Version May 2024
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
Nabumetone is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
NSAIDs cause an increased risk of serious GI adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious GI events.
Note: Safety: Use the lowest effective dose for the shortest duration of time. Avoid or use with caution in patients at risk for or with existing cardiovascular disease, GI disease, kidney impairment, chronic liver disease, or a bleeding diathesis due to greater risk for adverse events. Consider administering in combination with a proton pump inhibitor in patients at risk for GI bleeding (eg, taking dual antiplatelet therapy or an anticoagulant, ≥60 years of age, high doses) (Ref).
Note: Patients <50 kg are less likely to require doses >1 g/day.
Osteoarthritis: Oral: Initial: 1 g as a single dose; adjust dose based on patient response up to 2 g/day in 1 to 2 divided doses; doses >2 g/day have not been studied.
Rheumatoid arthritis: Oral: Initial: 1 g as a single dose; adjust dose based on patient response up to 2 g/day in 1 to 2 divided doses; doses >2 g/day have not been studied.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
In general, nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for use in patients with advanced renal disease, but the manufacturer of nabumetone does provide some guidelines for adjustment in renal impairment:
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 49 mL/minute: Initial maximum dose: 750 mg once daily; maximum 1.5 g/day.
CrCl <30 mL/minute: Initial maximum dose: 500 mg once daily; maximum 1 g/day.
Hemodialysis: Nondialyzable.
KDIGO 2012 guidelines provide the following recommendations for NSAIDs:
eGFR 30 to <60 mL/minute/1.73 m2: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.
eGFR <30 mL/minute/1.73 m2: Avoid use.
Hepatic impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling (data limited in severe impairment); use with caution. Prodrug activation and metabolism are hepatic function dependent and may be reduced in severe hepatic impairment.
Hepatotoxicity during treatment: Discontinue treatment if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur.
Note: Unless alternative agents are ineffective and a gastroprotective agent can be administered, avoid short-term scheduled use in combination with corticosteroids, anticoagulants, or antiplatelet agents or chronic use with or without medications that increase risk for bleeding (Ref).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Abdominal pain (12%), diarrhea (14%), dyspepsia (13%)
Hepatic: Increased liver enzymes (≤15%)
1% to 10%:
Cardiovascular: Edema (3% to 9%)
Dermatologic: Diaphoresis (1% to 3%), pruritus (3% to 9%), skin rash (3% to 9%)
Gastrointestinal: Constipation (3% to 9%), flatulence (3% to 9%), gastritis (1% to 3%), nausea (3% to 9%), occult blood in stools (3% to 9%), stomatitis (1% to 3%), vomiting (1% to 3%), xerostomia (1% to 3%)
Nervous system: Dizziness (3% to 9%), drowsiness (1% to 3%), fatigue (1% to 3%), headache (3% to 9%), insomnia (1% to 3%), nervousness (1% to 3%)
Otic: Tinnitus (3% to 9%)
<1%:
Cardiovascular: Acute myocardial infarction, angina pectoris, cardiac arrhythmia, hypertension, palpitations, syncope, thrombophlebitis, vasculitis
Dermatologic: Acne vulgaris, alopecia, bullous rash, erythema multiforme, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine: Albuminuria, hyperglycemia, hyperuricemia, hypokalemia, pseudoporphyria (cutanea tarda), weight gain, weight loss
Gastrointestinal: Anorexia, cholelithiasis, duodenal ulcer, duodenitis, dysphagia, eructation, gastric ulcer, gastroenteritis, gastrointestinal hemorrhage, gingivitis, glossitis, increased appetite, melena, pancreatitis
Genitourinary: Azotemia, dysuria, hematuria, impotence, nephrotic syndrome, vaginal hemorrhage
Hematologic & oncologic: Anemia, granulocytopenia, leukopenia, rectal hemorrhage
Hepatic: Hepatic failure, hyperbilirubinemia, jaundice
Hypersensitivity: Anaphylaxis, angioedema, nonimmune anaphylaxis
Nervous system: Agitation, anxiety, chills, confusion, depression, malaise, nightmares, paresthesia, taste disorder, vertigo
Neuromuscular & skeletal: Asthenia, tremor
Ophthalmic: Visual disturbance
Renal: Interstitial nephritis, nephrolithiasis, renal failure syndrome
Respiratory: Asthma, cough, dyspnea, eosinophilic pneumonitis, hypersensitivity pneumonitis, interstitial pneumonitis
Miscellaneous: Fever
Frequency not defined:
Cardiovascular: Cerebrovascular accident, coronary thrombosis
Gastrointestinal: Gastrointestinal inflammation, gastrointestinal perforation, gastrointestinal ulcer
Postmarketing:
Hematologic & oncologic: Thrombocytopenia
Hepatic: Hepatotoxicity (idiosyncratic) (Chalasani 2014)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Schlienger 2003)
Hypersensitivity to nabumetone or any component of the formulation; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs); use in the setting of coronary artery bypass graft surgery.
Canadian labeling: Additional contraindications (not in US labeling): Active duodenal, gastric, or peptic ulcer; active GI bleeding; cerebrovascular bleeding or other bleeding disorders; inflammatory bowel disease; severe renal impairment (CrCl <30 mL/minute) or deteriorating renal function; known hyperkalemia; severe uncontrolled heart failure; complete or partial syndrome of nasal polyps; significant hepatic impairment or active liver disease; concurrent use with other NSAIDs; pregnancy (third trimester); breastfeeding; pediatric patients <18 years of age.
Concerns related to adverse effects:
• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.
• Cardiovascular events: Relative risk of serious adverse cardiovascular thrombotic events appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure (FDA 2015). Avoid use in patients with a recent myocardial infarction (MI) unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.
• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.
• GI events: Avoid use in patients with active GI bleeding due to increased risk of serious GI events. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis (Strate 2016). Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (ACCF/ACG/AHA [Bhatt 2008]).
• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, liver necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.
• Photosensitivity reactions: May cause photosensitivity reactions.
• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, heart failure, hypovolemia, hepatic impairment, those taking diuretics and ACE inhibitors, and elderly patients are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.
• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning, discontinue use at first sign of skin rash (or any other hypersensitivity).
Disease-related concerns:
• Asthma: Contraindicated in patients with aspirin-sensitive asthma; severe and potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.
• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur (Bhangu 2014; Mechanick 2020). Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain (Chou 2016; Horsley 2019; Thorell 2016).
• Coronary artery bypass graft surgery: Risk of MI and stroke may be increased with use following coronary artery bypass graft surgery.
• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs. Closely monitor patients with any abnormal LFT.
• Renal impairment: Use with caution in patients with moderate impairment (CrCl 30 to 49 mL/minute); dosage adjustment may be needed. Avoid use in patients with advanced renal disease; monitor closely if therapy must be initiated.
Special populations:
• Older adult: Older adult patients are at greater risk for serious GI, cardiovascular, and/or renal adverse events; use with caution.
Other warnings/precautions:
• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Relafen: 500 mg [DSC], 750 mg [DSC]
Relafen DS: 1000 mg [scored]
Generic: 500 mg, 750 mg
Yes
Tablets (Nabumetone Oral)
500 mg (per each): $0.78 - $1.38
750 mg (per each): $0.82 - $1.62
Tablets (Relafen DS Oral)
1000 mg (per each): $61.36
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 500 mg
Oral: Administer with or without food
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM387559.pdf, must be dispensed with this medication.
Osteoarthritis: Relief of signs and symptoms of osteoarthritis.
Rheumatoid arthritis: Relief of signs and symptoms of rheumatoid arthritis.
Beers Criteria: Nabumetone is identified in the Beers Criteria as a potentially inappropriate medication to be avoided for chronic use in patients 65 years and older (unless alternative agents ineffective and patient can receive concomitant gastroprotective agent) due to increased risk of GI bleeding and peptic ulcer disease in older adults in high-risk category (eg, older than 75 years or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents). In addition, avoid for short-term scheduled use in combination with oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents unless alternatives are ineffective and patient can receive concomitant gastroprotective agent (Beers Criteria [AGS 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy
Abrocitinib: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor therapy
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Risk C: Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Bemiparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy
CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider therapy modification
Dabigatran Etexilate: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Edoxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Enoxaparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Heparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Risk D: Consider therapy modification
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Ketorolac (Systemic). Risk X: Avoid combination
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider therapy modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider therapy modification
Macimorelin: Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Avoid coadministration of higher dose methotrexate (such as that used for the treatment of oncologic conditions) and NSAIDs. Use caution if coadministering lower dose methotrexate and NSAIDs. Risk D: Consider therapy modification
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider therapy modification
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor therapy
Quinolones: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy
Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification
Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Tolperisone: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Tricyclic Antidepressants may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider therapy modification
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Nabumetone peak serum concentrations may be increased if taken with food or dairy products. Management: Administer without regard to food.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may delay or prevent rupture of ovarian follicles. This may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in patients having difficulty conceiving or those undergoing investigation of fertility (Matyas 2015; Micu 2011).
Based on available information, NSAIDs can be continued in males with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) close to conception may be associated with an increased risk of miscarriage due to cyclooxygenase-2 inhibition interfering with implantation (Bermas 2014; Bloor 2013).
Birth defects have been observed following in utero NSAID exposure in some studies; however, data are conflicting (Bloor 2013). Nonteratogenic effects, including prenatal constriction of the ductus arteriosus, persistent pulmonary hypertension of the newborn, oligohydramnios, necrotizing enterocolitis, renal dysfunction or failure, and intracranial hemorrhage have been observed in the fetus/neonate following in utero NSAID exposure (Bermas 2014; Bloor 2013). Maternal NSAID use may cause fetal renal dysfunction leading to oligohydramnios. Although rare, this may occur as early as 20 weeks' gestation and is more likely to occur with prolonged maternal use. Oligohydramnios may be reversible following discontinuation of the NSAID (Dathe 2019; FDA 2020). In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013).
Use of NSAIDs should be avoided beginning at 20 weeks' gestation. If NSAID use is necessary between 20 and 30 weeks' gestation, limit use to the lowest effective dose and shortest duration possible; consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found (FDA 2020). Because NSAIDs may cause premature closure of the ductus arteriosus, prescribing information for nabumetone specifically states use should be avoided late in pregnancy.
Based on available information, NSAIDs can be continued during the first 2 trimesters of pregnancy in patients with rheumatic and musculoskeletal diseases; use in the third trimester is not recommended (ACR [Sammaritano 2020]).
It is not known if nabumetone or 6MNA is present in breast milk.
Nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), are preferred for breastfeeding patients who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). NSAIDs are considered compatible for the treatment of rheumatic and musculoskeletal diseases in lactating patients; agents with a short half-life and established safety data in infants may be preferred (ACR [Sammaritano 2020]).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Maternal use of NSAIDs should be avoided if the breastfeeding infant has platelet dysfunction, thrombocytopenia, or a ductal-dependent cardiac lesion (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Bloor 2013).
CBC, chemistry profile, occult blood loss, and periodic liver function test renal function (urine output, serum BUN and creatinine); signs or symptoms of GI bleeding and/or hepatic impairment; blood pressure; periodic ophthalmic exam with long-term therapy.
Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties
Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.
Absorption: Well absorbed from GI tract
Onset of action: Several days
Distribution: Diffusion occurs readily into synovial fluid; Vdss: 6MNA: 29 to 82 L
Protein binding: 6MNA: >99%
Metabolism: Prodrug, rapidly metabolized in the liver to an active metabolite [6-methoxy-2-naphthylacetic acid (6MNA)] and inactive metabolites; extensive first-pass effect; ~35% converted to 6MNA and 50% converted to unidentified metabolites
Half-life elimination: 6MNA: ~24 hours; terminal half-life was increased ~50% in patients with CrCl 30 to 49 mL/minute
Time to peak, serum: 6MNA: Oral: Adults: 2.5 to 3 hours; Elderly: 4 hours
Excretion: 6MNA: Urine (~80%) and feces (9%)
Altered kidney function: Plasma levels and half-life of unbound 6MNA were increased ~50% in patients with CrCl 30 to 49 mL/minute.
Hepatic function impairment: Biotransformation of nabumetone to 6MNA and the further metabolism of 6MNA to inactive metabolites may be decreased in severe hepatic impairment.
Older adult: Steady-state concentrations are generally higher.
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