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Black Box Warning
WARNING
See full prescribing information for complete Boxed Warning.
WARNING
Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days) management of moderately severe acute pain that requires analgesia at the opioid level. It is NOT indicated for minor or chronic painful conditions. Ketorolac tromethamine is a potent NSAID analgesic, and its administration carries many risks. The resulting NSAID-related adverse events can be serious in certain patients for whom ketorolac tromethamine is indicated, especially when the drug is used inappropriately. Increasing the dose of ketorolac tromethamine beyond the label recommendations will not provide better efficacy but will result in increasing the risk of developing serious adverse events.
Gastrointestinal Effects
Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding and/or perforation. Therefore, 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.
Renal Effects
Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion (seeWARNINGS).
Risk of Bleeding
Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS andPRECAUTIONS). Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery and is CONTRAINDICATED intra-operatively when hemostasis is critical because of the increased risk of bleeding.
Hypersensitivity
Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred and appropriate counteractive measures must be available when administering the first dose of Ketorolac Tromethamine Injection Ketorolac tromethamine is CONTRAINDICATED in patients with previously demonstrated hypersensitivity to ketorolac tromethamine or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Intrathecal or Epidural Administration
Ketorolac tromethamine is CONTRAINDICATED for intrathecal or epidural administration due to its alcohol content.
Labor, Delivery and Nursing
The use of ketorolac tromethamine in labor and delivery is CONTRAINDICATED because it may adversely affect fetal circulation and the uterus.
The use of ketorolac tromethamine is CONTRAINDICATED in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.
Concomitant Use With NSAIDs
Ketorolac tromethamine is CONTRAINDICATED in patients currently receiving ASA or NSAIDs because of the cumulative risk of inducing serious NSAID-related side effects.
Dosage and Administration
Ketorolac Tromethamine Tablets
Ketorolac tromethamine tablets are indicated only as continuation therapy to Ketorolac Tromethamine Injection, and the combined duration of use of Ketorolac Tromethamine Injection and ketorolac tromethamine tablets is not to exceed five (5) days because of the increased risk of serious adverse events.
The recommended total daily dose of ketorolac tromethamine tablets (maximum 40 mg) is significantly lower than for Ketorolac Tromethamine Injection (maximum 120 mg)
Special Populations
Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs) of body weight and for patients with moderately elevated serum creatinine . Doses of Ketorolac Tromethamine Injection are not to exceed 60 mg (total dose per day) in these patients.
There is limited information regarding Ketorolac tromethamine (injection) FDA-Labeled Indications and Dosage (Adult) in the drug label.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ketorolac tromethamine (injection) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ketorolac tromethamine (injection) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Ketorolac tromethamine (injection) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ketorolac tromethamine (injection) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ketorolac tromethamine (injection) in pediatric patients.
Contraindications
Condition1
Warnings
WARNING
See full prescribing information for complete Boxed Warning.
WARNING
Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days) management of moderately severe acute pain that requires analgesia at the opioid level. It is NOT indicated for minor or chronic painful conditions. Ketorolac tromethamine is a potent NSAID analgesic, and its administration carries many risks. The resulting NSAID-related adverse events can be serious in certain patients for whom ketorolac tromethamine is indicated, especially when the drug is used inappropriately. Increasing the dose of ketorolac tromethamine beyond the label recommendations will not provide better efficacy but will result in increasing the risk of developing serious adverse events.
Gastrointestinal Effects
Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding and/or perforation. Therefore, 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.
Renal Effects
Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion (seeWARNINGS).
Risk of Bleeding
Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS andPRECAUTIONS). Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery and is CONTRAINDICATED intra-operatively when hemostasis is critical because of the increased risk of bleeding.
Hypersensitivity
Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred and appropriate counteractive measures must be available when administering the first dose of Ketorolac Tromethamine Injection Ketorolac tromethamine is CONTRAINDICATED in patients with previously demonstrated hypersensitivity to ketorolac tromethamine or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Intrathecal or Epidural Administration
Ketorolac tromethamine is CONTRAINDICATED for intrathecal or epidural administration due to its alcohol content.
Labor, Delivery and Nursing
The use of ketorolac tromethamine in labor and delivery is CONTRAINDICATED because it may adversely affect fetal circulation and the uterus.
The use of ketorolac tromethamine is CONTRAINDICATED in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.
Concomitant Use With NSAIDs
Ketorolac tromethamine is CONTRAINDICATED in patients currently receiving ASA or NSAIDs because of the cumulative risk of inducing serious NSAID-related side effects.
Dosage and Administration
Ketorolac Tromethamine Tablets
Ketorolac tromethamine tablets are indicated only as continuation therapy to Ketorolac Tromethamine Injection, and the combined duration of use of Ketorolac Tromethamine Injection and ketorolac tromethamine tablets is not to exceed five (5) days because of the increased risk of serious adverse events.
The recommended total daily dose of ketorolac tromethamine tablets (maximum 40 mg) is significantly lower than for Ketorolac Tromethamine Injection (maximum 120 mg)
Special Populations
Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs) of body weight and for patients with moderately elevated serum creatinine . Doses of Ketorolac Tromethamine Injection are not to exceed 60 mg (total dose per day) in these patients.
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Ketorolac tromethamine (injection) in the drug label.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Ketorolac tromethamine (injection) in the drug label.
Ketorolac tromethamine is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs). The chemical name for ketorolac tromethamine is (±)-5-benzoyl- 2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino- 2-(hydroxymethyl)-1,3-propanediol.
Ketorolac tromethamine is a racemic mixture of [-]S and [+]R ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. Ketorolac tromethamine has a pKa of 3.5 and an n-octanol/water partition coefficient of 0.26. The molecular weight of ketorolac tromethamine is 376.41.
Ketorolac tromethamine is available for intravenous (IV) or intramuscular (IM) administration as: 15 mg in 1 mL (1.5%) and 30 mg in 1 mL (3%) in sterile solution; 60 mg in 2 mL (3%) of ketorolac tromethamine in sterile solution is available for IM administration only. The solutions contain 10% (w/v) alcohol, USP, and 6.68 mg, 4.35 mg and 8.70 mg, respectively, of sodium chloride in sterile water. The pH is adjusted with sodium hydroxide and/or hydrochloric acid, and the solutions are packaged with nitrogen. The sterile solutions are clear and slightly yellow in color.
Pharmacodynamics
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID). Ketorolac tromethamine inhibits synthesis of prostaglandins and may be considered a peripherally acting analgesic. The biological activity of ketorolac tromethamine is associated with the S-form. Ketorolac tromethamine possesses no sedative or anxiolytic properties.
Pain relief was statistically different after ketorolac tromethamine dosing from that of placebo at 1/2 hour (the first time point at which it was measured) following the largest recommended doses of ketorolac tromethamine and by 1 hour following the smallest recommended doses. The peak analgesic effect occurred within 2 to 3 hours and was not statistically significantly different over the recommended dosage range of ketorolac tromethamine. The greatest difference between large and small doses of ketorolac tromethamine by either route was in the duration of analgesia.
Pharmacokinetics
Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the S-form having analgesic activity.
Comparison of IV, IM and Oral Pharmacokinetics
The pharmacokinetics of ketorolac tromethamine, following IV, IM and oral doses of ketorolac tromethamine are compared in Table 1. The extent of bioavailability following administration of the ORAL and IM forms of ketorolac tromethamine was equal to that following an IV bolus.
Linear Kinetics
Following administration of single ORAL, IM or IV doses of ketorolac tromethamine in the recommended dosage ranges, the clearance of the racemate does not change. This implies that the pharmacokinetics of ketorolac tromethamine in humans, following single or multiple IM, IV or recommended oral doses of ketorolac tromethamine, are linear. At the higher recommended doses, there is a proportional increase in the concentrations of free and bound racemate.
Binding and Distribution
The ketorolac tromethamine racemate has been shown to be highly protein bound (99%). Nevertheless, even plasma concentrations as high as 10 mcg/mL will only occupy approximately 5% of the albumin binding sites. Thus, the unbound fraction for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will result in increased free drug concentrations.
The mean apparent volume (Vß) of ketorolac tromethamine following complete distribution was approximately 13 liters. This parameter was determined from single-dose data.
Metabolism
Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated forms of the parent drug. The products of metabolism, and some unchanged drug, are excreted in the urine.
Clearance and Excretion
A single-dose study with 10 mg ketorolac tromethamine (n=9) demonstrated that the S-enantiomer is cleared approximately two times faster than the R-enantiomer and that the clearance was independent of the route of administration. This means that the ratio of S/R plasma concentrations decreases with time after each dose. There is little or no inversion of the R- to S-form in humans. The clearance of the racemate in normal subjects, elderly individuals and in hepatically and renally impaired patients is outlined in Table 2. The half-life of the ketorolac tromethamine S-enantiomer was approximately 2.5 hours (SD ± 0.4) compared with 5 hours (SD ± 1.7) for the R-enantiomer. In other studies, the half-life for the racemate has been reported to lie within the range of 5 to 6 hours.
Accumulation
Ketorolac tromethamine administered as an IV bolus every 6 hours for 5 days to healthy subjects (n=13), showed no significant difference in Cmax on Day 1 and Day 5. Trough levels averaged 0.29 mcg/mL (SD± 0.13) on Day 1 and 0.55 mcg/mL (SD ± 0.23) on Day 6. Steady state was approached after the fourth dose.
Accumulation of ketorolac tromethamine has not been studied in special populations (elderly patients, renal failure patients or hepatic disease patients).
Kinetics in Special Populations
Elderly Patients:
Based on single-dose data only, the half-life of the ketorolac tromethamine racemate increased from 5 to 7 hours in the elderly (65 to 78 years) compared with young healthy volunteers (24 to 35 years) (see Table 2). There was little difference in the Cmax for the two groups (elderly, 2.52 mcg/mL ± 0.77; young, 2.99 mcg/mL ± 1.03) (see PRECAUTIONS--USE IN THE ELDERLY).
Renally Impaired Patients:
Based on single-dose data only, the mean half-life of ketorolac tromethamine in renally impaired patients is between 6 and 19 hours and is dependent on the extent of the impairment. There is poor correlation between creatinine clearance and total ketorolac tromethamine clearance in the elderly and populations with renal impairment (r=0.5).
In patients with renal disease, the AUC∞ of each enantiomer increased by approximately 100% compared with healthy volunteers. The volume of distribution doubles for the S-enantiomer and increases by 1/5th for the R-enantiomer. The increase in volume of distribution of ketorolac tromethamine implies an increase in unbound fraction.
The AUC∞-ratio of the ketorolac tromethamine enantiomers in healthy subjects and patients remained similar, indicating there was no selective excretion of either enantiomer in patients compared to healthy subjects (seeWARNINGS - RENAL EFFECTS).
Hepatic Effects:
There was no significant difference in estimates of half-life, AUC∞ and Cmax in 7 patients with liver disease compared to healthy volunteers
Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Ketorolac tromethamine (injection) in the drug label.
Clinical Studies
There is limited information regarding Clinical Studies of Ketorolac tromethamine (injection) in the drug label.
How Supplied
Storage
There is limited information regarding Ketorolac tromethamine (injection) Storage in the drug label.
Images
Drug Images
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There is limited information regarding Patient Counseling Information of Ketorolac tromethamine (injection) in the drug label.
Precautions with Alcohol
Alcohol-Ketorolac tromethamine (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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