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Etodolac

Drug Reference 9 min 2039

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Created On: 01/10/2019

Etodolac is a member of the pyranocarboxylic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs).

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Introduction

Etodolac is a member of the pyranocarboxylic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). It is used for the treatment of osteoarthritis and rheumatoid arthritis. It exhibits anti-inflammatory, analgesic and antipyretic properties. It works by inhibiting prostaglandin synthetase and reduces hormones that cause inflammation and pain in the body.

Pharmacological class: NSAID

Indications

Mild to moderate pain
Osteoarthritis
Rheumatoid arthritis

Pharmachologic action

Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cyclooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site.

Dosage

For osteoarthritis

300 mg orally 2 to 3 times a day or 400 mg orally twice a day
Total daily dose should not exceed 1200 mg

Rheumatoid arthritis

300 mg orally 2 to 3 times a day or 400 mg orally twice a day
Total daily dose should not exceed 1200 mg

For pain

200 to 400 mg orally every 6 to 8 hours

For juvenile rheumatoid arthritis

6 to 16 years: dose based on weight, given orally once daily
For 20 to 30 kg, dose is 400 mg
For 31 to 45 kg, dose is 600 mg

Pharmacokinetics

Etodolac is well absorbed. The mean apparent volume of distribution of etodolac is approximately 390 mL/kg. It is extensively metabolized in the liver and the metabolites include 6-, 7-, and 8-hydroxylated-etodolac and etodolac glucuronide. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces.

Contraindications

In patients with known hypersensitivity to etodolac
In patients who have experienced asthma, utricaria or other allergic-type reactions after taking aspirin or other NSAIDs
For treating perioperative pain in the setting of coronary artery bypass graft surgery

Drug interaction

Etodolac with lithium elevates plasma lithium levels and causes reduction in renal lithium clearance. This produces signs of lithium toxicity
Etodolac when administered with cyclosporine, digoxin and methotrexate may result in their elevated serum levels and causes toxicity
NSAIDS when given with ACE-inhibitors may diminish their antihypertensive effect
When Etodolac administered with aspirin, its protein binding is reduced and the potential of adverse effects increases

Side effects

Common (affecting between 1 in 10 to 1 in 100):

Nausea
Vomiting
Stomach pain
Indigestion
Diarrhea
Constipation
Dizziness
Sore throat
Runny nose
Flu symptoms
Itching
Headache

Uncommon (affecting 1 in 100 to 1 in 1000):

Thirst, dry mouth
Insomnia, somnolence

Very rare (affecting less than 1 in 10,000):

GI bleeding
Hypertension, congestive heart failure
Ulcerative stomatitis, anorexia
Anemia, thrombocytopenia

Precautions

Avoid in patients who have abnormal liver function tests as they may get more prone to severe hepatic reactions
It should be used with caution in patients with fluid retention, hypertension, or heart failure
It should not be administered to patients having aspirin sensitivity or pre-existing asthma
Avoid in pregnant and breast feeding women

Clinical evidence

In a study, the efficacy of etodolac (600 mg/day) and placebo were compared in a 4-week double-blind, parallel-group study involving 104 patients with osteoarthritis of the knee and 106 with osteoarthritis of the hip. Patients with osteoarthritis of the knee taking etodolac had significantly (p<0.05) more improvement than placebo. Patients also had significantly (p<0.05) greater improvement in hip abduction, weight-bearing pain, joint tenderness, investigator's overall assessment, and patient's overall assessment. Results of laboratory evaluations indicated that etodolac therapy was associated with no more hepatic or renal enzyme abnormalities than was placebo.¹

In another study, Etodolac was compared with aspirin and placebo for efficacy and safety, and a minimum effective dose was established in 264 patients with adult-onset, active rheumatoid arthritis. In this six-week, patients received daily doses of etodolac at 50, 100, or 200 mg/d; aspirin at 3,900 mg/d; or placebo. Both etodolac at the highest dose and aspirin produced statistically significant improvement in all disease activity assessments measured at four- and six-week end points and were superior to placebo in the majority of assessments. Although, 100-mg/d dose was effective but 200-mg/d dose, was suggested as the minimum effective dose for the treatment of active rheumatoid arthritis.²