Does Lodine (etodolac) cause side effects?

Lodine (etodolac) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation associated with osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, tendinitis, bursitis, and menstrual cramps

Lodine blocks the enzyme that makes prostaglandins (cyclooxygenase), resulting in lower concentrations of prostaglandins. As a consequence, inflammation, pain and fever are reduced. The brand name Lodine is discontinued.

Common side effects of Lodine include

Serious side effects of Lodine include

Drug interactions of Lodine include

In late pregnancy, the third trimester, as with other NSAIDs, Lodine should be avoided because it may cause premature closure of the ductus arteriosus. 

It is unknown if Lodine is excreted in breast milk. Consult your doctor before breastfeeding

What are the important side effects of Lodine (etodolac)?

The most common side effects from etodolac are:

NSAIDs reduce the ability of blood to clot and therefore increase bleeding after an injury. Etodolac also may cause stomach and intestinal bleeding and ulcers. Sometimes, stomach ulceration and intestinal bleeding can occur without any abdominal pain. Black, tarry stools, weakness, and dizziness upon standing may be the only signs of the bleeding.

People who are allergic to other NSAIDs should not use etodolac. NSAIDs reduce the flow of blood to the kidneys and impair function of the kidneys. The impairment is most likely to occur in patients who already have impairment of kidney function or congestive heart failure, and treatment with NSAIDs in these patients should be done cautiously. Individuals with asthma are more likely to experience allergic reactions to etodolac and other NSAIDs.

Other important side effects of NSAIDs include:

Lodine (etodolac) side effects list for healthcare professionals

In patients taking etodolac or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are:

Additional Adverse Reactions Reported with NSAIDs

What drugs interact with Lodine (etodolac)?

Drug Interactions ACE-inhibitors

  • 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.

Antacids

  • The concomitant administration of antacids has no apparent effect on the extent of absorption of etodolac.
  • However, antacids can decrease the peak concentration reached by 15% to 20% but have no detectable effect on the time-to-peak.

Aspirin

  • When etodolac 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 etodolac and aspirin is not generally recommended because of the potential of increased adverse effects.

Cyclosporine, Digoxin, Methotrexate

  • Etodolac, 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 increase toxicity.
  • Nephrotoxicity associated with cyclosporine may also be enhanced.
  • Patients receiving these drugs who are given etodolac, 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.
  • 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.

Diuretics

  • Etodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide.
  • Nevertheless, clinical studies, as well as post marketing observations have shown that etodolac 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 sings of renal failure, as well as to assure diuretic efficacy.

Glyburide

  • Etodolac has no apparent pharmacokinetic interaction when administered with glyburide.

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.

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 phylbutazone, it is not recommended that they be coadministered.

Phenytoin

  • Etodolac has no apparent pharmacokinetic interaction when administered with phenytoin.

Warfarin

  • 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 etodolac 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 etodolac as measured by prothrombin time.
  • Thus, concomitant therapy with warfarin and etodolac 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 etodolac 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 etodolac.
  • Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed.
  • Etodolac 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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Medically Reviewed on 11/16/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.