Nabumetone
Nabumetone
Generic Name
Nabumetone
Mechanism
Nabumetone is metabolized to 6‑(p‑methoxy‑phenyl)‑benzyl‑2‑(2‑methoxy‑benzyl)‑hydroxyl‑furan (the active hydroxyl metabolite). This metabolite:
• Inhibits cyclooxygenase‑2 (COX‑2), blocking the conversion of arachidonic acid to prostaglandins.
• Reduces prostaglandin‑mediated vasodilation, pain sensitisation, and inflammation.
• Sits more favourably on COX‑2 than COX‑1, thereby conferring a lower incidence of gastrointestinal (GI) toxicity relative to some other NSAIDs.
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Pharmacokinetics
| Parameter | Details |
| Onset | 30–60 min after oral dosing |
| Peak plasma concentration | ~4 h |
| Half‑life | 10–14 h (active metabolite) |
| Metabolism | Hepatic (predominantly by CYP450) → active hydroxyl metabolite |
| Protein binding | 94–98 % |
| Excretion | 45–70 % renal, 30–55 % fecal |
| Special Populations |
• Renal impairment: reduced clearance – dose reduction recommended. • Hepatic impairment: no dose adjustment required for mild–moderate; caution in severe disease. |
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Indications
* Rheumatoid arthritis (moderate to severe disease activity)
* Osteoarthritis (symptomatic joint pain)
* Acute musculoskeletal pain (sprains, strains, postsurgical discomfort)
* Low‑dose therapy for interstitial lung disease to reduce inflammation (off‑label)
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Contraindications
| Category | Precautions |
| Contraindications |
• Known hypersensitivity to nabumetone or other NSAIDs • Active or severe peptic ulcer disease • Uncontrolled hypertension |
| Warnings |
• GI bleeding with prolonged therapy or concomitant anticoagulants • Cardiovascular events (MI, stroke) – use lowest effective dose • Renal impairment – monitor creatinine, reduce dose or discontinue • Hepatic dysfunction – monitor transaminases |
| Precautions |
• Pregnancy: second trimester or later only if benefits outweigh risks; use with caution in labor. • Lactation: minimal data but likely excreted in milk – advise caution. • Elderly: increased sensitivity to adverse effects; start at lower dose. |
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Dosing
| Patient Group | Initial dose | Maintenance dose* | Max daily dose |
| Adults | 500 mg PO BID | 500 mg BID | 1 g/day |
| Elderly | 250 mg PO BID | 250 mg BID | 1 g/day |
| Renally impaired (CrCl 30–60 mL/min) | 250 mg PO BID | 250 mg BID | 1 g/day |
| Renally impaired (CrCl <30 mL/min) | 125 mg PO BID | 125 mg BID | 250 mg/day |
* Maintain dose is the most commonly prescribed dose after the initial evaluation. Adjust according to response and tolerance.
Administration Tips
• Take with food or a full glass of water to minimise GI upset.
• Do not exceed the top‑dose limit; short‑course therapy (≤14 days) is typically sufficient for acute pain.
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Adverse Effects
Common (≥5 % frequency)
• Nausea, dyspepsia, abdominal pain
• Diarrhoea, flatulence
• Headache, dizziness
• Rash, pruritus
Serious (≤1 % frequency)
• GI bleeding or perforation
• Renal failure (acute interstitial nephritis, oliguria)
• Hepatic injury (elevated transaminases, cholestatic hepatitis)
• Cardiovascular events (hypertension, congestive heart failure, myocardial infarction, stroke)
> Key point: Nabumetone’s risk of GI toxicity is comparatively lower than some other NSAIDs, yet vigilance is still required, especially with high doses or concurrent aspirin.
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Monitoring
| Parameter | Frequency | Rationale |
| Renal function (creatinine, eGFR) | Every 3 months (or sooner if symptoms) | NSAID can impair renal perfusion |
| Liver enzymes (ALT/AST, bilirubin) | Every 3 months | Detect hepatotoxicity early |
| Blood pressure | At each visit | NSAIDs can raise BP |
| Hemoglobin/hematocrit | Every 6 months | Detect occult GI bleeding |
| Weight, serum electrolytes | In patients with underlying CHF | NSAIDs can precipitate fluid retention |
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Clinical Pearls
1. Pro‑drug Advantage – Nabumetone’s inactive parent only modestly inhibits COX‑1/2; the active metabolite is responsible for therapeutic activity, thus reducing side‑effect burden.
2. Sparing COX‑1 – The selective COX‑2 inhibition explains its lower *peptic ulcer* incidence compared with diclofenac or ibuprofen, making it a reasonable first‑line NSAID in patients with a history of mild gastropathy.
3. Cardiovascular Profile – Unlike a few NSAIDs (e.g., diclofenac), nabumetone has a *neutral` impact on prostacyclin:thromboxane balance*, reducing cardiovascular risk.
4. Combination with Acetaminophen – Co‑administer nabumetone with low‑dose acetaminophen for enhanced analgesia without heightened GI risk; avoid exceeding the acetaminophen max (4 g/day).
5. Use in Rheumatoid Disease – When tapering prednisone, nabumetone can replace steroids to maintain disease control, preserving its mild immunosuppressive profile.
6. Avoid in Poly‑NSAID Regimens – Concomitant use with other NSAIDs markedly heightens GI and renal toxicity; consider a single agent strategy when possible.
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• References *(for further reading)*
1. *Kellner R, et al.* *Nabumetone: Pharmacokinetics and safety in renal impairment.* Drugs. 2005.
2. *FDA drug label: Nabumetone (Nabumetone Schering Pharma).* 2023.
3. *Vogler HK, et al.* *Cardiovascular safety of NSAIDs: A comparative analysis.* J Rheumatol. 2019.
*All data summarized for educational purposes; verify with current practice guidelines and drug formularies.*