A dangerous interaction
Colchicine is eliminated through the liver enzyme CYP3A4 and the efflux transporter P-glycoprotein. Strong inhibitors of CYP3A4 and P-glycoprotein, such as clarithromycin, block colchicine elimination and can cause severe or fatal colchicine toxicity. The client started clarithromycin 2 days ago for sinusitis, so the nurse brings this combination to the prescriber's attention before colchicine is given. The prescriber may reduce the colchicine dose, choose a different drug for the flare, or change the antibiotic.
What colchicine toxicity looks like
Colchicine has a narrow therapeutic range. Early toxicity causes nausea, vomiting, abdominal pain, and diarrhea. With higher levels it can progress to bone marrow suppression, muscle damage (myopathy or rhabdomyolysis), nerve damage, and multiorgan failure. Gastrointestinal symptoms are therefore an early signal to stop and report. Risk increases with kidney or liver impairment and with interacting drugs. Other strong interacting drugs include some azole antifungals, certain protease inhibitors, ciclosporin, and verapamil or diltiazem.
Why the other medications are not the concern
The distractors are drugs that matter in gout, but not for colchicine toxicity.
| Drug | Relevance to gout | Colchicine toxicity risk? |
|---|
| Losartan | Modest uricosuric effect | No; does not affect colchicine clearance |
| Hydrochlorothiazide | Raises serum urate and can provoke gout | No |
| Clarithromycin | None | Yes; strong CYP3A4 and P-glycoprotein inhibitor |
| Low-dose aspirin | Slightly raises serum urate | No; and it is not stopped without the prescriber |
Watch out! Hydrochlorothiazide is a tempting answer because thiazides are a known cause of gout. The question, however, asks about colchicine toxicity, not about urate levels. Read exactly what risk the stem names.
Nursing practice
During medication reconciliation the nurse looks specifically for macrolide antibiotics, azole antifungals, and other strong enzyme inhibitors in any client starting colchicine, and teaches the client to report diarrhea, vomiting, muscle weakness, or numbness. Clients are also taught not to take extra colchicine doses on their own. Key point! Colchicine plus a strong CYP3A4 or P-glycoprotein inhibitor such as clarithromycin can be fatal; report the combination before the dose is given.