What is the typical dosing regimen for indomethacin (Nonsteroidal Anti-Inflammatory Drug (NSAID)) in a patient with moderate to severe pain or inflammation, considering factors such as age, weight, and impaired renal function?

Indomethacin Dosing

For acute gout, start indomethacin 50 mg three times daily until pain is tolerable, then rapidly taper and discontinue; for chronic inflammatory conditions like rheumatoid arthritis or ankylosing spondylitis, begin with 25 mg twice or three times daily and titrate weekly by 25-50 mg increments to a maximum of 150-200 mg/day based on response. 1

Acute Gout Dosing

• Initial dose: 50 mg three times daily until pain becomes tolerable 2, 1
• After pain control is achieved, rapidly reduce the dose to complete cessation 1
• Definite pain relief typically occurs within 2-4 hours, with tenderness and heat subsiding in 24-36 hours 1
• Swelling gradually disappears over 3-5 days 1
• The European League Against Rheumatism supports this regimen of 50 mg three times daily until resolution of the acute attack 3

Important caveat: At 50 mg four times daily (higher than recommended), 55% of patients experienced gastrointestinal adverse events in comparative trials 2. This underscores the importance of using the three-times-daily regimen rather than exceeding it.

Chronic Inflammatory Conditions (Rheumatoid Arthritis, Ankylosing Spondylitis, Osteoarthritis)

Initial Dosing

• Start with 25 mg twice or three times daily 1
• If well tolerated after one week, increase by 25 mg or 50 mg increments weekly until satisfactory response 1
• Maximum effective dose: 150-200 mg/day (doses above this generally do not increase effectiveness) 1

Maintenance Dosing

• For ankylosing spondylitis specifically, the American College of Rheumatology recommends 75-150 mg/day divided into several doses 3
• Long-term studies show that 81% of patients maintained on 75-100 mg daily for 3-20 years had good tolerability and efficacy 4
• For patients with persistent night pain or morning stiffness, give up to 100 mg of the total daily dose at bedtime 1

Titration Strategy

• If minor adverse effects develop during dose escalation, rapidly reduce to a tolerated dose and observe closely 1
• If severe adverse reactions occur, stop the drug immediately 1
• Once acute inflammation is controlled, repeatedly attempt to reduce to the smallest effective dose 1

Acute Painful Shoulder (Bursitis/Tendinitis)

• Dose: 75-150 mg daily in 3-4 divided doses 1
• Discontinue after signs and symptoms of inflammation have been controlled for several days 1
• Usual course of therapy: 7-14 days 1

Special Population Considerations

Elderly Patients

• Use with greater care in elderly patients as advancing age increases the possibility of adverse reactions 1
• Indomethacin should be used rarely and with extreme caution in older persons, only when safer therapies have failed 2
• Absolute contraindications in elderly: active peptic ulcer disease, chronic kidney disease, heart failure 2
• All elderly patients taking indomethacin must receive gastroprotection with a proton pump inhibitor or misoprostol 2

Renal Impairment

• Renal failure does not significantly affect serum concentrations of indomethacin 5
• However, NSAIDs including indomethacin should be used with extreme caution due to risk of acute kidney injury 2
• Chronic kidney disease is an absolute contraindication in elderly patients 2

Pediatric Patients

• Indomethacin should not ordinarily be prescribed for children 14 years of age and under 1

Critical Safety Considerations

Gastrointestinal Protection

• Indomethacin has high ulcerogenic potential - all patients should be considered for gastroprotective agents 2, 3
• Gastrointestinal adverse events were significantly more common with indomethacin (63%) compared to prednisolone (27%) in acute gout trials 2
• When used long-term, proton pump inhibitor or misoprostol co-prescription is mandatory 2

Cardiovascular and Renal Monitoring

• Routinely assess for gastrointestinal toxicity, renal toxicity, hypertension, and heart failure 2
• Particular attention needed in patients on ACE inhibitors, diuretics, or antiplatelets due to drug interactions 2
• Heart failure is a relative contraindication requiring extreme caution 2

Drug Interactions

• Patients taking aspirin for cardioprophylaxis should not use ibuprofen, though specific guidance on indomethacin-aspirin interaction is less clear 2
• Probenecid increases plasma concentrations of indomethacin, potentially enhancing both efficacy and side effects 5

Maximum Dose Limits

• Never exceed 200 mg total daily dose 1
• Use the lowest effective dose for the shortest duration consistent with treatment goals 1

Pharmacokinetic Considerations

• Peak plasma concentrations of 2-3 mcg/mL achieved within 1-2 hours after oral administration 5
• Food reduces and delays peak concentrations without reducing total absorption 5
• Half-life: 5-10 hours in adults 5
• Rectal administration offers no clinical advantages over equivalent oral dosing 6, 5