Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1026
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Ketorolac Tromethamine (Injection, Solution)
|
| dailymed-instance:descripti... |
Ketorolac tromethamine is a member of the pyrrolo-pyrrole
group of nonsteroidal anti-inflammatory drugs (NSAIDs). The chemical
name for ketorolac tromethamine is (��)-5-benzoyl-2, 3-dihydro-1H-pyrrolizine-1-carboxylic
acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol, 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 and the molecular
formula is CHNO. Ketorolac tromethamine is available for intravenous (IV)
or intramuscular (IM) administration as: 15 mg in 1 mL (1.5%), 30
mg in 1 mL (3%) in sterile solutions; 60 mg in 2 mL (3%) of ketorolac
tromethamine in sterile solution is available for IM administration
only. The solutions contain 10% (w/v) alcohol, and 6.68 mg, 4.35 mg,
and 8.70 mg, respectively, of sodium chloride in sterile water. The
pH is adjusted with sodium hydroxide and/or hydrochloric acid, and
the solutions are packaged with nitrogen. The sterile solutions are
clear and slightly yellow in color.
|
| dailymed-instance:clinicalP... |
PHARMACODYNAMICS Ketorolac tromethamine is a nonsteroidal anti-inflammatory
drug (NSAID) that exhibits analgesic activity in animal models. Ketorolac
tromethamine inhibits synthesis of prostaglandins and may be considered
a peripherally-acting analgesic. The biological activity of ketorolac
tromethamine is associated with the S-form. Ketorolac tromethamine
possesses no sedative or anxiolytic properties. 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
by either route 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, 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 dosesof 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. Distribution The mean apparent volume (V) 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, even plasma concentrations
as high as 10 mcg/mL will only occupy approximately 5% of the albumin
binding sites. Thus, the unbound fraction for each enantiomer will
be constant over the therapeutic range. A decrease in serum albumin,
however, will result in increased free drug concentrations. Ketorolac tromethamine is excreted in human milk (see
PRECAUTIONS: Lactation and Nursing). 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 two times faster than the R-enantiomer, and
that the clearance was independent of the route of administration.
This means that the ratio of S/R plasma concentrations decreases with
time after each dose. There is little or no inversion of the R- to
S- form in humans. The clearance of the racemate in normal subjects,
elderly individuals, and in hepatically and renally impaired patients,
is outlined in Table 2. The half-life of the
ketorolac tromethamine S-enantiomer was approximately 2.5 hours (SD��0.4)
compared with 5 hours (SD��1.7) for the R-enantiomer. In other
studies, the half-life for the racemate has been reported to lie within
the range of 5 to 6 hours. Accumulation Ketorolac tromethamine administered as an
IV bolus every 6 hours for 5 days to healthy subjects (n=13), showed
no significant difference in Con 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 Populations Geriatric
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 Cfor the two groups (elderly,
2.52 mcg/mL��0.77; young, 2.99 mcg/mL��1.03) (see PRECAUTIONS���Geriatric Use). Pediatric Patients Following a single intravenous bolus dose of 0.5 mg/kg in 10 children
4 to 8 years old, the half-life was 6 hours (range: 3.5 to 10 h),
the average clearance was 0.042 L/hr/kg and the Vd was 0.26 L/kg (range:
0.19 to 0.44 L/kg). In a second study, following a single intravenous
dose of 0.6 mg/kg in 24 children 3 to 18 years old, Cwas 4.3��1.7 mcg/mL, Twas 10.25��1.15
minutes, half-life was 3.8��2.6 hours, Cl was 0.0678 L/hr/kg
and Vd was 0.25 L/kg. The volume of distribution and clearance of
ketorolac in pediatric patients was twice that observed in adult subjects
(see Tables 1 and 2). There are no pharmacokinetic data available
for ketorolac tromethamine administration 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 AUC���of each enantiomer
increased by approximately 100% compared with healthy volunteers.
The volume of distribution doubles for the S-enantiomer and increases
by 1/5th for the R-enantiomer. The increase in volume of distribution
of ketorolac tromethamine implies an increase in unbound fraction. The AUC���ratio of the ketorolac tromethamine enantiomers
in healthy subjects and patients remained similar, indicating there
was no selective excretion of either enantiomer in patients compared
to healthy subjects (see WARNINGS���Renal Effects and Table
2). Hepatic
Insufficiency There was no significant
difference in estimates of half-life, AUC���and Cin 7 patients with liver disease compared to healthy volunteers
(see PRECAUTIONS���Hepatic Effects and Table 2). Race Pharmacokinetic differences due to race have not been
identified.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
(see also Boxed WARNING)
|
| dailymed-instance:supply |
Ketorolac Tromethamine Injection, USP for intramuscular
and intravenous use is available in an iSecuresterile
cartridge unit: 15 mg: 15 mg/mL, 1 mL iSecure
sterile cartridge unit (with Luer Lock) box of 10, NDC 0409-2288-21. 30 mg: 30 mg/mL, 1 mL iSecure sterile cartridge unit (with
Luer Lock) box of 10, NDC 0409-2287-21. Ketorolac
Tromethamine Injection, USP for intramuscular use only is available
in an iSecure sterile cartridge unit: 60 mg: 30 mg/mL, 2 mL iSecure sterile cartridge unit (with Luer Lock) box
of 10, NDC 0409-2287-22. Store at 20 to 25��C
(68 to 77��F). [See USP Controlled Room Temperature.] Retain in
carton until time of use. PROTECT FROM LIGHT. Revised: March, 2007 Directions
for iSecure Syringe 1. To release plunger rod, grasp syringe and depress rod until it
releases from the syringe. 2. Attach plunger rod to the syringe barrel
by inserting rod into the plunger end and turning clockwise. 3. Remove luer tip cover.
Attach needle or blunt cannula if applicable. 4. Expel air by pushing on the plunger rod.
Do not touch the syringe tip. Administer Drug. Note: To prevent needlestick injuries, needles and blunt cannulas
should not be recapped, purposely bent, or broken by hand.
|
| dailymed-instance:boxedWarn... |
WARNING Ketorolac tromethamine, a nonsteroidal
anti-inflammatory drug (NSAID), is indicated for the short-term (up
to 5 days) management of moderately severe acute pain that requires
analgesia at the opioid level. It is NOT indicated for minor or chronicpainful conditions. Ketorolac tromethamine is a potent NSAID analgesic,
and its administration carries many risks. The resulting NSAID-related
adverse events can be serious in certain patients for whom ketorolac
tromethamine is indicated, especially when the drug is used inappropriately.Increasing the dose of ketorolac tromethamine beyond the label recommendations
will not provide better efficacy but will result in increasing the
risk of developing serious adverse events. Gastrointestinal Effects Renal Effects Risk of Bleeding Hypersensitivity Intrathecal or Epidural
Administration Labor, Delivery and Nursing Concomitant Use with NSAIDs DOSAGE AND ADMINISTRATION Ketorolac Tromethamine
Tablets Special Populations
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
GENERAL:<br/>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). Advise patients not to give ketorolac
tromethamine tablets to other family members and to discard any unused
drug. Remember that the total duration of ketorolac
tromethamine therapy is not to exceed 5 (five) days in adults or a
single dose in pediatric patients ages 2 to 16 years.<br/>DRUG INTERACTIONS: Ketorolac is highly bound to human plasma protein
(mean 99.2%). 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 two-fold increase in unbound
ketorolac plasma levels. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam,
acetaminophen, phenytoin, and tolbutamide did not alter ketorolac tromethamine proteinbinding. In a study involving 12 volunteers,
ketorolac tromethamine tablets were co-administered with a single
dose of 25 mg warfarin, causing no significant changes in pharmacokinetics or pharmacodynamics
of warfarin. In another study, ketorolac tromethamine injection 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 6.0 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). Furosemide Ketorolac tromethamine
administered IV or IM reduced the diuretic response to furosemide in normovolemic healthy
subjects by approximately 20% (mean sodium and urinary output decreased
17%). Probenecid Concomitant
administration of ketorolac tromethamine tablets and probenecid resulted in decreased
clearance 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
and probenecid is contraindicated. Lithium Inhibition of renal lithium clearance, leading to an increase in plasma lithium
concentration, has been reported with some prostaglandin synthesis-inhibiting
drugs. The effect of ketorolac tromethamine on plasma lithium has
not been studied, but cases of increased lithium plasma levels during
ketorolac tromethamine therapy have been reported. Methotrexate Concomitant administration of methotrexate and some NSAIDs has
been reported to reduce the clearance of methotrexate, enhancing the
toxicity of methotrexate. The effect of ketorolac tromethamine on
methotrexate clearance has not been studied. Nondepolarizing Muscle Relaxants In postmarketing
experience, there have been reports of a possible interaction between
ketorolac tromethamine injection and nondepolarizing muscle relaxants that resulted in apnea.
The concurrent use of ketorolac tromethamine with muscle relaxants
has not been formally studied. ACE Inhibitors Concomitant use of ACE inhibitors may increase
the risk of renal impairment, particularly in volume-depleted patients. 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). Morphine Ketorolac tromethamine
injection has been administered concurrently with morphine in several clinical trials
of postoperative pain without evidence of adverse interactions. Do
not mix ketorolac tromethamine and morphine in the same syringe. There is no evidence in animal or human studies that ketorolac
tromethamine induces or inhibits hepatic enzymes capable of metabolizing
itself or other drugs.<br/>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 qid, 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.<br/>Pregnancy: 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 (1.0 times the human AUC)
in rats. Results of these studies did not reveal evidence of teratogenicity
to the fetus. Doses of ketorolac tromethamine tablets 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.<br/>Labor and Delivery: The use of ketorolac tromethamine is contraindicatedin 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).<br/>Lactation and Nursing: After a single administration of a 10 mg ketorolac
tromethamine tablet 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 (qid), 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.<br/>Pediatric Use: The safety and effectiveness of single doses of ketorolac
tromethamine injection have been established in pediatric patients
between the ages of 2 and 16 years. Ketorolac tromethamine injection
has been shown to be effective in the management of moderately severe
acute pain that requires analgesia at the opioid level, usually in
a postoperative setting. Safety and efficacy in pediatric patients
below the age of 2 have not been established. Therefore, ketorolac
tromethamine injection is not recommended in pediatric patients below
the age of 2. The risk of bleeding was greater in those patients administered
ketorolac tromethamine injection following tonsillectomy. Physicians
should consider the increased risk of bleeding before deciding to
administer ketorolac tromethamine injection in patients following
tonsillectomy (see WARNINGS: Hemorrhage and Pediatrics and Tonsillectomy). The risks identified in the adult population
with ketorolac tromethamine injection use also apply to pediatric
patients. Therefore, consult the CONTRAINDICATIONS, WARNINGS, PRECAUTIONS,
and ADVERSE REACTIONS sections when prescribing ketorolac tromethamine
injection to pediatric patients.<br/>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 adverse effects of NSAIDs (see WARNINGS���Renal Effects), extra caution and reduced dosages (see DOSAGE AND
ADMINISTRATION) must be used when treating the elderly with ketorolac
tromethamine injection. The lower end of the ketorolac tromethamine
injection dosage range is recommended for patients over 65 years of
age and total daily dose is not to exceed 60 mg. The incidence and
severity of gastrointestinal complications increases with increasing
dose of, and duration of treatment with, ketorolac tromethamine.
|
| dailymed-instance:overdosag... |
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. 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
usualdose). In controlled overdosage, daily
doses of 360 mg of ketorolac tromethamine injection given for 5 days
(three times the highest recommended dose), caused abdominal pain
and peptic ulcers which healed after discontinuation of dosing. Metabolic
acidosis has been reported following intentional overdosage. 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. Dialysis does not significantly
clear ketorolac tromethamine from the blood stream.
|
| dailymed-instance:genericMe... |
Ketorolac Tromethamine
|
| dailymed-instance:fullName |
Ketorolac Tromethamine (Injection, Solution)
|
| dailymed-instance:adverseRe... |
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. The Adverse Reactions Listed Below Were
Reported In Clinical Trials As Probably Related To KETOROLAC TROMETHAMINE. (Percentage of incidence in parentheses for those
events reported in 3% or more patients) Body as a Whole: edema (4%). Cardiovascular: hypertension. Dermatologic: pruritus,
rash. Gastrointestinal: nausea (12%), dyspepsia (12%), gastrointestinal pain (13%), diarrhea
(7%), constipation, flatulence, gastrointestinal fullness, vomiting,
stomatitis. Hemic
and Lymphatic: purpura. Nervous System: headache (17%), drowsiness
(6%), dizziness (7%), sweating. Injection-site pain was reported by 2%
of patients in multi-dose studies. Body as a Whole: weight gain, fever, infections, asthenia. Cardiovascular: palpitation,
pallor, syncope. Dermatologic: urticaria. Gastrointestinal: gastritis, rectal bleeding, eructation, anorexia, increased appetite. Hemic and Lymphatic: epistaxis, anemia, eosinophilia. Nervous System: tremors, abnormal dreams,
hallucinations, euphoria, extrapyramidal symptoms, vertigo, paresthesia,
depression, insomnia, nervousness, excessive thirst, dry mouth, abnormal
thinking, inability to concentrate, hyperkinesis, stupor. Respiratory: dyspnea,
pulmonary edema, rhinitis, cough. Special Senses: abnormal taste, abnormal
vision, blurred vision, tinnitus, hearing loss. Urogenital: hematuria, proteinuria,
oliguria, urinary retention, polyuria, increased urinary frequency. The Following Adverse Events
Were Reported From Postmarketing Experience. Body as a Whole: hypersensitivity
reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema,
tongue edema (see Boxed WARNING, WARNINGS), angioedema, myalgia. Cardiovascular: hypotension
and flushing. Dermatologic: Lyell's syndrome, Stevens-Johnson syndrome, exfoliative dermatitis,
maculo-papular rash, urticaria. Gastrointestinal: peptic ulceration, G.I.
hemorrhage, G.I. perforation (see Boxed WARNING, WARNINGS), melena,
acute pancreatitis, hematemesis, esophagitis. Hemic and Lymphatic: postoperative
wound hemorrhage rarely requiring blood transfusion (see Boxed WARNING,
WARNINGS and PRECAUTIONS), thrombocytopenia, leukopenia. Hepatic: hepatitis,
liver failure, cholestatic jaundice. Nervous System: convulsions, psychosis,
aseptic meningitis. Respiratory: asthma, bronchospasm. Urogenital: acute renal failure
(see Boxed WARNING, WARNINGS), flank pain with or without hematuria
and/or azotemia, nephritis, hyponatremia, hyperkalemia, hemolytic
uremic syndrome.
|
| dailymed-instance:warning |
(see also Boxed WARNING) ���The combined use of ketorolac tromethamine
injection and ketorolac tromethamine tablets is not to exceed 5 days
in adults. Only single doses of ketorolac tromethamine injection are recommended for use in pediatric patients. The most serious risks associated with ketorolac tromethamine are: In postmarketing experience, postoperative hematomas
and other signs of wound bleeding have been reported in associationwith the perioperative use of ketorolac tromethamine injection. Therefore,
perioperative use of ketorolac tromethamine should be avoided and
postoperative use be undertaken with caution when hemostasis is critical
(see WARNINGS and PRECAUTIONS). Pediatrics and Tonsillectomy: Physicians
should consider the increased risk of bleeding before deciding to
administer ketorolac tromethamine injection in patients following
tonsillectomy. Ketorolac tromethamine injection is not recommended
for use in pediatric patients below the age of 2 years. In a retrospective
analysis of patients having undergone tonsillectomy with or without
adenoidectomy, the risk of bleeding was 10.1% in patients administered
ketorolac tromethamine injection comparedto 2.2% in those receiving
opioids. The postoperative hemorrhage rate in patients 12 years and
younger was 6.5% and 3.3% with and without ketorolac tromethamine
injection, respectively. In a prospective study of ketorolac tromethamine
injection in pediatric patients (ages 3 to 9 years) undergoing tonsillectomy
with or without adenoidectomy, the overall incidence of bleeding was
similar between the patients receiving ketorolac tromethamine injection
and morphine (16.3% versus 17%, respectively). However, during the
first 24 hours after surgery, a higher incidence of bleeding was observed
in the ketorolac tromethamine injection group (14.3%) versus the morphine
group (4.2%). Renal Effects: 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. Because patients with
underlying renal insufficiency are at increased risk of developing
acute renal failure, the risks and benefits should be assessed prior
to giving ketorolac tromethamine to these patients. Hence, in patients
with moderately elevated serum creatinine, it is recommended that
the daily dose of ketorolac tromethamine injection be reduced by half,
not to exceed 60 mg/day. Ketorolac tromethamine is CONTRAINDICATED
IN PATIENTS WITH SERUM CREATININE CONCENTRATIONS INDICATING ADVANCED
RENAL IMPAIRMENT (see CONTRAINDICATIONS). Hypovolemia should be corrected before treatment with ketorolac tromethamine is
initiated.
|
| dailymed-instance:indicatio... |
Adult Patients: Ketorolac tromethamine is 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 IV or IM ketorolac tromethamine, and the
oral dosage form is to be used only as continuation treatment, if
necessary. Combined use of IV/IM and the oral dosage form is not toexceed 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 therapy is not to
exceed 5 days. Pediatric Patients: The safety and effectiveness of single
doses of ketorolac tromethamine injection have been established in
pediatric patients between the ages of 2 and 16 years. Ketorolac tromethamine
as a single injectable dose, has been shown to be effective in the
management of moderately severe acute pain that requires analgesia
at the opioid level, usually in the postoperative setting. There is
limited data available to support the use of multiple doses of ketorolac
tromethamine injection in pediatric patients. Safety and effectiveness
have not been established in pediatric patients below the age of 2
years. Use of ketorolac tromethamine injection in pediatric patients
is supported by evidence from adequate and well-controlled studies
of ketorolac tromethamine injection in adults with additional pharmacokinetic,
efficacy and safety data on its use in pediatric patients available
in the published literature (see CLINICAL PHARMACOLOGY: Clinical Studies, WARNINGS, and PRECAUTIONS). Ketorolac tromethamine injection has been used concomitantly
with morphine and meperidine and has shown an opioid-sparing effect.
For breakthrough pain, it is recommended to supplement the lower end
of the ketorolac tromethamine injection dosage range with low doses
of narcotics prn, unless otherwise contraindicated. Ketorolac tromethamine
and narcotics should not be administered in the same syringe (see
DOSAGE AND ADMINISTRATION���Pharmaceutical
Information for Ketorolac Tromethamine Injection).
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Ketorolac Tromethamine
|