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Ketorolac Tromethamine

Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: CN103
Chemical Name: (±)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid compd. with 2-Amino-2-(hydroxymethyl)-1,3-propanediol (1:1)
Molecular Formula: C15H13O3•C4H11NO3
CAS Number: 74103-07-4


    Appropriate Use
  • Indicated for short-term (≤5 days in adults) management of moderately severe acute pain that requires analgesia at opiate level.1 Not indicated for use in minor or chronic painful conditions.1

  • A potent NSAIA; administration associated with risks.1 Serious NSAIA-related adverse effects can occur in patients in whom the drug is indicated, especially when the drug is used inappropriately.1 Increasing the dose beyond the recommended dose will not result in improved efficacy and increases the risk of serious adverse effects.1

    GI Effects
  • Can cause peptic ulcers, GI bleeding, and/or perforation.1 Contraindicated in patients with active peptic ulcer disease, recent GI bleeding or perforation, or a history of peptic ulcer disease or GI bleeding.1

  • Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.198 Geriatric individuals are at greater risk for serious GI events.198 (See GI Effects under Cautions.)

    Renal Effects
  • Contraindicated in patients with advanced renal impairment and those at risk of renal failure because of volume depletion.1

    Hematologic Effects
  • Inhibits platelet function.1 Contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, or incomplete hemostasis and in patients at a high risk of bleeding.1

  • Contraindicated as prophylactic analgesic before major surgery; contraindicated as intraoperative analgesic during procedures where hemostasis is critical.1 Increased risk of bleeding in these patients.1

    Cardiovascular Risk
  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).198 502 508 Risk may occur early in treatment and may increase with duration of use.500 502 505 506 508 (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.508

    Sensitivity Reactions
  • Hypersensitivity reactions (e.g., bronchospasm, anaphylactic shock) reported; appropriate counteractive measures must be available when administering the first dose.1 Contraindicated in patients with known hypersensitivity to ketorolac, aspirin, or other NSAIAs.1

    Intrathecal or Epidural Administration
  • Contraindicated for intrathecal or epidural administration because of alcohol content in parenteral formulation.1

    Labor and Delivery
  • Contraindicated during labor and delivery.1 (See Pregnancy under Cautions.)

  • Contraindicated in nursing women.1

    Concomitant Use with NSAIAs
  • Contraindicated in patients receiving aspirin or other NSAIAs because of cumulative risk of serious adverse effects.1

    Dosage and Administration
  • Oral formulation is used as continuation therapy in adults; total combined duration of parenteral and oral therapy in adults should not exceed 5 days because of increased risk of serious adverse effects.1

  • Maximum daily oral dosage (40 mg) is lower than the maximum daily parenteral dosage (120 mg).1

    Special Populations
  • Adjust dosage in patients ≥65 years of age, adults weighing <50 kg, and those with moderately increased Scr.1 Daily parenteral dosage should not exceed 60 mg in these patients.1 (See Dosage and Administration.)

  • Administer only a single parenteral dose in children; maximum 30 mg IM or 15 mg IV.1


Prototypical NSAIA;1 2 3 21 32 33 70 91 92 93 96 140 pyrrolizine carboxylic acid derivative;2 3 21 32 33 70 91 92 93 96 140 structurally related to tolmetin and indomethacin.2 33 47 70 83

Uses for Ketorolac Tromethamine


Consider potential benefits and risks of ketorolac therapy as well as alternative therapies before initiating therapy with the drug.198 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.198

Short-term (i.e., up to 5 days) management of moderately severe, acute pain that requires analgesia at opiate level in adults; mainly used in the postoperative setting.1 47 48 49 50 51 52 54 55 56 57 58 59 60 61 68 70 71 72 73 74 75 76 91 99 101 159 161 162 165 196 197

Management of moderately severe, acute pain in children 2–16 years of age (single IV or IM dose); studies usually have evaluated pain in the postoperative setting (e.g., pain following tonsillectomy).1 196 197 Limited data available to support administration of >1 parenteral dose in pediatric patients.1 196 197

Parenteral ketorolac has been used concomitantly with opiate agonist analgesics (e.g., meperidine, morphine) for the management of moderate to severe postoperative pain without apparent adverse drug interactions.1 91 Combined use can result in reduced opiate analgesic requirements.1 49 (See Syringe Compatibility under Stability.)

Ketorolac Tromethamine Dosage and Administration


  • Current principles of pain management indicate that analgesics, including ketorolac, should be administered at regularly scheduled intervals, although the drug also has been administered on an as-needed basis (i.e., withholding subsequent doses until pain returns).1 91 140

  • Consider potential benefits and risks of ketorolac therapy as well as alternative therapies before initiating therapy with the drug.198


Administer IV, IM, or orally in adults; administer IV or IM in children 2–16 years of age.1

Initiate therapy in adults with parenteral (IV or IM) ketorolac; oral formulation is used as continuation therapy, as required.1 154 Administer IV or IM as a single dose or every 6 hours; administer orally every 4–6 hours.1

In children 2–16 years of age, administer as a single IV or IM dose.1

Switch patients to alternate analgesic therapy as soon as clinically possible.1 154

Oral Administration

Manufacturer makes no specific recommendations regarding administration with meals; high-fat meal may decrease rate but not extent of absorption and reduce peak plasma concentrations.1

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Rate of Administration

Administer over ≥15 seconds.1

IM Administration

Administer IM slowly and deeply into the muscle.1

For drug compatibility information, see Compatibility under Stability.


Available as ketorolac tromethamine; dosage expressed in terms of the salt.1

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.198 Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.198

For breakthrough pain, supplement with low doses of opiate analgesics (unless contraindicated) as needed rather than higher or more frequent doses of ketorolac.1 142

Pediatric Patients

Single Dose

Children 2–16 years of age: One dose of 0.5 mg/kg (maximum 15 mg).1


Children 2–16 years of age: One dose of 1 mg/kg (maximum 30 mg).1



When switching from parenteral to oral therapy, the first oral dose is 20 mg, followed by 10 mg every 4–6 hours (maximum 40 mg in a 24-hour period).1

Weight <50 kg: When switching from parenteral to oral therapy, 10 mg every 4–6 hours (maximum 40 mg in a 24-hour period).1

Single Dose

30 mg.1

Weight <50 kg: 15 mg.1


60 mg.1

Weight <50 kg: 30 mg.1

Multiple Dose
IV or IM

30 mg every 6 hours.1

Weight <50 kg: 15 mg every 6 hours.1

Prescribing Limits

Pediatric Patients


Only a single parenteral dose is recommended.1

Single Dose

15 mg.1


30 mg.1



Total combined duration of parenteral and oral therapy should not exceed 5 days.1 137 142 143 154


All adults: Maximum 40 mg in a 24-hour period.1

Multiple Dose
IV or IM

Maximum 120 mg in a 24-hour period.1

Weight <50 kg: Maximum 60 mg in a 24-hour period.1

Special Populations

Hepatic Impairment

Need for dosage adjustment not fully established;1 70 evidence in patients with cirrhosis suggests that dosage adjustment may not be necessary.137

Renal Impairment


Safety not established in patients with Scr >5 mg/dL and/or those undergoing dialysis.1


When switching from parenteral to oral therapy, 10 mg every 4–6 hours (maximum 40 mg in a 24-hour period).1

Single Dose

15 mg.1


30 mg.1

Multiple Dose
IV or IM

15 mg every 6 hours.1 Maximum 60 mg in a 24-hour period.1

Geriatric Patients

Dosage recommendations are the same as those for patients with moderately increased Scr or for those weighing <50 kg.1

Cautions for Ketorolac Tromethamine


  • Peptic ulcer disease, recent GI bleeding or perforation, or history of peptic ulcer disease or GI bleeding.1

  • Advanced renal impairment or risk of renal failure secondary to volume depletion.1

  • Labor and delivery.1

  • Nursing women.1

  • Known hypersensitivity to ketorolac or any ingredient in the formulation.1

  • History of asthma, urticaria, or other sensitivity reactions precipitated by aspirin or other NSAIAs.1

  • Use as a prophylactic analgesic before major surgery; intraoperative use when hemostasis is critical.1

  • In the setting of CABG surgery.508

  • Suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, or incomplete hemostasis; high risk of bleeding.1

  • Concomitant use with aspirin or NSAIAs.1

  • Neuraxial (epidural or intrathecal) administration.1

  • Concomitant use with probenecid.1



Duration of Therapy

Total combined duration of parenteral and oral therapy in adults should not exceed 5 days.1 137 142 143 154

Only single doses of parenteral ketorolac are recommended in pediatric patients.1

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.500 502 508

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information500 501 502 indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.500

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.500 502 506 508

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500 502 505 506 508

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.508

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.505 508

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;500 508 511 absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.508 511

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.202 203 204 206 500 501 502 503 506 FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.500

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.198 500 508

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.505 511 512 516 Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.508 Contraindicated in the setting of CABG surgery.508

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.198 502 508 (See Specific Drugs under Interactions.)

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, those in poor general health, and those receiving >90 mg of parenteral ketorolac tromethamine daily.1 91 124 125 141 149 150 192 193 195 (See Contraindications under Cautions.)

Hematologic Effects

May inhibit platelet aggregation and prolong bleeding time.1 2 23 24 34 65 70 91 141 Use with caution and careful monitoring in patients with coagulation disorders.1 (See Contraindications under Cautions.)

Hematomas and other signs of wound bleeding reported in patients receiving the drug perioperatively; undertake postoperative administration with caution when hemostasis is critical.1 (See Contraindications under Cautions.)

Increased risk of intramuscular hematoma following IM administration in patients receiving anticoagulants.1 154

Administer with caution in patients receiving therapeutic doses of anticoagulants (e.g., heparin, warfarin).1 154 Concurrent use with prophylactic low-dose heparin (2500–5000 units every 12 hours), warfarin, or dextrans not studied extensively, but also may be associated with increased risk of bleeding.1 154 Administer with caution when the potential benefits justify the possible risks.1 91 145 154 (See Specific Drugs under Interactions.)

Increased risk of bleeding following tonsillectomy in pediatric patients.1 174 196 197 Consider the increased risk when using ketorolac in pediatric patients undergoing tonsillectomy.1

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1 154 Interstitial nephritis and nephrotic syndrome reported in patients receiving ketorolac.1

Potential for overt renal decompensation.1 154 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure; in patients with volume depletion; in geriatric patients; and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 91 147 154 201 205 (See Renal Impairment and also Contraindications under Cautions, and Renal Impairment under Dosage and Administration.)

Correct hypovolemia before initiating ketorolac therapy.1


Hypertension and worsening of preexisting hypertension reported;1 91 198 either event may contribute to the increased incidence of cardiovascular events.198 Use with caution in patients with hypertension; monitor BP.198

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.198 508 509 (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.1 70 91 140 508

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.500 501 504 507 508

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.508 (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.508

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.507

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions (e.g., anaphylaxis, angioedema) reported.1

Immediate medical intervention and discontinuance for anaphylaxis.1

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1 2

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 91 198 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).198

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.1 198

Elevations in ALT or AST reported.1 91

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.198 Discontinue ketorolac if associated with abnormal liver function test results.1

Specific Populations


Category C.1 Avoid use in the third trimester because of possible premature closure of the ductus arteriosus.1 133 140 154 May inhibit uterine contractions during labor and delivery.1 (See Contraindications under Cautions.)


Distributed into milk; contraindicated in nursing women.1

Pediatric Use

Safety and efficacy of parenteral ketorolac administered as a single dose established in children 2–16 years of age.1 Safety and efficacy not established in children <2 years of age.1

Bleeding reported following tonsillectomy.1 174 196 197 (See Hematologic Effects under Cautions.)

Geriatric Use

Geriatric patients appear to tolerate NSAIA-induced adverse effects less well than younger adults.1 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.1

Caution and reduced dosages advised.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Severe hepatic reactions possible.1 Use with caution in patients with hepatic impairment or a history of liver disease.1 91 92 154 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution in patients with renal impairment or a history of kidney disease; monitor closely.1 91 92 154 (See Contraindications under Cautions.)

Clearance may be decreased.1 Dosage adjustment necessary in patients with moderately elevated Scr.1 (See Renal Impairment under Dosage and Administration.)

Patients with underlying renal insufficiency are at risk of developing acute renal failure; consider risks and benefits before instituting therapy in these patients.1 154

Common Adverse Effects

Headache,1 23 70 91 34 somnolence or drowsiness,1 23 47 50 51 53 61 70 91 134 140 dizziness,1 23 50 53 70 91 dyspepsia,1 50 70 91 140 nausea,1 23 47 50 51 53 70 91 134 140 GI pain, 1 53 140 diarrhea,1 91 140 edema.1

Interactions for Ketorolac Tromethamine

Does not induce or inhibit hepatic enzymes involved in drug metabolism; unlikely to alter its own metabolism of that or other drugs metabolized by CYP isoenzymes.1

Protein-bound Drugs

Could be displaced from binding sites by, or could displace from binding sites, some other protein-bound drugs.1 91

Drugs Affecting Hemostasis

Possible increased risk of bleeding complications;1 carefully monitor patients receiving therapy that affects hemostasis.1 91 145 154

Specific Drugs




ACE inhibitors

Increased risk of renal impairment1

Reduced BP response to ACE inhibitor198

Monitor BP198


No alteration in the protein binding of ketorolac1 91

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist205

Possible deterioration of renal function in individuals with renal impairment205

Monitor BP205


No effect on the extent of oral ketorolac absorption1


Seizures reported in patients receiving carbamazepine or phenytoin1

Phenytoin does not alter the protein binding of ketorolac1 91

CNS agents (alprazolam, fluoxetine, thiothixene)

Hallucinations reported in patients receiving fluoxetine, thiothixene, or alprazolam1


Possible increased risk of bleeding1

Carefully monitor patients1 91 145 154


No alteration in the protein binding of either drug1 91 140

Diuretics (furosemide, thiazides)

Reduced natriuretic effect1 104 198


Increased risk of bleeding complications1

Increased bleeding time when administered with heparin 5000 units; concurrent use with heparin 2500–5000 units sub-Q every 12 hours not studied extensively1

Extreme caution advised in patients receiving therapeutic doses of heparin;1 91 145 154 carefully monitor patients1 91 145 154


Increased plasma lithium concentrations1 157 158

Monitor for lithium toxicity1 158


Increased plasma methotrexate concentrations in patients receiving other NSAIAs; studies with ketorolac have not been undertaken1

Caution advised198

Nondepolarizing skeletal muscle relaxants

May potentiate the effects of the muscle relaxant resulting in apnea1


NSAIAs including aspirin: Potential for increased risk of GI toxicity1 154 198

Aspirin: No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs198 502 508

Therapeutic anti-inflammatory concentrations of salicylates (300 mcg/mL) may displace ketorolac from binding sites; ibuprofen, naproxen, or piroxicam does not alter the protein binding of ketorolac1 91

Concomitant use contraindicated1 154


Increased plasma concentrations and AUC of ketorolac1

Concomitant use contraindicated1 154

Thrombolytic agents

Possible increased risk of bleeding1

Carefully monitor patients1 91 145 154


No alteration in the protein binding of ketorolac1 91


Increased risk of bleeding complications;1 concurrent use not studied extensively1

Possible slight displacement of warfarin (but not ketorolac) from binding sites;1 91 other pharmacokinetic interactions unlikely1

Extreme caution advised in patients receiving therapeutic doses of warfarin;1 91 145 154 carefully monitor patients1 91 145 154

Ketorolac Tromethamine Pharmacokinetics



Rapidly and completely absorbed following IM administration.1 2 36 37 38 140 173

Rapid and almost completed absorbed following oral administration; 1 2 36 37 38 70 95 173 bioavailability reported to be 80–100%.1 2 36 37 38 70 95 173


IM administration: Onset in 10 minutes, with peak analgesia at 75–150 minutes.1 47 50 51 53

Oral administration: Onset in 30–60 minutes, with peak analgesia at 1.5–4 hours.55 56 57 58 59 60 61 137 138


Oral or IM administration: 6–8 hours.47 50 51 53 55 56 57 58 59 60 61 137 138


Food decreases rate but not extent of absorption.1 2 70 83

Special Populations

Rate of absorption from GI tract may be decreased in patients with hepatic43 70 or renal44 70 impairment and in geriatric individuals.43 70



Not distributed widely.1 2 37 70 140 Crosses the blood-brain barrier poorly.1 91

Crosses the placenta;1 2 41 65 91 173 distributed into milk.1 40 70 91 92

Plasma Protein Binding

>99%.1 2 37 38 70



Metabolized in the liver by hydroxylation; 1 91 also undergoes conjugation with glucuronic acid.1 37 38 173

Elimination Route

Excreted in urine (92%) as parent drug (60%) or metabolites (40%) and in feces (6%).1 38 70 173


4–6 hours in adults;1 2 36 37 38 70 80 91 97 140 173 3.8–6.1 hours in pediatric patients.1 173 197

Special Populations

Hepatic impairment (e.g., cirrhosis) does not appear to substantially affect half-life.1 2 43 173 In patients with cirrhosis, half-life of about 4.5–5.4 hours reported.1 43 91 173

Renal impairment: Half-life is about 9–10 hours (range: 3.2–19 hours);1 2 44 91 173 in patients undergoing dialysis, half-life of about 13.6 hours (range: 8–39.1 hours) reported.1

Geriatric individuals: Half-life is about 5–7 hours (range: 4.3–8.6 hours).1 2 42 70 80 91 173








15–30°C; protect from light.1


For information on systemic interactions resulting from concomitant use, see Interactions.


Solution CompatibilityHID


Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Plasma-Lyte A, pH 7.4

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Syringe Compatibility1HID


Sufentanil citrate


Haloperidol lactate

Hydroxyzine HCl

Meperidine HCl

Morphine Sulfate


Prochlorperazine edisylate

Promethazine HCl

Thiethylperazine maleate



Hydromorphone HCl

Ketorolac tromethamine 1 mg/mL tested.HID

Y-Site CompatibilityHID


Dexmedetomidine HCl

Fentanyl citrate

Hetastarch in lactated electrolyte injection (Hextend)

Hydromorphone HCl

Methadone HCl

Morphine sulfate

Remifentanil HCl

Sufentanil citrate



Fenoldopam mesylate


  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.91

  • Pharmacologic actions similar to those of other prototypical NSAIAs; 2 21 32 33 91 exhibits anti-inflammatory, analgesic, and antipyretic activity.1 2 21 32 33 70 91 140

Advice to Patients

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.198

  • Risk of serious cardiovascular events (e.g., MI, stroke).198 500 508

  • Risk of GI bleeding and ulceration.1 167 181

  • Risk of bleeding following tonsillectomy.1

  • Risk of serious skin reactions.198 Risk of anaphylactoid and other sensitivity reactions.1

  • Risk of hepatotoxicity.1

  • Risk of kidney failure.1

  • Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.198 500 508

  • Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1

  • Importance of discontinuing ketorolac and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.198 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1

  • Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.198

  • Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.508

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of avoiding ketorolac in late pregnancy (third trimester).1

  • Importance of not exceeding recommended duration of therapy.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ketorolac Tromethamine


Dosage Forms


Brand Names



Tablets, film-coated

10 mg*

Ketorolac Tromethamine Tablets


Injection, for IM or IV use

15 mg/mL*

Ketorolac Tromethamine Injection

30 mg/mL*

Ketorolac Tromethamine Injection

Injection, for IM use

30 mg/mL*

Ketorolac Tromethamine Injection

AHFS DI Essentials. © Copyright 2018, Selected Revisions November 21, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Roche Laboratories. Toradol IV, IM, and oral (ketorolac tromethamine) prescribing information. Nutley, NJ; 2002 Sep.

2. Gannon R. Focus on ketorolac: a nonsteroidal, anti-inflammatory agent for the treatment of moderate to severe pain. Hosp Formul. 1989; 24:695-702.

3. Budavari S, ed. The Merck index. 11th ed. Rahway, NJ: Merck & Co, Inc; 1989:836.

4. Gu L, Chiang HS, Johnson D. Light degradation of ketorolac tromethamine. Int J Pharm. 1988; 41:105-13.

5. Guzman A, Yuste F, Toscano RA et al. Absolute configuration of (-)-5-benzoyl-1,2-dihydro-3H -pyrrolo[1,2-a]pyrrole-1-carboxylic acid, the active enantiomer of ketorolac. J Med Chem. 1986; 29:589-91. [PubMed 3959034]

6. Wilson DE. Antisecretory and mucosal protective actions of misoprostol. Am J Med. 1987; 83(Suppl 1A):2-8. [PubMed 3113241]

7. Aadland E, Fausa O, Vatn M et al. Protection by misoprostol against naproxen-induced gastric mucosal damage. Am J Med. 1987; 83(Suppl 1A):37-40. [PubMed 3113244]

8. Rainsford KD, Willis C. Relationship of gastric mucosal damage induced in pigs by antiinflammatory drugs to their effects on prostaglandin production. Dig Dis Sci. 1982; 27:624-35. [PubMed 6953009]

9. Kobayashi K, Arakawa T, Satoh H et al. Effect of indomethacin, tiaprofenic acid and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2. Prostaglandins. 1985; 30: 609-18. [PubMed 3909233]

10. Oliw E, Lunden I, Anggard E. In vivo inhibition of prostaglandin synthesis in rabbit kidney by non-steroidal anti-inflammatory drugs. Acta Pharmacol Toxicol (Copenh). 1978; 42:179-84. [PubMed 580346]

11. Abramson S, Edelson H, Kaplan H et al. Inhibition of neutrophil activation by nonsteroidal anti-inflammatory drugs. Am J Med. 1984; 10:3-6.

12. Moncada S, Flower RJ, Vane JR. Prostaglandins, prostacyclin, thromboxane A2, and leukotrienes. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York; Macmillan Publishing Company; 1985: 660-73.

13. Deraedt R, Jouquey S, Benzoni J et al. Inhibition of prostaglandin biosynthesis by non-narcotic analgesic drugs. Arch Int Pharmacodyn Ther. 1976; 224:30-42. [PubMed 13749]

14. Atkinson DC, Collier HOJ. Salicylates: molecular mechanism of therapeutic action. Adv Pharmacol Chemother. 1980; 17:233-88. [PubMed 7004141]

15. Robinson DR. Prostaglandins and the mechanism of action of anti-inflammatory drugs. Am J Med. 1983; 10:26-31.

16. O’Brien WM. Pharmacology of nonsteroidal anti-inflammatory drugs. Am J Med. 1983; 10:32-9.

17. Koch-Weser J. Nonsteroidal antiinflammatory drugs (first of two parts). N Engl J Med. 1980; 302:1179-85. [PubMed 6988717]

18. Ferreira SH, Lorenzetti BB, Correa FMA. Central and peripheral antialgesic action of aspirin-like drugs. Eur J Pharmacol. 1978; 53:39-48. [PubMed 310771]

19. Hart FD. Rheumatic disorders. In: Avery GS, ed. Drug treatment: principles and practice of clinical pharmacology and therapeutics. 2nd ed. New York: ADIS Press; 1987:846-61.

20. Bernheim HA, Block LH, Atkins E. Fever: pathogenesis, pathophysiology, and purpose. Ann Intern Med. 1979; 91:261-70. [PubMed 223485]

21. Rooks WH II, Tomolonis AJ, Maloney PJ et al. The analgesic and anti-inflammatory profile of (±) -5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2a]pyrrole -1-carboxylic acid (RS-37619). Agents Actions. 1982; 12:684-90. [PubMed 6984594]

22. Fraser-Smith EB, Matthews TR. Effect of ketorolac on phagocytosis of candida albicans by peritoneal macrophages. Immunopharmacology. 1988; 16:151-5. [PubMed 3075603]

23. Conrad KA, Fagan TC, Mackie MJ et al. Effects of ketorolac tromethamine on hemostasis in volunteers. Clin Pharmacol Ther. 1988; 43:542-6. [PubMed 3259170]

24. Spowart K, Greer IA, McLaren M et al. Haemostatic effects of ketorolac with and without concomitant heparin in normal volunteers. Thromb Haemost. 1988; 60:382-6. [PubMed 3266379]

25. Murray AW, Brockway MS, Kenny GNC. Comparison of the cardiorespiratory effects of ketorolac and alfentanil during propofol anaesthesia. Br J Anaesth. 1989; 63:601-3. [PubMed 2605079]

26. Brandon Bravo LJC, Mattie H, Spierdijk J et al. The effects of ventilation of ketorolac in comparison with morphine. Eur J Clin Pharmacol. 1988; 35:491-4. [PubMed 3148470]

27. Fraser-Smith EB, Matthews TR. Effect of ketorolac on pseudomonas aeruginosa ocular infection in rabbits. J Ocul Pharmacol. 1988; 4:101-9. [PubMed 3262701]

28. Fraser-Smith EB, Matthews TR. Effect of ketorolac on candida albicans ocular infection in rabbits. Arch Ophthalmol. 1987; 105:264-7. [PubMed 3492994]

29. Fraser-Smith EB, Matthews TR. Effect of ketorolac on herpes simplex virus type one ocular infection in rabbits. J Ocul Pharmacol. 1988; 4: 321-6.

30. Oates JA, FitzGerald GA, Branch RA et al. Clinical implications of prostaglandin and thromboxane A2 formation (first of two parts). N Engl J Med. 1988; 319:689-98. [PubMed 3045550]

31. Lanza FL, Karlin DA, Yee JP. A double-blind placebo controlled endoscopic study comparing the mucosal injury seen with an orally and parenterally administered new nonsteroidal analgesic ketorolac tromethamine at therapeutic and supratherapeutic doses. Am J Gastroenterol. 1987; 82:939.

32. Rooks WH II, Maloney PJ, Shott LD et al. The analgesic and anti-inflammatory profile of ketorolac and its tromethamine salt. Drugs Exp Clin Res. 1985; 11:479-92. [PubMed 3879752]

33. Muchowski JM, Unger SH, Ackrell J et al. Synthesis and antiinflammatory and analgesic activity of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a] pyrrole-1-carboxylic acids and related compounds. J Med Chem. 1985; 28:1037-49. [PubMed 4020827]

34. Roe RL, Bruno JJ, Ellis DJ. Effects of a new nonsteroidal anti-inflammatory agent on platelet function in male and female subjects. Clin Pharmacol Ther. 1981; 29:277.

35. Rubin P, Yee JP, Murthy VS et al. Ketorolac tromethamine (KT) analgesia: no post-operative respiratory depression and less constipation. Clin Pharmacol Ther. 1987; 41:182.

36. Jung D, Mroszczak EJ, Wu A et al. Pharmacokinetics of ketorolac and p-hydroxyketorolac following oral and intramuscular administration of ketorolac tromethamine. Pharm Res. 1989; 6:62-5. [PubMed 2717521]

37. Jung D, Mroszczak E, Bynum L. Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration. Eur J Clin Pharmacol. 1988; 35:423-5. [PubMed 3264245]

38. Mroszczak EJ, Lee FW, Combs D et al. Ketorolac tromethamine absorption, distribution, metabolism, excretion, and pharmacokinetics in animals and humans. Drug Metab Dispos. 1987; 15:618-26. [PubMed 2891477]

39. Gu L, Chiang HS, Becker A. Kinetics and mechanisms of the autoxidation of ketorolac tromethamine in aqueous solution. Int J Pharm. 1988; 41:95-104.

40. Wischnik A, Manth SM, Lloyd J. The excretion of ketorolac tromethamine into breast milk after multiple oral dosing. Eur J Clin Pharmacol. 1989; 36:521-4. [PubMed 2787750]

41. Walker JJ, Johnstone J, Lloyd J et al. The transfer of ketorolac tromethamine from maternal to foetal blood. Eur J Clin Pharmacol. 1988; 34:509-11. [PubMed 3264528]

42. Montoya-Iraheta C, Garg DC, Jallad NS et al. Pharmacokinetics of single dose oral and intramuscular ketorolac tromethamine in elderly vs. young healthy subjects. J Clin Pharmacol. 1986; 26:545.

43. Pages LJ, Martinez JJ, Garg DC et al. Pharmacokinetics of ketorolac tromethamine in hepatically impaired vs. young healthy subjects. J Clin Pharmacol. 1987; 27:724.

44. Martinez JJ, Garg DC, Pages LJ et al. Single dose pharmacokinetics of ketorolac in healthy young and renal impaired subjects. J Clin Pharmacol. 1987; 27:722.

45. Ling TL, Combs DL. Ocular bioavailability and tissue distribution of [14C]ketorolac tromethamine in rabbits. J Pharm Sci. 1987; 76: 289-94. [PubMed 3598886]

46. Mroszczak EJ, Ling T, Yee J et al. Ketorolac tromethamine (KT) absorption and pharmacokinetics in humans. Clin Pharmacol Ther. 1985; 37:215.

47. Yee JP, Koshiver JE, Allbon C et al. Comparison of intramuscular ketorolac tromethamine and morphine sulfate for analgesia of pain after major surgery. Pharmacotherapy. 1986; 6:253-61. [PubMed 3540877]

48. Yee J, Brown C, Allison C et al. Analgesia from intramuscular ketorolac tromethamine compared to morphine (MS) in “severe” pain following “major” surgery. Clin Pharmacol Ther. 1985; 37:239.

49. Gillies GWA, Kenny GNC, Bullingham RES et al. The morphine sparing effect of ketorolac tromethamine. Anaesthesia. 1987; 42:727-31. [PubMed 3307518]

50. O’Hara DA, Fragen RJ, Kinzer M et al. Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. Clin Pharmacol Ther. 1987; 41:556-61. [PubMed 3568540]

51. Estenne B, Julien M, Charleux H et al. Comparison of ketorolac, pentazocine, and placebo in treating postoperative pain. Curr Ther Res. 1988; 43:1173-82.

52. Brown CR, Wild VM, Bynum L. Comparison of intravenous ketorolac tromethamine and morphine sulfate in postoperative pain. Clin Pharmacol Ther. 1988; 43:142.

53. Staquet MJ. A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain. J Clin Pharmacol. 1989; 29:1031-6. [PubMed 2689472]

54. Fricke J, Angelocci D. The analgesic efficacy of I.M. ketorolac and meperidine for the control of postoperative dental pain. Clin Pharmacol Ther. 1987; 41:181.

55. McQuay HJ, Poppleton P, Carroll D et al. Ketorolac and acetaminophen for orthopedic postoperative pain. Clin Pharmacol Ther. 1986; 39: 89-93. [PubMed 3510797]

56. Vangen O, Doessland S, Lindbaek E. Comparative study of ketorolac and paracetamol/codeine in alleviating pain following gynaecological surgery. J Int Med Res. 1988; 16:443-51. [PubMed 3069519]

57. Johansson S, Josefsson G, Malstam J et al. Analgesic efficacy and safety comparison of ketorolac tromethamine and doleron for the alleviation of orthopaedic post-operative pain. J Int Med Res. 1989; 17:324-32. [PubMed 2676649]

58. Kagi P. A multiple-dose comparison of oral ketorolac and pentazocine in the treatment of postoperative pain. Curr Ther Res. 1989; 45:1049-59.

59. Galasko CSB, Russel S, Lloyd J. Double-blind investigation of the efficacy of multiple oral doses of ketorolac tromethamine compared with dihydrocodeine and placebo. Curr Ther Res. 1989; 45:844-52.

60. Honig WJ, Van Ochten J. A multiple-dose comparison of ketorolac tromethamine with diflunisal and placebo in postmeniscectomy pain. J Clin Pharmacol. 1986; 26:700-5. [PubMed 3540032]

61. Arsac M, Frileux C. Comparative analgesic efficacy and tolerability of ketorolac tromethamine and glafenine in patients with post-operative pain. Curr Med Res Opin. 1988; 11:214-20. [PubMed 2905636]

62. Flach AJ, Graham J, Kruger LP et al. Quantitative assessment of postsurgical breakdown of the blood-aqueous barrier following administration of 0.5% ketorolac tromethamine solution. Arch Ophthalmol. 1988; 106:344-7. [PubMed 3345153]

63. Flach AJ, Kraff MC, Sanders DR et al. The quantitative effect of 0.5% ketorolac tromethamine solution and 0.1% dexamethasone sodium phosphate solution on postsurgical blood-aqueous barrier. Arch Ophthalmol. 1988; 106:480-3. [PubMed 3355415]

64. Flach AJ, Dolan BJ, Irvine AR. Effectiveness of ketorolac tromethamine 0.5% ophthalmic solution for chronic aphakic and pseudophakic cystoid macular edema. Am J Ophthalmol. 1987; 103:479-86. [PubMed 3551617]

65. Greer IA, Johnston J, Tulloch I et al. Effect of maternal ketorolac administration on platelet function in the newborn. Eur J Obstet Gynecol Reprod Biol. 1988; 29:257-60. [PubMed 3265921]

66. Macdonald FC, Gough KJ, Nicoll RAG et al. Psychomotor effects of ketorolac in comparison with buprenorphine and diclofenac. Br J Clin Pharmacol. 1989; 27:453-9. [PubMed 2785813]

67. Saarialho-Kere U. Psychomotor effects of ketorolac. Br J Clin Pharmacol. 1989; 28:495. [PubMed 2590610]

68. Yee J, Bradley R, Stanski D et al. A comparison of analgesic efficacy of intramuscular ketorolac tromethamine and meperidine in postoperative pain. Clin Pharmacol Ther. 1986; 39:237.

69. Floy BJ, Royko CG, Fleitman JS. Compatibility of ketorolac tromethamine injection with common infusion fluids and administration sets. Am J Hosp Pharm. 1990; 47:1097-100. [PubMed 2337102]

70. Buckley MMT, Brogden RN. Ketorolac: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs. 1990; 39:86-109. [PubMed 2178916]

71. Sunshine A, Richman H, Cordone R et al. Analgesic efficacy and onset of oral ketorolac in postoperative pain. Clin Pharmacol Ther. 1988; 43:159.

72. Brown CR, Moodie JE, Evans SA et al. Efficacy of intramuscular (I.M.) ketorolac and meperidine in pain following major oral surgery. Clin Pharmacol Ther. 1988; 43:161.

73. Bloomfield SS, Cissell G, Peters N et al. Ketorolac analgesia for postoperative pain. Clin Pharmacol Ther. 1988; 43:160.

74. Rubin P, Murthy VS, Yee J. Long-term safety and efficacy comparison study of ketorolac tromethamine (KT) and aspirin (ASA) in the treatment of chronic pain. Clin Pharmacol Ther. 1987; 41:229.

75. Forbes JA, Butterworth GA, Kehm CK et al. Two clinical evaluations of ketorolac tromethamine in postoperative oral surgery pain. Clin Pharmacol Ther. 1987; 41:162.

76. Yee J, Brown CR, Sevelius H et al. The analgesic efficacy of (±)-5-benzoyl-1,2-dihydro -3H-pyrrolo [1,2a] pyrrole-1-carboxylic acid, tromethamine salt (B) in post-operative pain. Clin Pharmacol Ther. 1984; 35:285.

77. Flach AJ, Jaffe NS, Akers WA. The effect of ketorolac tromethamine in reducing postoperative inflammation: double-mask parallel comparison with dexamethasone. Ann Ophthalmol. 1989; 21:407-11. [PubMed 2619149]

78. Haynes WL, Proia AD, Klintworth GK. Effect of inhibitors of arachidonic acid metabolism on corneal neovascularization in the rat. Invest Ophthalmol Vis Sci. 1989; 30:1588-93. [PubMed 2473047]

79. Domer F. Characterization of the analgesic activity of ketorolac in mice. Eur J Pharmacol. 1990; 177:127-35. [PubMed 2311674]

80. Jallad NS, Garg DC, Martinez JJ et al. Pharmacokinetics of single-dose oral and intramuscular ketorolac tromethamine in the young and elderly. J Clin Pharmacol. 1990; 30:76-81. [PubMed 2303585]

81. Staquet M, Lloyd J, Bullingham R. The comparative efficacy of single doses of ketorolac tromethamine (KT) and placebo (P) to relieve cancer pain. Clin Pharmacol Ther. 1988; 43:159.

82. Flach AJ, Lavelle CJ, Olander KW et al. The effect of ketorolac tromethamine solution 0.5% in reducing postoperative inflammation after cataract extraction and intraocular lens implantation. Ophthalmology. 1988; 95:1279-84. [PubMed 3062540]

83. Bloomfield SS, Mitchell J, Cissell GB et al. Ketorolac versus aspirin for postpartum uterine pain. Pharmacotherapy. 1986; 6:247-52. [PubMed 3540876]

84. Adams DH, Howie AJ, Michael J et al. Non-steroidal anti-inflammatory drugs and renal failure. Lancet. 1986; 1:57-9. [PubMed 2867313]

85. Weinberger M. Analgesic sensitivity in children with asthma. Pediatrics. 1978; 62(Suppl):910-5. [PubMed 103067]

86. Pleskow WW, Stevenson DD, Mathison DA et al. Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol. 1982; 69(1 Part 1):11-9. [PubMed 7054250]

87. VanArsdel PP Jr. Aspirin idiosyncracy and tolerance. J Allergy Clin Immunol. 1984; 73:431-3. [PubMed 6423718]

88. Stevenson DD. Diagnosis, prevention, and treatment of adverse reactions to nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol. 1984; 74(4 Part 2):617-22. [PubMed 6436354]

89. Stevenson DD, Mathison DA. Aspirin sensitivity in asthmatics: when may this drug be safe? Postgrad Med. 1985; 78:111-3,116-9. (IDIS 205854)

90. Settipane GA. Aspirin and allergic diseases: a review. Am J Med. 1983; 74(Suppl):102-9. [PubMed 6344621]

91. Syntex Laboratories Inc. Toradol product monograph. Palo Alto, CA; 1992 Apr.

92. Syntex Laboratories Inc. Toradol pharmacy information. Palo Alto, CA; 1990 Mar.

93. Syntex Laboratories Inc. Toradol formulary facts. Palo Alto, CA; 1990.

94. Mahoney JM, Waterbury LD. Drug effects on the neovascularization response to silver nitrate cauterization of the rat cornea. Curr Eye Res. 1985; 4:531-5. [PubMed 2410194]

95. Lee F, Mroszczak E, Fass M et al. Ketorolac tromethamine (KT) absorption, metabolism and pharmacokinetics in animals and man. Fed Proc. 1985; 44:1118.

96. Hillier K. Ketorolac. Drugs Future. 1981; 6:669-70.

97. Sarnquist FH, Mroszczak EJ, Sevelius H. Absorption and metabolism of a new anti-inflammatory, analgesic agent. Clin Pharmacol Ther. 1981; 29:280.

98. Bruno JJ, Yang D, Taylor LA. Differing effects of ticlopidine and two prostaglandin synthetase inhibitors on maximum rate of ADP-induced aggregation. Thromb Haemost. 1981; 46:412.

99. Fragen RJ, O’Hara D. A comparison of intramuscularly injected ketorolac and morphine in postoperative pain. Clin Pharmacol Ther. 1987; 41:212.

100. Yee JP, Waterbury LD. Ketorolac tromethamine is a new analgesic with efficacy comparable to morphine that does not bind to opioid receptors and has low addictive potential. Clin Res. 1987; 35:163A.

101. Hougard K, Kjaergard J, Andersen HB et al. Ketorolac and ketobemidone for postoperative pain: a randomised study. Pain. 1987; 5(Suppl 4):S56.

102. Mehlisch D. Safety of intramuscular administered ketorolac tromethamine in subjects age 65 and over. Pain. 1987; 5(Suppl 4):S304.

103. Lopez M, Waterbury LD, Michel A et al. Lack of addictive potential of ketorolac tromethamine. Pharmacologist. 1987; 29:136.

104. Brater DC. Drug-drug and drug-disease interactions with nonsteroidal anti-inflammatory drugs. Am J Med. 1986; 80(Suppl 1A):62-70. [PubMed 3511686]

105. Ellison NM, Servi RJ. Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration. Cancer Treat Rep. 1985; 69:342-3. [PubMed 3978662]

106. Singh RR, Malaviya AN, Pandey JN et al. Fatal interaction between methotrexate and naproxen. Lancet. 1986; 1:1390. [PubMed 2872507]

107. Day RO, Graham GG, Champion GD et al. Anti-rheumatic drug interactions. Clin Rheum Dis. 1984; 10:251-75. [PubMed 6150784]

108. Daly HM, Scott GL, Boyle J et al. Methotrexate toxicity precipitated by azapropazone. Br J Dermatol. 1986; 114:733-5. [PubMed 3718865]

109. Hansten PD, Horn JR. Methotrexate interactions: ketoprofen (Orudis). Drug Interact Newsl. 1986; 6(Updates):U5-6.

110. Maiche AG. Acute renal failure due to concomitant action of methotrexate and indomethacin. Lancet. 1986; 1:1390. [PubMed 2872506]

111. Thyss A, Milano G, Kubar J et al. Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet. 1986; 1:256-8. [PubMed 2868265]

112. Reviewers’ comments (personal observations): ketoprofen; 1986 Aug.

113. Singer L, Imbs JL, Danion JM et al. Risque d’intoxication par le lithium en cas de traitement associé par les anti-inflammatoires non steroidiens. (French; with English abstract.) Therapie. 1981; 36:323-6.

114. Reimann IW, Frolich JC. Effects of diclofenac on lithium kinetics. Clin Pharmacol Ther. 1981; 30:348-52. [PubMed 7273598]

115. D’Arcy PF. Drug interactions with new drugs. Pharm Int. 1983; 4:285-91.

116. Monk JP, Clissold SP. Misoprostol: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease. Drugs. 1987; 33:1-30. [PubMed 3102205]

117. Wilson DE. Misoprostol and gastroduodenal mucosal protection (cytoprotection). Postgrad Med J. 1988; 64(Suppl 1):7-11. [PubMed 3138683]

118. Miller TA. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol. 1983; 245:G601-23. [PubMed 6195926]

119. Konturek SJ, Pawlik W. Physiology and pharmacology of prostaglandins. Dig Dis Sci. 1986; 31(Suppl):6-19S.

120. Taha AS, McLaughlin S, Holland PJ et al. Prevention of NSAID-induced gastric ulcer with prostaglandin analogues. Lancet. 1989; 1:52. [PubMed 2563038]

121. Fromm D. How do non-steroidal anti-inflammatory drugs affect gastric mucosal defenses? Clin Invest Med. 1987; 10:251-8.

122. Hawkey CJ. Non-steroidal anti-inflammatory drugs and peptic ulcers. Br Med J. 1990; 300:278-84.

123. Schoen RT, Vender RJ. Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Am J Med. 1989; 86:449-58. [PubMed 2648824]

124. Roth SH. Nonsteroidal anti-inflammatory drugs: gastropathy, deaths, and medical practice. Ann Intern Med. 1988; 109:353-4. [PubMed 3044208]

125. Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med. 1988; 109:359-63. [PubMed 3261560]

126. Masi AT. Nonsteroidal anti-inflammatory drugs and peptic ulcer. Ann Intern Med. 1989; 110:246-7. [PubMed 2912366]

127. Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drugs and peptic ulcer. Ann Intern Med. 1989; 110:247. [PubMed 2912367]

128. Wolf RE. Nonsteroidal anti-inflammatory drugs. Arch Intern Med. 1984; 144:1658-60. [PubMed 6235791]

129. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med. 1984; 310:563-72. [PubMed 6363936]

130. Henrich WL. Nephrotoxicity of nonsteroidal anti-inflammatory agents. Am J Kidney Dis. 1983; 2:478-84. [PubMed 6823966]

131. Kimberly RP, Bowden RE, Keiser HR et al. Reduction of renal function by newer nonsteroidal anti-inflammatory drugs. Am J Med. 1978; 64:804-7. [PubMed 645744]

132. Corwin HL, Bonventre JV. Renal insufficiency associated with nonsteroidal anti-inflammatory agents. Am J Kidney Dis. 1984; 4:147-52. [PubMed 6475945]

133. Indocin (indomethacin capsules, oral suspension, and suppositories USP) prescribing information. In: Barnhart ER, ed. Physicians’ desk reference. 44th ed. Oradell, NJ: Medical Economics Company Inc; 1990:1395-8.

134. Brown CR. Results from three studies of the multiple-dose safety and efficacy of intramuscularly (IM) administered ketorolac tromethamine in patients with pain from major surgery. In: Abstracts of the Fifth World Congress on Pain, Hamburg, FRG, 2–7 August 1987. Amsterdam: Elsevier; 1987. Abstract No. 4.

135. Camu F, Van Overberghe L, Bullingham R et al. Hemodynamic effects of ketorolac tromethamine in comparison to morphine in anesthetised patients. In: 9th World Congress of Anaesthesiologists, Abstracts Volume I: Scientific Papers A0001 to A0506. May 22-28, 1988. USA, 1988:A0167. Abstract.

136. Brandon Bravo LJC, Mattie H, Spierdijk J et al. A study of the comparative effects on respiration of ketorolac tromethamine and morphine. Acta Pharmacol Toxicol (Copenh). 1986; 59(Suppl 5):119.

137. Syntex Laboratories, Inc, Palo Alto, CA.

138. Reviewers comments (personal observations); 1990 Jul.

139. Gu L, Strickley RG. Preformulation salt selection. Physical property comparisons of the tris(hydroxymethyl)aminomethane (THAM) salts of four analgesic/antiinflammatory agents with the sodium salts and the free acids. Pharm Res. 1987; 4:255-7. [PubMed 3509292]

140. Anon. Ketorolac tromethamine. Med Lett Drugs Ther. 1990; 32:97-82.

141. Soll AH, Weinstein WM, Kurata J et al. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991; 114:307-19. [PubMed 1987878]

142. Hagler L, Medd BH. Dear doctor letter regarding safety information related to the appropriate use of ketorolac tromethamine. Palo Alto, CA: Syntex; 1993 Oct.

143. Choo V, Lewis S. Ketorolac doses reduced. Lancet. 1993; 342:109. [PubMed 8100870]

144. Anon. Syntex Toradol labeling changes reported in “dear doctor” letter. Prescription Pharm Biotechnol. 1993; Nov 1:9-10.

145. McDonald E, Marino C, Schwartz E et al. Toradol and the risk of gastrointestinal complications in the elderly. J Am Geriatrics Soc. 1993; 41:90-1.

146. Zikowski D, Hord AH, Haddox JD et al. Ketorolac-induced bronchospasm. Anesth Analg. 1993; 76:417-9. [PubMed 8424524]

147. Pearce CJ, Gonzalez FM, Wallin JD. Renal failure and hyperkalemia associated with ketorolac tromethamine. Arch Intern Med. 1993; 153:1000-2. [PubMed 8481061]

148. Haddow GR, Riley E, Isaacs R et al. Ketorolac, nasal polyposis, and bronchial asthma: a cause for concern. Anesth Analg. 1993; 76:420-2. [PubMed 8424525]

149. Fuller DK, Kalekas PJ. Ketorolac and gastrointestinal ulceration. Ann Pharmacother. 1993; 27:978-8. [PubMed 8364288]

150. Estes LL, Fuhs DW, Heaton AH et al. Gastric ulcer perforation associated with the use of injectable ketorolac. Ann Pharmacother. 1993; 27:42-3. [PubMed 8431619]

151. Goetz CM, Sterchele JA, Harchelroad FP. Anaphylactoid reaction following ketorolac tromethamine administration. Ann Pharmacother. 1992; 26:1237-8. [PubMed 1421646]

152. Rotenberg FA, Giannini VS. Hyperkalemia associated with ketorolac. Ann Pharmacother. 1992; 26:778-9. [PubMed 1611159]

153. The United States pharmacopeia, 23rd rev, and The national formulary, 18th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1994(Suppl 1):2473-4.

154. Carter ML. Dear doctor letter regarding important drug warnings and labeling changes for ketorolac tromethamine. Nutley, NJ: Roche Laboratories; 1995 Feb.

155. Perlin E, Finke H, Castro O et al. Enhancement of pain control with ketorolac tromethamine in patients with sickle cell vasoocclusive crisis. Am J Hematol. 1994; 46:43-7. [PubMed 7514356]

156. Goodman E. Use of ketorolac in sickle-cell disease and vasoocclusive crisis. Lancet. 1991; 338:641-2. [PubMed 1679183]

157. Iyer I. Ketorolac (Toradol) induced lithium toxicity. Headache. 1994; 34:442-4. [PubMed 7928331]

158. Langlois R, Paquette D. Increased serum lithium levels due to ketorolac therapy. CMAJ. 1994; 150:1455-6. [PubMed 8168010]

159. Morrison NA, Repka MX. Ketorolac versus acetaminophen or ibuprofen in controlling postoperative pain in patients with strabismus. Ophthalmology. 1994; 101:915-8. [PubMed 8190480]

160. Myers KG, Trotman IF. Use of ketorolac by continuous subcutaneous infusion for the control of cancer-related pain. Postgrad Med J. 1994; 70:359-62. [PubMed 8016008]

161. Ready LB, Brown CR, Stahlgren LH et al. Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain: a double-blind, placebo-controlled, multicenter study. Anesthesiology. 1994; 80:1277-86. [PubMed 8010474]

162. Sevarino FB, Sinatra RS, Paige D et al. Intravenous ketorolac as an adjunct to patient-controlled analgesia (PCA) for management of postgynecologic surgical pain. J Clin Anesth. 1994; 6:23-7. [PubMed 8142094]

163. Larsen LS, Miller A, Allegra JR. The use of intravenous ketorolac for the treatment of renal colic in the emergency department. Am J Emerg Med. 1993; 11:197-9. [PubMed 8489656]

164. Miller LJ, Kramer MA. Pain management with intravenous ketorolac. 1993; 27:307-8.

165. Wong HY, Carpenter RL, Kopacz DJ et al. A randomized, double-blind evaluation of ketorolac tromethamine for postoperative analgesia in ambulatory surgery patients. Anesthesiolgy. 1993; 41:90-1.

166. Haragsim L, Dalal R, Bagga H et al. Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. Am J Kidney Dis. 1994; 24:578-80. [PubMed 7942813]

167. Perazella MA, Buller GK. NSAID nephrotoxicity revisited: acute renal failure due to parenteral ketorolac. South Med J. 1993; 86:1421-4. [PubMed 8272928]

168. Quan DJ, Kayser SR. Ketorolac-induced acute renal failure following a single dose. J Toxicol Clin Toxicol. 1994; 32:305-9. [PubMed 8007038]

169. Shapiro N. Acute angioedema after ketorolac ingestion: report of a case. J Oral Maxillofac Surg. 52:626-7.

170. Corelli RL, Gericke KR. Renal insufficiency associated with intramuscular administration of ketorolac tromethamine. Ann Pharmacother. 1993; 27:1055-7. [PubMed 8219436]

171. Schoch PH, Ranno A, North DS. Acute renal failure in an elderly woman following intramuscular ketorolac administration. Ann Pharmacother. 1992; 26:1233-6. [PubMed 1421645]

172. Maunuksela EL, Kokki H, Bullingham RE. Comparison of intravenous ketorolac with morphine for postoperative pain in children. Clin Pharmacol Ther. 1992; 52:436-43. [PubMed 1424417]

173. Brocks DR, Jamali F. Clinical pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet. 1992; 23:415-27. [PubMed 1458761]

174. Rusy LM, Houck CS, Sullivan LJ et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg. 1995; 80:226-9. [PubMed 7818104]

175. Buck ML. Clinical experience with ketorolac in children. Ann Pharmacother. 1994; 28:1009-13. [PubMed 7803871]

176. Rubin P, Yee JP, Ruoff G. Comparison of long-term safety of ketorolac tromethamine and aspirin in the treatment of chronic pain. Pharmacotherapy. 1990; 10(6 Part 2):106S-10S. [PubMed 2082305]

177. Ciba Geigy, Ardsley, NY: Personal communication on diclofenac 28:08.04.

178. Reviewers’ comments (personal observations) on diclofenac 28:08.04.

179. Searle. Cytotec (misoprostol) prescribing information. 1989 Jun.

180. Corticosteroid interactions: nonsteroidal anti-inflammatory drugs (NSAIDs). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver WA: Applied Therapeutics, Inc; 1993:562.

181. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994; 343:769-72. [PubMed 7907735]

182. Hollander D. Gastrointestinal complications of nonsteroidal anti-inflammatory drugs: prophylactic and therapeutic strategies. Am J Med. 1994; 96:274-81. [PubMed 8154516]

183. Schubert TT, Bologna SD, Yawer N et al. Ulcer risk factors: Interaction between Helicobacter pylori infection, nonsteroidal use, and age. Am J Med. 1993; 94:413-7. [PubMed 8475935]

184. Piper JM, Ray WA, Daugherty JR et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991; 114:735-40. [PubMed 2012355]

185. Bateman DN, Kennedy JG. Non-steroidal anti-inflammatory drugs and elderly patients: the medicine may be worse than the disease. BMJ. 1995; 310:817-8. [PubMed 7711609]

186. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14. [PubMed 9929039]

187. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8. [PubMed 8967954]

188. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmacol. 1997; 75:1088-95. [PubMed 9365818]

189. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.

190. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase—a review. Prostaglandins Other Lipid Mediators. 1998; 56:341-61. [PubMed 9990677]

191. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(Suppl 5B):37-42S.

192. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999; 340:1888-99. [PubMed 10369853]

193. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999; 26(suppl 56):18-24.

194. Lanza FL, and the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol. 1998; 93:2037-46. [PubMed 9820370]

195. Pharmacia. Daypro (oxaprozin) caplets prescribing information. Chicago, IL; 2002 May.

196. Kokki H. Nonsteroidal anti-inflammatory drugs for postoperative pain: a focus on children. Paediatr Drugs. 2003; 5:103-23. [PubMed 12529163]

197. Forrest JB, Heitlinger EL, Revell S. Ketorolac for postoperative pain management in children. Drug Saf. 1997; 16:309-29. [PubMed 9187531]

198. US Food and Drug Administration. Proposed NSAID Package Insert Labeling Template 1. From the FDA website ( Accessed 10 Oct 2005.

199. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.

200. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology website (). Accessed 2005 Oct 12.

201. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.

202. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44. [PubMed 16968831]

203. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5. [PubMed 16740558]

204. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6. [PubMed 16968830]

205. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

206. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at: .

500. Food and Drug Administration. Drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Silver Spring, MD; 2015 Jul 9. From the FDA web site. Accessed 2016 Mar 22.

501. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382:769-79. [PubMed 23726390]

502. Food and Drug Administration. FDA briefing document: Joint meeting of the arthritis advisory committee and the drug safety and risk management advisory committee, February 10-11, 2014. From FDA web site

503. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011; 342:c7086. [PubMed 21224324]

504. Gislason GH, Rasmussen JN, Abildstrom SZ et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med. 2009; 169:141-9. [PubMed 19171810]

505. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation. 2011; 123:2226-35. [PubMed 21555710]

506. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011; 8:e1001098. [PubMed 21980265]

507. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 62:e147-239. [PubMed 23747642]

508. Teva. Ketorolac tromethamine tablets prescribing information. North Wales, PA; 2015 Jul.

509. Cumberland Pharmaceuticals Inc. Caldolor (ibuprofen) injection prescribing information. Nashville, TN; 2016 Apr.

511. Olsen AM, Fosbøl EL, Lindhardsen J et al. Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study. Circulation. 2012; 126:1955-63. [PubMed 22965337]

512. Olsen AM, Fosbøl EL, Lindhardsen J et al. Cause-specific cardiovascular risk associated with nonsteroidal anti-inflammatory drugs among myocardial infarction patients--a nationwide study. PLoS One. 2013; 8:e54309.

516. Bavry AA, Khaliq A, Gong Y et al. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. Am J Med. 2011; 124:614-20. [PubMed 21596367]

HID. Trissel LA. Handbook on Injectable Drugs. Bethesda, MD: American Society of Health-System Pharmacists.