In addition to a history of peptic ulcer disease, predisposing factors that increase the risk of gastrointestinal bleeding in patients receiving NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, alcohol consumption, older age, and poor general health. Most spontaneous reports of gastrointestinal deaths have involved elderly or debilitated patients, and caution should be exercised when prescribing to this population.
To minimize the potential risk of gastrointestinal adverse events, the lowest effective dose of ketorolac tromethamine should be used for the shortest duration possible. Patients should be monitored for signs and symptoms of gastrointestinal adverse events and bleeding during NSAID therapy and appropriate treatment should be initiated as necessary. Such measures should include discontinuation of ketorolac tromethamine until symptoms of serious gastrointestinal adverse events have resolved. Alternative treatments that do not involve NSAIDs should be considered in patients at high risk of such adverse events.
NSAIDs should be prescribed with caution to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) due to the risk of exacerbation.
Anemia has been reported in patients receiving NSAIDs. This may be due to occult or significant blood loss, fluid retention, or an effect on erythropoiesis that has not yet been fully characterized. If a patient develops any signs or symptoms of anemia while receiving ketorolac tromethamine, hemoglobin or hematocrit should be monitored. In some patients, NSAIDs inhibit platelet aggregation and have been shown to increase bleeding time. In contrast to acetylsalicylic acid, their effect on platelet function is quantitatively smaller, less prolonged, and reversible. Patients with bleeding disorders or those receiving anticoagulants should be closely monitored.
Since prostaglandins play an important role in hemostasis and NSAIDs also affect platelet aggregation, the use of ketorolac tromethamine in patients with bleeding disorders should be carried out with special caution and under medical supervision. Patients receiving therapeutic doses of anticoagulants (e.g. heparin or dicumarol derivatives) are at increased risk of bleeding; therefore, such concomitant therapy should be used with extreme caution. The simultaneous use of ketorolac tromethamine and prophylactic low-dose heparin (2500 to 5000 units every 12 hours), warfarin and dextrans has not been studied, but this regimen may also increase the risk of bleeding. In the absence of data from such studies, it is necessary to assess the benefit/risk ratio and use such concomitant therapy in patients with special caution. Patients taking other medications that adversely affect hemostasis should be closely monitored when using ketorolac tromethamine.
Post-marketing experience with perioperative intramuscular use of ketorolac tromethamine has shown the occurrence of postoperative hematomas and other signs of wound bleeding. Therefore, perioperative and postoperative use of ketorolac tromethamine should be avoided; caution should be exercised when used in patients at increased risk of bleeding.
Effects on the kidneys
Long-term use of NSAIDs has led to renal medullary necrosis and other renal disorders.
Nephrotoxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. In such patients, the use of NSAIDs may cause a dose-dependent decrease in prostaglandin production and, as a result, a decrease in renal blood flow, which may cause marked decompensation of renal function. Patients at increased risk of developing these reactions include patients with impaired renal function, dehydration, hypovolemia, heart failure, liver disease, patients taking diuretics, ACE inhibitors, and elderly patients. Discontinuation of the drug is usually accompanied by a return to the state observed before the start of treatment.
Ketorolac tromethamine and its metabolites are excreted primarily by the kidneys, which in patients with reduced creatinine clearance leads to a decrease in drug clearance. Therefore, ketorolac tromethamine should be used with caution and under close medical supervision in patients with impaired renal function (see section 4.2). Acute renal failure, interstitial nephritis, and nephrotic syndrome have been reported.
Kidney dysfunction
Ketorolac tromethamine is contraindicated in patients with severe renal impairment (see Contraindications). Because ketorolac tromethamine is a potent inhibitor of prostaglandin synthesis, it should be used with caution in patients with pre-existing renal impairment or a history of renal disease. Because patients with renal impairment are at increased risk of developing acute renal decompensation or failure, the benefits and risks of using ketorolac tromethamine in such patients should be weighed.
Anaphylactic reactions
As with other NSAIDs, anaphylactic reactions may occur in patients without ketorolac tromethamine. The drug should not be prescribed to patients with the aspirin triad. This symptom complex usually occurs in patients with asthma and diagnosed rhinitis with or without nasal polyps, or in whom severe, potentially fatal bronchospasm is observed against the background of the use of acetylsalicylic acid or other NSAIDs (see sections "Contraindications" and "Special instructions for use"). In case of anaphylactic reactions, medical help should be sought.
Effects on the cardiovascular system
Clinical trials of several selective and nonselective COX-2 inhibitors of the NSAID class of drugs of up to 3 years duration have shown an increased risk of serious thrombotic adverse events, including myocardial infarction and stroke, which can be fatal. Based on the available data, it is unclear whether the risk of thrombotic cardiovascular events is similar for all NSAIDs. The relative increase in the incidence of serious thrombotic cardiovascular events compared to baseline, which is associated with the use of NSAIDs, occurs both in patients with known cardiovascular disease and risk factors for it, and in patients without such diseases and factors. However, patients with known cardiovascular disease or risk factors for cardiovascular disease had an even higher absolute incidence of serious thrombotic cardiovascular events due to the increased incidence of these factors and conditions at baseline. Some observational studies have found that this increased risk of serious thrombotic cardiovascular events was evident as early as the first weeks of treatment. The increased risk of thrombotic cardiovascular events was most consistently observed at higher doses.
To minimize the potential risk of cardiovascular adverse reactions in patients taking NSAIDs, the lowest effective dose should be used for the shortest possible duration of treatment. Physicians and patients should be closely monitored for the development of such reactions throughout the course of treatment, even in the absence of a history of cardiovascular symptoms. Patients should be informed of the symptoms of serious cardiovascular adverse reactions and the measures to be taken if they occur.
There is no direct evidence that concomitant use of acetylsalicylic acid reduces the increased risk of serious thrombotic cardiovascular events associated with the use of NSAIDs. Concomitant use of acetylsalicylic acid and NSAIDs, including ketorolac tromethamine, increases the risk of serious gastrointestinal reactions (see section "Special warnings and precautions for use").
Condition after coronary artery bypass graft surgery
Two large controlled clinical trials of COX-2 selective NSAIDs for pain control in the first 10–14 days after coronary artery bypass grafting showed an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in coronary artery bypass grafting (see section 4.3).
Patients after myocardial infarction
In an observational study conducted by the Danish National Registry, it was demonstrated that patients who used NSAIDs in the period after myocardial infarction were at increased risk of recurrent infarction, cardiovascular death, and death from any cause, starting from the first week of treatment. In the same group of patients who used NSAIDs, the incidence of death in the first year after myocardial infarction was 20 cases per 100 person-years compared with 12 cases per 100 person-years among patients who did not use NSAIDs. Although the absolute number of deaths decreases after the first year after myocardial infarction, analysis of the results of at least four subsequent years of follow-up showed that the increased relative risk of death in patients who used NSAIDs persists.
Ketorolac tromethamine should be avoided in patients with recent myocardial infarction unless the expected benefit of treatment outweighs the risk of recurrent thrombotic cardiovascular events. If ketorolac tromethamine is used in patients with recent myocardial infarction, the patient should be monitored for signs of cardiac ischemia.
Arterial hypertension
The use of NSAIDs, including ketorolac tromethamine, may lead to the development of arterial hypertension or aggravation of pre-existing arterial hypertension, and in each case an increase in the frequency of adverse reactions from the cardiovascular system is possible. Patients taking thiazide diuretics or loop diuretics may experience an impaired response to these drugs when using NSAIDs. NSAIDs, including ketorolac tromethamine, should be used with caution in patients with arterial hypertension. Blood pressure should be monitored when initiating treatment with NSAIDs and throughout the course of therapy.
Heart failure and edema
Results from the Trialists' Collaboration meta-analysis and randomized controlled trials of coxibs and traditional NSAIDs demonstrated an approximately two-fold increase in hospitalizations for heart failure in patients treated with COX-2 selective and non-selective drugs, and in patients treated with non-selective NSAIDs, compared with patients treated with placebo.
In addition, fluid retention and edema have been observed in some patients taking NSAIDs. The use of ketorolac tromethamine may attenuate the cardiovascular effects of several medicinal products used to treat these conditions (e.g. diuretics, ACE inhibitors or angiotensin receptor blockers) (see section "Interaction with other medicinal products and other forms of interaction").
Ketorolac tromethamine should be avoided in patients with severe heart failure unless the expected benefit of treatment outweighs the risk of worsening heart failure. If ketorolac tromethamine is used in patients with severe heart failure, patients should be monitored for signs of worsening heart failure.
Serious skin reactions
Ketorolac tromethamine can cause serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which can be fatal. These serious reactions can occur without warning symptoms.
Patients should be informed of the signs and symptoms of serious skin reactions and the need to discontinue ketorolac tromethamine at the first appearance of a skin rash or any other sign of hypersensitivity.
Pregnancy
Ketorolac tromethamine, like other NSAIDs, may cause premature closure of the ductus arteriosus, so the drug should be avoided in pregnant women in later stages of pregnancy.
Liver dysfunction
Ketorolac tromethamine should be used with caution in patients with impaired hepatic function or a history of liver disease. Elevations of hepatic enzymes have been observed in 15% of patients receiving NSAIDs, including ketorolac tromethamine. These laboratory abnormalities may progress or may remain unchanged, or may be transient with continued therapy. Significant elevations of serum ALT and AST (greater than 3 times the upper limit of normal) have been observed in less than 1% of patients in controlled clinical trials. In addition, isolated cases of severe hepatic reactions, including fatal fulminant hepatitis, hepatic necrosis, and hepatic failure, some fatal, have been reported.
Patients with symptoms and signs of liver dysfunction or with abnormal liver function tests should be evaluated for evidence of more severe hepatic impairment. Ketorolac tromethamine should be discontinued if clinical symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) develop.
The total dose for patients aged 65 years and over should not exceed 60 mg.
Exacerbation of bronchial asthma associated with sensitivity to acetylsalicylic acid
Patients with bronchial asthma may have aspirin-induced asthma. The use of acetylsalicylic acid in patients with aspirin-induced asthma associated with severe bronchospasm may be fatal. Since cross-reactivity, including bronchospasm, between acetylsalicylic acid and other NSAIDs has been reported in such acetylsalicylic acid-sensitive patients, ketorolac tromethamine should not be prescribed to patients with this form of acetylsalicylic acid sensitivity and should be used with caution in patients with bronchial asthma.
Monitoring of laboratory test results
Since serious gastrointestinal bleeding, hepatotoxicity, and renal injury may occur without warning symptoms and signs, consideration should be given to monitoring patients receiving the drug for a long period with periodic complete blood count and biochemical blood tests.
This medicine contains a small amount of ethanol (alcohol), less than 100 mg/dose.
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Data obtained for animals
Reproductive studies were conducted during organogenesis using daily oral doses of ketorolac tromethamine of 3.6 mg/kg (0.37 times the human AUC) in rabbits and 10 mg/kg (1.0 times the human AUC) in rats. These studies revealed no evidence of teratogenicity to the fetus. Animal studies are not always adequate to assess the potential for adverse developmental effects in humans.
Data obtained for humans
There are no adequate and well-controlled studies of ketorolac tromethamine in pregnant women. The use of ketorolac tromethamine during pregnancy is recommended only if the benefit to the mother outweighs the potential risk to the fetus.
Due to the known effects of NSAIDs on the fetal cardiovascular system (premature closure of the ductus arteriosus), the use of the drug should be avoided during pregnancy (especially in the third trimester).
Labor and delivery
The use of ketorolac tromethamine is contraindicated during labor and delivery because, due to its inhibitory effect on prostaglandin synthesis, it may have a negative effect on fetal circulation and suppress uterine contractions, thereby increasing the risk of bleeding.
The use of ketorolac tromethamine, as with any drug that inhibits cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Discontinuation of ketorolac tromethamine should be considered in women who have difficulty conceiving or who are undergoing investigation of infertility.
Breast-feeding
Limited data from one published study of 10 mothers who breastfed for 2–6 days postpartum suggest low levels of ketorolac in breast milk. Levels were undetectable (less than 5 mg/mL) in 4 patients. After a single 10 mg dose of ketorolac, the maximum milk concentration was 7.3 ng/mL, and the maximum milk-to-plasma ratio was 0.037.
After daily dosing of ketorolac (10 ml every 6 hours), the maximum milk concentration was 7.9 ng/ml and the maximum milk-to-plasma ratio was 0.025. Based on daily intake of 400–1000 ml of breast milk and a maternal body weight of 60 kg, the maximum daily dose for infants was calculated to be 0.00263 mg/kg, 0.4% of the maternal weight-adjusted dose.
Do not use during breastfeeding due to the possible negative effects of prostaglandin synthesis inhibitors on infants.
Ability to influence reaction speed when driving vehicles or other mechanisms
During the treatment period, it is necessary to refrain from potentially dangerous activities that require increased attention and speed of psychomotor reactions due to the possible development of adverse reactions from the nervous system.
Method of administration and doses
After intramuscular administration, the analgesic effect is observed after approximately 30 minutes, and maximum analgesia occurs 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 last more than 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 of the drug or after a period of intramuscular administration, patients no longer required analgesic therapy. The likelihood 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 tromethamine, solution for intramuscular injection, is 10 mg, followed by 10-30 mg every 4-6 hours (if necessary). In the initial postoperative period, ketorolac tromethamine can be administered every 2 hours if necessary. The minimum effective dose should be prescribed. The total daily dose should not exceed 90 mg for young patients, 60 mg for elderly patients, patients with renal insufficiency and body weight less than 50 kg. The maximum duration of treatment should not exceed 2 days. The dose should be reduced in patients weighing less than 50 kg. Concomitant use of opioid analgesics (morphine, pethidine) is possible. Ketorolac does not adversely affect opioid receptor binding and does not increase the respiratory depression or sedative effect of opioid drugs. For parenterally treated patients who are switched to oral ketorolac tromethamine 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), and on the day of the change, the dose of the oral component should not exceed 40 mg. Patients should be switched to the oral formulation as soon as possible.
Elderly patients
Because ketorolac tromethamine is more slowly absorbed in elderly patients, especially those who are susceptible to dose-related adverse reactions, it is recommended that the lowest dosage be used and that patients be monitored for adverse reactions.
Patients with renal impairment
Ketorolac tromethamine is contraindicated in renal impairment.
