What colchicine dose and duration is appropriate for an acute knee pseudogout flare in an older adult with normal renal function and no CYP3A4 or P‑gp inhibitor interactions?

Colchicine Dosing for Acute Knee Pseudogout in an Older Adult with Normal Renal Function

For an acute knee pseudogout flare in an older adult with normal renal function and no drug interactions, administer colchicine 1.2 mg orally at the first sign of symptoms, followed by 0.6 mg one hour later (total 1.8 mg over one hour); after a 12-hour pause, continue 0.6 mg once or twice daily until the attack completely resolves, typically within a few days. 1, 2, 3

Critical Timing Window

• Initiate treatment within 12–24 hours of symptom onset to achieve maximum therapeutic benefit; effectiveness declines sharply after 24 hours. 1
• Do not start colchicine after 36 hours from symptom onset, as efficacy drops dramatically beyond this window. 1, 2, 3

Standard Dosing Protocol for Normal Renal Function

Acute Loading Phase

• Loading dose: 1.2 mg (two 0.6 mg tablets) orally at the first sign of flare. 1, 2, 3
• Second dose: 0.6 mg one hour after the loading dose (total 1.8 mg in the first hour). 1, 2, 3

Maintenance Phase

• Wait 12 hours after the initial loading doses before resuming colchicine. 1
• Maintenance dosing: 0.6 mg once or twice daily (maximum 1.2 mg/day) until the attack completely resolves. 1, 2
• Duration: Continue until complete symptom resolution, typically 3–7 days. 1

Evidence Supporting Low-Dose Regimen

• This low-dose protocol (total 1.8 mg over one hour) achieves ≥50% pain reduction with a number needed to treat of 3–5 and is as effective as obsolete high-dose regimens (4.8 mg over 6 hours) while causing significantly fewer gastrointestinal adverse effects (23% vs 77% diarrhea rate). 1, 4
• The FDA-approved regimen is based on the AGREE trial, which demonstrated equal efficacy to high-dose colchicine for pain reduction at 24 hours. 1, 2

Pseudogout-Specific Considerations

• Although most colchicine dosing studies focus on gout, colchicine 0.6 mg twice daily has demonstrated effectiveness in pseudogout, reducing attack frequency from 3.2 episodes/patient/year to 1 episode/patient/year (p < 0.001). 5
• The same acute dosing regimen used for gout is appropriate for pseudogout flares. 1

Alternative Treatment Options

If colchicine is ineffective or contraindicated:

• Oral prednisone 30–35 mg daily for 5 days (no taper needed) provides Level A evidence of efficacy equivalent to colchicine. 1
• Intra-articular corticosteroid injection (triamcinolone acetonide 40 mg for the knee) is highly effective for monoarticular pseudogout. 1, 3
• NSAIDs at full anti-inflammatory doses (naproxen 500 mg twice daily or indomethacin 50 mg three times daily) until complete resolution. 1, 3

Safety Considerations in Older Adults

• Gastrointestinal toxicity occurs in 23–26% of patients receiving the low-dose regimen, primarily diarrhea. 1
• With normal renal function and no CYP3A4/P-glycoprotein inhibitors, standard dosing is safe and requires no adjustment. 1, 2, 3
• Monitor for drug interactions with statins, which can increase risk of myopathy when combined with colchicine, especially in the presence of any renal impairment. 3

Common Pitfalls to Avoid

• Never use the obsolete high-dose regimen (0.5 mg every 2 hours until relief or toxicity), which causes severe diarrhea in most patients without additional benefit. 1, 3
• Do not exceed 1.8 mg total in the first hour; higher doses provide no additional efficacy and markedly increase adverse effects. 1, 3
• Do not taper the maintenance dose early; continue 0.6 mg once or twice daily until complete symptom resolution. 1
• Do not delay treatment initiation; every hour beyond symptom onset reduces therapeutic effectiveness. 1, 3