Ketorolac Ketorolac

Tromethamine Tromethamine
Injection, USP Injection, USP

% Dose excreted in urine = 91 Ketorolac tromethamine injection has been used concomitantly with morphine and meperidine and has shown an opioidsparing effect. For
Ketorolac Tromethamine Injection, USP % Plasma protein binding = 99 breakthrough pain, it is recommended to supplement the lower end of the ketorolac tromethamine injection dosage range with low doses
2
Peak plasma concentration of narcotics prn, unless otherwise contraindicated. Ketorolac tromethamine injection and narcotics should not be administered in the same
*
Derived from PO pharmacokinetic studies in 77 normal fasted volunteers syringe (see DOSAGE AND ADMINISTRATION: Pharmaceutical Information for Ketorolac Tromethamine Injection).
3
Trough plasma concentration
CONTRAINDICATIONS (See also Boxed WARNING)

Derived from IM pharmacokinetic studies in 54 normal volunteers
Ketorolac tromethamine injection is contraindicated in patients with previously demonstrated hypersensitivity to ketorolac tromethamine.
4
Average plasma concentration

Derived from IV pharmacokinetic studies in 24 normal volunteers Ketorolac tromethamine injection is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal
WARNING 5
Volume of distribution bleeding or perforation and in patients with a history of peptic ulcer disease or gastrointestinal bleeding.
Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days in adults),
Mean value was simulated from observed plasma concentration data and standard deviation was simulated from percent coefficient of Ketorolac tromethamine injection should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after
management of moderately severe acute pain that requires analgesia at the opioid level. Oral ketorolac tromethamine is indicated only
variation for observed Cmax and Tmax data taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients
as continuation treatment following IV or IM dosing of ketorolac tromethamine, if necessary. The total combined duration of use of oral ||
Not applicable because 60 mg is only recommended as a single dose
ketorolac tromethamine and ketorolac tromethamine injection should not exceed 5 days. (see WARNINGS: Anaphylactoid Reactions, and PRECAUTIONS: Preexisting Asthma).
Linear Kinetics
Ketorolac tromethamine is not indicated for use in pediatric patients and it is NOT indicated for minor or chronic painful conditions. Ketorolac tromethamine injection is contraindicated as prophylactic analgesic before any major surgery.
In adults, following administration of single ORAL, IM or IV doses of ketorolac tromethamine in the recommended dosage ranges, the
Increasing the dose of ketorolac tromethamine beyond the label recommendations will not provide better efficacy but will increase the risk Ketorolac tromethamine injection is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft
clearance of the racemate does not change. This implies that the pharmacokinetics of ketorolac tromethamine in adults, following single or
of developing serious adverse events. (CABG) surgery (see WARNINGS).
multiple IM, IV or recommended oral doses of ketorolac tromethamine, are linear. At the higher recommended doses, there is a proportional
GASTROINTESTINAL RISK increase in the concentrations of free and bound racemate. Ketorolac tromethamine injection is contraindicated in patients with advanced renal impairment or in patients at risk for renal failure due to
Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding and/or perforation of the stomach or intestines, which
Distribution volume depletion (see WARNINGS for correction of volume depletion).
can be fatal. These events can occur at any time during use and without warning symptoms. Therefore, ketorolac tromethamine
The mean apparent volume (V) of ketorolac tromethamine following complete distribution was approximately 13 liters. This parameter was Ketorolac tromethamine injection is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may
is CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation,
determined from single-dose data. The ketorolac tromethamine racemate has been shown to be highly protein bound (99%). Nevertheless,
and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Elderly patients are at greater risk for serious adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage.
plasma concentrations as high as 10 mcg/mL will only occupy approximately 5% of the albumin binding sites. Thus, the unbound fraction
gastrointestinal events (see WARNINGS). Ketorolac tromethamine inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular
for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will result in increased free drug
CARDIOVASCULAR RISK concentrations. bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS and PRECAUTIONS).
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be Ketorolac tromethamine injection is contraindicated in patients currently receiving asprin or NSAIDs because of the cumulative risks of
Ketorolac tromethamine is excreted in human milk (see PRECAUTIONS: Nursing mothers).
fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may inducing serious NSAID-related adverse events.
be at greater risk (see WARNINGS and CLINICAL TRIALS). Metabolism
Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated forms of the parent drug. The concomitant use of ketorolac tromethamine injection and probenecid is contraindicated.
Ketorolac tromethamine is CONTRAINDICATED for the treatment of peri-operative pain in the setting of coronary artery bypass
The products of metabolism, and some unchanged drug, are excreted in the urine. The concomitant use of ketorolac tromethamine injection and pentoxifylline is contraindicated.
graft (CABG) surgery (see WARNINGS).
Excretion Ketorolac tromethamine injection is contraindicated for neuraxial (epidural or intrathecal) administration due to its alcohol content.
RENAL RISK
The principal route of elimination of ketorolac and its metabolites is renal. About 92% of a given dose is found in the urine, approximately
Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment and in patients at risk for renal failure WARNINGS (See also Boxed WARNING)
40% as metabolites and 60% as unchanged ketorolac. Approximately 6% of a dose is excreted in the feces. A single-dose study with
due to volume depletion (see WARNINGS). The total combined duration of use of oral ketorolac tromethamine and IV or IM dosing of ketorolac tromethamine is not to exceed 5 days in
10 mg ketorolac tromethamine (n=9) demonstrated that the S-enantiomer is cleared approximately two times faster than the R-enantiomer
RISK OF BLEEDING and that the clearance was independent of the route of administration. This means that the ratio of S/R plasma concentrations decreases adults. Ketorolac tromethamine injection is not indicated for use in pediatric patients.
Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed 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, The most serious risks associated with ketorolac tromethamine are:
cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding elderly individuals and in hepatically and renally impaired patients is outlined in Table 2 (see CLINICAL PHARMACOLOGY: Kinetics in Gastrointestinal Effects
(see WARNINGS and PRECAUTIONS). Special Populations). Risk of Ulceration, Bleeding, and Perforation
Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery. 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 Ketorolac tromethamine is contraindicated in patients with previously documented peptic ulcers and/or GI bleeding. Ketorolac tromethamine
HYPERSENSITIVITY R-enantiomer. In other studies, the half-life for the racemate has been reported to lie within the range of 5 to 6 hours. can cause serious gastrointestinal (GI) adverse events including bleeding, ulceration and perforation, of the stomach, small intestine, or large
Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred and appropriate counteractive Accumulation intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated
measures must be available when administering the first dose of ketorolac tromethamine injection (see CONTRAINDICATIONS Ketorolac tromethamine administered as an IV bolus, every 6 hours for 5 days to healthy subjects (n = 13), showed no significant difference with ketorolac tromethamine.
and WARNINGS). Ketorolac tromethamine is CONTRAINDICATED in patients with previously demonstrated hypersensitivity to 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 Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Minor upper gastrointestinal
ketorolac tromethamine or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). state was approached after the fourth dose. problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. The incidence and severity of
INTRATHECAL OR EPIDURAL ADMINISTRATION Accumulation of ketorolac tromethamine has not been studied in special populations (geriatric, pediatric, renal failure or hepatic disease gastrointestinal complications increases with increasing dose of, and duration of treatment with, ketorolac tromethamine. Do not use
Ketorolac tromethamine is CONTRAINDICATED for intrathecal or epidural administration due to its alcohol content. patients). ketorolac tromethamine for more than five days. However, even short-term therapy is not without risk. In addition to past history of ulcer
disease, other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids,
RISK DURING LABOR AND DELIVERY Kinetics in Special Populations or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous
The use of ketorolac tromethamine in labor and delivery is CONTRAINDICATED because it may adversely affect fetal circulation Geriatric Patients
reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
and inhibit uterine contractions. 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 To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration.
CONCOMITANT USE WITH NSAIDS
(elderly, 2.52 mcg/mL 0.77; young, 2.99 mcg/mL 1.03) (see PRECAUTIONS: Geriatric use). Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly
Ketorolac tromethamine is CONTRAINDICATED in patients currently receiving aspirin or NSAIDs because of the cumulative risk of
initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of ketorolac
inducing serious NSAID-related side effects. Pediatric Patients
tromethamine until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be
SPECIAL POPULATIONS Limited information is available regarding the pharmacokinetics of dosing of ketorolac tromethamine in the pediatric population. Following
a single intravenous bolus dose of 0.5 mg/kg in 10 children 4 to 8 years old, the half-life was 5.8 1.6 hours, the average clearance was considered. NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohns disease)
Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs.) of body weight (see DOSAGE as their condition may be exacerbated.
AND ADMINISTRATION) and for patients with moderately elevated serum creatinine (see WARNINGS). Doses of ketorolac 0.042 0.01 L/hr/kg, the volume of distribution during the terminal phase (V) was 0.34 0.12 L/kg and the volume of distribution at steady
tromethamine injection are not to exceed 60 mg (total dose per day) in these patients. state (Vss) was 0.26 0.08 L/kg. The volume of distribution and clearance of ketorolac in pediatric patients was higher than those observed Hemorrhage
in adult subjects (see Table 1). There are no pharmacokinetic data available for administration of ketorolac tromethamine by the IM route Because prostaglandins play an important role in hemostasis and NSAIDs affect platelet aggregation as well, use of ketorolac tromethamine in
DOSAGE AND ADMINISTRATION in pediatric patients. patients who have coagulation disorders should be undertaken very cautiously, and those patients should be carefully monitored. Patients on
Ketorolac Tromethamine Tablets therapeutic doses of anticoagulants (e.g., heparin or dicumarol derivatives) have an increased risk of bleeding complications if given ketorolac
Ketorolac tromethamine tablets are indicated only as continuation therapy to ketorolac tromethamine injection, and the combined Renally Insufficiency
Based on single-dose data only, the mean half-life of ketorolac tromethamine in renally impaired patients is between 6 and 19 hours, and tromethamine concurrently; therefore, physicians should administer such concomitant therapy only extremely cautiously. The concurrent use
duration of use of ketorolac tromethamine injection and ketorolac tromethamine tablets is not to exceed 5 (five) days, because of of ketorolac tromethamine and therapy that affects hemostasis, including prophylactic low-dose heparin (2,500 to 5,000 units q12h), warfarin
is dependent on the extent of the impairment. There is poor correlation between creatinine clearance and total ketorolac tromethamine
the increased risk of serious adverse events. and dextrans have not been studied extensively, but may also be associated with an increased risk of bleeding. Until data from such studies are
clearance in the elderly and populations with renal impairment (r = 0.5).
The recommended total daily dose of ketorolac tromethamine tablets (maximum 40 mg) is significantly lower than for ketorolac available, physicians should carefully weigh the benefits against the risks and use such concomitant therapy in these patients only extremely
In patients with renal disease, the AUC of each enantiomer increased by approximately 100% compared with healthy volunteers. The cautiously. Patients receiving therapy that affects hemostasis should be monitored closely.
tromethamine injection (maximum 120 mg) (see DOSAGE AND ADMINISTRATION).
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. In postmarketing experience, postoperative hematomas and other signs of wound bleeding have been reported in association with the
DESCRIPTION peri-operative use of IV or IM dosing of ketorolac tromethamine. Therefore, peri-operative use of ketorolac tromethamine should be avoided
Ketorolac tromethamine is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs). The chemical name The AUC-ratio of the ketorolac tromethamine enantiomers in healthy subjects and patients remained similar, indicating there was no
and postoperative use be undertaken with caution when hemostasis is critical (see PRECAUTIONS).
for ketorolac tromethamine is ()-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3- selective excretion of either enantiomer in patients compared to healthy subjects (see WARNINGS: Renal Effects).
propanediol (1:1), and the structural formula is below: Renal Effects
Hepatic Insufficiency
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in
O There was no significant difference in estimates of half-life, AUC and Cmax in 7 patients with liver disease compared to healthy volunteers
patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a
(see PRECAUTIONS: Hepatic Effects and Table 2).
NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt
Race renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those
OH
OH Pharmacokinetic differences due to race have not been identified. taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment
Table 2 state.
N
NH2 The Influence of Age, Liver and Kidney Function, on the Clearance and Terminal Half-life of Ketorolac tromethamine and its metabolites are eliminated primarily by the kidneys, which, in patients with reduced creatinine clearance,
HO OH Ketorolac Tromethamine (IM1 and ORAL2) in Adult Populations will result in diminished clearance of the drug (see CLINICAL PHARMACOLOGY). Therefore, ketorolac tromethamine should be used with
Total Clearance [in L/h/kg] 3
Terminal Half-life [in hours] caution in patients with impaired renal function (see DOSAGE AND ADMINISTRATION) and such patients should be followed closely. With
C15H13NO3C4H11NO3 Type of Subjects IM ORAL IM ORAL the use of ketorolac tromethamine, there have been reports of acute renal failure, interstitial nephritis and nephrotic syndrome.
O
Mean (range) Mean (range) Mean (range) Mean (range) Impaired Renal Function
Ketorolac tromethamine, USP is a white to off-white, crystalline powder and is a racemic mixture of [-]S and [+]R ketorolac tromethamine. Normal Subjects 0.023 0.025 5.3 5.3 Ketorolac tromethamine is contraindicated in patients with serum creatinine concentrations indicating advanced renal impairment
Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. Ketorolac tromethamine has a pKa of 3.5 and IM (n=54) (0.010 to 0.046) (0.013 to 0.050) (3.5 to 9.2) (2.4 to 9.0) (see CONTRAINDICATIONS). Ketorolac tromethamine should be used with caution in patients with impaired renal function or a history
an n-octanol/water partition coefficient of 0.26. The molecular weight of ketorolac tromethamine is 376.40. mean age=32, range=18 to 60 of kidney disease because it is a potent inhibitor of prostaglandin synthesis. Because patients with underlying renal insufficiency are at
Oral (n=77) increased risk of developing acute renal decompensation or failure, the risks and benefits should be assessed prior to giving ketorolac
Ketorolac Tromethamine Injection, USP 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 and 60 mg in 2 mL (3%) of ketorolac tromethamine in sterile solution is available for IM administration mean age=32, range=20 to 60 tromethamine to these patients.
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 Healthy Elderly Subjects 0.019 0.024 7.0 6.1 Anaphylactoid Reactions
pH range is 6.9 to 7.9 and is adjusted with sodium hydroxide and/or hydrochloric acid. The sterile solutions are clear and slightly yellow in IM (n=13), Oral (n=12) (0.013 to 0.034) (0.018 to 0.034) (4.7 to 8.6) (4.3 to 7.6) As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to ketorolac tromethamine. Ketorolac
color. mean age=72, range=65 to 78 tromethamine should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who
CLINICAL PHARMACOLOGY experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other
Patients with Hepatic Dysfunction 0.029 0.033 5.4 4.5 NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS: Preexisting Asthma). Emergency help should be sought in cases where an
Pharmacodynamics IM and Oral (n=7) (0.013 to 0.066) (0.019 to 0.051) (2.2 to 6.9) (1.6 to 7.6)
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits analgesic activity in animal models. The mechanism anaphylactoid reaction occurs.
mean age=51, range=43 to 64
of action of ketorolac, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition. The Cardiovascular Effects
biological activity of ketorolac tromethamine is associated with the S-form. Ketorolac tromethamine possesses no sedative or anxiolytic Patients with Renal Impairment 0.015 0.016 10.3 10.8 Cardiovascular Thrombotic Events
properties. IM (n=25), Oral (n=9) (0.005 to 0.043) (0.007 to 0.052) (5.9 to 19.2) (3.4 to 18.9) Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious
serum creatinine=1.9 to 5.0 mg/dL cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and
The peak analgesic effect of ketorolac tromethamine occurs within 2 to 3 hours and is not statistically significantly different over the
mean age (IM)=54, range 35 to 71 nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the
recommended dosage range of ketorolac tromethamine. The greatest difference between large and small doses of ketorolac tromethamine
mean age (Oral)=57, range=39 to 70 potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration
is in the duration of analgesia.
Renal Dialysis Patients 0.016 ---- 13.6 ---- possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms.
Pharmacokinetics
IM and Oral (n=9) (0.003 to 0.036) (8.0 to 39.1) Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
Ketorolac tromethamine is a racemic mixture of [-]S and [+]R-enantiomeric forms, with the S-form having analgesic activity.
mean age=40, range=27 to 63 There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with
Comparison of IV, IM and Oral Pharmacokinetics:
1
Estimated from 30 mg single IM doses of ketorolac tromethamine NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see Gastrointestinal Effects: Risk
The pharmacokinetics of ketorolac tromethamine, following IV, IM and oral doses of ketorolac tromethamine are compared in Table 1. In
2
Estimated from 10 mg single oral doses of ketorolac tromethamine of Ulceration, Bleeding, and Perforation). Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the
adults, the extent of bioavailability following administration of the ORAL and IM forms of ketorolac tromethamine was equal to that following
3
Liters/hours/kilogram first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).
an IV bolus.
Table 1 IV Administration Hypertension
Table of Approximate Average Pharmacokinetic Parameters (Mean SD) Following Oral, In normal adult subjects (n=37), the total clearance of 30 mg IV-administered ketorolac tromethamine was 0.030 (0.017 to 0.051) L/h/kg. NSAIDs, including ketorolac tromethamine, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which
Intramuscular and Intravenous Doses of Ketorolac Tromethamine The terminal half-life was 5.6 (4.0 to 7.9) hours (see Kinetics in Special Populations for use of IV dosing of ketorolac tromethamine in may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these
pediatric patients). therapies when taking NSAIDs. NSAIDs, including ketorolac tromethamine, should be used with caution in patients with hypertension. Blood
Pharmacokinetic Oral* Intramuscular Intravenous Bolus pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Parameters (units) 10 mg 15 mg 30 mg 60 mg 15 mg 30 mg Clinical Studies
Congestive Heart Failure and Edema
Adult Patients
Bioavailability (extent) 100% Fluid retention, edema, retention of NaCl, oliguria, elevations of serum urea nitrogen and creatinine have been reported in clinical trials with
In a postoperative study, where all patients received morphine by a PCA device, patients treated with ketorolac tromethamine IV as fixed
ketorolac tromethamine. Therefore, ketorolac tromethamine should be used only very cautiously in patients with cardiac decompensation,
Tmax1 (min) 4434 3321 4429 3321 1.10.7 2.91.8 intermittent boluses (e.g., 30 mg initial dose followed by 15 mg q3h), required significantly less morphine (26%) than the placebo group.
hypertension or similar conditions.
Analgesia was significantly superior, at various postdosing pain assessment times, in the patients receiving ketorolac tromethamine IV plus
Cmax2 (mcg/mL) 0.870.22 1.140.32 2.420.68 4.551.27 2.470.51 4.650.96
PCA morphine as compared to patients receiving PCA-administered morphine alone. Skin Reactions
[single-dose]
NSAIDs, including ketorolac tromethamine, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson
Cmax(mcg/mL) 1.050.26 1.560.44 3.110.87 N/A|| 3.091.17 6.852.61 INDICATIONS AND USAGE
Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients
[steady state qid] Carefully consider the potential benefits and risks ketorolac tromethamine injection and other treatment options before deciding to use
should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first
ketorolac. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). appearance of skin rash or any other sign of hypersensitivity.
Cmin3 (mcg/mL) 0.290.07 0.470.13 0.930.26 N/A 0.610.21 1.040.35
[steady state qid] Acute Pain in Adult Patients Pregnancy
Ketorolac tromethamine injection is indicated for the short-term (5 days) management of moderately severe acute pain that requires In late pregnancy, as with other NSAIDs, ketorolac tromethamine should be avoided because it may cause premature closure of the ductus
Cavg4 (mcg/mL) 0.590.20 0.940.29 1.880.59 N/A 1.090.30 2.170.59 analgesia at the opioid level, usually in a postoperative setting. Therapy should always be initiated with IV or IM dosing of ketorolac
[steady state qid] arteriosus.
tromethamine injection, and oral ketorolac tromethamine is to be used only as continuation treatment, if necessary.
V5 (L/kg) 0.1750.039 0.2100.044 PRECAUTIONS
The total combined duration of use of ketorolac tromethamine injection and oral ketorolac tromethamine is not to exceed 5 days of use General
% Dose metabolized = <50 because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses Ketorolac tromethamine cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of
% Dose excreted in feces = 6 (see WARNINGS, PRECAUTIONS, DOSAGE AND ADMINISTRATION, and ADVERSE REACTIONS). Patients should be switched to corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a
1
Time-to-peak plasma concentration alternative analgesics as soon as possible, but ketorolac tromethamine therapy is not to exceed 5 days. decision is made to discontinue corticosteroids.
The pharmacological activity of ketorolac tromethamine in reducing inflammation may diminish the utility of this diagnostic sign in detecting muscle relaxants that resulted in apnea. The concurrent use of ketorolac tromethamine with muscle relaxants has not been formally studied. Nervous System
complications of presumed noninfectious, painful conditions. aseptic meningitis, convulsions, coma, psychosis
Selective Serotonin Reuptake Inhibitors (SSRIs)
Hepatic Effects There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs. Respiratory
Ketorolac tromethamine should be used with caution in patients with impaired hepatic function or a history of liver disease. Borderline Caution should be used when NSAIDs are administered concomitantly with SSRIs. bronchospasm, respiratory depression, pneumonia
elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including ketorolac tromethamine. These laboratory
Carcinogenesis, mutagenesis, impairment of fertility Special Senses
abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST
(approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with An 18-month study in mice with oral doses of ketorolac tromethamine at 2 mg/kg/day (0.9 times the human systemic exposure at the conjunctivitis
NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, recommended IM or IV dose of 30 mg qid, based on area-under-the-plasma-concentration curve [AUC]), and a 24-month study in rats at
Urogenital
some of them with fatal outcomes have been reported. 5 mg/kg/day (0.5 times the human AUC) showed no evidence of tumorigenicity. flank pain with or without hematuria and/or azotemia, hemolytic uremic syndrome
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for Ketorolac tromethamine was not mutagenic in the Ames test, unscheduled DNA synthesis and repair, and in forward mutation assays. Postmarketing Surveillance Study
evidence of the development of a more severe hepatic reaction while on therapy with ketorolac tromethamine. If clinical signs and symptoms Ketorolac tromethamine did not cause chromosome breakage in the in vivo mouse micronucleus assay. At 1590 mcg/mL and at higher A large postmarketing observational, nonrandomized study, involving approximately 10,000 patients receiving ketorolac tromethamine,
consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), ketorolac tromethamine should be concentrations, ketorolac tromethamine increased the incidence of chromosomal aberrations in Chinese hamster ovarian cells. demonstrated that the risk of clinically serious gastrointestinal (GI) bleeding was dose-dependent (see Tables 3A and 3B). This was
discontinued. Impairment of fertility did not occur in male or female rats at oral doses of 9 mg/kg (0.9 times the human AUC) and 16 mg/kg particularly true in elderly patients who received an average daily dose greater than 60 mg/day of ketorolac tromethamine (see Table 3A).
Hematological Effects (1.6 times the human AUC) of ketorolac tromethamine, respectively. Table 3
Anemia is sometimes seen in patients receiving NSAIDs, including ketorolac tromethamine. This may be due to fluid retention, occult or gross Pregnancy Incidence of Clinically Serious G.I. Bleeding as Related to Age, Total Daily Dose,
GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including ketorolac Teratogenic Effects and History of G.I. Perforation, Ulcer, Bleeding (PUB) after up to 5 Days of Treatment with Ketorolac Tromethamine Injection
tromethamine, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. NSAIDs inhibit platelet Pregnancy Category C A. Adult Patients without History of PUB
aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively Reproduction studies have been performed during organogenesis using daily oral doses of ketorolac tromethamine at 3.6 mg/kg
less, of shorter duration, and reversible. Patients receiving ketorolac tromethamine who may be adversely affected by alterations in platelet Age of Patients Total Daily Dose of Ketorolac Tromethamine Injection
(0.37 times the human AUC) in rabbits and at 10 mg/kg (1.0 times the human AUC) in rats. Results of these studies did not reveal evidence
function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored. of teratogenicity to the fetus. However, animal reproduction studies are not always predictive of human response. 60 mg >60 to 90 mg >90 to 120 mg >120 mg
Preexisting Asthma <65 years of age 0.4% 0.4% 0.9% 4.6%
Nonteratogenic Effects
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated
Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use 65 years of age 1.2% 2.8% 2.2% 7.7%
with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal
during pregnancy (particularly late pregnancy) should be avoided. Oral doses of ketorolac tromethamine at 1.5 mg/kg (0.14 times the human AUC),
anti-inflammatory drugs has been reported in such aspirin-sensitive patients, ketorolac tromethamine should not be administered to patients
administered after gestation Day 17, caused dystocia and higher pup mortality in rats. B. Adult Patients with History of PUB
with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
There are no adequate and well-controlled studies of ketorolac tromethamine in pregnant women. Ketorolac tromethamine should be used Age of Patients Total Daily Dose of Ketorolac Tromethamine Injection
Information for Patients
Ketorolac tromethamine is a potent NSAID and may cause serious side effects such as gastrointestinal bleeding or kidney failure, which may during pregnancy only if the potential benefit justifies the potential risk to the fetus. 60 mg >60 to 90 mg >90 to 120 mg >120 mg
result in hospitalization and even fatal outcome. Labor and Delivery <65 years of age 2.1% 4.6% 7.8% 15.4%
Physicians, when prescribing ketorolac tromethamine, should inform their patients or their guardians of the potential risks of ketorolac The use of ketorolac tromethamine is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory
effect, it may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage 65 years of age 4.7% 3.7% 2.8% 25.0%
tromethamine treatment (see Boxed WARNING, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS sections), instruct patients to
seek medical advice if they develop treatment-related adverse events, and advise patients not to give oral ketorolac tromethamine to other (see CONTRAINDICATIONS).
To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088
family members and to discard any unused drug. Effects on Fertility or www.fda.gov/medwatch.
Remember that the total combined duration of use of oral ketorolac tromethamine and IV or IM dosing of ketorolac tromethamine is not to The use of ketorolac tromethamine, as with any drug known to inhibit cyclooxygenase/ prostaglandin synthesis, may impair fertility and is OVERDOSAGE
exceed 5 days in adults. Ketorolac tromethamine is not indicated for use in pediatric patients. not recommended in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of infertility, Symptoms and Signs
withdrawal of ketorolac tromethamine should be considered. Symptoms following acute NSAIDs overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are
Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing
therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed. Nursing Mothers generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and
Limited data from one published study that included 10 breastfeeding women 2 to 6 days postpartum showed low levels of ketorolac coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following
1. Ketorolac tromethamine, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in an overdose.
in breast milk and were undetectable (less than 5 ng/mL) in 4 of the patients. After a single administration of 10 mg of oral ketorolac
hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for
the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice tromethamine, the maximum milk concentration observed was 7.3 ng/mL, and the maximum milk-to-plasma ratio was 0.037. After 1 day Treatment
when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up of dosing (10 mg every 6 hours), the maximum milk concentration was 7.9 ng/mL, and the maximum milk-to-plasma ratio was 0.025. Patients should be managed by symptomatic and supportive care following a NSAIDs overdose. There are no specific antidotes. Emesis and/or
(see WARNINGS, Cardiovascular Effects). Assuming a daily intake of 400 to 1,000 mL of human milk per day and a maternal body weight of 60 kg, the calculated maximum daily infant activated charcoal (60 g to 100 g in adults, 1 g/kg to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within
2. Ketorolac tromethamine, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and exposure was 0.00263 mg/kg/day, which is 0.4% of the maternal weight-adjusted dose. 4 hours of ingestion with symptoms or following a large oral overdose (5 to 10 times the usual dose). Forced diuresis, alkalization of urine,
bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur Exercise caution when ketorolac is administered to a nursing woman. Available information has not shown any specific adverse events in hemodialysis or hemoperfusion may not be useful due to high protein binding.
without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should nursing infants; however, instruct patients to contact their infants healthcare provider if they note any adverse events. Single overdoses of ketorolac tromethamine have been variously associated with abdominal pain, nausea, vomiting, hyperventilation, peptic
ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and ulcers and/or erosive gastritis and renal dysfunction which have resolved after discontinuation of dosing.
hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects: Pediatric Use
Risk of Ulceration, Bleeding, and Perforation). Ketorolac tromethamine is not indicated for use in pediatric patients. The safety and effectiveness of ketorolac tromethamine in pediatric DOSAGE AND ADMINISTRATION
3. Ketorolac tromethamine, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, patients below the age of 17 have not been established. Carefully consider the potential benefits and risks of ketorolac tromethamine injection and other treatment options before
which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients Geriatric Use (65 years of age) deciding to use ketorolac tromethamine. Use the lowest effective dose for the shortest duration consistent with individual patient
should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and treatment goals. In adults, the combined duration of use of IV or IM dosing of ketorolac tromethamine injection and oral ketorolac
Because ketorolac tromethamine may be cleared more slowly by the elderly (see CLINICAL PHARMACOLOGY) who are also more
should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug tromethamine is not to exceed 5 days. In adults, the use of oral ketorolac tromethamine is only indicated as continuation therapy
sensitive to the dose-related adverse effects of NSAIDs (see WARNINGS: Gastrointestinal Effects: Risk of Ulceration, Bleeding, and
immediately if they develop any type of rash and contact their physicians as soon as possible. to IV or IM dosing of ketorolac tromethamine injection. See package insert for ketorolac tromethamine tablets for transition from IV
Perforation), extreme caution, reduced dosages (see DOSAGE AND ADMINISTRATION), and careful clinical monitoring must be used
4. Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians. or IM dosing of ketorolac tromethamine (single- or multiple-dose) to multiple-dose oral ketorolac tromethamine.
when treating the elderly with ketorolac tromethamine.
5. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, Note
jaundice, right upper quadrant tenderness, and flu-like symptoms). If these occur, patients should be instructed to stop therapy ADVERSE REACTIONS
Oral formulation should not be given as an initial dose
and seek immediate medical therapy. Adverse reaction rates increase with higher doses of ketorolac tromethamine. Practitioners should be alert for the severe complications
of treatment with ketorolac tromethamine, such as G.I. ulceration, bleeding and perforation, postoperative bleeding, acute renal failure, Use minimum effective dose for the individual patient
6. Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If
these occur, patients should be instructed to seek immediate emergency help (see WARNINGS). anaphylactic and anaphylactoid reactions and liver failure (see Boxed WARNING, WARNINGS, PRECAUTIONS, and DOSAGE AND Total duration of treatment in adult patients:
7. In late pregnancy, as with other NSAIDs, ketorolac tromethamine should be avoided because it will cause premature closure of ADMINISTRATION). These NSAID-related complications can be serious in certain patients for whom ketorolac tromethamine is indicated, The combined duration of use of IV or IM dosing of ketorolac tromethamine and oral ketorolac tromethamine is not to exceed 5 days.
the ductus arteriosus. especially when the drug is used inappropriately.
Ketorolac Tromethamine Injection
Laboratory Tests In patients taking ketorolac tromethamine or other NSAIDs in clinical trials, the most frequently reported adverse experiences in approximately Ketorolac tromethamine injection may be used as a single or multiple dose on a regular or prn schedule for the management of moderately
Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms 1% to 10% of patients are: severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Hypovolemia should be corrected prior to the
of GI bleeding. Patients on long-term treatment with NSAIDs, should have their CBC and a chemistry profile checked periodically. If clinical Gastrointestinal (GI) experiences including: administration of ketorolac tromethamine (see WARNINGS: Renal Effects). Patients should be switched to alternative analgesics as soon
signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash etc.) or if abnormal abdominal pain constipation/diarrhea dyspepsia as possible, but ketorolac tromethamine therapy is not to exceed 5 days.
liver tests persist or worsen, ketorolac tromethamine should be discontinued. flatulence GI fullness GI ulcers (gastric/duodenal) When administering ketorolac tromethamine injection, the IV bolus must be given over no less than 15 seconds. The IM administration should
Drug Interactions gross bleeding/perforation heartburn nausea* be given slowly and deeply into the muscle. The analgesic effect begins in ~30 minutes with maximum effect in 1 to 2 hours after dosing
Ketorolac is highly bound to human plasma protein (mean 99.2%). There is no evidence in animal or human studies that ketorolac stomatitis vomiting IV or IM. Duration of analgesic effect is usually 4 to 6 hours.
tromethamine induces or inhibits hepatic enzymes capable of metabolizing itself or other drugs. Other experiences: Single-Dose Treatment
Warfarin, Digoxin, Salicylate, and Heparin abnormal renal function anemia dizziness The Following Regimen Should Be Limited To Single Administration Use Only
The in vitro binding of warfarin to plasma proteins is only slightly reduced by ketorolac tromethamine (99.5% control vs 99.3%) when drowsiness edema elevated liver enzymes
headaches* hypertension increased bleeding time IM Dosing:
ketorolac plasma concentrations reach 5 to 10 mcg/mL. Ketorolac does not alter digoxin protein binding. In vitro studies indicate that, Patients < 65 years of age: One dose of 60 mg.
at therapeutic concentrations of salicylate (300 mcg/mL), the binding of ketorolac was reduced from approximately 99.2% to 97.5%, injection site pain pruritus purpura
Patients 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 30 mg.
representing a potential twofold increase in unbound ketorolac plasma levels. Therapeutic concentrations of digoxin, warfarin, ibuprofen, rashes tinnitus sweating
naproxen, piroxicam, acetaminophen, phenytoin and tolbutamide did not alter ketorolac tromethamine protein binding. *
Incidence greater than 10% IV Dosing:
Patients < 65 years of age: One dose of 30 mg.
In a study involving 12 adult volunteers, oral ketorolac tromethamine was coadministered with a single dose of 25 mg warfarin, Additional adverse experiences reported occasionally (<1% in patients taking ketorolac tromethamine or other NSAIDs in clinical trials)
Patients 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 15 mg.
causing no significant changes in pharmacokinetics or pharmacodynamics of warfarin. In another study, ketorolac tromethamine include:
dosed IV or IM was given with two doses of 5,000 units of heparin to 11 healthy volunteers, resulting in a mean template bleeding time Multiple-Dose Treatment (IV or IM)
Body as a Whole
of 6.4 minutes (3.2 to 11.4 min) compared to a mean of 6 minutes (3.4 to 7.5 min) for heparin alone and 5.1 minutes (3.5 to 8.5 min) for Patients < 65 years of age: The recommended dose is 30 mg ketorolac tromethamine injection every 6 hours. The maximum
fever, infections, sepsis daily dose for these populations should not exceed 120 mg.
placebo. Although these results do not indicate a significant interaction between ketorolac tromethamine and warfarin or heparin, the
administration of ketorolac tromethamine to patients taking anticoagulants should be done extremely cautiously, and patients should Cardiovascular For patients 65 years of age, renally impaired patients (see WARNINGS), and patients less than 50 kg (110 lbs): The
be closely monitored (see WARNINGS and PRECAUTIONS: Hematological Effects). congestive heart failure, palpitation, pallor, tachycardia, syncope recommended dose is 15 mg ketorolac tromethamine injection every 6 hours. The maximum daily dose for these populations
should not exceed 60 mg.
The effects of warfarin and NSAIDs, in general, on GI bleeding are synergistic, such that the users of both drugs together have a risk of Dermatologic
serious GI bleeding higher than the users of either drug alone. alopecia, photosensitivity, urticaria For breakthrough pain, do not increase the dose or the frequency of ketorolac tromethamine. Consideration should be given to supplementing
these regimens with low doses of opioids prn unless otherwise contraindicated.
Aspirin Gastrointestinal
When ketorolac tromethamine is administered with aspirin, its protein binding is reduced, although the clearance of free ketorolac anorexia, dry mouth, eructation, esophagitis, excessive thirst, gastritis, glossitis, hematemesis, hepatitis, increased appetite, jaundice, Pharmaceutical Information for Ketorolac Tromethamine Injection
tromethamine is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant melena, rectal bleeding Ketorolac tromethamine injection should not be mixed in a small volume (e.g., in a syringe) with morphine sulfate, meperidine hydrochloride,
administration of ketorolac tromethamine and aspirin is not generally recommended because of the potential of increased adverse effects. promethazine hydrochloride or hydroxyzine hydrochloride; this will result in precipitation of ketorolac from solution.
Hemic and Lymphatic
Diuretics ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever
Clinical studies, as well as postmarketing observations, have shown that ketorolac tromethamine can reduce the natriuretic effect solution and container permit.
Metabolic and Nutritional
of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During HOW SUPPLIED
concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS: Renal Effects), as weight change
Ketorolac Tromethamine Injection, USP is supplied as follows:
well as to assure diuretic efficacy. Nervous System
abnormal dreams, abnormal thinking, anxiety, asthenia, confusion, depression, euphoria, extrapyramidal symptoms, hallucinations, NDC Ketorolac Tromethamine Injection, USP (15 mg per mL) Package Factor
Probenecid 25021-700-01 15 mg per 1 mL Single-Dose Vial 25 vials per carton
Concomitant administration of oral ketorolac tromethamine and probenecid resulted in decreased clearance and volume of distribution hyperkinesis, inability to concentrate, insomnia, nervousness, paresthesia, somnolence, stupor, tremors, vertigo, malaise
of ketorolac and significant increases in ketorolac plasma levels (total AUC increased approximately threefold from 5.4 to 17.8 mcg/h/mL) Reproductive, female NDC Ketorolac Tromethamine Injection, USP (30 mg per mL) Package Factor
and terminal half-life increased approximately twofold from 6.6 to 15.1 hours. Therefore, concomitant use of ketorolac tromethamine and 25021-701-01 30 mg per 1 mL Single-Dose Vial 25 vials per carton
infertility
probenecid is contraindicated. *25021-701-02 60 mg per 2 mL Single-Dose Vial 25 vials per carton
Respiratory
Lithium *For IM Use Only
asthma, cough, dyspnea, pulmonary edema, rhinitis
NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium Storage Conditions
concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition Special Senses
Store at 20 to 25C (68 to 77F). [See USP Controlled Room Temperature.]
of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed abnormal taste, abnormal vision, blurred vision, hearing loss
Protect from light. Retain in carton until time of use.
carefully for signs of lithium toxicity. Urogenital Discard unused portion.
Methotrexate cystitis, dysuria, hematuria, increased urinary frequency, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure, urinary retention Sterile, Nonpyrogenic, Preservative-free.
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could Other rarely observed reactions (reported from postmarketing experience in patients taking ketorolac tromethamine or other NSAIDs) are: The container closure is not made with natural rubber latex.
enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
Body as a Whole
ACE Inhibitors/Angiotensin II Receptor Antagonists angioedema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema
Concomitant use of ACE inhibitors and/or angiotensin II receptor antagonists may increase the risk of renal impairment, particularly (see WARNINGS), myalgia
in volume-depleted patients. Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors and/or angiotensin II
receptor antagonists. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors and/or Cardiovascular
angiotensin II receptor antagonists. arrhythmia, bradycardia, chest pain, flushing, hypotension, myocardial infarction, vasculitis Mfd. for SAGENT Pharmaceuticals

2036645
Dermatologic Schaumburg, IL 60195 (USA)
Antiepileptic Drugs Made in India
Sporadic cases of seizures have been reported during concomitant use of ketorolac tromethamine and antiepileptic drugs (phenytoin, exfoliative dermatitis, erythema multiforme, Lyells syndrome, bullous reactions including Stevens-Johnson syndrome and toxic epidermal
2014 Sagent Pharmaceuticals, Inc.
carbamazepine). necrolysis
February 2014
Psychoactive Drugs Gastrointestinal
Hallucinations have been reported when ketorolac tromethamine was used in patients taking psychoactive drugs (fluoxetine, thiothixene, acute pancreatitis, liver failure, ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohns disease)
alprazolam). Hemic and Lymphatic
Pentoxifylline agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, post operative wound hemorrhage (rarely requiring
When ketorolac tromethamine is administered concurrently with pentoxifylline, there is an increased tendency to bleeding. blood transfusion see Boxed WARNING, WARNINGS, and PRECAUTIONS)
Nondepolarizing Muscle Relaxants Metabolic and Nutritional
In postmarketing experience there have been reports of a possible interaction between ketorolac tromethamine IV/IM and nondepolarizing hyperglycemia, hyperkalemia, hyponatremia