A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Toradol Side Effects, and Drug Interactions - Ketorolac
Toradol Side Effects, and Drug Interactions - Ketorolac
SIDE EFFECTS
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.
Incidence 1% Or Less
- 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 vision,
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),
myalgia.
Cardiovascular: hypotension
and flushing.
Dermatologic: Lyell's syndrome, Stevens-Johnson syndrome,
exfoliative dermatitis,
maculopapular
rash, urticaria.
Gastrointestinal: peptic,
ulceration, GI hemorrhage,
GI perforation (see BOXED
WARNING, WARNINGS),
melena, acute pancreatitis.
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.
Ophthalmic Solution: In
patients with allergic
conjunctivitis, the most adverse events reported with the use of
Acular (ketorolac tromethamine) ophthalmic solution
have been transient
stinging and burning on instillation. These events were reported
by approximately 40% of the patients treated with Acular ophthalmic
solution. In all development
studies conducted, other adverse events reported during treatment
with Acular include ocular irritation (3%), allergic
reactions (3%), superficial
ocular infections (0.5%)
and superficial
keratitis (1%).
DRUG INTERACTIONS
Ketorolac is highly bound
to human plasma
proteins (mean 99.2%).
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 digoxinprotein
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 protein
binding.
In a study involving 12 volunteers, oral
ketorolac tromethamine
was 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
IV/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 (3.2-11.4 min) compared to a mean
of 6.0 minutes (3.4-7.5 min) for heparin
alone and 5.1 minutes (3.5-8.5 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).
Ketorolac tromethamine
IV/IM reduced the diuretic
response to furosemide
in normovolemic healthy
subjects by approximately 20% (mean sodium
and urinary output decreased
17%).
Concomitant administration
of oral ketorolac tromethamineand
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.
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.
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.
In postmarketing experience, there have been three reports of a
possible interaction between ketorolac tromethamine
IV/IM and non-depolarizing muscle relaxants, that
resulted in apnea. The concurrent use of ketorolac tromethamine
with muscle relaxants
has not been formally studied.
Concomitant use of ACE inhibitors may increase the risk
of renal impairment, particularly in volume-depleted patients.
Sporadic cases of seizures have been reported during concomitant
use of ketorolac tromethamine
and antiepilectic drugs (Dilantin, Tegretol).
Hallucinations have been reported when ketorolac tromethamine
was used in patients taking psychoactive drugs (Prozac,
Navane, Xanax).
Ketorolac tromethamine
IV/IM 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.
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