What are the guidelines for using Indomethacin (Nonsteroidal Anti-Inflammatory Drug (NSAID))?

Indomethacin Use Guidelines

Indomethacin is FDA-approved for moderate to severe rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute painful shoulder (bursitis/tendinitis), and acute gouty arthritis, but should be used at the lowest effective dose for the shortest duration due to significant gastrointestinal, renal, and cardiovascular risks. 1

FDA-Approved Indications

Indomethacin is indicated for:

• Moderate to severe rheumatoid arthritis (including acute flares of chronic disease) 1
• Moderate to severe ankylosing spondylitis 1
• Moderate to severe osteoarthritis 1
• Acute painful shoulder (bursitis and/or tendinitis) 1
• Acute gouty arthritis 1

Dosing Principles

Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. 1

• Typical dosing range: 50-150 mg daily, with most patients tolerating 75-100 mg daily 2
• For acute gout: Indomethacin 50 mg three times daily for 2 days, then 25 mg daily for the next 3 days has been used, though no evidence suggests indomethacin is more efficacious than other NSAIDs like naproxen or ibuprofen 3
• Starting dose: 250-500 mg twice daily is commonly used when initiating therapy 3

Specific Clinical Scenarios

Acute Gout Management

For acute gout, corticosteroids should be considered first-line therapy over NSAIDs including indomethacin, as they are generally safer with fewer adverse effects. 3

• Indomethacin is commonly prescribed for gout but has no proven superiority over other NSAIDs such as naproxen or ibuprofen 3
• When NSAIDs are used for gout, any NSAID is acceptable—the choice should be based on safety profile and contraindications, not efficacy 3

Headache Management in Idiopathic Intracranial Hypertension (IIH)

Indomethacin may have some advantage for headaches in IIH due to its effect of reducing intracranial pressure. 3

• Short-term use of NSAIDs including indomethacin may be helpful in the first few weeks following IIH diagnosis 3
• Caution is required with potential NSAID side effects, and gastric protection may be needed 3
• Patients must be warned about medication overuse headache (use of NSAIDs on more than 15 days per month for more than 3 months) 3

Cancer Pain

NSAIDs including indomethacin can be added to opioids to reduce opioid dose when sedation or CNS effects become burdensome, but significant precautions apply 3

Absolute Contraindications

Do not use indomethacin in patients with:

• Active peptic ulcer disease 4
• Severe renal impairment (low creatinine clearance or chronic kidney disease) 3, 4
• Congestive heart failure 3
• Cirrhosis 3
• Aspirin/NSAID-induced asthma 3
• Pregnancy (especially late pregnancy due to risk of premature ductus arteriosus closure) 1
• Concurrent use with anticoagulants (unless absolutely necessary with appropriate monitoring) 3, 1

Mandatory Precautions and Monitoring

Gastrointestinal Protection

All elderly patients taking oral indomethacin must receive a proton pump inhibitor (PPI) for gastrointestinal protection. 4

• Risk of serious GI bleeding ranges from 1 in 2,100 in adults <45 years to 1 in 12 in adults >65 years 3
• Concomitant anticoagulant use increases GI bleeding risk 5-6 fold 3
• Consider PPIs, double-dose H2 blockers, or misoprostol for patients with history of NSAID-associated ulcers 3
• Patients with untreated H. pylori infection have increased risk of GI bleeding 3

Renal Monitoring

Monitor renal function (serum creatinine, eGFR) every 3-6 months, or 1-2 weeks after starting indomethacin. 4

• Indomethacin can cause acute intrinsic renal failure, particularly in volume-contracted patients or those with compromised prerenal status 5
• Avoid in patients with preexisting renal disease, congestive heart failure, or cirrhosis to prevent acute renal failure 3
• Consider monitoring serum creatinine after initiation in patients at risk of renal failure and those taking ACE inhibitors or ARBs 3
• Discontinue immediately if signs of renal dysfunction develop 4

Cardiovascular Monitoring

Assess blood pressure, signs of fluid retention/edema, and cardiovascular symptoms at each visit. 4

• Indomethacin may increase risk of cardiovascular thrombotic events, myocardial infarction, and stroke 1
• Patients should be alert for chest pain, shortness of breath, weakness, or slurring of speech 1
• Discontinue if congestive heart failure or hypertension develops or worsens 3
• Indomethacin can blunt the antihypertensive effect of beta-blockers and ACE inhibitors 1

Drug Interactions

Critical interactions to monitor:

• Aspirin: Combined use not recommended; increases GI side effects significantly and decreases indomethacin blood levels by ~20% 1
• Anticoagulants (warfarin): If concurrent use necessary, anticipate increased INR, monitor closely, and provide GI prophylaxis 3, 1
• ACE inhibitors/ARBs: May result in further renal function deterioration, including possible acute renal failure 1
• Diflunisal: Do not use concomitantly—associated with fatal GI hemorrhage 1
• Cyclosporine: Increased cyclosporine toxicity; use with caution and monitor renal function 1

Special Populations

Elderly Patients

Acetaminophen should be the initial pharmacotherapy for musculoskeletal pain in older adults, optimized to full therapeutic dosing (1000 mg per dose, up to 4000 mg daily) before considering indomethacin. 4

• If acetaminophen fails at maximum dosing, NSAIDs may be considered only with mandatory gastroprotection (PPI) and strict patient selection 4
• Use the lowest effective dose for the shortest duration possible (ideally ≤2 weeks for acute conditions) 4
• Increased risk of adverse drug reactions including GI complications, renal toxicity, and cardiovascular events 4

Breastfeeding

Indomethacin is safe to use in breastfeeding women. 3

Critical Care/ICU Patients

The panel suggests not routinely using indomethacin as an adjunct to opioid therapy for pain management in critically ill adults. 3

• Small beneficial effect is balanced by serious potential safety concerns (bleeding and kidney injury), particularly with multiple doses 3
• May be considered in select patients without contraindications 3

Perioperative Use

NSAIDs including indomethacin should be used with caution in the perioperative period due to risk of platelet dysfunction with bleeding and effect on renal blood flow. 3

• Can be introduced postoperatively once renal function is not impaired and risk of bleeding has passed 3
• Patients undergoing emergency laparotomy have high risk of acute kidney injury 3

Common Pitfalls to Avoid

1. Do not assume indomethacin is superior to other NSAIDs for gout—no evidence supports this common practice 3
2. Do not prescribe without gastric protection in elderly patients—mandatory PPI co-prescription 4
3. Do not use in volume-depleted or hemodynamically compromised patients—high risk of acute renal failure 5
4. Do not combine with aspirin—no additional therapeutic benefit and significantly increased GI side effects 1
5. Do not use as monotherapy for neuropathic pain—ineffective; use gabapentin or duloxetine instead 4
6. Do not prescribe for chronic pain without regular monitoring—check renal function, blood pressure, and GI symptoms at each visit 4

Warning Signs Requiring Immediate Discontinuation

Instruct patients to stop indomethacin and seek immediate medical attention if they develop:

• Signs of GI bleeding: epigastric pain, dyspepsia, melena, hematemesis 1
• Cardiovascular symptoms: chest pain, shortness of breath, weakness, slurring of speech 1
• Heart failure symptoms: unexplained weight gain, edema 1
• Hepatotoxicity signs: nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, flu-like symptoms 1
• Allergic reactions: difficulty breathing, swelling of face or throat, skin rash, blisters, fever 1
• Signs of renal dysfunction: decreased urine output, fluid retention 4