AHFS Class:

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

Generic Name(s):

• Nabumetone

Nabumetone is a prototypical nonsteroidal anti-inflammatory agent (NSAIA)1 that is a prodrug and has little pharmacologic activity until it undergoes oxidation in the liver to form an active metabolite that is structurally similar to naproxen.2,3

Nabumetone is used for anti-inflammatory and analgesic effects in the symptomatic treatment of osteoarthritis and rheumatoid arthritis.1 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 Adults, in Methotrexate 10:00.

The potential benefits and risks of nabumetone therapy as well as alternative therapies should be considered prior to initiating nabumetone 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 nabumetone, 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.4,5,6,500,502,508 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 nabumetone, 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 nabumetone therapy as well as alternative therapies should be considered prior to initiating nabumetone therapy.1

Nabumetone is administered orally.1 Although the rate of GI nabumetone absorption and of subsequent systemic metabolism to 6-methoxy-2-naphthylacetic acid (6-MNA), the active form, may be increased by concomitant administration of the drug with food, the manufacturer states that nabumetone can be administered orally without regard to meals since the extent of 6-MNA formation is not affected.1

Dosage

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

Nabumetone is recommended for use in adults.1 The manufacturer states that safety and efficacy in pediatric patients have not been established.1

For the symptomatic treatment of osteoarthritis or rheumatoid arthritis, the usual initial adult dosage of nabumetone is 1 g once daily.1 The usual adult maintenance dosage is 1-2 g daily, given as single or 2 divided doses daily.2,3 Patients weighing less than 50 kg are less likely to require a nabumetone dosage that exceeds 1 g daily.1 The manufacturer states that dosages exceeding 2 g daily have not been studied.1

Dosage in Renal Impairment

Modification of nabumetone dosage generally is not necessary in patients with mild renal impairment (creatinine clearance of 50 mL/minute or greater).1

For the symptomatic treatment of osteoarthritis or rheumatoid arthritis in patients with moderate renal impairment (creatinine clearance of 30-49 mL/minute), the initial dosage should not exceed 750 mg once daily.1 After careful monitoring of renal function, dosage may be increased, if needed, to a maximum dosage of 1.5 g daily.1

For the symptomatic treatment of osteoarthritis or rheumatoid arthritis in patients with severe renal impairment (creatinine clearance less than 30 mL/minute), the initial dosage should not exceed 500 mg once daily.1 After careful monitoring of renal function, dosage may be increased, if needed, to a maximum dosage of 1 g daily.1

Because formation of the active metabolite depends on biotransformation in the liver, such formation could be decreased in patients with severe hepatic impairment; therefore, the manufacturer states that the drug should be used cautiously in such patients.1

Description

Nabumetone, a naphthylalkanone derivative, is a prototypical nonsteroidal anti-inflammatory agent (NSAIA).1 Nabumetone is a prodrug and has little pharmacologic activity until it undergoes oxidation in the liver and forms 6-methoxy-2-naphthylacetic acid (6-MNA).1 This active metabolite is structurally similar to naproxen.2,3

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.

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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. Sandoz. Nabumetone tablets prescribing information. Princeton, NJ; 2015 Jul.

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

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.