Plain-language summary, compiled from the cited regulatory records
Ketorolac is an active ingredient belonging to the drug class of acetic acid derivatives and related substances [1].
Ketorolac tromethamine is indicated for the short-term management of moderately severe acute pain that requires analgesia at the opioid level, typically in a postoperative setting [1]. The duration of use should not exceed 5 days [1]. When considering ketorolac, it is important to carefully evaluate its potential benefits and risks alongside other treatment options [1]. The lowest effective dose should be used for the shortest duration necessary to achieve individual patient treatment goals [1].
This medication is sold under several brand names [1].
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised April 5, 2026[1]
INDICATIONS AND USAGE
Carefully consider the potential benefits and risks of ketorolac tromethamine tablets, USP and other treatment options before deciding to use ketorolac tromethamine tablets, USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
Acute Pain in Adult Patients Ketorolac tromethamine tablets, USP are indicated for the short-term (≤ 5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting.
Therapy should always be initiated with IV or IM dosing of ketorolac tromethamine and ketorolac tromethamine tablets, USP are to be used only as continuation treatment, if necessary. The total combined duration of use of ketorolac tromethamine tablets, USP and ketorolac tromethamine is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses (see WARNINGS , PRECAUTIONS , DOSAGE AND ADMINISTRATION , and ADVERSE REACTIONS ).
CACanada· Health Canada
4 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
Intramuscular injection of Ketorolac Tromethamine Injection USP (ketorolac tromethamine injection) is indicated for: • the short-term management (not to exceed 2 days) of moderate to severe acute pain, including pain following major abdominal, orthopedic and gynecological operative procedures.
The total combined duration of intramuscular and oral treatment should not exceed 5 days. For patients with an increased risk of developing CV and/or GI adverse events, other management strategies that do NOT include the use of NSAIDs should be considered first (see
How to take
Drug interactions
Known interactions involving Ketorolac. Select one for details. This list is informational and not a complete interaction checker.
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[1]FDA DailyMed · 0749f61d-12e6-42… · revised April 5, 2026 [PDF]
[2]Health Canada (DPD) · 02239944 · revised March 22, 2025
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
Patients should be switched to alternative analgesics as soon as possible, but Ketorolac Tromethamine Tablet USP therapy is not to exceed 5 days.
How to take
USOfficial regulatory label· revised April 5, 2026[1]
DOSAGE AND ADMINISTRATION
Carefully consider the potential benefits and risks of ketorolac tromethamine tablets and other treatment options before deciding to use ketorolac tromethamine tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
In adults, the combined duration of use of IV or IM dosing of ketorolac tromethamine and ketorolac tromethamine tablets is not to exceed 5 days. In adults, the use of ketorolac tromethamine tablets is only indicated as continuation therapy to IV or IM dosing of ketorolac tromethamine.
Transition from IV or IM dosing of ketorolac tromethamine (single- or multiple-dose) to multiple-dose ketorolac tromethamine tablets: Patients age 17 to 64: 20 mg PO once followed by 10 mg q4 to 6 hours prn not > 40 mg/day Patients age ≥ 65, renally impaired, and/or weight < 50 kg (110 lbs): 10 mg PO once followed by 10 mg q4 to 6 hours prn not > 40 mg/day Note: Oral formulation should not be given as an initial dose .
Use minimum effective dose for the individual patient. Do not shorten dosing interval of 4 to 6 hours. Total duration of treatment in adult patients: the combined duration of use of IV or IM dosing of ketorolac tromethamine and ketorolac tromethamine tablets is not to exceed 5 days.
The following table summarizes ketorolac tromethamine tablet dosing instructions in terms of age group: Table 4: Summary of Dosing Instructions Patient Population Ketorolac Tromethamine Tablets (following IV or IM dosing of ketorolac tromethamine) Age < 17 years Oral not approved Adult Age 17 to 64 years 20 mg once, then 10 mg q4 to 6 hours prn not > 40 mg/day Adult Age ≥ 65 years, renally impaired, and/or weight < 50 kg 10 mg once, then 10 mg q4 to 6 hours prn not > 40 mg/day
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised April 5, 2026[1]
ADVERSE REACTIONS
Adverse reaction rates increase with higher doses of ketorolac tromethamine. Practitioners should be alert for the severe complications of treatment with ketorolac tromethamine, such as GI ulceration, bleeding and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions and liver failure (see Boxed WARNING , WARNINGS , PRECAUTIONS , and DOSAGE AND ADMINISTRATION ).
These NSAID-related complications can be serious in certain patients for whom ketorolac tromethamine is indicated, especially when the drug is used inappropriately. In patients taking ketorolac tromethamine or other NSAIDs in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are: Gastrointestinal (GI) experiences including: abdominal pain * constipation/diarrhea dyspepsia * flatulence GI fullness GI ulcers (gastric/duodenal) gross bleeding/perforation heartburn nausea * stomatitis vomiting Other experiences: abnormal renal function anemia dizziness drowsiness edema elevated liver enzymes headaches * hypertension increased bleeding time injection site pain pruritus purpura Rashes tinnitus sweating * Incidence greater than 10% Additional adverse experiences reported occasionally (< 1% in patients taking ketorolac tromethamine or other NSAIDs in clinical trials) include: Body as a Whole: fever, infections, sepsis Cardiovascular: congestive heart failure, palpitation, pallor, tachycardia, syncope Dermatologic: alopecia, photosensitivity, urticaria Gastrointestinal: anorexia, dry mouth, eructation, esophagitis, excessive thirst, gastritis, glossitis, hematemesis, hepatitis, increased appetite, jaundice, melena, rectal bleeding Hemic and Lymphatic: ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia Metabolic and Nutritional: weight change Nervous System: abnormal dreams, abnormal thinking, anxiety, asthenia, confusion, depression, euphoria, extrapyramidal symptoms, hallucinations, hyperkinesis, inability to concentrate, insomnia, nervousness, paresthesia, somnolence, stupor, tremors, vertigo, malaise Reproductive, female: infertility Respiratory: asthma, cough, dyspnea, pulmonary edema, rhinitis Special Senses: abnormal taste, abnormal vision, blurred vision, hearing loss Urogenital: cystitis, dysuria, hematuria, increased urinary frequency, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure, urinary retention Other rarely observed reactions (reported from postmarketing experience in patients taking ketorolac tromethamine or other NSAIDs) are: Body as a Whole: angioedema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema (see WARNINGS ), myalgia Cardiovascular: arrhythmia, bradycardia, chest pain, flushing, hypotension, myocardial infarction, vasculitis Dermatologic: exfoliative dermatitis, erythema multiforme, Lyell’s syndrome, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, and fixed drug eruption (FDE) Gastrointestinal: acute pancreatitis, liver failure, ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease) Hemic and Lymphatic: agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, postoperative wound hemorrhage (rarely requiring blood transfusion - see Boxed WARNING , WARNINGS , and PRECAUTIONS ) Metabolic and Nutritional: hyperglycemia, hyperkalemia, hyponatremia Nervous System: aseptic meningitis, convulsions, coma, psychosis Respiratory: bronchospasm, respiratory depression, pneumonia Special Senses: conjunctivitis Urogenital: flank pain with or without hematuria and/or azotemia, hemolytic uremic syndrome Postmarketing Surveillance Study A large postmarketing observational, nonrandomized study, involving approximately 10,000 patients receiving ketorolac tromethamine IV/IM , demonstrated that the risk of clinically serious gastrointestinal (GI) bleeding was dose-dependent (see Tables 3A and 3B).
This was particularly true in elderly patients who received an average daily dose greater than 60 mg/day of ketorolac tromethamine IV/IM (see Table 3A).
Table 3:
Incidence of Clinically Serious GI Bleeding as Related to Age, Total Daily Dose, and History of GI Perforation, Ulcer, Bleeding (PUB) After up to 5 Days of Treatment With Ketorolac Tromethamine IV/IM A. 7% B. gov/medwatch.
USOfficial regulatory label· Warnings and precautions· revised April 5, 2026[1]
) The total combined duration of use of ketorolac tromethamine tablets and IV or IM dosing of ketorolac tromethamine is not to exceed 5 days in adults. Ketorolac tromethamine tablets are not indicated for use in pediatric patients.
The most serious risks associated with ketorolac tromethamine are:
Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation Ketorolac tromethamine is contraindicated in patients with previously documented peptic ulcers and/or GI bleeding. Ketorolac tromethamine can cause serious gastrointestinal (GI) adverse events including bleeding, ulceration and perforation, of the stomach, small intestine, or large intestine, which can be fatal.
These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with ketorolac tromethamine. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic.
Minor upper gastrointestinal problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. The incidence and severity of gastrointestinal complications increases with increasing dose of, and duration of treatment with, ketorolac tromethamine.
Do not use ketorolac tromethamine for more than five days. However, even short-term therapy is not without risk. In addition to past history of ulcer disease, other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids, or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status.
Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration.
Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of ketorolac tromethamine until a serious GI adverse event is ruled out.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised April 5, 2026[1]
) Ketorolac tromethamine is contraindicated in patients with previously demonstrated hypersensitivity to ketorolac tromethamine. Ketorolac tromethamine is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation and in patients with a history of peptic ulcer disease or gastrointestinal bleeding.
Ketorolac tromethamine should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS , Anaphylactoid Reactions and PRECAUTIONS , Preexisting Asthma ).
Ketorolac tromethamine is contraindicated as prophylactic analgesic before any major surgery. Ketorolac tromethamine is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ). Ketorolac tromethamine is contraindicated in patients with advanced renal impairment or in patients at risk for renal failure due to volume depletion (see WARNINGS for correction of volume depletion).
Ketorolac tromethamine is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage.
Ketorolac tromethamine inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS and PRECAUTIONS ).
Ketorolac tromethamine is contraindicated in patients currently receiving aspirin or NSAIDs because of the cumulative risks of inducing serious NSAID-related adverse events. The concomitant use of ketorolac tromethamine and probenecid is contraindicated.
The concomitant use of ketorolac tromethamine and pentoxifylline is contraindicated.
This is not medical advice. Consult a qualified healthcare professional.
CAOfficial regulatory label· revised March 22, 2025[2]
1 Dosing Considerations Use of Ketorolac Tromethamine Injection USP should be limited to the lowest effective dose for the shortest possible duration of treatment (see 1 INDICATIONS). Conversion from Parenteral to Oral Therapy When ketorolac tromethamine tablets are used as a follow-on therapy to parenteral ketorolac, the total combined daily dose of ketorolac (oral + parenteral) should not exceed 120 mg in younger adult patients or 60 mg in elderly patients on the day the change of formulation is made.
On subsequent days, oral dosing should not exceed the recommended daily maximum of 40 mg. Ketorolac Tromethamine Injection USP should be replaced by an oral analgesic as soon as feasible. The total combined duration of intramuscular and oral treatment should not exceed 5 days.
2 Recommended Dose and Dosage Adjustment Adults (>18 years of age): Dosage should be adjusted according to the severity of the pain and the response of the patient.
The recommended usual initial dose is 10-30 mg, according to pain severity. Subsequent dosing may be 10 mg to 30 mg every 4-6 hours as needed to control pain. The lowest effective dose should be administered. The administration of Ketorolac Tromethamine Injection USP should be limited to short-term therapy (not to exceed 2 days) and the total daily dose should not exceed 120 mg.
The risk of toxicity increases with longer use and at higher than recommended doses (see 7 WARNINGS AND PRECAUTIONS). The administration of continuous multiple daily doses of ketorolac tromethamine has not been extensively studied. There has been limited experience with intramuscular dosing beyond 2 days since the vast majority of patients have transferred to oral medication or no longer required analgesic therapy after this time.
Renal Impairment Ketorolac Tromethamine Injection USP is contraindicated in patients with moderate to severe renal impairment (serum creatinine >442 mcmol/L). Ketorolac tromethamine should be used with caution in patients with lesser renal impairment (serum creatinine 170-442 mcmol/L).
Such patients should receive a reduced dose of Ketorolac Tromethamine Injection USP, and their renal status should be closely monitored. It is recommended that the daily dose be reduced by half; a total daily dose of 60 mg should not be exceeded.
Dialysis does not significantly clear ketorolac from bloodstream. 3 Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency. Ketorolac Tromethamine Injection USP Page 8 of 54 Hepatic Impairment Ketorolac Tromethamine Injection USP is contraindicated in patients with severe liver impairment or active liver disease.
Caution should be observed in giving Ketorolac Tromethamine Injection USP to patient with mild to moderate hepatic insufficiency. 3 Pharmacokinetics, Special Populations and Conditions, Hepatic Insufficiency. Elderly, Frail or Debilitated Patients These patients are at increased risk of the serious consequences of adverse reactions.
The lower end of the dosage range is recommended. The initial dose should be 10 mg. The total daily dose of Ketorolac Tromethamine Injection USP in the elderly should not exceed 60 mg. 4 Geriatrics. 4 Administration Parenteral drug products should be inspected visually for particulate material and discoloration prior to use.
5 Missed Dose The missed dose should be taken as soon as remembered, and then the regular dosing schedule should be continued. Two doses of ketorolac should not be taken at the same time.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
1 Adverse Reaction Overview The most common adverse reactions encountered with non-steroidal anti-inflammatory drugs are gastrointestinal, of which peptic ulcer, with or without bleeding is the most severe. Fatalities have occurred, particularly in the elderly.
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The adverse reactions listed below were reported in ketorolac tromethamine injection clinical efficacy trials.
In these trials patients (N=660) received either single 30 mg doses (N=151) or multiple 30 mg doses (N=509) over a time period of 5 days or less for pain resulting from surgery. These reactions may or may not be drug related. 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Clinical Trial Findings Elevations of blood urea nitrogen (BUN) and creatinine have been reported in clinical trials with ketorolac.
5 Post-Market Adverse Reactions Additional reports of adverse events temporally associated with ketorolac tromethamine during worldwide post-marketing experience are included below. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or clearly establish a causal relationship to ketorolac tromethamine exposure.
The following post-marketing adverse experiences have been reported for patients who have received ketorolac tromethamine (tablets and injection): Ketorolac Tromethamine Injection USP Page 22 of 54 Blood and lymphatic system disorder: postoperative wound hemorrhage, rarely requiring blood transfusion (see 7 WARNINGS AND PRECAUTIONS, Hematologic), thrombocytopenia, epistaxis, leukopenia, hematomata, increased bleeding time, eosinophilia, agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy and pancytopenia.
Gastrointestinal disorders: gastrointestinal hemorrhage, peptic ulceration, gastrointestinal perforation, gastrointestinal obstruction, pancreatitis, melena, esophagitis, hematemesis, vomiting, ulcerative stomatitis, abdominal pain /discomfort, eructation, rectal bleeding, dry mouth, fullness, exacerbation of colitis and Crohn’s disease have been reported following administration.
Less frequently, gastritis has been observed. General disorders and administration site condition: malaise and fatigue. Hepatobiliary disorders: jaundice, hepatitis, liver failure, cholestatic jaundice. Immune system disorders: anaphylaxis, anaphylactoid reactions, bronchospasm, laryngeal edema, hypotension, flushing, rash and angioedema.
Such reactions have occurred in patients with no prior history of hypersensitivity. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome. Infections and infestations: infection, conjunctivitis. Investigations: abnormal liver function tests, raised serum urea and creatinine.
Renal and urinary disorders: acute renal failure, flank pain with or without hematuria and/or azotemia, nephritis, hyponatremia, hyperkalemia, hemolytic uremic syndrome, urinary retention, interstitial nephritis, renal papillary necrosis, nephrotic syndrome, hematuria.
As with other drugs that inhibit renal prostaglandin synthesis, signs of renal impairment, such as, but not limited to elevations of creatinine and potassium can occur after one dose of Ketorolac IV. Reproductive System and […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
1 Pregnant Women 04/2022 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests 04/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES .............................................................................................
2 TABLE OF CONTENTS ............................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION .......................................................................
8 5 OVERDOSAGE ............................................................................................................... 8 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................... 9 7 WARNINGS AND PRECAUTIONS ....................................................................................
1 Special Populations ................................................................................................... 1 Pregnant Women ..................................................................................................
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
, 7 WARNINGS AND PRECAUTIONS, Cardiovascular and 7 WARNINGS AND PRECAUTIONS, Gastrointestinal). Use of Ketorolac Tromethamine Injection USP should be limited to the lowest effective dose for the shortest possible duration of treatment in order to minimize the potential risk for cardiovascular or gastrointestinal adverse events (see 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS).
Ketorolac Tromethamine Injection USP, as a NSAID, does NOT treat clinical disease or prevent its progression. Ketorolac Tromethamine Injection USP, as a NSAID, only relieves symptoms and decreases inflammation for as long as the patient continues to take it.
1 Pediatrics Pediatrics (< 18 years of age): Ketorolac Tromethamine Injection USP is contraindicated in the pediatric population (see 2 CONTRAINDICATIONS). 2 Recommended Dose and Dosage Adjustment). 2 CONTRAINDICATIONS Ketorolac Tromethamine Injection USP is contraindicated in: • The peri-operative setting of coronary artery bypass graft surgery (CABG).
Although ketorolac tromethamine has NOT been studied in this patient population, a selective COX-2 inhibitor NSAID studied in such a setting has led to an increased incidence of Ketorolac Tromethamine Injection USP Page 5 of 54 cardiovascular/thromboembolic events, deep surgical infections and sternal wound complications.
• The third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus and prolonged parturition. • Labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine musculature, thus increasing the risk of uterine hemorrhage.
• Women who are breastfeeding, because of the potential for serious adverse reactions in nursing infants. • Severe uncontrolled heart failure. • Known hypersensitivity to ketorolac tromethamine or to other NSAIDs, including any of the components/excipients (see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).
e. complete or partial syndrome of ASA-intolerance - rhinosinusitis, urticaria/angioedema, nasal polyps, asthma). Fatal anaphylactoid reactions have occurred in such individuals. Individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse reaction.
The potential for cross-reactivity between different NSAIDs must be kept in mind (see 7 WARNINGS AND PRECAUTIONS, Immune, Anaphylactoid Reactions). • Active gastric / duodenal / peptic ulcer, active GI bleeding. • Inflammatory bowel disease.
• Cerebrovascular bleeding or other bleeding disorders. • Coagulation disorders, post-operative patients with high hemorrhagic risk or incomplete hemostasis in patients with suspected or confirmed cerebrovascular bleeding. • Immediately before any major surgery and intraoperatively when hemostasis is critical because of the increased risk of bleeding.
• Severe liver impairment or active liver disease. 5 mL/sec) or deteriorating renal disease (individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored) (see 7 WARNINGS AND PRECAUTIONS, Renal).
• Known hyperkalemia (see 7 WARNINGS AND PRECAUTIONS, Renal, Fluid and Electrolyte Balance). 1 Serious Drug Interactions). • Neuraxial (epidural or intrathecal) administration of Ketorolac Tromethamine Injection USP due to its alcohol content.
1 Serious Drug Interactions). 1 Serious Drug Interactions). Ketorolac Tromethamine Injection USP Page 6 of 54 • Children and adolescents aged less than 18 years.
This is not medical advice. Consult a qualified healthcare professional.
For high risk patients, alternate therapies that do not involve NSAIDs should be considered. NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated.
Hemorrhage Because prostaglandins play an important role in hemostasis and NSAIDs affect platelet aggregation as well, use of ketorolac tromethamine in patients who have coagulation disorders should be undertaken very cautiously, and those patients should be carefully monitored.
, heparin or dicumarol derivatives) have an increased risk of bleeding complications if given ketorolac tromethamine concurrently; therefore, physicians should administer such concomitant therapy only extremely cautiously. The concurrent use of ketorolac tromethamine and therapy that affects hemostasis, including prophylactic low-dose heparin (2500 to 5000 units q12h), warfarin and dextrans have not been studied extensively, but may also be associated with an increased risk of bleeding.
Until data from such studies are available, physicians should carefully weigh the benefits against the risks and use such concomitant therapy in these patients only extremely cautiously. Patients receiving therapy that affects hemostasis should be monitored closely.
In postmarketing experience, postoperative hematomas and other signs of wound bleeding have been reported in association with the peri-operative use of IV or IM dosing of ketorolac tromethamine. Therefore, peri-operative use of ketorolac tromethamine should be avoided and postoperative use be undertaken with caution when hemostasis is critical (see PRECAUTIONS ).
Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion.
In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.
Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Ketorolac tromethamine and its metabolites are eliminated primarily by the kidneys, which, in patients with reduced creatinine clearance, will result in diminished clearance of the drug (see CLINICAL PHARMACOLOGY ).
Therefore, ketorolac tromethamine should be used with caution in patients with impaired renal function (see DOSAGE AND ADMINISTRATION ) and such patients should be followed closely. With the use of ketorolac tromethamine, there have been reports of acute renal failure, interstitial nephritis and nephrotic syndrome.
Impaired Renal Function Ketorolac tromethamine is contraindicated in patients with serum creatinine concentrations indicating advanced renal impairment (see CONTRAINDICATIONS ). Ketorolac tromethamine should be used with caution in patients with impaired renal function or a history of kidney disease because it is a potent inhibitor of prostaglandin synthesis.
Because patients with underlying renal insufficiency are at increased risk of developing acute renal decompensation or failure, the risks and benefits should be assessed prior to giving ketorolac tromethamine to these patients. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without a known previous exposure or hypersensitivity to ketorolac tromethamine.
Ketorolac tromethamine should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS , Preexisting Asthma ).
Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome. Emergency help should be sought in cases where an anaphylactoid reaction occurs. Cardiovascular Effects Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal.
Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those 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 excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment.
The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible.
Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as ketorolac tromethamine, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ).
Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.
NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS ). Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment.
In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.
Avoid the use of ketorolac tromethamine tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If ketorolac tromethamine tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
Hypertension NSAIDs, including ketorolac tromethamine, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs.
NSAIDs, including ketorolac tromethamine, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Heart Failure and Edema The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients.
In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs.
, diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see DRUG INTERACTIONS ). Avoid the use of ketorolac tromethamine tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure.
If ketorolac tromethamine tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Serious 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.
NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of ketorolac tromethamine tablets at the first appearance of skin rash or any other sign of hypersensitivity.
Ketorolac tromethamine tablets are contraindicated in patients with previous serious skin reactions to NSAIDs (see CONTRAINDICATIONS ). Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as ketorolac tromethamine tablets.
Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis.
Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.
If such signs or symptoms are present, discontinue ketorolac tromethamine tablets and evaluate the patient immediately.
Fetal Toxicity Premature Closure of Fetal Ductus Arteriosus:
Avoid use of NSAIDs, including ketorolac tromethamine tablets, in pregnant women at about 30 weeks gestation and later. NSAIDs including ketorolac tromethamine tablets, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.
Oligohydramnios/Neonatal Renal Impairment:
Use of NSAIDs, including ketorolac tromethamine tablets, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.
Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit ketorolac tromethamine tablets use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if ketorolac tromethamine tablets treatment extends beyond 48 hours.
Discontinue ketorolac tromethamine tablets if oligohydramnios occurs and follow up according to clinical practice (see PRECAUTIONS ; Pregnancy ).
1 Adverse Reaction Overview ...................................................................................... 2 Clinical Trial Adverse Reactions ................................................................................. 3 Less Common Clinical Trial Adverse Reactions ..........................................................
4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data ................................................................................................................ 5 Post-Market Adverse Reactions ................................................................................
21 9 DRUG INTERACTIONS .................................................................................................. 1 Serious Drug Interactions ..........................................................................................
7 Drug-Laboratory Test Interactions ............................................................................ 31 10 CLINICAL PHARMACOLOGY ......................................................................................... 1 Mechanism of Action ................................................................................................
3 Pharmacokinetics ...................................................................................................... 32 11 STORAGE, STABILITY AND DISPOSAL ...........................................................................
34 12 SPECIAL HANDLING INSTRUCTIONS ............................................................................. 34 PART II: SCIENTIFIC INFORMATION ........................................................................................
35 13 PHARMACEUTICAL INFORMATION ............................................................................. 35 14 CLINICAL TRIALS ..........................................................................................................