WARNINGKetorolac tromethamine tablets, a non-steroidal
anti-inflammatory drug (NSAID), are indicated for the short-term (up to 5 days
in adults), management of moderately severe acute pain that requires analgesia
at the opioid level and only as continuation treatment following IV or IM dosing
of ketorolac tromethamine, if necessary. The total combined duration of use of
ketorolac tromethamine should not exceed 5 days. Ketorolac tromethamine tablets are not indicated for use in
pediatric patients and it is NOT indicated for minor or chronic painful
conditions. Increasing the dose of ketorolac tromethamine tablets beyond a daily
maximum of 40 mg in adults will not provide better efficacy but will increase
the risk of developing serious adverse events. GASTROINTESTINAL RISK
Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding
and/or perforation of the stomach or intestines, which can be fatal. These
events can occur at any time during use and without warning symptoms. 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.
Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS).
CARDIOVASCULAR RISK
NSAIDs may cause an increased risk of serious cardiovascular thrombotic
events, myocardial infarction and stroke, which can be fatal. This risk may
increase with duration of use. Patients with cardiovascular disease or risk
factors for cardiovascular disease may be at greater risk (see WARNINGS and CLINICAL
TRIALS).
Ketorolac tromethamine is CONTRAINDICATED for the treatment of perioperative
pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
RENAL RISK
Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal
impairment and in patients at risk for renal failure due to volume depletion
(see WARNINGS).
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 and PRECAUTIONS).
Ketorolac tromethamine is CONTRAINDICATED as prophylactic
analgesic before any major surgery. RISK DURING LABOR AND DELIVERY
The use of ketorolac tromethamine in labor and delivery is contraindicated
because it may adversely affect fetal circulation and inhibit uterine
contractions. 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
aspirin or NSAIDs because of the cumulative risk of inducing serious
NSAID-related side effects.
SPECIAL POPULATIONS
Dosage should be adjusted for patients 65 years or older, for patients under
50 kg (110 lbs) of body weight (see DOSAGE AND
ADMINISTRATION) and for patients with moderately elevated serum creatinine
(see WARNINGS).
Ketorolac tromethamine tablets, a non-steroidal
anti-inflammatory drug (NSAID), are indicated for the short-term (up to 5 days
in adults), management of moderately severe acute pain that requires analgesia
at the opioid level and only as continuation treatment following IV or IM dosing
of ketorolac tromethamine, if necessary. The total combined duration of use of
ketorolac tromethamine should not exceed 5 days.
Ketorolac tromethamine tablets are not indicated for use in
pediatric patients and it is NOT indicated for minor or chronic painful
conditions. Increasing the dose of ketorolac tromethamine tablets beyond a daily
maximum of 40 mg in adults will not provide better efficacy but will increase
the risk of developing serious adverse events.
GASTROINTESTINAL RISK
Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding
and/or perforation of the stomach or intestines, which can be fatal. These
events can occur at any time during use and without warning symptoms. 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.
Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS).
CARDIOVASCULAR RISK
NSAIDs may cause an increased risk of serious cardiovascular thrombotic
events, myocardial infarction and stroke, which can be fatal. This risk may
increase with duration of use. Patients with cardiovascular disease or risk
factors for cardiovascular disease may be at greater risk (see WARNINGS and CLINICAL
TRIALS).
Ketorolac tromethamine is CONTRAINDICATED for the treatment of perioperative
pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
RENAL RISK
Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal
impairment and in patients at risk for renal failure due to volume depletion
(see WARNINGS).
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 and PRECAUTIONS).
Ketorolac tromethamine is CONTRAINDICATED as prophylactic
analgesic before any major surgery.
RISK DURING LABOR AND DELIVERY
The use of ketorolac tromethamine in labor and delivery is contraindicated
because it may adversely affect fetal circulation and inhibit uterine
contractions. 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
aspirin or NSAIDs because of the cumulative risk of inducing serious
NSAID-related side effects.
SPECIAL POPULATIONS
Dosage should be adjusted for patients 65 years or older, for patients under
50 kg (110 lbs) of body weight (see DOSAGE AND
ADMINISTRATION) and for patients with moderately elevated serum creatinine
(see WARNINGS).
Description
Ketorolac tromethamine is a member of the pyrrolo-pyrrole group
of non-steroidal 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, and the structural formula is:
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.
Each tablet for oral administration contains 10 mg ketorolac tromethamine,
USP. In addition, each tablet contains the following inactive ingredients:
anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium,
hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose,
polyethylene glycol, sodium lauryl sulfate, titanium dioxide and triacetin.
Clinical Pharmacology
Pharmacodynamics Ketorolac tromethamine is a non-steroidal anti-inflammatory drug
(NSAID) that exhibits analgesic activity in animal models. The mechanism of
action of ketorolac, like that of other NSAIDs, is not completely understood but
may be related to prostaglandin synthetase inhibition. The biological activity
of ketorolac tromethamine is associated with the S-form. Ketorolac tromethamine
possesses no sedative or anxiolytic properties.
The peak analgesic effect of ketorolac tromethamine occurs within 2 to 3
hours and is not statistically significantly different over the recommended
dosage range of ketorolac tromethamine. The greatest difference between large
and small doses of ketorolac tromethamine is 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 tablets, are compared in Table 1. In adults, 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 In adults, 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 adults, 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. Absorption Ketorolac tromethamine is 100% absorbed after oral administration
(see Table 1). Oral
administration of ketorolac tromethamine after a high-fat meal resulted in
decreased peak and delayed time-to-peak concentrations of ketorolac tromethamine
by about one hour. Antacids did not affect the extent of absorption. Distribution The mean apparent volume (Vβ) of ketorolac
tromethamine following complete distribution was approximately 13 liters. This
parameter was determined from single-dose data. The ketorolac tromethamine
racemate has been shown to be highly protein bound (99%). Nevertheless, 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.
Ketorolac tromethamine is excreted in human milk (see PRECAUTIONS: Nursing
Mothers). 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. Excretion The principal route of elimination of ketorolac and its
metabolites is renal. About 92% of a given dose is found in the urine,
approximately 40% as metabolites and 60% as unchanged ketorolac. Approximately
6% of a dose is excreted in the feces. A single-dose study with 10 mg ketorolac
tromethamine (n = 9) demonstrated that the S-enantiomer is cleared approximately
2 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 (see CLINICAL
PHARMACOLOGY: Kinetics in Special Populations).
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 (geriatric, pediatric, renal failure or hepatic disease
patients). Kinetics in Special PopulationsGeriatric 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:
Geriatric Use). Pediatric Patients 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 0.042 ± 0.01 L/hr/kg,
the volume of distribution during the terminal phase (Vβ)
was 0.34 ± 0.12 L/kg and the volume of distribution at steady 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 in
adult subjects (see Table
1). There are no pharmacokinetic data available for administration of
ketorolac tromethamine by the IM route in pediatric patients. Renal 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 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 AUCâž 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 AUCâž-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 (see WARNINGS: Renal
Effects). Hepatic Insufficiency There was no significant difference in estimates of half-life,
AUCâžand Cmax in seven patients
with liver disease compared to healthy volunteers (see PRECAUTIONS:
General: Hepatic Effect and Table 2). Race Pharmacokinetic differences due to race have not been
identified.
TABLE 1: Table of Approximate Average Pharmacokinetic Parameters
(Mean ± SD) Following Oral, Intramuscular and Intravenous Doses of Ketorolac
Tromethamine
% Dose metabolized = <50% Dose excreted in feces = 6% Dose excreted in urine = 91% Plasma protein binding = 99
1 Time-to-peak plasma concentration
2 Peak plasma concentration
3 Trough plasma concentration
4 Average plasma concentration
5 Volume of Distribution
*Derived from PO pharmacokinetic studies in 77 normal fasted volunteers
†Derived from IM pharmacokinetic studies in 54 normal volunteers
‡Derived from IV pharmacokinetic studies in 24 normal volunteers
§Mean value was simulated from observed plasma concentration data and standard deviation was simulated from percent coefficient of variation for observed Cmax and Tmax data.
¶Not Applicable because 60 mg is only recommended as a single-dose
TABLE 2: The Influence of Age, Liver and Kidney Function on the
Clearance and Terminal Half-life of Ketorolac Tromethamine (IM1 and Oral2) in Adult
Populations
Types
ofSubjects
Total
Clearance[in L/h/kg]3
Terminal Half-Life[in
hours]
IMMean (range)
ORALMean (range)
IMMean (range)
ORALMean
(range)
Normal SubjectsIM (n = 54) mean age = 32, range
= 18 to 60Oral (n = 77) mean age = 32, range = 20 to 60
0.023(0.010 to 0.046)
0.025(0.013 to 0.050)
5.3(3.5 to 9.2)
5.3(2.4 to 9)
Healthy Elderly SubjectsIM (n = 13), Oral (n =
12)mean age = 72, range = 65 to 78
0.019(0.013 to 0.034)
0.024(0.018 to 0.034)
7(4.7 to 8.6)
6.1(4.3 to 7.6)
Patients with Hepatic DysfunctionIM and Oral (n
= 7)mean age = 51, range = 43 to 64
0.029(0.013 to 0.066)
0.033(0.019 to 0.051)
5.4(2.2 to 6.9)
4.5(1.6 to 7.6)
Patients with Renal ImpairmentIM (n = 25), Oral
( n = 9)serum creatinine = 1.9 to 5 mg/dLmean age (IM) = 54, range 35 to
71mean age (oral) = 57, range = 39 to 70
0.015(0.005 to 0.043)
0.016(0.007 to 0.052)
10.3(5.9 to 19.2)
10.8(3.4 to 18.9)
Renal Dialysis PatientsIM and Oral (n
=9),mean age = 40, range = 27 to 63
0.016(0.003 to 0.036)
――
13.6(8.0 to 39.1)
――
1 Estimated from 30 mg single IM doses of ketorolac tromethamine
2 Estimated from 10 mg single oral doses of ketorolac tromethamine
3 Liters/hour/kilogram
IV Administration In normal subjects (n = 37), the total clearance of 30 mg IV
administered ketorolac tromethamine was 0.030 (0.017 to 0.051) L/h/kg. The
terminal half-life was 5.6 (4 to 7.9) hours. (see Kinetics in Special
Populations for use of IV dosing of ketorolac tromethamine in pediatric
patients).
Clinical Studies
Adult patients In a postoperative study, where all patients received morphine by
a PCA device, patients treated with ketorolac tromethamine-IV as fixed
intermittent boluses (e.g., 30 mg initial dose followed by 15 mg q3h), required
significantly less morphine (26%) than the placebo group. Analgesia was
significantly superior, at various postdosing pain assessment times, in the
patients receiving ketorolac tromethamine-IV plus PCA morphine as compared to
patients receiving PCA-administered morphine alone. Pediatric Patients There is no data available to support the use of ketorolac
tromethamine tablets in pediatric patients.
Indications And Usage
Carefully consider the potential benefits and risks of ketorolac
tromethamine and other treatment options before deciding to use ketorolac
tromethamine. Use the lowest effective dose for the shortest duration consistent
with individual patient treatment goals. Acute Pain in Adult Patients Ketorolac tromethamine tablets are indicated for the short-term
(≤ 5 days) management of moderately severe acute pain that requires analgesia at
the opioid level, usually in a postoperative setting. Therapy should always be
initiated with ketorolac tromethamine-IV or IM and ketorolac tromethamine
tablets are to be used only as continuation treatment, if necessary.
The total combined duration of use of ketorolac tromethamine-IV/IM and
ketorolac tromethamine tablets is not to exceed 5 days of use because of the
potential of increasing the frequency and severity of adverse reactions
associated with the recommended doses (see WARNINGS, PRECAUTIONS,
DOSAGE AND
ADMINISTRATION and ADVERSE
REACTIONS). Patients should be switched to alternative analgesics as soon as
possible, but ketorolac tromethamine tablet therapy is not to exceed 5 days.
Contraindications
(see also Boxed WARNING)
Ketorolac tromethamine is contraindicated in patients with previously
demonstrated hypersensitivity to ketorolac tromethamine.
Ketorolac tromethamine is contraindicated in patients with active peptic
ulcer disease, in patients with recent gastrointestinal bleeding or perforation,
and in patients with a history of peptic ulcer disease or gastrointestinal
bleeding.
Ketorolac tromethamine should not be given to patients who have experienced
asthma, urticaria or allergic-type reactions after taking aspirin or other
NSAIDS. Severe, rarely fatal, anaphylactic-like reactions to NSAIDS have been
reported in such patients (see WARNINGS:
Anaphylactoid Reactions and PRECAUTIONS:
Preexisting Asthma).
Ketorolac tromethamine is contraindicated as prophylactic analgesic before
any major surgery.
Ketorolac tromethamine is contraindicated for the treatment of perioperative
pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
Ketorolac tromethamine is contraindicated in patients with advanced renal
impairment or in patients at risk for renal failure due to volume depletion (see
WARNINGS for
correction of volume depletion).
Ketorolac tromethamine is contraindicated in labor and delivery because,
through its prostaglandin synthesis inhibitory effect, it may adversely affect
fetal circulation and inhibit uterine contractions, thus increasing the risk of
uterine hemorrhage.
The use of ketorolac tromethamine is contraindicated in nursing mothers
because of the potential adverse effects of prostaglandin-inhibiting drugs on
neonates.
Ketorolac tromethamine inhibits platelet function and is, therefore,
contraindicated in patients with suspected or confirmed cerebrovascular
bleeding, hemorrhagic diathesis, incomplete homeostasis and those at high risk
of bleeding (see WARNINGS and PRECAUTIONS).
Ketorolac tromethamine is contraindicated in patients currently receiving
aspirin or NSAIDs because of the cumulative risks of inducing serious
NSAID-related adverse events.
The concomitant use of ketorolac tromethamine and probenecid is
contraindicated.
The concomitant use of ketorolac tromethamine and pentoxifylline is
contraindicated.
Warnings
(see also Boxed WARNING)
The total combined duration of use of ketorolac tromethamine-IV/IM and
ketorolac tromethamine tablets is not to exceed 5 days in adults. Ketorolac
tromethamine tablets are not indicated for use in pediatric patients.
The most serious risks associated with ketorolac tromethamine are: Gastrointestinal Effects – Risk of Ulceration,
Bleeding and Perforation Ketorolac tromethamine is contraindicated in patients with
previously documented peptic ulcers and/or GI bleeding. Ketorolac tromethamine
can cause serious gastrointestinal (GI) adverse events including bleeding,
ulceration and perforation, of the stomach, small intestine or large intestine,
which can be fatal. These serious adverse events can occur at any time, with or
without warning symptoms, in patients treated with ketorolac tromethamine.
Only one in five patients who develop a serious upper GI adverse event on
NSAID therapy is symptomatic. Minor upper gastrointestinal problems, such as
dyspepsia, are common and may also occur at any time during NSAID therapy. The
incidence and severity of gastrointestinal complications increases with
increasing dose of, and duration of treatment with, ketorolac tromethamine. Do
not use ketorolac tromethamine for more than 5 days. However, even short-term
therapy is not without risk. In addition to past history of ulcer disease, other
factors that increase the risk for GI bleeding in patients treated with NSAIDs
include concomitant use of oral corticosteroids, or anticoagulants, longer
duration of NSAID therapy, smoking, use of alcohol, older age and poor general
health status. Most spontaneous reports of fatal GI events are in elderly or
debilitated patients and therefore, special care should be taken in treating
this population.
To minimize the potential risk for an adverse GI event, the
lowest effective dose should be used for the shortest possible duration.
Patients and physicians should remain alert for signs and symptoms of GI
ulceration and bleeding during NSAID therapy and promptly initiate additional
evaluation and treatment if a serious GI adverse event is suspected. This should
include discontinuation of ketorolac tromethamine until a serious GI adverse
event is ruled out. For high risk patients, alternate therapies that do not
involve NSAIDs should be considered.
NSAIDs should be given with care to patients with a history of inflammatory
bowel disease (ulcerative colitis, Crohn’s disease) as their condition may be
exacerbated. Hemorrhage Because prostaglandins play an important role in hemostasis and
NSAIDs affect platelet aggregation as well, use of ketorolac tromethamine in
patients who have coagulation disorders should be undertaken very cautiously,
and those patients should be carefully monitored. Patients on therapeutic doses
of anticoagulants (e.g., heparin or dicumarol derivatives) have an increased
risk of bleeding complications if given ketorolac tromethamine concurrently;
therefore, physicians should administer such concomitant therapy only extremely
cautiously. The concurrent use of ketorolac tromethamine and therapy that
affects hemostasis, including prophylactic low-dose heparin (2500 to 5000 units
q12h), warfarin and dextrans have not been studied extensively, but may also be
associated with an increased risk of bleeding. Until data from such studies are
available, physicians should carefully weigh the benefits against the risks and
use such concomitant therapy in these patients only extremely cautiously.
Patients receiving therapy that affects hemostasis should be monitored
closely.
In post-marketing experience, postoperative hematomas and other signs of
wound bleeding have been reported in association with the perioperative use of
IV or IM dosing of ketorolac tromethamine. Therefore, perioperative use of
ketorolac tromethamine should be avoided and postoperative use be undertaken
with caution when hemostasis is critical (see PRECAUTIONS). Renal Effects Long-term administration of NSAIDs has resulted in renal
papillary necrosis and other renal injury. Renal toxicity has also been seen in
patients in whom renal prostaglandins have a compensatory role in the
maintenance of renal perfusion. In these patients, administration of a NSAID may
cause a dose-dependent reduction in prostaglandin formation and, secondarily, in
renal blood flow, which may precipitate overt renal decompensation. Patients at
greatest risk of this reaction are those with impaired renal function, heart
failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the
elderly. Discontinuation of NSAID therapy is usually followed by recovery to the
pretreatment state.
Ketorolac tromethamine and its metabolites are eliminated primarily by the
kidneys, which, in patients with reduced creatinine clearance, will result in
diminished clearance of the drug (see CLINICAL
PHARMACOLOGY). Therefore, ketorolac tromethamine should be used with caution
in patients with impaired renal function (see DOSAGE AND
ADMINISTRATION) and such patients should be followed closely. With the use
of ketorolac tromethamine, there have been reports of acute renal failure,
interstitial nephritis and nephrotic syndrome. Impaired Renal Function Ketorolac tromethamine is contraindicated
in patients with serum creatinine concentrations indicating advanced renal
impairment (see CONTRAINDICATIONS).
Ketorolac tromethamine should be used with caution in patients with impaired
renal function or a history of kidney disease because it is a potent inhibitor
of prostaglandin synthesis. Because patients with underlying renal insufficiency
are at increased risk of developing acute renal decompensation or failure, the
risks and benefits should be assessed prior to giving ketorolac tromethamine to
these patients. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in
patients without a known previous exposure or hypersensitivity to ketorolac
tromethamine. Ketorolac tromethamine should not be given to patients with the
aspirin triad. This symptom complex typically occurs in asthmatic patients who
experience rhinitis with or without nasal polyps, or who exhibit severe,
potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS
and PRECAUTIONS:
Preexisting Asthma). Anaphylactoid reactions, like anaphylaxis, may have a
fatal outcome. Emergency help should be sought in cases where an anaphylactoid
reaction occurs. Cardiovascular EffectsCardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective
NSAIDs of up to 3 years duration have shown an increased risk of serious
cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which
can be fatal. All NSAIDs, both COX-2 selective and 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 potential risk for an adverse CV event in
patients treated with an NSAID, the lowest effective dose should be used for the
shortest duration possible. Physicians and patients should remain alert for the
development of such events, even in the absence of previous CV symptoms.
Patients should be informed about the signs and/or symptoms of serious CV events
and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the
increased risk of serious CV thrombotic events associated with NSAID use. The
concurrent use of aspirin and an NSAID does increase the risk of serious GI
events (see Gastrointestinal
Effects – Risk of Ulceration, Bleeding and Perforation). Two large,
controlled clinical trials of a COX-2 selective NSAID for the treatment of pain
in the first 10 to 14 days following CABG surgery found an increased incidence
of myocardial infarction and stroke (see CONTRAINDICATIONS). Hypertension NSAIDs, including ketorolac tromethamine, can lead to onset of
new hypertension or worsening of preexisting hypertension, either of which may
contribute to the increased incidence of CV events. Patients taking thiazides or
loop diuretics may have impaired response to these therapies when taking NSAIDs.
NSAIDs, including ketorolac tromethamine, should be used with caution in
patients with hypertension. Blood pressure (BP) should be monitored closely
during the initiation of NSAID treatment and throughout the course of
therapy. Congestive Heart Failure and Edema Fluid retention, edema, retention of NaCl, oliguria, elevations
of serum urea nitrogen and creatinine have been reported in clinical trials with
ketorolac tromethamine. Therefore, ketorolac tromethamine should be used only
very cautiously in patients with cardiac decompensation, hypertension or similar
conditions. Skin Reactions NSAIDS, including ketorolac tromethamine, can cause serious skin
adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS)
and toxic epidermal necrolysis (TEN), which can be fatal. These serious events
may occur without warning. Patients should be informed about the signs and
symptoms of serious skin manifestations and use of the drug should be
discontinued at the first appearance of skin rash, mucosal lesions or any other
sign of hypersensitivity. Pregnancy In late pregnancy, as with other NSAIDs, ketorolac tromethamine
should be avoided because it may cause premature closure of the ductus
arteriosus.
Precautions
General Ketorolac tromethamine cannot be expected to substitute for
corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation
of corticosteroids may lead to disease exacerbation. Patients on prolonged
corticosteroid therapy should have their therapy tapered slowly if a 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
complications of presumed noninfectious, painful conditions. Hepatic Effect Ketorolac tromethamine should be used with caution in patients
with impaired hepatic function or a history of liver disease. Borderline
elevations of one or more liver tests may occur in up to 15% of patients taking
NSAIDs including ketorolac tromethamine. These laboratory abnormalities may
progress, may remain unchanged or may be transient with continuing therapy.
Notable elevations of ALT or AST (approximately 3 or more times the upper limit
of normal) have been reported in approximately 1% of patients in clinical trials
with NSAIDs. In addition, rare cases of severe hepatic reactions, including
jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some
of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom
an abnormal liver test has occurred, should be evaluated for evidence of the
development of a more severe hepatic reaction while on therapy with ketorolac
tromethamine. If clinical signs and symptoms consistent with liver disease
develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.),
ketorolac tromethamine should be discontinued. Hematologic Effect Anemia is sometimes seen in patients receiving NSAIDs, including
ketorolac tromethamine. This may be due to fluid retention, occult or gross GI
blood loss, or an incompletely described effect upon erythropoiesis. Patients on
long-term treatment with NSAIDs, including ketorolac tromethamine, should have
their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of
anemia. NSAIDs inhibit platelet aggregation and have been shown to prolong
bleeding time in some patients. Unlike aspirin, their effect on platelet
function is quantitatively less, of shorter duration, and reversible. Patients
receiving ketorolac tromethamine who may be adversely affected by alterations in
platelet function, such as those with coagulation disorders or patients
receiving anticoagulants, should be carefully monitored. Preexisting Asthma Patients with asthma may have aspirin-sensitive asthma. The use
of aspirin in patients with aspirin-sensitive asthma has been associated with
severe bronchospasm which can be fatal. Since cross-reactivity, including
bronchospasm, between aspirin and other non-steroidal anti-inflammatory drugs
has been reported in such aspirin-sensitive patients, ketorolac tromethamine
should not be administered to patients with this form of aspirin sensitivity and
should be used with caution in patients with preexisting asthma. Information for Patients Ketorolac tromethamine is a potent NSAID and may cause serious
side effects such as gastrointestinal bleeding or kidney failure, which may
result in hospitalization and even fatal outcome.
Physicians, when prescribing ketorolac tromethamine, should inform their
patients or their guardians of the potential risks of ketorolac 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 ketorolac tromethamine tablets to other
family members and to discard any unused drug.
Remember that the total combined duration of use of ketorolac tromethamine
tablet and ketorolac tromethamine IV or IM dosing is not to exceed 5 days in
adults. Ketorolac tromethamine tablets are not indicated for use in pediatric
patients.
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.
Ketorolac tromethamine, like other NSAIDs, may cause serious CV side
effects, such as MI or stroke, which may result in 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 when observing
any indicative sign or symptoms. Patients should be apprised of the importance
of this follow-up (see WARNINGS:
Cardiovascular Effects).
Ketorolac tromethamine, like other NSAIDs, can cause GI discomfort and
rarely, serious GI side effects, such as ulcers and bleeding, which may result
in hospitalization and even death. Although serious GI tract ulcerations and
bleeding can occur without warning symptoms, patients should be alert for the
signs and symptoms of ulcerations and bleeding, and should ask for medical
advice when observing any indicative sign or symptoms including epigastric pain,
dyspepsia, melena and hematemesis. Patients should be apprised of the importance
of this follow-up (see WARNINGS:
Gastrointestinal Effects – Risk of Ulceration, Bleeding, and
Perforation).
Ketorolac tromethamine, like other NSAIDs, can cause serious skin side
effects such as exfoliative dermatitis, SJS and TEN, which may result in
hospitalizations and even death. Although serious skin reactions may occur
without warning, patients should be alert for the signs and symptoms of skin
rash and bulers, fever or other signs of hypersensitivity such as itching, and
should ask for medical advice when observing any indicative signs or symptoms.
Patients should be advised to stop the drug immediately if they develop any type
of rash and contact their physicians as soon as possible.
Patients should promptly report signs or symptoms of unexplained weight gain
or edema to their physicians.
Patients should be informed of the warning signs and symptoms of
hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper
quadrant tenderness and “flu-like” symptoms). If these occur, patients should be
instructed to stop therapy and seek immediate medical therapy.
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).Â
In late pregnancy, as with other NSAIDs, ketorolac tromethamine should be
avoided because it will cause premature closure of the ductus
arteriosus.
Laboratory Tests Because serious GI tract ulcerations and bleeding can occur
without warning symptoms, physicians should monitor for signs or symptoms of GI
bleeding. Patients on long-term treatment with NSAIDs, should have their CBC and
a chemistry profile checked periodically. If clinical signs and symptoms
consistent with liver or renal disease develop, systemic manifestations occur
(e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen,
ketorolac tromethamine should be discontinued. Drug Interactions Ketorolac is highly bound to human plasma protein (mean 99.2%).
There is no evidence in animal or human studies that ketorolac tromethamine
induces or inhibits hepatic enzymes capable of metabolizing itself or other
drugs.
Warfarin, Digoxin, Salicylate and Heparin
The in vitro binding of warfarin
to plasma proteins is only slightly reduced by
ketorolac tromethamine (99.5% control vs. 99.3%) when ketorolac plasma
concentrations reach 5 to 10 mcg/mL. Ketorolac does not alter digoxin
protein binding. In vitro studies indicate that, at therapeutic
concentrations of salicylate
(300 mcg/mL), the binding of ketorolac was reduced from approximately 99.2% to
97.5%, representing a potential 2-fold increase in unbound ketorolac plasma
levels. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen,
phenytoin
and tolbutamide
did not alter ketorolac tromethamine
protein binding.
In a study involving 12 adult volunteers, ketorolac tromethamine tablets were
coadministered with a single-dose of 25 mg warfarin
,causing no significant changes in
pharmacokinetics or pharmacodynamics of warfarin. In another study, ketorolac
tromethamine dosed IV or IM was given with two doses of 5000 U of heparin
to 11 healthy volunteers,
resulting in a mean template bleeding time 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 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 be closely monitored
(see WARNINGS and PRECAUTIONS:
Hematologic Effect).
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 serious
GI bleeding higher than the users of either drug alone. Aspirin When ketorolac tromethamine is administered with aspirin, its
protein binding is reduced, although the clearance of free ketorolac
tromethamine is not altered. The clinical significance of this interaction is
not known; however, as with other NSAIDs, concomitant administration of
ketorolac tromethamine and aspirin is not generally recommended because of the
potential of increased adverse effects. Diuretics Clinical studies, as well as post-marketing observations, have
shown that ketorolac tromethamine can reduce the natriuretic effect of
furosemide and thiazides in some patients. This response has been attributed to
inhibition of renal prostaglandin synthesis. During concomitant therapy with
NSAIDs, the patient should be observed closely for signs of renal failure (see
WARNINGS: Renal
Effects), as well as to assure diuretic efficacy. Probenecid Concomitant administration of ketorolac tromethamine tablets and
probenecid
resulted in
decreased clearance and volume of distribution of ketorolac and significant
increases in ketorolac plasma levels (total AUC increased approximately 3-fold
from 5.4 to 17.8 mcg/h/mL) and terminal half-life increased approximately 2-fold
from 6.6 to 15.1 hours. Therefore, concomitant use of ketorolac tromethamine
tablets and probenecid is contraindicated. Lithium NSAIDs have produced an elevation of plasma lithium levels and a
reduction in renal lithium clearance. The mean minimum lithium concentration
increased 15% and the renal clearance was decreased by approximately 20%. These
effects have been attributed to inhibition of renal prostaglandin synthesis by
the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects
should be observed carefully for signs of lithium toxicity. Methotrexate NSAIDs have been reported to competitively inhibit methotrexate
accumulation in rabbit kidney slices. This may indicate that they could enhance
the toxicity of methotrexate. Caution should be used when NSAIDs are
administered concomitantly with methotrexate. ACE Inhibitors/Angiotension II Receptor
Antagonists Concomitant use of ACE
inhibitors and/or angiotension II receptor antagonists
may
increase the risk of renal impairment, particularly in volume-depleted patients.
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE
inhibitors and/or angiotension II receptor antagonists. This interaction should
be given consideration in patients taking NSAIDs concomitantly with ACE
inhibitors and/or angiotension II receptor antagonists. Antiepileptic Drugs Sporadic cases of seizures have been reported during concomitant
use of ketorolac tromethamine and antiepileptic drugs
(phenytoin,
carbamazepine). Psychoactive Drugs Hallucinations have been reported when ketorolac tromethamine was
used in patients taking psychoactive drugs
(fluoxetine, thiothixene, alprazolam). Pentoxifylline When ketorolac tromethamine is administered concurrently with
pentoxifylline, there is an increased tendency to bleeding. Nondepolarizing Muscle Relaxants In post-marketing experience there have been reports of a
possible interaction between ketorolac tromethamine IV/IM and nondepolarizing muscle relaxants
that resulted in apnea. The concurrent use of ketorolac
tromethamine with muscle relaxants has not been formally studied. Selective Serotonin Reuptake Inhibitors (SSRIs) There is an increased risk of gastrointestinal bleeding when
selective serotonin re-uptake inhibitors (SSRIs) are combined with NSAIDs.
Caution should be used when NSAIDs are administered concomitantly with
SSRIs. Carcinogenesis, Mutagenesis and Impairment of
Fertility 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
recommended IM or IV dose of 30 mg q.i.d., based on
area-under-the-plasma-concentration curve [AUC]), and a 24-month study in rats
at 5 mg/kg/day (0.5 times the human AUC) showed no evidence of
tumorigenicity.
Ketorolac tromethamine was not mutagenic in the Ames test, unscheduled DNA
synthesis and repair, and in forward mutation assays. Ketorolac tromethamine did
not cause chromosome breakage in the in vivo mouse
micronucleus assay. At 1590 mcg/mL and at higher concentrations, ketorolac
tromethamine increased the incidence of chromosomal aberrations in Chinese
hamster ovarian cells.
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 (1.6 times the human AUC) of
ketorolac tromethamine, respectively. PregnancyTeratogenic Effects. Pregnancy Category C Reproduction studies have been performed during organogenesis
using daily oral doses of ketorolac tromethamine at 3.6 mg/kg (0.37 times the
human AUC) in rabbits and at 10 mg/kg (1 times the human AUC) in rats. Results
of these studies did not reveal evidence of teratogenicity to the fetus.
However, animal reproduction studies are not always predictive of human
response. Nonteratogenic Effects Because of the known effects of non-steroidal anti-inflammatory
drugs on the fetal cardiovascular system (closure of ductus arteriosus), use
during pregnancy (particularly late pregnancy) should be avoided. Oral doses of
ketorolac tromethamine at 1.5 mg/kg (0.14 times the human AUC), administered
after gestation day 17, caused dystocia and higher pup mortality in rats.
There are no adequate and well controlled studies of ketorolac tromethamine
in pregnant women. Ketorolac tromethamine should be used during pregnancy only
if the potential benefit justifies the potential risk to the fetus. Labor and Delivery 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 (see CONTRAINDICATIONS). Effects on Fertility The use of ketorolac tromethamine, as with any drug known to
inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not
recommended in women attempting to conceive. In women who have difficulty
conceiving or are undergoing investigation of infertility, withdrawal of
ketorolac tromethamine should be considered. Nursing Mothers After a single administration of 10 mg of oral ketorolac
tromethamine to humans, the maximum milk concentration observed was 7.3 ng/mL
and the maximum milk-to-plasma ratio was 0.037. After one day of dosing
(q.i.d.), the maximum milk concentration was 7.9 ng/mL and the maximum
milk-to-plasma ratio was 0.025. Because of the possible adverse effects of
prostaglandin-inhibiting drugs on neonates, use in nursing mothers is
contraindicated. Pediatric Use Ketorolac tromethamine tablets are not indicated for use in
pediatric patients. The safety and effectiveness of ketorolac tromethamine
tablets in pediatric patients below the age of 17 have not been
established. Geriatric Use (≥ 65 years of age) Because ketorolac tromethamine may be cleared more slowly by the
elderly (see CLINICAL
PHARMACOLOGY) who are also more sensitive to the dose related adverse
effects of NSAIDs (see WARNINGS:
Gastrointestinal Effects – Risk of Ulceration, Bleeding and Perforation),
extreme caution, reduced dosages (see DOSAGE AND
ADMINISTRATION) and careful clinical monitoring must be used when treating
the elderly with ketorolac tromethamine.
Adverse Reactions
Adverse reaction rates increase with higher doses of ketorolac
tromethamine. Practitioners should be alert for the severe complications of
treatment with ketorolac tromethamine, such as G.I. ulceration, bleeding and
perforation, postoperative bleeding, acute renal failure, anaphylactic and
anaphylactoid reactions and liver failure (see Boxed WARNING, WARNINGS, PRECAUTIONS,
and DOSAGE
AND ADMINISTRATION). These NSAID-related complications can be serious in
certain patients for whom ketorolac tromethamine is indicated, especially when
the drug is used inappropriately.
In patients taking ketorolac tromethamine or other NSAIDs in clinical trials,
the most frequently reported adverse experiences in approximately 1% to 10% of
patients are:
*Incidence greater than 10%
Additional adverse experiences reported occasionally (<1% in patients
taking ketorolac tromethamine or other NSAIDs in clinical trials) include:
Other rarely observed reactions (reported from post-marketing experience in
patients taking ketorolac tromethamine or other NSAIDs) are:
Body as a Whole: angioedema, death, hypersensitivity
reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue
edema (see WARNINGS),
myalgia
Urogenital: flank pain with or without hematuria
and/or azotemia, hemolytic uremic syndrome
Post-Marketing Surveillance Study: A large
post-marketing observational, nonrandomized study, involving approximately
10,000 patients receiving ketorolac tromethamine IV or IM, demonstrated that the
risk of clinically serious gastrointestinal (G.I.) bleeding was dose dependent
(see Tables 3A and 3B). This was particularly true in elderly patients who
received an average daily dose greater than 60 mg/day of ketorolac tromethamine
IV or IM (see Table 3A).
Table 3: Incidence of Clinically Serious G.I. Bleeding as Related to
Age, Total Daily Dose and History of G.I. Perforation, Ulcer, Bleeding
(PUB)after up to 5 Days of Treatment with Ketorolac Tromethamine IV/IM
A. Adult Patients without
History of PUB
Age of Patients
Total Daily Dose of Ketorolac Tromethamine
IV/IM
< 60 mg
> 60 to 90 mg
> 90 to 120 mg
> 120 mgÂ
< 65 years of age
0.4%
0.4%
0.9%
4.6%
> 65 years of age
1.2%
2.8%
2.2%
7.7%
B. Adult Patients with
History of PUB
Age of Patients
Total Daily Dose of Ketorolac Tromethamine
IV/IM
< 60 mg
> 60 to 90 mg
> 90 to 120 mg
> 120 mg
< 65 years of age
2.1%
4.6%
7.8%
15.4%
> 65 years of age
4.7%
3.7%
2.8%
25%
Overdosage
Symptoms and Signs Symptoms following acute NSAIDs overdoses are usually limited to
lethargy, drowsiness, nausea, vomiting and epigastric pain, which are generally
reversible with supportive care. Gastrointestinal bleeding can occur.
Hypertension, acute renal failure, respiratory depression and coma may occur,
but are rare. Anaphylactoid reactions have been reported with therapeutic
ingestion of NSAIDs and may occur following an overdose. Treatment Patients should be managed by symptomatic and supportive care
following a NSAIDs overdose. There are no specific antidotes. Emesis and/or
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 4 hours of
ingestion with symptoms or following a large oral overdose (5 to 10 times the
usual dose). Forced diuresis, alkalization of urine, hemodialysis or
hemoperfusion may not be useful due to high protein binding.
Single overdoses of ketorolac tromethamine have been variously associated
with abdominal pain, nausea, vomiting, hyperventilation, peptic ulcers and/or
erosive gastritis and renal dysfunction which have resolved after
discontinuation of dosing.
Dosage And Administration
Carefully consider the potential benefits and
risks of ketorolac tromethamine and other treatment options before deciding to
use ketorolac tromethamine. Use the lowest effective dose for the shortest
duration consistent with individual patient treatment goals. In adults, the
combined duration of use of IV or IM dosing of ketorolac tromethamine and
ketorolac tromethamine tablets is not to exceed 5 days. In adults, the use of
ketorolac tromethamine tablets is only indicated as continuation therapy to IV
or IM dosing of ketorolac tromethamine.
Transition from IV or IM dosing of ketorolac
tromethamine (single- or multiple-dose) to multiple-dose ketorolac tromethamine
tablets: Patients age 17
to 64:
20 mg PO once followed by 10 mg q4 to 6 hours prn not >40 mg/day
Patients age
>65, renally impaired, and/or weight <50 kg (110 lbs):
10 mg PO
once followed by 10 mg q4 to 6 hours prn not >40
mg/day
Note: Oral formulation should not be given as an initial dose
Use minimum effective dose for the individual
patient
Do not shorten dosing interval of 4 to 6 hours
Total duration of treatment in adult patients: the
combined duration of use of IV or IM dosing of ketorolac tromethamine and
ketorolac tromethamine tablets is not to exceed 5 days.
The following table summarizes ketorolac tromethamine tablets dosing
instructions in terms of age group:
Table 4: Summary of Dosing Instructions
Patient
Population
Ketorolac
Tromethamine Tablets(following IV or IM dosing ofketorolac
tromethamine)
Age < 17 years
Oral not approved
Adult Age 17 to 64 years
20 mg once, then 10 mg q4 to 6hours
prn not > 40 mg/day
Adult Age > 65 years,renally
impaired and/or weight <50 kg
10 mg once, then 10 mg q4Â to 6hours
prn not > 40 mg/day
How Supplied
Ketorolac Tromethamine Tablets, USP are available containing 10
mg of ketorolac tromethamine, USP. The tablets are white film-coated, round,
unscored tablets debossed with M over 134 on one side and blank on the other side. They are
available as follows:
Bottles of 12
NDC 42549-538-12
Bottles of 20
NDC 42549-538-20
Store at 20° to 25°C (68° to 77°F). [See USP for Controlled
Room Temperature.]
Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.
PHARMACIST: Dispense a Medication Guide with each
prescription.
Mylan Pharmaceuticals Inc.Morgantown, WVÂ 26505
REVISED AUGUST 2008KTLC:R6mc
Relabeling and Repackaging by:
STAT Rx USA LLCGainesville, GAÂ 30501
Spl Medguide Section
MEDICATION GUIDE FOR NON-STEROIDAL ANTI-INFLAMMATORY
DRUGS (NSAIDs) (See the end of this Medication Guide for a
ul of prescription NSAID medicines.)
What is the most important information I should know about
medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines may increase the chance of a heart attack or
stroke that can lead to death. This chance increases:
with longer use of NSAID medicines
in people who have heart disease
NSAID medicines should never be used right before or after a
heart surgery called a “coronary artery bypass graft (CABG).”
NSAID medicines can cause ulcers and bleeding in the stomach
and intestines at any time during treatment. Ulcers and bleeding:
can happen without warning symptoms
may cause death
The chance of a person getting an ulcer or bleeding
increases with:
taking medicines called “corticosteroids” and “anticoagulants”
longer use
smokingÂ
drinking alcoholÂ
older ageÂ
having poor health
NSAID medicines should only be used:
exactly as prescribedÂ
at the lowest dose possible for your treatmentÂ
for the shortest time needed
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines are used to treat pain and redness, swelling, and heat
(inflammation) from medical conditions such as:
different types of arthritisÂ
menstrual cramps and other types of short-term pain
Who should not take a Non-Steroidal Anti-Inflammatory Drug
(NSAID)?
Do not take an NSAID medicine:
if you had an asthma attack, hives, or other allergic reaction with aspirin
or any other NSAID medicineÂ
for pain right before or after heart bypass surgery
Tell your healthcare provider:
about all of your medical conditions.
about all of the medicines you take. NSAIDs and some other medicines can
interact with each other and cause serious side effects. Keep a
ul of your medicines to show to your healthcare provider and
pharmacist.Â
if you are pregnant. NSAID medicines should not be used by
pregnant women late in their pregnancy.
if you are breastfeeding. Talk to your doctor.
What are the possible side effects of Non-Steroidal
Anti-Inflammatory Drugs (NSAIDs)?
Serious side effects include:
heart attack
stroke
high blood pressure
heart failure from body swelling (fluid retention)
kidney problems including kidney failure
bleeding and ulcers in the stomach and intestine
low red blood cells (anemia)
life-threatening skin reactions
life-threatening allergic reactions
liver problems including liver failure
asthma attacks in people who have asthma
Other side effects include:
stomach pain
constipation
diarrhea
gas
heartburn
nausea
vomiting
dizziness
Get emergency help right away if you have any of the
following symptoms:
shortness of breath or trouble breathingÂ
chest painÂ
weakness in one part or side of your bodyÂ
slurred speechÂ
swelling of the face or throat
Stop your NSAID medicine and call your healthcare provider
right away if you have any of the following symptoms:
nauseaÂ
more tired or weaker than usualÂ
itchingÂ
your skin or eyes look yellowÂ
stomach painÂ
flu-like symptomsÂ
vomit bloodÂ
there is blood in your bowel movement or it is black and sticky like
tarÂ
unusual weight gainÂ
skin rash or bulers with feverÂ
swelling of the arms and legs, hands and feet
These are not all the side effects with NSAID medicines. Talk to your
healthcare provider or pharmacist for more information about NSAID medicines.
Other information about Non-Steroidal Anti-Inflammatory
Drugs (NSAIDs)
Aspirin is an NSAID medicine but it does not increase the chance of a heart
attack. Aspirin can cause bleeding in the brain, stomach, and intestines.
Aspirin can also cause ulcers in the stomach and intestines.Â
Some of these NSAID medicines are sold in lower doses without a prescription
(over-the-counter). Talk to your healthcare provider before using
over-the-counter NSAIDs for more than 10 days.
NSAID medicines that need a
prescription
Generic
Name
Tradename
Celecoxib
Celebrex
Diclofenac
Cataflam, Voltaren, Arthrotec (combined with
misoprostol)
Diflunisal
Dolobid
Etodolac
Lodine, Lodine XL
Fenoprofen
Nalfon, Nalfon 200
Flurbiprofen
Ansaid
Ibuprofen
Motrin, Tab-Profen, Vicoprofen* Â (combined with
hydrocodone),Combunox (combined with oxycodone)
Indomethacin
Indocin, Indocin SR, Indo-Lemmon,
Indomethagan
Ketoprofen
Oruvail
Ketorolac
Toradol
Mefenamic Acid
Ponstel
Meloxicam
Mobic
Nabumetone
Relafen
Naproxen
Naprosyn, Anaprox, Anaprox DS, EC-Naprosyn,
Naprelan,Naprapac (copackaged with lansoprazole)
Oxaprozin
Daypro
Piroxicam
Feldene
Sulindac
Clinoril
Tolmetin
Tolectin, Tolectin DS, Tolectin
600
*Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC)
NSAIDs, and is usually used for less than 10 days to treat pain. The OTC NSAID
label warns that long-term continuous use may increase the risk of heart attack
or stroke.
Call your doctor for medical advice about side effects. You
may report side effects to FDA at 1-800-FDA-1088.
This Medication Guide has been approved by the U.S. Food
and Drug Administration.
Principal Display Panel
KETOROLAC TROMETHAMINE TABLETS, USP 10 mg
PHARMACIST: PLEASE DISPENSE WITH MEDICATION GUIDE PROVIDED SEPARATELY.
(Rx only)
Dispense in a tight, light-resistant container as defined in the
USP using a child-resistant closure.
Keep container tightly closed.
Keep this and all medication out of the reach of
children.
Store at 20° to 25°C (68° to 77°F). [See USP for
Controlled Room Temperature.]
Usual Adult Dosage: See accompanying prescribing
information.
Relabeling and Repackaging by:
STAT Rx USA LLCGainesville, GAÂ 30501
DISCLAIMER:
"This tool does not provide medical advice, and is for informational and educational purposes only, and is not a substitute for professional medical advice, treatment or diagnosis. Call your doctor to receive medical advice. If you think you may have a medical emergency, please dial 911."
"Do not rely on openFDA to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. We may limit or otherwise restrict your access to the API in line with our Terms of Service."
"This product uses publicly available data from the U.S. National Library of Medicine (NLM), National Institutes of Health, Department of Health and Human Services; NLM is not responsible for the product and does not endorse or recommend this or any other product."
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