What are the considerations for using mefenamic acid (Nonsteroidal Anti-Inflammatory Drug (NSAID)) in an elderly patient with foot pain and potential comorbidities, such as Impaired Renal Function, gastrointestinal issues, and cardiovascular disease?

Mefenamic Acid Should Be Avoided in Elderly Patients with Foot Pain

Mefenamic acid is not recommended for elderly patients with foot pain due to high risks of gastrointestinal bleeding, renal toxicity, and cardiovascular complications that substantially outweigh potential benefits, particularly when safer alternatives exist. 1, 2

Why Mefenamic Acid Is Particularly Problematic in the Elderly

Age-Related Pharmacokinetic Concerns

• Mefenamic acid requires dosage reduction in healthy elderly patients due to age-related alterations in drug handling. 3
• The drug is substantially excreted by the kidney, and elderly patients are more likely to have decreased renal function, creating greater risk for toxic reactions. 2
• Mefenamic acid should not be administered to patients with pre-existing renal disease or significantly impaired renal function. 2

Severe Adverse Event Profile

• NSAIDs, including mefenamic acid, were implicated in 23.5% of hospitalizations due to adverse drug reactions in older adults. 1
• Non-oliguric renal failure has been documented in elderly women taking 1-2 grams daily for only 2-6 weeks for musculoskeletal pain. 4
• Elderly patients face 2- to 5-fold increased risk of serious peptic ulcer complications (hemorrhage or perforation), with this risk particularly elevated in elderly women. 3

FDA-Mandated Warnings

• The FDA explicitly states that elderly patients are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions compared to younger patients. 2
• If anticipated benefit outweighs risks, dosing must start at the low end of the range with close monitoring for adverse effects. 2

Recommended Treatment Algorithm for Elderly Patients with Foot Pain

First-Line: Non-Pharmacologic Approaches

• Initiate with footwear modifications (shock-absorbing properties), foot orthoses, and routine foot care, which are effective at reducing foot pain in older people. 5, 6
• Consider assistive devices such as walking sticks for those with specific problems in activities of daily living. 5
• Implement local heat or cold applications. 5

Second-Line: Acetaminophen

• Prescribe acetaminophen up to 1,000 mg every 6 hours (maximum 4 grams/24 hours) as scheduled dosing for mild to moderate pain. 5, 7
• Acetaminophen provides pain relief comparable to NSAIDs without gastrointestinal, renal, or cardiovascular risks. 5, 7
• This is particularly critical in elderly patients with impaired renal function, as acetaminophen does not require renal excretion. 7

Third-Line: Topical NSAIDs

• If acetaminophen provides insufficient relief, add topical NSAIDs (such as diclofenac gel) rather than systemic NSAIDs. 5, 7
• Topical formulations offer reduced systemic absorption and lower renal risk while maintaining local analgesic efficacy. 5, 7

Fourth-Line: Systemic NSAIDs (If Absolutely Necessary)

• If systemic NSAIDs must be considered after safer therapies have failed, use the lowest effective dose for the shortest possible duration. 5
• Mandatory co-prescription of a proton pump inhibitor is required for gastrointestinal protection. 5, 1
• Absolute contraindications include active peptic ulcer disease, heart failure, and chronic kidney disease or creatinine clearance <30 mL/min. 1

Alternative Consideration: Duloxetine

• For osteoarthritis pain in multiple joints incompletely controlled with topical NSAIDs, duloxetine can be considered before systemic NSAIDs. 5

Critical Monitoring Requirements If NSAIDs Are Used Despite Warnings

Baseline Assessment Before Initiating Any NSAID

• Document absence of active peptic ulcer disease, gastrointestinal bleeding history, heart failure, and renal impairment. 1
• Obtain baseline blood pressure, BUN, creatinine, liver function tests, complete blood count, and stool occult blood test. 8
• Review all concurrent medications for dangerous interactions with ACE inhibitors, diuretics, and antiplatelets. 1, 8

Ongoing Surveillance Every 3 Months

• Repeat renal function (BUN, creatinine), blood pressure, liver function tests, complete blood count, and stool occult blood test. 7, 8
• Assess for gastrointestinal toxicity, renal function deterioration, blood pressure elevation, heart failure exacerbation, and drug-drug interactions. 1

Common Pitfalls and How to Avoid Them

Pitfall #1: Overlooking Over-the-Counter NSAID Use

• Elderly patients frequently use over-the-counter NSAIDs without reporting them, creating dangerous cumulative exposure. 5
• Take detailed medication histories including all OTC medications before prescribing any additional NSAIDs. 5

Pitfall #2: Ignoring Drug-Disease Interactions

• NSAIDs carry considerable risk of drug-disease interactions with congestive heart failure, hypertension, and hepatic/renal disease. 5
• The American Geriatrics Society recommends that naproxen (a similar NSAID to mefenamic acid) should be used rarely and with extreme caution, reserved only for highly selected individuals after safer therapies have failed. 1

Pitfall #3: Assuming Short-Term Use Is Safe

• Gastrointestinal toxicity is both dose-related and time-dependent, with serious complications occurring even with short-term use (2-6 weeks). 1, 4
• The documented cases of mefenamic acid nephropathy occurred within 2-6 weeks of therapy. 4

Pitfall #4: Failing to Provide Gastroprotection

• All elderly patients taking any oral NSAID must receive concurrent proton pump inhibitor or misoprostol for gastrointestinal protection. 1
• This is a strong recommendation with high-quality evidence supporting it. 1

Why This Matters for Morbidity and Mortality

The evidence overwhelmingly demonstrates that mefenamic acid and similar NSAIDs substantially increase morbidity and mortality in elderly patients through gastrointestinal bleeding requiring hospitalization, acute kidney injury requiring dialysis, and cardiovascular events. 1, 3, 9 The American Geriatrics Society's position that similar NSAIDs should be used "rarely and with extreme caution" after safer therapies have failed reflects the serious nature of these risks. 1 Given that effective alternatives exist (acetaminophen, topical NSAIDs, foot orthoses), exposing elderly patients to mefenamic acid's substantial toxicity profile cannot be justified for foot pain management. 5, 7, 6