• Arthritis/rheumatic disorders

Nabumetone Generic Name & Formulations

General Description

Nabumetone 500mg, 750mg; tabs.

Pharmacological Class

NSAID (naphthylalkanone).

How Supplied

Contact supplier


Store at 20° to 25° C (68° to 77° F).

Nabumetone Indications


Rheumatoid arthritis. Osteoarthritis.

Nabumetone Dosage and Administration


Individualize. Initially 1g once daily; max 2g/day in 1 or 2 divided doses. Renal insufficiency (CrCl 30–49mL/min): initial max 750mg once daily, may increase to 1.5g/day; (CrCl <30mL/min): initial max 500mg once daily, may increase to 1g/day.


Not established.

Nabumetone Contraindications


Aspirin allergy. 3rd trimester pregnancy. Coronary artery bypass graft surgery.

Nabumetone Boxed Warnings

Boxed Warning

Increased risk of cardiovascular thrombotic events. Increased risk of serious GI adverse events.

Nabumetone Warnings/Precautions


Advanced renal disease: not recommended. History of upper GI disease or other ulcer risk. Cardiovascular disease. Renal or severe hepatic impairment. Fluid retention. Heart failure. Hypertension. Asthma. Monitor BP, renal and hepatic function. Discontinue if hepatic dysfunction or skin rash occurs. Monitor hemoglobin or hematocrit if signs of anemia occur. Avoid sun, UV light. Elderly. Debilitated. Labor & delivery. Pregnancy (Cat.C). Nursing mothers: not recommended.


Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to 3 years duration have shown an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke.

  • Incidence of serious cardiovascular thrombotic events greater in patients with known cardiovascular disease or risk factors.
  • Increased risk has been observed as early as the first weeks of treatment (based on observational studies).
  • doses have been linked to increased cardiovascular thrombotic risk.
  • To minimize risk, use the lowest effective dose for the shortest time possible.
  • Evidence regarding use of aspirin to mitigate risk has not been consistent; aspirin coadministered with nabumetone may increase the risk of serious GI adverse events.

NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Based on findings from 2 large studies evaluating a COX-2 selective NSAID, use in the first 10-14 days after CABG resulted in an increased incidence of MI and stroke.

Post-MI Patients

Among patients treated with NSAIDs in the post-MI period, there was an increase in the risk of reinfarction, cardiovascular-related death, and all-cause mortality beginning in the first week of treatment, according to observational studies.

  • Incidence of death in the first year in the NSAID cohort: 20 per 100 person years
  • Incidence of death in the first year in the non-NSAID cohort: 12 per 100 person years
  • The relative risk of death in NSAID users persisted over at least the next 4 years of follow up.

Avoid the use of nabumetone in patients with recent MI unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. Monitor for signs of cardiac ischemia if used in patients with recent MI.


  • NSAIDs can lead to new onset hypertension or worsening of pre-existing hypertension.
  • Impaired responses to thiazides and loop diuretics possible when taken with NSAIDs.
  • Use with caution in patients with hypertension; monitor BP.

Heart Failure and Edema

  • Meta-analysis of randomized controlled trials showed ~2-fold increase in hospitalizations for heart failure in patients treated with COX-2 selective and nonselective NSAIDs compared with placebo.
  • NSAID use was also associated with increased risk of MI, hospitalization for heart failure and death in a Danish National Registry study of patients with heart failure.
  • Fluid retention and edema have been observed in some patients treated with NSAIDs.
  • Nabumetone may blunt the cardiovascular effects of diuretics, ACE inhibitors, ARBs.
  • Avoid use in patients with severe heart failure unless benefits outweigh risk of worsening heart failure.
  • Monitor for signs of worsening heart failure if nabumetone is used in patients with severe heart failure.

Gastrointestinal (GI) Effects

  • NSAIDs can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine.
  • These can occur at any time, with or without warning symptoms (only 1 in 5 patients who develop a serious upper GI adverse event on NSAIDs is symptomatic),
  • Incidence of upper GI ulcers, gross bleeding, or perforation with NSAIDs: ~1% of patients treated for 3-6 months and 2-4% of patients treated for 1 year.
  • Prior history of ulcer disease or GI bleeding: prescribe with caution; these patients have a >10-fold increased risk for developing GI bleed vs those without these risk factors.
  • Other factors that increase risk of GI bleed in patients treated with NSAIDs: concomitant oral corticosteroids, anticoagulants; longer duration of NSAID use; smoking; alcohol; older age; and poor general health status.
  • Use the lowest effective dose for the shortest possible duration to minimize the potential for GI adverse events.
  • If a serious GI adverse event occurs, discontinue NSAID therapy.
  • Alternative therapies should be explored for patients considered at high risk for GI effects.

Hepatic Effects

  • Borderline elevations of 1 or more liver tests without any other signs and symptoms may occur in up to 15% of patients taking NSAIDs.
  • For patients with symptoms/signs suggesting liver dysfunction, or in whom abnormal liver test has occurred: evaluate for more severe hepatic reaction.
  • Discontinue nabumetone if abnormal liver tests persist or worsen, if clinical signs/symptoms of liver disease develop, or if systemic manifestations (eg, eosinophilia, rash) occur

Renal Effects

  • Long-term NSAID use has been associated with renal papillary necrosis and other renal injury.
  • Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in these patients administration of NSAIDs may cause a dose-dependent reduction in prostaglandin formation and, secondarily in renal blood flow, which may result in overt renal decompensation.
  • Patients with impaired renal function, heart failure, liver dysfunction, on diuretics or ACE inhibitors, those who are volume-depleted and the elderly are at greatest risk of this reaction.
  • Discontinuing NSAID therapy usually leads to recovery.

Anaphylactic/Anaphylactoid Reactions

  • Nabumetone should not be given to patients with the aspirin triad.
  • This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Skin Reactions

  • NSAIDs can cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
  • Discontinue treatment at the first appearance of skin rash or any other sign of hypersensitivity.

Hematological Effects

  • Anemia is sometimes seen in patients receiving NSAIDs.
    Check hemoglobin/hematocrit if patients exhibit signs/symptoms of anemia during long-term treatment.
  • Patients who may be adversely affected by alterations in platelet function (eg, those with coagulation disorders or receiving anticoagulants) should be carefully monitored.

Preexisting Asthma

  • Patients with asthma may have aspirin-sensitive asthma.
  • Use of aspirin in patients with aspirin-sensitive asthma has been associated with the severe bronchospasm.
  • Cross reactivity (including bronchospasm) between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients; nabumetone should not be administered to patients with this form of aspirin sensitivity.
  • Use with caution in patients with preexisting asthma.


  • Based on ultraviolet light photosensitivity testing, nabumetone may be associated with more reactions to sun exposure than might be expected based on skin tanning types.

Pregnancy Considerations

There are no adequate and well-controlled studies in pregnant women. Nabumetone should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.

The effects of nabumetone on labor and delivery in pregnant women are unknown.

Nursing Mother Considerations

It is not known whether this drug is excreted in human milk, however 6MNA is excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from nabumetone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Considerations

Safety and effectiveness in pediatric patients have not been established.

Geriatric Considerations

As with any NSAIDs, caution should be exercised in treating the elderly (65 years and older). Of the 1,677 patients in U.S. clinical studies who were treated with nabumetone, 411 patients (24%) were 65 years of age or older; 22 patients (1%) were 75 years of age or older. No overall differences in efficacy or safety were observed between these older patients and younger ones.

Renal Impairment Considerations

Monitor patients with impaired renal function closely.

Treatment with nabumetone is not recommended in patients with advanced renal disease; if needed, close monitoring of the patient’s renal function is advisable.

Hepatic Impairment Considerations

Data in patients with severe hepatic impairment are limited.

Biotransformation of nabumetone to 6MNA and the further metabolism of 6MNA to inactive metabolites is dependent on hepatic function and could be reduced in patients with severe hepatic impairment (history of or biopsy-proven cirrhosis).

Nabumetone Pharmacokinetics


After oral administration, approximately 80% of a radiolabeled dose of nabumetone is found in the urine, indicating that nabumetone is well absorbed from the gastrointestinal tract. Nabumetone itself is not detected in the plasma because, after absorption, it undergoes rapid biotransformation to the principal active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA).


6MNA is >99% bound to plasma proteins.


6MNA undergoes biotransformation in the liver, producing inactive metabolites that are eliminated as both free metabolites and conjugates.


Approximately 75% of a radiolabeled dose was recovered in urine in 48 hours. Approximately 80% was recovered in 168 hours. A further 9% appeared in the feces. 

Following oral administration of dosages of 1000 mg to 2000 mg to steady state, the mean plasma clearance of 6MNA is 20-30 mL/min and the elimination half-life is approximately 24 hours.

Nabumetone Interactions


Increased risk of GI toxicity with aspirin, other NSAIDs, alcohol, smoking.
Renal toxicity potentiated with diuretics. May potentiate lithium levels. May antagonize ACE inhibitors. Monitor oral anticoagulants (eg, warfarin). Caution with methotrexate.

Nabumetone Adverse Reactions

Adverse Reactions

GI bleeding, diarrhea, dyspepsia, abdominal pain, constipation, flatulence, nausea, positive stool guaiac, edema, photosensitivity, dizziness, headache, fatigue, sweating, insomnia, nervousness, somnolence, rash (discontinue if occurs), pruritus, tinnitus. Risk of cardiovascular events: see full labeling.

Nabumetone Clinical Trials

Clinical Trials


The use of nabumetone in relieving the signs and symptoms of osteoarthritis (OA) was assessed in double-blind, controlled trials in which 1,047 patients were treated for 6 weeks to 6 months. In these trials, nabumetone in a dose of 1000 mg/day administered at night was comparable to naproxen 500 mg/day and to aspirin 3600 mg/day.

Rheumatoid Arthritis

The use of nabumetone in relieving the signs and symptoms of rheumatoid arthritis (RA) was assessed in double-blind, randomized, controlled trials in which 770 patients were treated for 3 weeks to 6 months. Nabumetone, in a dose of 1000 mg/day administered at night was comparable to naproxen 500 mg/day and to aspirin 3600 mg/day.

In controlled clinical trials of rheumatoid arthritis patients, nabumetone has been used in combination with gold, d-penicillamine and corticosteroids.

Nabumetone Note


Formerly known under the brand name Relafen.

Nabumetone Patient Counseling

Patient Counseling

Be alert to the symptoms of cardiovascular thrombotic events, as the use of NSAIDs may increase the risk of these events. 

Be alert to the signs/symptoms of GI tract ulcerations and bleeding (eg, epigastric pain, dyspepsia, melena, and hematemesis); follow-up is important if GI effects occur. 

Be alert to the signs/symptoms of serious skin reactions (eg, SJS, TEN, exfoliative dermatitis); use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Be alert to the symptoms of CHF (eg, shortness of breath, unexplained weight gain, or edema).

Hepatotoxicity is possible; discontinue therapy if symptoms such as nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms occur.

Seek immediate emergency help if anaphylactic/anaphylactoid reaction (eg, difficulty breathing, swelling of the face or throat) occurs.

Pregnant patients: avoid nabumetone during late pregnancy due to possible premature closure of the ductus arteriosus.