Brands, Medical Use, Clinical Data
- Nonsteroidal Antiinflammatory Agents (NSAIDs)
- Tablet (extended-release)
Brands / Synonyms
Etodolac; Etodolac [Usan:Ban:Inn]; Etodolacetodolic acid; Etodolaco [Inn-Spanish]; Etodolacum [Inn-Latin]; Etodolic Acid; Lodine; Lodine XL; Ultradol
For acute and long-term use in the management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain.
Etodolac, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.
Mechanism of Action
The antiinflammatory effects of etodolac may result from the inhibition of the enzyme cycooxygenase and the subsequent peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, their inhibition accounts for the peripheral analgesic effects of etodolac. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.
Based on mass balance studies, the systemic availability of etodolac from either the tablet or capsule formulation, is at least 80%.
Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.
Biotrnasformation / Drug Metabolism
Etodolac is extensively metabolized in the liver, with renal elimination of etodolac and its metabolites being the primary route of excretion.
Lodine is contraindicated in patients with known hypersensitivity to etodolac. Lodine should not be given to
patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other
NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be
given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
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
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
Cyclosporine, Digoxin, 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 cyclosporine, digoxin, 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.
Etodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide.
Nevertheless, clinical studies, as well as postmarketing observations have shown that Lodine 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, as well as to assure diuretic efficacy.
Etodolac has no apparent pharmacokinetic interaction when administered with glyburide.
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.
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.
Etodolac has no apparent pharmacokinetic interaction when administered with phenytoin.
The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a
risk of serious GI bleeding higher than that of users of either drug alone. 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, caution should be exercised
because there have been a few spontaneous reports of prolonged prothrombin times, with or without bleeding, in
etodolac-treated patients receiving concomitant warfarin therapy.
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.