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


• 
  

  Contraindicated for the treatment of pain in the setting of CABG surgery.¹⁹⁸

  
  


• 
  

  Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).¹⁹⁸ Risk may increase with duration of use.¹⁹⁸ Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.¹⁹⁸ (See Cardiovascular Effects under Cautions.)

  
  

• 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.)

  
  

• Lactation


• 
  

  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 S_cr.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

  
  

Introduction

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

Pain

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

General

• 
  

  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

  
  

Administration

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.

Dosage

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

Pain

Single Dose

IV

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

IM

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

Adults

Pain

Oral

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

IV

30 mg.¹

Weight <50 kg: 15 mg.¹

IM

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

Pain

Only a single parenteral dose is recommended.¹

Single Dose

IV

15 mg.¹

IM

30 mg.¹

Adults

Pain

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

Oral

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

Pain

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

Oral

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

Single Dose

IV

15 mg.¹

IM

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 S_cr or for those weighing <50 kg.¹

Cautions for Ketorolac Tromethamine

Contraindications

• 
  

  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

  
  


• 
  

  Treatment of perioperative pain in the setting of CABG surgery.¹⁹⁸

  
  


• 
  

  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

  
  

Warnings/Precautions

Warnings

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 Effects

Selective COX-2 inhibitors have been associated with an increased risk of serious cardiovascular events in certain situations.¹⁹⁹ Several prototypical NSAIAs also have been associated with an increased risk of cardiovascular events.^{202 203 204} Current data insufficient to assess risk associated with ketorolac.^{202 203 204}

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events).¹⁹⁸

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).¹⁹⁹

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

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 certain diuretics may occur.¹⁹⁸ (See Specific Drugs under Interactions.)

Fluid retention and edema reported.^{1 70 91 140} Caution in patients with fluid retention or heart failure.¹

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

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

Pregnancy

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.)

Lactation

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 S_cr.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

Drug	Interaction	Comments
ACE inhibitors	Increased risk of renal impairment1 Reduced BP response to ACE inhibitor198	Monitor BP198
Acetaminophen	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
Antacids	No effect on the extent of oral ketorolac absorption1
Anticonvulsants	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
Dextrans	Possible increased risk of bleeding1	Carefully monitor patients1 91 145 154
Digoxin	No alteration in the protein binding of either drug1 91 140
Diuretics (furosemide, thiazides)	Reduced natriuretic effect1 104 198
Heparin	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
Lithium	Increased plasma lithium concentrations1 157 158	Monitor for lithium toxicity1 158
Methotrexate	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	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 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
Probenecid	Increased plasma concentrations and AUC of ketorolac1	Concomitant use contraindicated1 154
Thrombolytic agents	Possible increased risk of bleeding1	Carefully monitor patients1 91 145 154
Tolbutamide	No alteration in the protein binding of ketorolac1 91
Warfarin	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

Absorption

Bioavailability

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}

Onset

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}

Duration

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

Food

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 hepatic^{43 70} or renal^{44 70} impairment and in geriatric individuals.^{43 70}

Distribution

Extent

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}

Elimination

Metabolism

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}

Half-life

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}

Stability

Storage

Oral

Tablets

15–30°C.¹

Parenteral

Injection

15–30°C; protect from light.¹

Compatibility

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

Parenteral

Solution Compatibility^HID

Compatible
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

Compatible
Sufentanil citrate
Incompatible
Haloperidol lactate
Hydroxyzine HCl
Meperidine HCl
Morphine Sulfate
Nalbuphine
Prochlorperazine edisylate
Promethazine HCl
Thiethylperazine maleate
Variable
Diazepam
Hydromorphone HCl

Ketorolac tromethamine 1 mg/mL tested.^HID

Y-Site CompatibilityHID

Compatible
Dexmedetomidine HCl
Fentanyl citrate
Hetastarch in lactated electrolyte injection (Hextend)
Hydromorphone HCl
Methadone HCl
Morphine sulfate
Remifentanil HCl
Sufentanil citrate
Incompatible
Azithromycin
Fenoldopam mesylate

ActionsActions

• 
  

  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 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 notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.¹⁹⁸

  
  


• 
  

  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

  
  


• 
  

  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 clinician