Nabumetone is a nonsteroidal anti-inflammatory agent (NSAIA)1,2 It 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.3,4
Nabumetone is used for the symptomatic treatment of osteoarthritis and rheumatoid arthritis.1,2
The potential benefits and risks of nabumetone therapy as well as alternative therapies should be considered prior to initiating the drug.1,2 The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed.1,2
Nabumetone has been compared to naproxen and aspirin for the treatment of signs and symptoms of osteoarthritis in double-blind, controlled trials; in these trials, patients were treated for up to 6 months, and nabumetone 1000 mg/day was found to be comparable to naproxen 500 mg/day and aspirin 3600 mg/day in terms of efficacy.1,8,9,10,11,12,13 In a 4-week, double-blind study comparing nabumetone 1500 mg/day to controlled-release naproxen sodium 1000 mg/day and placebo in adults with osteoarthritis of the knee, controlled-release naproxen sodium was found to be at least as effective as nabumetone, with superior efficacy demonstrated in some measures.14 In randomized, double-blind, 6-week studies comparing nabumetone 1000 mg/day to indomethacin 75 mg/day and piroxicam 20 mg/day for the treatment of osteoarthritis, nabumetone demonstrated comparable efficacy and increased tolerability (i.e., fewer GI events) compared to indomethacin or piroxicam.15,16 A 4-week, randomized, double-blind trial comparing nabumetone 1500 mg/day to etodolac 800 mg/day and placebo for the treatment of osteoarthritis found that etodolac is at least as effective as nabumetone, and equally well-tolerated; etodolac resulted in earlier improvements in investigator assessment scores compared to nabumetone, as well as greater improvements in investigator and patient overall assessment scores at the final study visit.17 Two 6-week, double-blind trials compared different doses of nabumetone (1000 mg/day or 1500 mg/day) to oxaprozin 1200 mg/day and placebo in patients with moderate-to-severe osteoarthritis of the knee; the study comparing nabumetone 1000 mg/day to oxaprozin 1200 mg/day found that oxaprozin was more effective, but the study comparing nabumetone 1500 mg/day to oxaprozin 1200 mg/day did not find any substantial differences in efficacy between treatments.18,19
Nabumetone has been compared to naproxen and aspirin for the treatment of signs and symptoms of rheumatoid arthritis in randomized, double-blind, controlled trials; in these trials, patients were treated for up to 6 months, and nabumetone 1000 mg/day was found to be comparable to naproxen 500 mg/day and aspirin 3600 mg/day in terms of efficacy.1,13,20,21,22 Additional randomized, double-blind trials have compared higher doses of nabumetone (2000 mg/day) to higher doses of naproxen (1000 mg/day) for 3 months, and generally found these doses to result in comparable efficacy.23,24
A randomized, open label trial compared nabumetone to diclofenac, naproxen, ibuprofen, and piroxicam in 4411 adults with osteoarthritis or rheumatoid arthritis.7 Treatment was initiated at 1000 mg/day for nabumetone, 100 mg/day for diclofenac, 500 mg/day for naproxen, 1200 mg/day for ibuprofen, and 10 mg/day for piroxicam.7 Dosages could be increased after a minimum of 2 weeks at the investigator's discretion, and treatment was continued for 12 weeks.7 Concomitant use of disease-modifying antirheumatic drugs (DMARDs), stable doses of prednisone (up to 10 mg/day), intra-articular corticosteroid injections, and anti-ulcer agents was permitted.7 Efficacy was measured using physician and patient global assessments of disease activity (with ratings of “very good,” “good,” “fair,” “poor,” or “very poor”); improvement or worsening was defined by a change of at least one rating level from baseline.7 In patients with osteoarthritis, no differences in physician or patient global assessments were observed when nabumetone was compared to individual comparator nonsteroidal anti-inflammatory agents (NSAIAs) or a pooled comparator NSAIA group.7 The percentage of patients demonstrating improvement from baseline was similar with each NSAIA and ranged from 42-47% across groups.7 In patients with rheumatoid arthritis, more patients receiving nabumetone demonstrated improvement in physician global assessment (39%) and patient global assessment (37%) compared to those receiving ibuprofen (25 and 28%, respectively) and piroxicam (29 and 23%, respectively); the percentage of patients demonstrating improvement was similar for nabumetone (39 and 37%, respectively), diclofenac (33 and 34%, respectively), and naproxen (36 and 30%, respectively).7
Medical management of osteoarthritis of the hip, knee, and/or hand includes both pharmacologic therapy and nonpharmacologic (e.g., educational, behavioral, psychosocial, physical) interventions to reduce pain, maintain and/or improve joint mobility, limit functional impairment, and enhance overall well-being.2002 The ACR strongly recommends exercise, weight loss when necessary in patients with osteoarthritis of the knee and/or hip, self-efficacy and self-management programs, tai chi, cane use, hand orthoses, knee bracing, topical NSAIAs for osteoarthritis of the knee, oral NSAIAs, and intra-articular glucocorticoid injections for osteoarthritis of the knee or hip.2002 Other pharmacologic or nonpharmacologic interventions may be recommended conditionally.2002 Interventions and the order of their selection are patient specific.2002 Factors to consider when making decisions regarding therapy for osteoarthritis include patients' values and preferences, the presence of risk factors for serious adverse GI effects, existing comorbidities (e.g., hypertension, heart failure, other cardiovascular disease, chronic kidney disease), injuries, disease severity, surgical history, and access to and availability of the interventions.2002 Pharmacologic therapy should be initiated with treatments resulting in the least systemic exposure or toxicity.2002 For some patients with limited disease, topical NSAIAs may be an appropriate initial choice for pharmacologic therapy; for other patients, particularly those with osteoarthritis of the hip or with polyarticular involvement, oral NSAIAs may be more appropriate.2002
The American College of Rheumatology (ACR) guideline on the treatment of rheumatoid arthritis recommends initiation of a DMARD in DMARD-naïve patients; methotrexate is recommended over other DMARDs for the initial treatment of patients with moderate-to-high disease activity, while hydroxychloroquine is recommended initially for patients with low disease activity.2001 Addition of a biologic or target-specific DMARD is recommended for patients who do not attain treatment goals on methotrexate monotherapy (“treat-to-target” approach).2001 The role of NSAIAs is not discussed in the current ACR guideline on rheumatoid arthritis.2001
Nabumetone is administered orally.1,2 It is available as a tablet and may be administered without regard to meals.1,2
Store tablets at 20-25°C;1,2 excursions permitted between 15-30°C for the generic tablets.1
For the symptomatic treatment of osteoarthritis, the recommended initial dosage of nabumetone is 1 g daily given as a single dose.1,2 Some patients may obtain more symptomatic relief from 1.5 g to 2 g daily.1,2 Nabumetone may be given in either a single or twice daily dose.1,2
Patients weighing less than 50 kg may be less likely to require dosages greater than 1 g.1,2 Nabumetone dosages exceeding 2 g daily have not been studied.1,2
Adjust dose based on the response to initial therapy and to meet individual patients' requirements.1,2
For the symptomatic treatment of rheumatoid arthritis, the recommended initial dosage of nabumetone is 1 g daily given as a single dose.1,2 Some patients may obtain more symptomatic relief from 1.5 g to 2 g daily.1,2 Nabumetone may be given in either a single or twice daily dose.1,2
Patients weighing less than 50 kg may be less likely to require dosages greater than 1 g.1,2 Nabumetone dosages exceeding 2 g daily have not been studied.1,2
Adjust dose based on the response to initial therapy and to meet individual patients' requirements.1,2
The manufacturer makes no recommendations for dosage adjustment in patients with hepatic impairment.1,2 Nabumetone undergoes hepatic biotransformation to an active metabolite, which is dependent on hepatic function and could be reduced in patients with severe hepatic impairment.1,2 The impact of hepatic impairment on the efficacy of nabumetone is unknown.1,2
The manufacturer states that no dosage adjustment is required in patients with mild renal insufficiency (creatinine clearance ≥50 mL/minute).1,2 Dosage adjustment is warranted in patients with moderate renal impairment (creatinine clearance 30 to 49 mL/minute).1,2 Nabumetone has not been studied in patients with severe renal impairment (creatinine clearance <30 mL/minute) and is not recommended for use in such patients.1,2 If used in patients with moderate or severe renal insufficiency, do not exceed a starting dose of 750 mg or 500 mg, respectively, once daily.1,2 Increase to a higher daily dosage of 1.5 g in patients with moderate renal insufficiency or 1 g in patients with severe renal insufficiency only if close monitoring of renal function is possible.1,2
The manufacturer makes no recommendation for dosage adjustment in geriatric patients; however, increased monitoring for adverse effects is advised in this population.1,2
Cytochrome P-450 Isoenzyme 2C9 Variants
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines state that the pharmacokinetics of nabumetone are not significantly impacted by cytochrome P-450 (CYP) isoenzyme 2C9 genetic variants despite in vitro evidence indicating the role of CYP2C9 in metabolism of nabumetone's active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA).5,520 The guideline does not make a recommendation to guide clinical practice on modifying the use of nabumetone in patients with CYP2C9 genetic variants.520
A boxed warning regarding the increased risk of serious cardiovascular (CV) thrombotic events is included in the prescribing information for nabumetone.1,2 Findings from clinical trials of several cyclooxygenase (COX)-2 selective and nonselective NSAIAs of up to 3 years' duration have shown an increased risk of serious CV thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal.1,2 It is unclear based on available evidence if the thrombotic risk is similar for all NSAIAs.1,2 Although the relative increase in cardiovascular risk appears to be similar in patients with or without known underlying cardiovascular disease (CVD) or risk factors for CVD, the absolute incidence of serious NSAIA-associated CV thrombotic events was higher in those with CVD or risk factors for CVD because of their elevated baseline risk.1,2 This increased risk may occur as early as the first weeks of treatment.1,2 The increase in CV thrombotic risk has been observed most consistently at higher doses.1,2 To minimize the potential risk of adverse CV events in patients receiving NSAIAs, use the lowest effective dosage for the shortest possible duration.1,2 Monitor all patients for the possible development of CV events throughout therapy.1,2 Inform patients about the signs and symptoms of serious CV events and instruct them to seek immediate medical attention if such symptoms occur.1,2 There is no consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious CV events associated with NSAIAs.1,2 Concomitant use of aspirin and an NSAIA, such as nabumetone, increases the risk for serious GI events.1,2 In 2 large controlled clinical trials of a COX-2 selective NSAIA for the management of pain in the first 10-14 days following CABG surgery, the incidence of MI and stroke was increased.1,2 Do not use NSAIAs in the setting of CABG.1,2
A boxed warning regarding the increased risk of serious GI events is included in the prescribing information for nabumetone.1,2 Serious, sometimes fatal, adverse GI effects, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, can occur at any time in patients receiving NSAIAs, and such effects may not be preceded by warning signs or symptoms.1,2 Only 1 in 5 patients who develop a serious upper GI adverse event while receiving NSAIA therapy is symptomatic.1,2 Longer duration of therapy with an NSAIA increases the likelihood of a serious adverse GI event.1,2 However, short-term therapy is not without risk.1,2 The frequency of NSAIA-associated upper GI ulcers, gross bleeding, or perforation is approximately 1% in patients receiving NSAIA therapy for 3-6 months and approximately 2-4% in those receiving therapy for one year.1,2 In studies involving 1677 patients treated with nabumetone (1140 followed for 1 year and 927 followed for 2 years), the cumulative incidence of peptic ulcers was 0.3% at 3 to 6 months, 0.5% at 1 year and 0.8% at 2 years.1,2 In patients with an active peptic ulcer, weigh the benefits of nabumetone against possible hazards, institute an appropriate ulcer treatment regimen, and monitor the patients' progress carefully.1,2 Use extreme caution when using NSAIAs in patients with a prior history of ulcer disease or GI bleeding.1,2 Studies have shown that patients with a history of peptic ulcer disease and/or GI bleeding who are receiving NSAIAs have a greater than 10-fold increased risk of developing GI bleeding than patients without these risk factors.1,2 Other risk factors for GI bleeding in patients treated with NSAIAs include the concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAIA therapy, smoking, alcohol use, older age, and poor general health status.1,2 Most spontaneous reports of fatal GI effects have been in geriatric or debilitated patients.1,2 To minimize the potential risk of adverse GI effects, use the lowest effective dosage for the shortest possible duration.1,2 Closely monitor for signs and symptoms of GI ulceration and bleeding during NSAIA therapy.1,2 Promptly initiate additional evaluation and treatment if a serious adverse GI event is suspected and hold NSAIA therapy until a serious adverse GI event is ruled out.1,2 For high-risk patients, consider non-NSAIA therapy.1,2
Observational studies conducted in the Danish National Registry have demonstrated that patients who received NSAIAs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment.1,2 Patients who received NSAIAs had a higher mortality rate in the first year post-MI compared with those who did not receive NSAIAs (20 versus 12 deaths per 100 person-years).1,2 Although the absolute mortality rate declined somewhat after the first year following the MI, the increased relative risk of death in patients who received NSAIAs persisted over at least the next 4 years of follow-up.1,2
Avoid use of nabumetone in patients with recent MI unless the benefits of therapy are expected to outweigh the risk of recurrent CV thrombotic events; if nabumetone is used in such patients, monitor for signs of cardiac ischemia.1,2
Use of NSAIAs, including nabumetone, can result in the onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events.1,2 Patients receiving NSAIAs may have an impaired response to thiazide or loop diuretics. 1,2
Use NSAIAs, including nabumetone, with caution in patients with hypertension.1,2 Monitor blood pressure closely during initiation of an NSAIA and throughout therapy.1,2
The Coxib and traditional NSAIA Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately twofold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAIA-treated patients compared to placebo-treated patients.1,2 In a Danish National Registry study of patients with heart failure, NSAIA use increased the risk of MI, hospitalization for heart failure, and death.1,2
Fluid retention and edema have been observed in some patients treated with NSAIAs.1,2 Use of nabumetone may blunt the CV effects of several therapeutic agents used to treat these medical conditions, such as diuretics, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor antagonists.1,2
Avoid use of nabumetone in patients with severe heart failure unless the benefits of therapy are expected to outweigh the risk of worsening heart failure.1,2 If nabumetone is used in patients with severe heart failure, monitor for signs of worsening heart failure.1,2
Long-term administration of NSAIAs has resulted in renal papillary necrosis and other renal injury.1,2
Renal toxicity has been observed in patients in whom renal prostaglandins have a compensatory role in maintaining renal perfusion.1,2 Administration of an NSAIA to such patients results in a dose-dependent reduction in prostaglandin formation and, secondarily, in a reduction of renal blood flow, which may precipitate overt renal decompensation.1,2 Patients at greatest risk of this reaction are those with impaired renal function, heart failure, hepatic dysfunction, those taking diuretics, and the elderly.1,2 Recovery of renal function to pretreatment levels usually occurs following discontinuance of NSAIA therapy.1,2
Since no information from clinical trials is available on use of nabumetone in patients with advanced renal disease, use of nabumetone is not recommended in these patients.1,2 If nabumetone is initiated, monitor renal function closely.1,2
As with other NSAIAs, anaphylactoid reactions may occur in patients without known prior exposure to nabumetone.1,2 Do not give nabumetone to patients with the aspirin triad.1,2 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 NSAIAs.1,2 Seek emergency help if an anaphylactoid reaction occurs.1,2
NSAIAs, including nabumetone can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which can be fatal.1,2 NSAIAs can also cause fixed drug eruption (FDE), which can present as a more severe, potentially life-threatening, variant known as generalized bullous fixed drug eruption.1,2 These events can occur without warning.1,2
Inform patients about the signs and symptoms of serious skin manifestations; use of nabumetone should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.1,2 Nabumetone is contraindicated in patients with previous serious skin reactions to NSAIAs.1,2
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Drug reaction with eosinophilia and systemic symptoms (DRESS), a potentially fatal or life-threatening syndrome, has been reported in patients receiving NSAIAs, such as nabumetone.1,2 The typical, though not exclusive, clinical presentation of DRESS is fever, rash, lymphadenopathy, and/or facial swelling.1,2 Eosinophilia is often present.1,2 Other clinical manifestations may include hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis.1,2 Symptoms can sometimes resemble an acute viral infection.1,2 Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) can present without an evident rash.1,2 If DRESS is suspected, discontinue nabumetone and evaluate the patient immediately.1,2
Fetal/Neonatal Morbidity and Mortality
Use of NSAIAs, including nabumetone, during pregnancy at about 30 weeks' gestation or later can cause premature closure of the fetal ductus arteriosus; use at about 20 weeks' gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.1,2 Fetal renal dysfunction has been observed, on average, after days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy.1,2 Oligohydramnios is often, but not always, reversible following discontinuance of NSAIA therapy.1,2 Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.1,2 Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis.1,2
Avoid use of NSAIAs, including nabumetone, in pregnant women at about 30 weeks' gestation or later.1,2 If NSAIA therapy is necessary between about 20 and 30 weeks' gestation, use the lowest effective dosage for the shortest possible duration.1,2 Consider ultrasound monitoring of amniotic fluid if nabumetone treatment extends beyond 48 hours.1,2 Discontinue nabumetone if oligohydramnios occurs and follow up according to clinical practice.1,2
Borderline elevations (less than 3 times the upper limit of normal) in one or more liver function test results may occur in up to 15% of patients treated with NSAIAs, including nabumetone.1,2 Meaningful (3 or more times the upper limit of normal) elevations in serum ALT or AST were reported in approximately 1% of patients receiving NSAIAs in controlled clinical studies.1,2
Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure, have been reported.1,2 Evaluate patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, for evidence of the development of a more severe hepatic reaction while taking nabumetone.1,2 Discontinue nabumetone if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations, such as eosinophilia or rash, occur.1,2
Anemia, due to fluid retention, occult or gross GI blood loss, or an effect on erythropoiesis, may occur in patients receiving NSAIAs, including nabumetone.1,2 If patients on long-term treatment with NSAIAs exhibit any signs or symptoms of anemia, check hemoglobin or hematocrit levels.1,2
NSAIAs inhibit platelet aggregation and can prolong bleeding time in some patients.1,2 The effect of NSAIAs on platelets is qualitatively less, of shorter duration, and reversible compared to aspirin.1,2 Monitor patients with coagulation disorders or receiving anticoagulants more closely while taking nabumetone.1,2
Some patients with asthma may have aspirin-sensitive asthma and can experience severe, potentially fatal, bronchospasm if they receive aspirin.1,2 Since cross-reactivity, including bronchospasm, between aspirin and other NSAIAs has been reported in such aspirin-sensitive patients, do not administer nabumetone to patients with this form of aspirin sensitivity.1,2 Use caution in all patients with preexisting asthma.1,2
Nabumetone may be associated with more reactions to sun exposure than might be expected based on skin tanning types.1,2
Masking of Inflammation and Fever
The pharmacologic activity of nabumetone in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of noninfectious, painful conditions.1,2
Nabumetone is not a substitute for corticosteroids, nor can it treat corticosteroid insufficiency.1,2 Avoid abrupt discontinuation of corticosteroids and manage corticosteroid use according to standard of care guidelines.1,2
The manufacturer and the Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for cytochrome P-450 (CYP) isoenzyme 2C9 and NSAIAs do not provide information on modification of nabumetone use based on pharmacogenetic testing. 1,2,520 CPIC guidelines state that the pharmacokinetics of nabumetone are not significantly impacted by CYP2C9 genetic variants despite in vitro evidence indicating the role of CYP2C9 in metabolism of nabumetone's active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA).520
Use of NSAIAs, including nabumetone, during pregnancy at about 30 weeks' gestation or later increases the risk of premature closure of the fetal ductus arteriosus.1,2 NSAIA use at about 20 weeks' gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.1,2
Oligohydramnios or neonatal renal impairment has occurred, on average, after days to weeks of treatment.1,2 Infrequently, oligohydramnios has been reported as soon as 48 hours after initiation.1,2 The decrease in amniotic fluid is generally transient in most, but not all, cases, and is reversible upon cessation of the drug.1,2 A limited number of case reports describe maternal NSAIA use and irreversible neonatal dysfunction without oligohydramnios.1,2 Some cases required invasive procedures, such as exchange transfusion or dialysis.1,2 A reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use is unknown due to the inherent limitations of postmarketing studies and reports.1,2 Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIAs through maternal use is uncertain.1,2
Observational data regarding other embryofetal risks with NSAIAs during the first or second trimester of pregnancy are inconclusive.1,2 Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization.1,2 In animal studies, inhibitors of prostaglandin synthesis, such as nabumetone, resulted in increased pre- and post-implantation loss.1,2 Prostaglandins also have an important role in fetal kidney development.1,2 In animal studies, inhibitors of prostaglandin synthesis have been reported to impair kidney development at clinically relevant doses.1,2
Nabumetone should be used in pregnancy only if the potential benefit justifies the potential fetal risk.1,2 If used, limit the dose and duration of nabumetone use between 20 and 30 weeks' gestation.1,2 Avoid nabumetone use at about 30 weeks' gestation and later in pregnancy.1,2
The effects of nabumetone on labor and delivery are unknown.1,2 In animal studies with NSAIAs, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred.1,2
The distribution of nabumetone in human milk is unknown.1,2 The presence of 6-methoxy-2- naphthylacetic acid (6-MNA) has been detected in the milk of lactating rats.1,2 Due to the potential for serious adverse reactions in nursing infants from nabumetone, discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.1,2
Safety and effectiveness in pediatric patients have not been established.1,2
Of the 1677 patients treated with nabumetone in clinical studies, 411 patients (24%) were 65 years or older; 22 patients (1%) were 75 years or older.1,2 No overall differences in efficacy or safety were observed between older and younger patients.1,2 Similar results were observed in a 1-year, non-US postmarketing surveillance study of 10,800 patients treated with nabumetone, of whom 4577 (42%) were 65 years or older.1,2 As with any NSAIAs, exercise caution in treating patients 65 years and older.1,2
There is limited data on the use of nabumetone in patients with severe hepatic impairment.1,2 Formation of the active metabolite, 6-MNA, and its metabolism to inactive metabolites may be reduced in patients with severe hepatic impairment.1,2
No information is available on use of nabumetone in patients with advanced renal disease, and its use is not recommended in such patients.1,2 In patients with moderate renal impairment (creatinine clearance, 30 to 49 mL/minute), a 50% increase in unbound plasma 6-MNA (the active metabolite) occurs.1,2 The oxidized and conjugated metabolites of 6-MNA are renally eliminated.1,2
If nabumetone is initiated in patients with moderate or advanced renal impairment, adjust the dose and monitor renal function closely.1,2
Adverse effects reported in >3% of patients receiving nabumetone in clinical trials include diarrhea, dyspepsia, abdominal pain, constipation, flatulence, nausea, positive stool guaiac, dizziness, headache, pruritus, rash, tinnitus, and edema.1,2
Nabumetone and its active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), undergo hepatic biotransformation via conjugation and O-demethylation.6 In vitro studies suggest that the cytochrome P-450 (CYP) isoenzyme 2C9 is involved in the metabolism of 6-MNA.5 In vitro studies have shown that 6-MNA may displace other protein-bound drugs from their binding site.1,2
No information is available indicating nabumetone or its metabolites inhibit microsomal enzymes or transporter proteins.1,2
In vitro studies have shown that 6-MNA may displace other protein-bound drugs from their binding site, and some drugs (e.g., aspirin) may displace 6-MNA.1,2
The bioavailability of the active metabolite, 6-MNA, was not shown to be significantly affected by concomitant administration of an aluminum-containing antacid.1,2
Angiotensin-Converting Enzyme Inhibitors
Concomitant use of nonsteroidal anti-inflammatory agents (NSAIAs) with angiotensin-converting enzyme (ACE) inhibitors may reduce the blood pressure response to the antihypertensive agent.1,2 Consider this interaction in patients taking NSAIAs concomitantly with ACE inhibitors.1,2
Use of nabumetone may blunt the cardiovascular (CV) effects of several therapeutic agents used to treat heart failure, such as ACE inhibitors.1,2 Monitor for signs of worsening heart failure.1,2
Angiotensin II Receptor Antagonists
Use of nabumetone may blunt the CV effects of several therapeutic agents used to treat heart failure, such as angiotensin II receptor antagonists.1,2 Monitor for signs of worsening heart failure.1,2
Concomitant use of nabumetone is not recommended due to the potential for increased adverse effects.1,2 When nabumetone tablets are administered with aspirin, its protein binding is reduced, although the clearance of free nabumetone is not altered; the clinical importance of this interaction is not known.1,2
Due to inhibition of renal prostaglandin synthesis, nabumetone can reduce the natriuretic response to furosemide and thiazides in some patients.1,2 When used concomitantly, monitor for diuretic efficacy and signs of renal failure.1,2
Use of nabumetone may blunt the CV effects of several therapeutic agents used to treat heart failure such as diuretics.1,2 Monitor for signs of worsening heart failure.1,2
Due to inhibition of renal prostaglandin synthesis, NSAIAs can decrease renal clearance of lithium by approximately 20%, which can increase mean minimum serum or plasma lithium concentrations by 15%.1,2 When used concomitantly, monitor patients for signs of lithium toxicity.1,2
NSAIAs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices, indicating possible enhanced methotrexate toxicity.1,2 Use caution with concomitant use.1,2
The risk of serious GI bleeding is increased with concomitant use of warfarin and NSAIAs.1,2 The active metabolite of nabumetone, 6-MNA, may displace other protein-bound drugs (e.g., warfarin) from their binding site.1,2 Use caution with concomitant use.1,2
Nabumetone, a naphthylalkanone derivative, is a prototypical nonsteroidal anti-inflammatory agent (NSAIA).1,2 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).1,2 This active metabolite is structurally similar to naproxen and exhibits analgesic, antipyretic, and anti-inflammatory activity partially attributed to inhibition of prostaglandin synthesis.1,4,5
After oral administration, about 80% of a radiolabeled dose of nabumetone is found in the urine, suggesting significant oral absorption.1,2 Approximately 35% of a 1000 mg oral dose of nabumetone is converted to 6-MNA and 50% is converted into other metabolites.1,2 The 6-MNA metabolite is over 99% bound to plasma proteins.1,2 The mean time to maximum plasma concentration of 6-MNA ranges from 2.5 to 4 hours, with the shorter time observed in young adults and the longer time in geriatric patients.1,2 Steady-state plasma concentrations were generally higher in geriatric patients than in young healthy subjects. 1,2 Conjugation and O-demethylation are the primary mechanisms of 6-MNA metabolism.6 An in vitro study evaluating the cytochrome P-450 (CYP) isoform that catalyzes 6-MNA oxidation found CYP2C9 to have the highest catalytic activity in human liver microsomes.5 In vitro and in vivo studies suggest that there is no evidence of enterohepatic recirculation of 6-MNA.1,2 Approximately 75% of a radiolabeled dose is recovered in urine at 48 hours and 80% in 168 hours.1,2 About 9% is recovered in feces.1,2 The elimination half-life of 6-MNA is approximately 24 hours.1,2
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.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 500 mg* | Nabumetone Tablets | |
750 mg* | Nabumetone Tablets | |||
1 g* | Nabumetone Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions March 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Westminster Pharmaceuticals. Nabumetone tablets prescribing information. Nashville, TN: 2024 Aug.
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