What is the recommended dose of Nabumetone (nonsteroidal anti-inflammatory drug (NSAID)) for elderly patients, particularly those with impaired renal function or a history of gastrointestinal disease?

Nabumetone Dosing in the Elderly

Elderly patients should start nabumetone at 1,000 mg once daily, with a maximum dose not exceeding 2,000 mg per day, and those with moderate or severe renal impairment require reduced starting doses of 750 mg or 500 mg once daily, respectively. 1

Standard Dosing Recommendations

The FDA-approved starting dose for elderly patients with osteoarthritis or rheumatoid arthritis is 1,000 mg once daily, taken with or without food 1. Some patients may require 1,500-2,000 mg daily for adequate symptom control, but dosages beyond 2,000 mg have not been studied 1.

Patients weighing under 50 kg are less likely to require doses beyond 1,000 mg, and the dose should be adjusted based on individual response 1.

Pharmacokinetic Considerations in the Elderly

Elderly patients demonstrate significantly altered drug handling compared to younger adults:

• Steady-state plasma concentrations are generally higher in elderly patients 1
• The elimination half-life increases from approximately 22 hours in young adults to 29.8 hours in elderly patients 1
• Plasma clearance decreases from 26.1 mL/min in young adults to 18.6 mL/min in elderly patients 1
• Peak plasma concentrations occur later (median 4 hours vs. 3 hours in younger patients) 1
• The accumulation ratio is higher in elderly (1.8) compared to young patients (1.6) 2

Due to decreased elimination, elderly patients may require lower doses than younger adults 2.

Renal Impairment Dosing Algorithm

Nabumetone requires careful dose adjustment based on creatinine clearance:

Mild Renal Insufficiency (CrCl ≥50 mL/min)

• No dosage adjustment generally necessary 1

Moderate Renal Insufficiency (CrCl 30-49 mL/min)

• Maximum starting dose: 750 mg once daily 1
• After careful monitoring, may increase to maximum 1,500 mg daily 1
• Terminal half-life increases by approximately 50% (39.2 hours vs. 26.9 hours) 1
• Plasma levels of unbound active metabolite increase by 50% 1
• Renal excretion decreases by 33% 1

Severe Renal Insufficiency (CrCl <30 mL/min)

• Maximum starting dose: 500 mg once daily 1
• After careful monitoring, may increase to maximum 1,000 mg daily 1
• Similar increases in terminal half-life observed 1

Hemodialysis

• No dosage adjustment required - steady-state concentrations similar to healthy subjects 1
• The active metabolite (6-MNA) is not dialyzable due to extensive protein binding 1

Safety Considerations Specific to the Elderly

NSAIDs including nabumetone are identified as potentially inappropriate medications (PIMs) in elderly patients, particularly those with multimorbidity, disability, polypharmacy, poor functional status, or renal impairment 3. NSAIDs are a common cause of preventable adverse drug reactions, frailty, falls, cognitive impairment, and hospitalizations in this population 3.

Gastrointestinal Risk

• Elderly patients (≥75 years) are at increased risk for gastrointestinal bleeding 3
• NSAID-associated gastrointestinal toxicity increases in frequency and severity with age 3
• Consider concomitant proton pump inhibitor therapy in patients at increased risk (age ≥75 years, peptic ulcer disease history, history of GI bleeding, or concurrent use of anticoagulants, antiplatelets, SSRIs, or glucocorticoids) 3

Cardiovascular Risk

• Avoid NSAIDs in elderly patients with cardiovascular disease or multiple cardiovascular risk factors 3
• NSAIDs should be avoided in combination with anticoagulants, antiplatelets, thrombolytics, SNRIs, or SSRIs 3

Renal Monitoring

• Regular monitoring of renal function is essential, particularly in patients with pre-existing renal compromise 4
• NSAIDs can worsen renal function in patients with chronic kidney disease or those taking nephrotoxic drugs 3
• NSAIDs can worsen or precipitate heart failure through renal effects 3

Hepatic Impairment

Data in patients with severe hepatic impairment are limited 1. Biotransformation of nabumetone to its active metabolite (6-MNA) is dependent on hepatic function and could be reduced in patients with severe hepatic impairment (history of or biopsy-proven cirrhosis) 1. Dosage adjustment may be required in patients with hepatic impairment 5.

Common Pitfalls to Avoid

• Do not use standard adult dosing without considering renal function - elderly patients commonly have declining renal function even with normal serum creatinine 1
• Do not exceed 2,000 mg daily - higher doses have not been studied 1
• Do not prescribe without assessing cardiovascular and gastrointestinal risk factors 3
• Do not combine with other NSAIDs, anticoagulants, or antiplatelet agents without gastroprotection 3
• Avoid in patients with active peptic ulcer disease, GI bleeding, or severe renal impairment 4

Monitoring Requirements

• Baseline and periodic renal function assessment (creatinine clearance calculation, not just serum creatinine) 1
• Blood pressure monitoring - NSAIDs can impair blood pressure control 3
• Assessment for signs of gastrointestinal bleeding (melena, hematemesis, anemia) 3
• Evaluation for fluid retention and heart failure exacerbation 3

Treatment Duration

Use the lowest effective dose for the shortest duration consistent with treatment goals 1. The safety profile of nabumetone remains relatively constant over long-term use, with over 1,000 patients in clinical trials receiving treatment for one year or more 6. However, the principle of minimizing NSAID exposure in elderly patients should guide duration decisions 3.