AHFS Class:

• Reversible COX-1/COX-2 Inhibitors 28:08.04.04

Generic Name(s):

• Etodolac

Etodolac is a prototypical nonsteroidal anti-inflammatory agent (NSAIA).

Conventional capsules and tablets and extended-release tablets of etodolac are used for anti-inflammatory and analgesic effects in the acute and chronic symptomatic treatment of osteoarthritis and rheumatoid arthritis.1,2 Extended-release tablets of etodolac also are used for the symptomatic treatment of juvenile rheumatoid arthritis in pediatric patients 6-16 years of age.2 Conventional capsules and tablets of etodolac also are used for the relief of pain.1 Extended-release tablets of etodolac are not recommended for the management of acute pain.2 For additional information on the management of osteoarthritis, see Uses: Osteoarthritis, in Celecoxib 28:08.04.08. For additional information on the management of rheumatoid arthritis, see Uses: Rheumatoid Arthritis, in Methotrexate 10:00.

The potential benefits and risks of etodolac therapy as well as alternative therapies should be considered prior to initiating etodolac therapy.1 The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed.1

Patients should be advised that etodolac, like other NSAIAs, is not free of potential adverse effects, including some that can cause discomfort, and that more serious effects (e.g., myocardial infarction, stroke, GI bleeding), which may require hospitalization and may even be fatal, also can occur.1,500,508 NSAIAs, including selective cyclooxygenase-2 (COX-2) inhibitors and prototypical NSAIAs, increase the risk of serious adverse cardiovascular thrombotic events, including myocardial infarction and stroke, in patients with or without cardiovascular disease or risk factors for cardiovascular disease.6,7,8,500,502,508 Available data suggest that the increase in risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500,502,505,506,508 Use of NSAIAs also is associated with an increased risk of heart failure.500,508 (See Cautions: Cardiovascular Effects, in Celecoxib 28:08.04.08.) The risk of potentially serious adverse GI effects also should be considered in patients receiving etodolac, particularly in patients receiving chronic therapy with the drug.1 (See Cautions: GI Effects, in Naproxen 28:08.04.92.) NSAIAs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.508 Patients should be advised to read the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.1

Administration

The potential benefits and risks of etodolac therapy as well as alternative therapies should be considered prior to initiating etodolac therapy.1

Etodolac is administered orally.1 While the extent of GI absorption of etodolac administered as conventional capsules or tablets does not appear to be affected substantially by concomitant administration with food or antacids, peak concentrations may be reduced by about 50 or 15-20%, respectively;1 in addition, the time to peak concentration may be delayed substantially by concomitant administration with food but not antacids.1

The extent of GI absorption of etodolac administered as extended-release tablets is not affected substantially by concomitant administration with food or antacids; however, peak plasma concentrations are increased by 54% when the extended-release preparation is administered with food and reduced by 15-20% when administered with antacid.2 Concomitant administration with antacids does not affect time to peak concentrations.2

Dosage

The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed.1 Dosage of etodolac must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage.1

The manufacturers state that safety and efficacy of etodolac conventional capsules and tablets have not been established in children.1 Safety and efficacy of extended-release tablets of etodolac have not been established in pediatric patients younger than 6 years of age.2

Pain

For the relief of acute pain, the usual recommended adult dosage of etodolac as conventional capsules or tablets is up to 1 g daily given in divided doses of 200-400 mg every 6-8 hours.1 Etodolac dosages exceeding 1 g daily have not been evaluated in controlled clinical studies.1

Inflammatory Diseases

For the acute or chronic symptomatic treatment of osteoarthritis or rheumatoid arthritis in adults, the usual initial dosage of etodolac as conventional capsules or tablets is 600-1000 mg daily, usually administered in 2 divided doses;1 dosages of 900 mg daily usually are given in 3 divided doses.1 For the symptomatic treatment of osteoarthritis or rheumatoid arthritis, the usual initial dosage of etodolac as extended-release tablets is 400-1000 mg once daily.2 Subsequent dosage should be adjusted according to the patient's response and tolerance.2

Some adults receiving long-term therapy with etodolac may respond to dosages of 600 mg daily.1 Etodolac dosages exceeding 1 g daily as conventional capsules or tablets or 1.2 g daily as extended-release tablets, respectively, have not been evaluated in controlled clinical studies.1,3

During chronic therapy, a therapeutic response generally is evident within 2 weeks (sometimes within 1 week);1,2 when a satisfactory response occurs, dosage of the drug should be reviewed and adjusted as needed.1

For the symptomatic treatment of juvenile rheumatoid arthritis in pediatric patients 6-16 years of age, the recommended dosage of etodolac as extended-release tablets is 400 mg once daily in those weighing 20-30 kg, 600 mg once daily in those weighing 31-45 kg, 800 mg once daily in those weighing 46-60 kg, or 1 g once daily in those weighing more than 60 kg.2

Description

Etodolac, an indole acetic acid derivative, is a prototypical nonsteroidal anti-inflammatory agent (NSAIA).

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Wyeth. Lodine^® (etodolac) capsules and tablets prescribing information. Philadelphia, PA; 2006 Apr.

2. Wyeth. Lodine^® XL (etodolac) extended-release tablets prescribing information. Philadelphia, PA; 2003 Oct.

3. Taro Pharmaceutical Industries. Etodolac extended-release tablets prescribing information. Haifa Bay, Israel; 2003 Feb.

4. Jenkins JK and Seligman PJ. Analysis and recommendations for Agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6. From FDA website. [Web]

5. Merck & Co. Clinoril^® (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

6. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA . 2006; 296: 1633-44. [PubMed 16968831]

7. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ . 2006; 332: 1302-5. [PubMed 16740558][PubMedCentral]

8. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA . 2006; 296:1653-6. [PubMed 16968830]

500. Food and Drug Administration. Drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Silver Spring, MD; 2015 Jul 9. From the FDA web site. Accessed 2016 Mar 22. [Web]

501. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet . 2013; 382:769-79. [PubMed 23726390][PubMedCentral]

502. Food and Drug Administration. FDA briefing document: Joint meeting of the arthritis advisory committee and the drug safety and risk management advisory committee, February 10-11, 2014. From FDA web site [Web]

503. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ . 2011; 342:c7086. [PubMed 21224324][PubMedCentral]

504. Gislason GH, Rasmussen JN, Abildstrom SZ et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med . 2009; 169:141-9. [PubMed 19171810]

505. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation . 2011; 123:2226-35. [PubMed 21555710]

506. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med . 2011; 8:e1001098. [PubMed 21980265][PubMedCentral]

507. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2013; 62:e147-239. [PubMed 23747642]

508. ANI Pharmaceuticals, Inc. Etodolac capsules prescribing information. Baudette, MN; 2015 Aug.

509. Cumberland Pharmaceuticals Inc. Caldolor^® (ibuprofen) injection prescribing information. Nashville, TN; 2016 Apr.

511. Olsen AM, Fosbøl EL, Lindhardsen J et al. Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study. Circulation . 2012; 126:1955-63. [PubMed 22965337]

512. Olsen AM, Fosbøl EL, Lindhardsen J et al. Cause-specific cardiovascular risk associated with nonsteroidal anti-inflammatory drugs among myocardial infarction patients--a nationwide study. PLoS One . 2013; 8:e54309.

516. Bavry AA, Khaliq A, Gong Y et al. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. Am J Med . 2011; 124:614-20. [PubMed 21596367][PubMedCentral]

1200. US Food and Drug Administration. FDA drug safety communication: FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid. 2020 Oct 15. From the FDA website. [Web]

1201. ANI Pharmaceuticals. Etodolac capsules prescribing information. Baudette, MN; 2020 Nov.

1202. Actavis Pharma. Sulindac tablets prescribing information. Parsippany, NJ; 2020 Oct.

1203. Jubilant Cadista Pharmaceuticals. Indomethacin extended-release capsules prescribing information. Salisbury, MD; 2020 Nov.