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
Lodine Side Effects, and Drug Interactions - Etodolac
Lodine Side Effects, and Drug Interactions - Etodolac
SIDE EFFECTS
Adverse-reaction information for Lodine was derived from 2,629
arthritic patients treated with Lodine (etodolac capsules and tablets) in double-blind
and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing
surveillance studies. In clinical trials, most adverse reactions were mild and
transient. The discontinuation rate in controlled clinical trials, because of
adverse events, was up to 10% for patients treated with Lodine.
New patient complaints (with an incidence greater than or equal
to 1%) are listed below by body system. The incidences were determined from
clinical trials involving 465 patients with osteoarthritis treated with 300
to 500 mg of Lodine b.i.d. (i.e., 600 to 1000 mg/day).
INCIDENCE GREATER THAN OR EQUAL TO 1%—PROBABLY CAUSALLY RELATED
Body as a whole—Chills and fever.
Digestive system—Dyspepsia (10%), abdominal pain*, diarrhea*,
flatulence*, nausea*, constipation, gastritis, melena, vomiting.
Nervous system—Asthenia/malaise*, dizziness*, depression, nervousness.
Skin and appendages—Pruritus, rash.
Special senses—Blurred vision, tinnitus.
Urogenital system—Dysuria, urinary frequency.
*Drug-related patient complaints occurring in 3 to 9% of patients
treated with Lodine. Drug-related patient-complaints occurring in fewer than
3%, but more than 1%, are unmarked.
INCIDENCE LESS THAN 1% —PROBABLY CAUSALLY RELATED
(Adverse reactions reported only in worldwide postmarketing
experience, not seen in clinical trials, are considered rarer and are italicized.)
Body as a whole—Allergic reaction, anaphylactic/anaphylactoid
reactions (including shock).
Cardiovascular system—Hypertension, congestive heart failure,
flushing, palpitations, syncope, vasculitis (including necrotizing and allergic).
Digestive system—Thirst, dry mouth, ulcerative stomatitis,
anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis,
cholestatic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis,
peptic ulcer with or without bleeding and/or perforation, intestinal
ulceration, pancreatitis.
Hemic and lymphatic system—Ecchymosis, anemia, thrombocytopenia,
bleeding time increased, agranulocytosis, hemolytic anemia, leukopenia, neutropenia,
pancytopenia.
Metabolic and nutritional—Edema, serum creatinine increase,
hyperglycemia in previously controlled diabetic patients.
Nervous system—Insomnia, somnolence.
Respiratory system—Asthma, pulmonary infiltration with eosinophilia.
Skin and appendages—Angioedema, sweating, urticaria, vesiculobullous
rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic
epidermal necrolysis, hyperpigmentation, erythema multiforme.
Special senses—Photophobia, transient visual disturbances.
Urogenital system—Elevated BUN, renal failure, renal insufficiency,
renal papillary necrosis.
INCIDENCE LESS THAN 1% —CAUSAL RELATIONSHIP UNKNOWN (Medical
events occurring under circumstances where causal relationship to Lodine is
uncertain. These reactions are listed as alerting information for physicians.)
Body as a whole—Infection, headache.
Cardiovascular system—Arrhythmias, myocardial infarction, cerebrovascular
accident.
Digestive system—Esophagitis with or without stricture or cardiospasm,
colitis.
Metabolic and nutritional—Change in weight.
Nervous system—Paresthesia, confusion.
Respiratory system— Bronchitis, dyspnea, pharyngitis, rhinitis,
sinusitis.
Skin and appendages—Alopecia, maculopapular rash, photosensitivity,
skin peeling.
Special senses—Conjunctivitis, deafness, taste perversion.
Urogenital system—Cystitis, hematuria, leukorrhea, renal calculus,
interstitial nephritis, uterine bleeding irregularities.
DRUG INTERACTIONS
Antacids
The concomitant administration of antacids has no apparent
effect on the extent of absorption of Lodine. However, antacids can decrease
the peak concentration reached by 15% to 20% but have no detectable effect on
the time-to-peak.
Aspirin
When Lodine is administered with aspirin, its protein binding
is reduced, although the clearance of free etodolac is not altered. The clinical
significance of this interaction is not known; however, as with other NSAIDs,
concomitant administration of Lodine and aspirin is not generally recommended
because of the potential of increased adverse effects.
Warfarin
Short-term pharmacokinetic studies have demonstrated that concomitant
administration of warfarin and LodineÒ(etodolac
capsules and tablets) results in reduced protein binding of warfarin, but there
was no change in the clearance of free warfarin. There was no significant difference
in the pharmacodynamic effect of warfarin administered alone and warfarin administered
with Lodine as measured by prothrombin time. Thus, concomitant therapy with
warfarin and Lodine should not require dosage adjustment of either drug. However,
there have been a few spontaneous reports of prolonged prothrombin times, with
or without bleeding, in Lodine-treated patients receiving concomitant warfarin
therapy. Caution should be exercised because interactions have been seen with
other NSAIDs.
Cyclosporine, Digoxin, Lithium, Methotrexate
Lodine, like other NSAIDs, through effects on renal prostaglandins,
may cause changes in the elimination of these drugs leading to elevated serum
levels of digoxin, lithium, and methotrexate and increased toxicity. Nephrotoxicity
associated with cyclosporine may also be enhanced. Patients receiving these
drugs who are given Lodine, or any other NSAID, and particularly those patients
with altered renal function, should be observed for the development of the specific
toxicities of these drugs.
Phenylbutazone
Phenylbutazone causes increase (by about 80) in the
free fraction of etodolac. Although in vivo studies have not been done
to see if etodolac clearance is changed by coadministration of phenylbutazone,
it is not recommended that they be coadministered.
DRUG/LABORATORY TEST INTERACTIONS
The urine of patients who take Lodine can give a false-positive
reaction for urinary bilirubin (urobilin) due to the presence of phenolic metabolites
of etodolac. Diagnostic dip-stick methodology, used to detect ketone bodies
in urine, has resulted in false-positive findings in some patients treated with
Lodine. Generally, this phenomenon has not been associated with other clinically
significant events. No dose relationship has been observed.
Lodine treatment is associated with a small decrease in serum
uric acid levels. In clinical trials, mean decreases of 1 to 2 mg/dL were observed
in arthritic patients receiving etodolac (600 mg to 1000 mg/day) after 4 weeks
of therapy. These levels then remained stable for up to 1 year of therapy.
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