Ketorol Express dispersible tablets 10 mg No. 10

Instructions for Ketorol Express dispersible tablets 10 mg No. 10

Composition

active ingredient: ketorolac tromethamine;

1 tablet contains ketorolac tromethamine 10 mg;

excipients: microcrystalline cellulose, silicon dioxide, butylhydroxyanisole (E 320), mannitol (E 421), crospovidone, sucralose, magnesium stearate, dye (Lake Of Quinoline Yellow WS), flavoring (Spearmint Flavor).

Dosage form

Orodispersible tablets.

Main physicochemical properties: round, flat tablets of pale yellow color, with beveled edges and embossed "׀" on one side.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs. Ketorolac. ATC code M01A B15.

Pharmacological properties

Pharmacodynamics

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID), has a pronounced analgesic (pain-relieving) effect, also exhibits anti-inflammatory and weak antipyretic activity. The analgesic effect of the drug is based on its ability to inhibit the synthesis of cyclooxygenase enzymes (COX-1 and COX-2). In this regard, prostaglandins that contribute to inflammation, fever and pain are not formed in the body's tissues. In terms of the strength of the analgesic effect, ketorolac can be compared with morphine, which significantly exceeds other NSAIDs.

Ketorolac does not affect opiate receptors, does not depress respiration, does not cause drug dependence, and does not have a sedative or anxiolytic effect.

The onset of analgesic effect is observed 1 hour after internal administration of the drug. The maximum analgesic effect is achieved within 2–3 hours and does not have statistically significant differences within the recommended dosage range of ketorolac tromethamine. The largest difference between high and low doses of ketorolac tromethamine is the duration of analgesia.

Pharmacokinetics

After oral administration, ketorolac is rapidly and completely absorbed with peak plasma concentrations of 0.52–1.31 μg/mL occurring within 35 minutes after a single 10 mg dose under fasting conditions. A high-fat meal delays the rate (by approximately 1 hour) but not the extent of absorption. Antacids did not affect absorption. Ketorolac pharmacokinetics are linear.

Ketorolac tromethamine crosses the placental barrier and is excreted in breast milk in very small amounts.

More than 99% of the racemate ketorolac tromethamine is extensively bound to plasma proteins. Steady-state concentrations are reached within 24 hours after administration of 10 mg ketorolac 4 times daily.

The drug is extensively metabolized in the liver to form inactive metabolites.

Ketorolac and its metabolites are excreted mainly by the kidneys: on average 91.4% of the administered dose is excreted in the urine, 6.1% in the feces.

The half-life in patients with normal renal function is approximately 5–6 hours.

In patients aged 65 years and older, the half-life may increase from 5 to 7 hours. The average half-life of ketorolac in patients with renal insufficiency depends on the severity of the disease and ranges from 6 to 19 hours, indicating the need for dose adjustment.

Liver dysfunction does not affect the half-life of the drug.

Not removed by hemodialysis.

Indication

Ketorol Express is indicated for short-term (no more than 5 days) treatment of moderate pain, as well as acute pain of various origins, including postoperative pain.

Contraindication

Hypersensitivity to ketorolac or any component of the drug; patients with active peptic ulcer, recent gastrointestinal bleeding or perforation, with a history of peptic ulcer or gastrointestinal bleeding; bronchial asthma, rhinitis, angioedema or urticaria caused by the use of acetylsalicylic acid or other NSAIDs (due to the possibility of severe anaphylactic reactions); history of bronchial asthma; do not use as an analgesic before and during surgery and after manipulations on the coronary vessels; severe heart failure; nasal polyposis with complete or partial obstruction, Quincke's edema or bronchospasm; do not use in patients who have had surgery with a high risk of hemorrhage or incomplete hemostasis and patients receiving anticoagulants, including low-dose heparin (2500-5000 units every 12 hours); hepatic or moderate/severe renal failure (serum creatinine clearance over 160 μmol/l); ketorolac is contraindicated during labor and delivery, as due to its inhibitory effect on prostaglandin synthesis, it may adversely affect fetal circulation and suppress 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; concomitant treatment with other NSAIDs (including selective cyclooxygenase inhibitors), acetylsalicylic acid, warfarin, pentoxifylline, probenecid or lithium salts; hypovolemia, dehydration; risk of renal failure due to fluid volume depletion.

Interaction with other medicinal products and other types of interactions

Ketorolac is extensively bound to plasma proteins (average 99.2%). There is no evidence from animal or human studies that ketorolac tromethamine induces or inhibits hepatic enzymes that metabolize it or other drugs.

Warfarin, digoxin, salicylates and heparin.

Ketorolac tromethamine slightly reduced the plasma protein binding of warfarin in vitro (99.5% in control vs. 99.3%) at ketorolac plasma concentrations of 5–10 μg/mL. Ketorolac tromethamine 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 did not alter the plasma protein binding of ketorolac tromethamine.

The effects of warfarin and NSAIDs in general on gastrointestinal (GI) bleeding are synergistic, such that patients taking these drugs together have a higher risk of serious GI bleeding than patients taking either drug alone.

Acetylsalicylic acid.

When ketorolac tromethamine is administered with acetylsalicylic acid, its binding to plasma proteins is reduced, although the clearance of free ketorolac tromethamine is not altered. The clinical significance of this interaction is unknown; however, as with other NSAIDs, concomitant administration of ketorolac tromethamine and acetylsalicylic acid is generally not recommended due to the potential for increased adverse effects.

Diuretics.

Clinical studies and post-marketing surveillance have shown that in some patients ketorolac tromethamine may reduce the natriuretic effect of furosemide and thiazides. This effect is due to inhibition of prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be closely monitored for signs of renal failure, as well as to ensure the effectiveness of the diuretic.

Probenecid.

Concomitant administration of ketorolac tromethamine tablets and probenecid resulted in a decrease in ketorolac clearance and volume of distribution and a significant increase in plasma levels (total AUC increased approximately 3-fold from 5.4 to 17.8 μg/h/mL) and ketorolac half-life increased approximately 2-fold from 6.6 to 15.1 hours. Therefore, concomitant administration of ketorolac tromethamine tablets and probenecid is contraindicated.

Lithium.

NSAIDs have been shown to increase plasma lithium levels and decrease renal lithium clearance. Mean trough lithium concentrations were increased by 15% and renal clearance was decreased by approximately 20%. These effects were due to the inhibition of prostaglandin synthesis in the kidney by NSAIDs. Therefore, patients should be carefully observed for signs of lithium toxicity when NSAIDs are used concomitantly with lithium.

Methotrexate.

NSAIDs have been reported to competitively inhibit the accumulation of methotrexate in rabbit kidney slices. This may indicate that they may potentiate the toxicity of methotrexate. Caution should be exercised when NSAIDs and methotrexate are used concomitantly.

ACE inhibitors/angiotensin II receptor antagonists.

Concomitant use of ACE inhibitors and/or angiotensin II receptor antagonists may increase the risk of renal dysfunction, particularly in patients with reduced interstitial fluid volume.

There are reports that NSAIDs may reduce the antihypertensive effect of ACE inhibitors and/or angiotensin II receptor antagonists. This interaction should be borne in mind when prescribing NSAIDs to patients with ACE inhibitors and/or angiotensin II receptor antagonists.

Anticonvulsants.

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

Psychotropic drugs.

When ketorolac tromethamine was used in patients taking psychotropic drugs (fluoxetine, thiothixene, alprazolam), hallucinations were reported.

Pentoxifylline.

Concomitant use of ketorolac tromethamine and pentoxifylline increases the risk of bleeding.

Non-depolarizing muscle relaxants.

There have been postmarketing reports of a possible interaction between ketorolac tromethamine and non-depolarizing muscle relaxants resulting in apnea. Concomitant use of ketorolac tromethamine and muscle relaxants has not been formally studied.

Selective serotonin reuptake inhibitors (SSRIs).

There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are used in combination with NSAIDs. Caution should be exercised when NSAIDs and SSRIs are used concomitantly.

Application features

Ketorolac tablets, a nonsteroidal anti-inflammatory drug (NSAID), are indicated for short-term (up to 5 days in adult patients). The drug should be used for symptomatic treatment of moderately severe acute pain, including postoperative pain, requiring analgesia at the opioid level. Ketorolac tablets are not indicated for use in children, and are also not indicated for chronic pain syndrome. The total duration of combined use of ketorolac (as IV or IM injections and as tablets) should not exceed 5 days due to the possibility of an increase in the frequency and severity of adverse reactions associated with recommended doses.

The minimum effective dose should be used for the shortest duration for each individual patient.

The interval between doses should not be reduced from 4 to 6 hours.

Exceeding the maximum daily dose of ketorolac tablets 40 mg in adults will not provide better efficacy, but will increase the risk of serious adverse events.

Effects on the gastrointestinal tract – ulceration, bleeding and perforation

Ketorolac tromethamine is contraindicated in patients with a history of peptic ulcer and/or GI bleeding. Ketorolac tromethamine can cause serious GI adverse events, including bleeding, ulceration, and perforation of the stomach, small intestine, or colon, which can be fatal. These serious adverse events can occur in patients receiving ketorolac tromethamine at any time, with or without warning symptoms.

Only one in five patients who experienced serious upper GI adverse events with NSAIDs experienced symptoms. Minor upper GI problems, such as dyspepsia, are common and may occur at any time during NSAID treatment. The incidence and severity of GI complications increase with increasing dose and duration of treatment with ketorolac tromethamine. Ketorolac tromethamine should not be used for more than 5 days. However, even short-term therapy does not eliminate the risk. In addition to a history of peptic ulcer disease, other factors that increase the risk of GI 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 fatal gastrointestinal events have occurred in elderly or debilitated patients, so special care should be taken when treating this population.

To minimize the potential risk of gastrointestinal adverse events, the drug should be used at the lowest effective dose for the shortest possible duration. Patients and physicians should be alert for signs and symptoms of gastrointestinal ulceration and bleeding during NSAID therapy, and if a serious gastrointestinal adverse event is suspected, additional evaluation and treatment should be initiated promptly. This should include discontinuation of ketorolac tromethamine until the serious gastrointestinal adverse event has been ruled out. Alternative therapy that does not include NSAIDs should be considered for high-risk patients.

NSAIDs should be used with caution in patients with inflammatory bowel diseases (ulcerative colitis, Crohn's disease), as their condition may worsen.

Bleeding

Because prostaglandins play an important role in hemostasis and NSAIDs also affect platelet aggregation, ketorolac tromethamine should be used with caution in patients with coagulation disorders and should be closely monitored. Patients receiving therapeutic doses of anticoagulants (e.g., heparin or dicumarol derivatives) are at increased risk of bleeding when given concomitantly with ketorolac tromethamine; therefore, physicians should use such concomitant therapy with extreme caution. The concomitant use of ketorolac tromethamine and drugs that affect hemostasis, including prophylactic low-dose heparin (2500 to 5000 units every 12 hours), warfarin, and dextrans, has not been thoroughly studied but may also be associated with an increased risk of bleeding. Until such data are available, physicians should carefully weigh the benefits and risks and use such concomitant therapy in these patients with extreme caution. Patients receiving drugs that affect hemostasis should be carefully monitored.

Effects on the kidneys

Ketorolac tromethamine and its metabolites are excreted primarily by the kidneys, which in patients with reduced creatinine clearance will result in reduced clearance of the drug.

Therefore, ketorolac tromethamine should be used with caution in patients with impaired renal function, and such patients should be closely monitored. Acute renal failure, interstitial nephritis, and nephrotic syndrome have been reported with ketorolac tromethamine.

Kidney dysfunction

Ketorolac tromethamine is contraindicated in patients with serum creatinine levels indicative of progressive renal impairment. Ketorolac tromethamine should be used with caution in patients with impaired renal function or a history of renal disease because it is a potent inhibitor of prostaglandin synthesis. Because patients with renal impairment are at increased risk of developing acute renal decompensation or failure, the risks and benefits of treatment should be considered before prescribing ketorolac tromethamine to these patients.

Anaphylactoid reactions

As with all NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure or hypersensitivity to ketorolac tromethamine. Ketorolac tromethamine should not be given to patients with the aspirin triad. This symptom complex usually occurs in patients with bronchial asthma who have rhinitis with or without nasal polyps or who have experienced severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Anaphylactoid reactions, such as anaphylaxis, can be fatal. If an anaphylactoid reaction occurs, emergency medical attention should be sought.

Effects on the cardiovascular system

Cardiovascular thrombotic events

Clinical trials of several COX-2-selective and nonselective NSAIDs lasting up to 3 years have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on the available data, it is unclear whether the risk of CV thrombotic events is the same for all NSAIDs. The relative increase in the incidence of serious CV thrombotic events from baseline caused by NSAID use is similar in patients with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of additional serious CV thrombotic events due to their increased baseline incidence. Some observational studies have found that this increased risk of serious CV thrombotic events began within the first weeks of treatment. The increased risk of CV thrombotic events was greater with higher doses of the drug.

To minimize the potential risk of cardiovascular adverse events in patients receiving NSAIDs, the lowest effective dose should be used for the shortest possible duration. Physicians and patients should be alert for the development of such events throughout the course of treatment, even in the absence of previous cardiovascular symptoms. Patients should be informed of the symptoms of serious cardiovascular events and what to do if they occur.

There is no adequate evidence that concomitant use of acetylsalicylic acid reduces the increased risk of serious CV thrombotic events associated with NSAID use. Concomitant use of acetylsalicylic acid and NSAIDs such as ketorolac tromethamine increases the risk of serious gastrointestinal (GI) events.

Condition after coronary artery bypass grafting (CABG)

In two large controlled clinical trials of COX-2-selective NSAIDs for pain management during the first 10–14 days after CABG, an increased incidence of myocardial infarction and stroke was observed. NSAIDs are contraindicated during CABG.

Patients after myocardial infarction

Observational studies conducted in the Danish National Registry demonstrated that patients receiving NSAIDs after MI had an increased risk of recurrent infarction, CV death, and all-cause mortality from the first week of treatment. In the same cohort, the rate of death in the first year after MI was 20 per 100 patient-years in patients receiving NSAIDs compared with 12 per 100 patient-years in patients not receiving NSAIDs. Although the absolute rate of death decreased somewhat after the first year after MI, the increased relative risk of death in those taking NSAIDs persisted for at least the next 4 years of follow-up.

Ketorolac tromethamine should be avoided in patients with a recent MI unless the benefits of treatment are expected to outweigh the risk of recurrent CV thrombotic events. If ketorolac tromethamine is used in patients with a recent MI, patients should be monitored for signs of cardiac ischemia.

Arterial hypertension

In patients receiving thiazide or loop diuretics, the response to these drugs may be impaired when NSAIDs are used. NSAIDs, including ketorolac tromethamine, should be used with caution in patients with hypertension. Blood pressure (BP) should be closely monitored when initiating NSAID therapy and throughout the course of therapy.

Heart failure and edema

A meta-analysis of randomized controlled trials conducted by the Coxibs and Traditional NSAIDs Consortium demonstrated an approximately 2-fold increase in hospitalization for heart failure in patients treated with COX-2-selective and nonselective NSAIDs compared with patients treated with placebo. In the Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

In addition, fluid retention and edema have been observed in some patients treated with NSAIDs. The use of ketorolac tromethamine may reduce the cardiovascular effects of some drugs used to treat these conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)].

Ketorolac tromethamine should be avoided in patients with severe heart failure unless the benefits of treatment are expected to outweigh 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.

Skin reactions

NSAIDs, including ketorolac tromethamine, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed of the signs and symptoms of serious skin reactions and that the drug should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Pregnancy

In late pregnancy, as with other NSAIDs, the use of ketorolac tromethamine should be avoided as it may lead to premature closure of the ductus arteriosus.

PREVENTIVE MEASURES

General

Ketorolac tromethamine should not be expected to be a substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt withdrawal of corticosteroids may result in exacerbation of the disease. In patients receiving long-term corticosteroid therapy, if a decision is made to discontinue corticosteroids, the dose should be gradually reduced.

The pharmacological activity of ketorolac tromethamine in reducing inflammation may reduce the usefulness of this diagnostic feature in detecting complications of presumed non-infectious, painful conditions.

Effect on the liver

Ketorolac tromethamine should be used with caution in patients with impaired hepatic function or a history of liver disease. Borderline elevations of one or more liver function tests may occur in up to 15% of patients receiving NSAIDs, including ketorolac tromethamine. These laboratory abnormalities may progress with continued treatment, may remain stable, or may be transient. Significant elevations of ALT and AST (approximately 3 or more times the upper limit of normal) have been observed in approximately 1% of patients in clinical trials of NSAIDs. In addition, severe hepatic reactions, including jaundice and fatal fulminant hepatitis, hepatic necrosis, and hepatic failure, some of which were fatal, have been reported in isolated cases.

Patients with symptoms and/or signs suggestive of hepatic dysfunction, or who have had abnormal liver function tests, should be monitored for the development of a more severe hepatic reaction while receiving ketorolac tromethamine. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations (e.g., eosinophilia, rash) occur, ketorolac tromethamine should be discontinued.

Hematological effects

Anemia is occasionally observed in patients receiving NSAIDs, including ketorolac tromethamine. This may be due to fluid retention, occult or major gastrointestinal blood loss, or an incompletely described effect on erythropoiesis. In patients receiving long-term treatment with NSAIDs, including ketorolac tromethamine, hemoglobin or hematocrit should be checked if any signs or symptoms of anemia appear. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. In contrast to acetylsalicylic acid, their effect on platelet function is quantitatively smaller, less prolonged, and reversible. Patients receiving ketorolac tromethamine who may experience adverse effects in the form of changes in platelet function, such as in coagulation disorders or in patients receiving anticoagulants, should be closely monitored.

Aspirin-induced asthma may occur in patients with asthma. The use of acetylsalicylic acid in patients with aspirin-induced asthma has been associated with severe bronchospasm, which may be fatal. Since cross-reactions between acetylsalicylic acid and other NSAIDs, including bronchospasm, have been reported in such patients who are sensitive to acetylsalicylic acid, ketorolac tromethamine should not be prescribed to patients with this form of sensitivity to acetylsalicylic acid and should be used with caution in patients with pre-existing asthma.

Laboratory tests

Because serious gastrointestinal ulcers and bleeding may occur without warning symptoms, physicians should monitor for signs or symptoms of gastrointestinal bleeding. Patients receiving long-term NSAID therapy should have periodic blood counts and blood chemistry tests. If clinical signs and symptoms of liver or kidney disease develop, systemic manifestations (e.g., eosinophilia, rash) occur, or if liver function tests persist or worsen, ketorolac tromethamine should be discontinued.

Use in children

Ketorolac tromethamine tablets are not intended for use in children. The safety and effectiveness of ketorolac tromethamine tablets in children under 16 years of age have not been established.

Use in elderly patients (≥ 65 years)

Because ketorolac tromethamine may be eliminated more slowly in elderly patients, who are also more sensitive to the side effects of NSAIDs, the drug should be used with extreme caution, at reduced doses, and with close clinical monitoring when treating elderly patients with ketorolac tromethamine.

Ability to influence reaction speed when driving vehicles or other mechanisms

Some patients may experience dizziness, drowsiness, visual disturbances, headaches, vertigo, insomnia, or depression when taking ketorolac. If patients experience these or other similar side effects, they should not drive or operate machinery.

Use during pregnancy or breastfeeding

The safety of ketorolac during human pregnancy has not been established. Given the known effects of NSAIDs on the fetal cardiovascular system (risk of premature closure of the ductus arteriosus), ketorolac is contraindicated during pregnancy, labor and delivery. The onset of labor may be delayed and the duration prolonged with an increased tendency for bleeding in both mother and child.

Teratogenic effects. Pregnancy Category C

Reproductive toxicity studies were conducted during organogenesis using daily oral doses of ketorolac tromethamine of 3.6 mg/kg (0.37 of the human AUC) in rabbits and 10 mg/kg (equivalent to the human AUC) in rats. The results of these studies did not reveal any teratogenic effects on the fetus. However, reproductive toxicity studies in animals do not always reflect those in humans.

Nonteratogenic effects

Given the known effects of NSAIDs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ketorolac tromethamine during pregnancy (particularly in late pregnancy) should be avoided. Ketorolac tromethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and delivery

Ketorolac tromethamine is contraindicated during labor and delivery because, due to its inhibitory effect on prostaglandin synthesis, it may adversely affect fetal circulation and suppress uterine contractions, thereby increasing the risk of uterine bleeding.

Breast-feeding

Ketorolac passes into breast milk in very small amounts.

After 1 day of administration (10 mg every 6 hours), the maximum milk concentration was 7.9 ng/mL and the maximum milk/plasma ratio was 0.025. Assuming a daily human milk intake of 400–1000 mL/day and a maternal body weight of 60 kg, the estimated maximum daily exposure for the infant was 0.00263 mg/kg/day, which is 0.4% of the maternal weight-adjusted dose.

Caution should be exercised when ketorolac is administered to nursing mothers. Available information suggests that there are no specific adverse reactions in breastfed infants; however, patients should be advised to contact their infant's physician if any adverse reactions occur.

Impact on fertility

The use of ketorolac tromethamine, as with other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is therefore not recommended in women attempting to conceive. In women who are unable to conceive or are undergoing investigation of infertility, discontinuation of ketorolac tromethamine should be considered.

Method of administration and doses

Ketorol Express in the form of orodispersible tablets should be taken only with dry hands.

Taking tablets that disperse in the mouth does not require drinking water, does not affect saliva production, and allows patients with swallowing abnormalities due to behavioral or neurological disorders to take the drug.

To prevent indigestion, it is advisable to take the drug during or after a meal (main meal or snack) or with antacids.

Ketorol Express is administered orally once or several times a day, depending on the severity of the pain.

The recommended initial dose for adults is 10 mg. If repeated use is necessary, it is recommended to take 10 mg up to 4 times a day, with an interval of 4-6 hours. The maximum daily dose should not exceed 40 mg.

For patients receiving parenteral ketorolac, as IV or IM injections, and who are concurrently prescribed oral ketorolac, as tablets, the total combined dose should not exceed 90 mg (60 mg for the elderly, patients with renal impairment, and patients weighing less than 50 kg).

The table below summarizes the dosing instructions for ketorolac tablets in different age groups:

The drug is recommended only for short-term use (up to 5 days).

Children

Do not use in children under 16 years of age.

Overdose

Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting and epigastric pain, which are usually reversible with supportive treatment. Gastrointestinal bleeding may occur. Rarely, hypertension, acute renal failure, respiratory depression and coma may occur. Anaphylactoid reactions have been reported with therapeutic doses of NSAIDs and may occur after overdose.

Treatment

Treatment of NSAID overdose should be symptomatic and supportive. There is no specific antidote. If symptoms of overdose occur after administration of the drug or after a significant oral overdose (5-10 times the usual dose) within 4 hours, the patient may be induced to vomit and/or activated charcoal (60-100 g for adults, 1-2 g/kg for children) and/or an osmotic laxative may be administered. Forced diuresis, urine alkylation, hemodialysis, or blood transfusion may be ineffective due to the high protein binding of the drug.

Single overdoses of ketorolac tromethamine have been associated with abdominal pain, nausea, vomiting, hyperventilation, peptic ulcers and/or erosive gastritis, and renal dysfunction, which resolved after discontinuation of the drug.

Adverse reactions

The incidence of adverse reactions increases with increasing doses of ketorolac tromethamine. Physicians should be alert to the occurrence of serious complications of ketorolac tromethamine treatment, such as gastrointestinal ulceration, bleeding, and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions, and hepatic failure. These complications associated with NSAID use may be serious in some patients, especially in patients with