Introduction
Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. It belongs to the class of non-acidic NSAIDs and is a prodrug that undergoes hepatic metabolism to its active form. Nabumetone was first approved by the FDA in 1991 and is commonly prescribed for the management of osteoarthritis and rheumatoid arthritis symptoms.
Mechanism of Action
Nabumetone is a prodrug that is metabolized in the liver to its active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA). This active metabolite functions as a nonselective cyclooxygenase (COX) inhibitor, blocking both COX-1 and COX-2 enzymes. By inhibiting cyclooxygenase, nabumetone decreases the formation of prostaglandin precursors, resulting in reduced inflammation, pain, and fever. Unlike many other NSAIDs, nabumetone demonstrates relative COX-2 selectivity, which may contribute to its favorable gastrointestinal tolerability profile.
Indications
- Osteoarthritis: Management of signs and symptoms
- Rheumatoid arthritis: Management of signs and symptoms
- Off-label uses may include other inflammatory conditions, though evidence is limited
Dosage and Administration
Standard adult dosing:- Initial dose: 1000 mg once daily
- May be increased to 1500-2000 mg daily in divided doses
- Maximum recommended dose: 2000 mg daily
- Renal impairment: Use with caution; dose reduction recommended for moderate to severe impairment (CrCl <30 mL/min)
- Hepatic impairment: Use with caution; consider dose reduction
- Elderly: Start at lower end of dosing range
- Pediatric: Safety and efficacy not established
- Administer with food or milk to minimize gastrointestinal upset
- Tablets should be swallowed whole with water
Pharmacokinetics
Absorption: Well absorbed from the GI tract; bioavailability approximately 80% Distribution: Extensive protein binding (>99%); volume of distribution approximately 0.68 L/kg Metabolism: Hepatic metabolism via cytochrome P450 enzymes (primarily CYP1A2) to active metabolite 6-MNA and inactive metabolites Elimination: Renal excretion (approximately 80% as metabolites); elimination half-life of active metabolite is 22-30 hours Onset of action: Therapeutic effects typically observed within 1-2 weeks of continuous therapyContraindications
- Hypersensitivity to nabumetone, its components, or other NSAIDs
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
- Perioperative pain in coronary artery bypass graft (CABG) surgery
- Third trimester of pregnancy
Warnings and Precautions
Cardiovascular risk: Increased risk of serious cardiovascular thrombotic events, including MI and stroke GI risk: Risk of GI bleeding, ulceration, and perforation Hepatotoxicity: Severe hepatic reactions, including liver failure, have been reported Renal effects: May cause renal papillary necrosis and other renal injury Hypertension: May worsen existing hypertension or contribute to new-onset hypertension Heart failure: May cause fluid retention and exacerbate heart failure Anemia: May cause occult gastrointestinal blood loss Skin reactions: Serious skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysisDrug Interactions
Anticoagulants: Increased risk of bleeding with warfarin ACE inhibitors/ARBs: Reduced antihypertensive effect; increased risk of renal impairment Diuretics: Reduced diuretic and antihypertensive effects Lithium: Increased lithium levels and toxicity Methotrexate: Increased methotrexate toxicity Other NSAIDs: Avoid concomitant use due to additive toxicity SSRIs/SNRIs: Increased risk of gastrointestinal bleeding Cyclosporine: Increased risk of nephrotoxicity CYP1A2 inhibitors: May increase nabumetone exposureAdverse Effects
Common (≥1%):- Diarrhea (14%)
- Dyspepsia (13%)
- Abdominal pain (12%)
- Nausea (9%)
- Flatulence (9%)
- Headache (9%)
- Dizziness (7%)
- Constipation (6%)
- Rash (5%)
- Tinnitus (5%)
- Gastrointestinal bleeding and perforation
- Myocardial infarction and stroke
- Hepatotoxicity
- Renal impairment and failure
- Severe skin reactions
- Anaphylactic reactions
- Hematologic abnormalities (anemia, neutropenia)
Monitoring Parameters
- Baseline and periodic renal function (BUN, creatinine)
- Liver function tests (baseline and periodically)
- Complete blood count (for anemia)
- Blood pressure monitoring
- Signs/symptoms of GI bleeding
- Therapeutic response and pain control
- Signs of fluid retention
- Ophthalmologic exams with long-term use
Patient Education
- Take with food or milk to reduce stomach upset
- Report any signs of GI bleeding (black stools, abdominal pain, vomiting blood)
- Monitor for signs of cardiovascular events (chest pain, shortness of breath, weakness)
- Watch for skin reactions or allergic symptoms
- Avoid alcohol during treatment
- Do not take other NSAIDs or aspirin concurrently
- Inform all healthcare providers about nabumetone use before any procedures
- Report any unusual bruising or bleeding
- Notify provider if pregnancy is planned or suspected
- Be aware of potential dizziness or drowsiness
References
1. FDA Prescribing Information: Nabumetone Tablets (2022) 2. Drug Facts and Comparisons (2023 edition) 3. American College of Rheumatology Guidelines for Osteoarthritis Management (2019) 4. UpToDate: Nabumetone drug information (2023) 5. Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th edition) 6. Clinical Pharmacology [database online] (2023) 7. Micromedex Solutions: Nabumetone monograph (2023) 8. Journal of Rheumatology: "Long-term safety of nabumetone in the treatment of arthritis" (2018) 9. British Journal of Clinical Pharmacology: "Pharmacokinetics of nabumetone" (2021)
Note: This monograph is for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.