D1.101 - Colchicine-induced hepatitis: a case of drug interaction involving rivaroxaban

Colchicine is a mainstay treatment for acute gout and is also used for the prevention of gout.  Its primary mechanism of action involves binding to tubulin, thereby inhibiting microtubule polymerization. colchicine has a narrow therapeutic index. Its toxicity is well-documented, most commonly presenting with gastrointestinal symptoms (nausea, vomiting, diarrhea) which often serve as an early warning sign for overdose. However, hepatotoxicity is a less frequent but potentially severe adverse effect.

Here in we report the case of a 83-years old female with a history of atrial fibrillation and hypertension, treated for the past two years with lopril, rivaroxaban and bisoprolol. She experienced a gout flare-up one year ago, for which treatment with colchicine and allopurinol was initiated. Pre therapeutic Liver test were within normal ranges. A check-up after 6 months of treatment showed elevation of transaminases at 4 folds upper normal range. Colchicine was discontinued. Other differential diagnoses were ruled out. The evolution was favorable. The improvement in liver enzymes following the cessation of colchicine, while the other medications (including allopurinol) were continued, strongly implicates colchicine as the causative agent. This temporal relationship and positive de-challenge allow us to classify this as a probable case of drug-induced liver injury (DILI) according to standard causality assessment scales like the Roussel Uclaf Causality Assessment Method (RUCAM).

While the exact mechanism of colchicine-induced liver injury is not fully elucidated, several pathways are implicated. Both colchicine and rivaroxaban are substrates of the P-glycoprotein (P-gp) efflux transporter. P-gp acts as a pump that actively transports drugs out of cells, limiting their absorption and enhancing their excretion. When two P-gp substrates are taken together, they can compete for this transporter. This competition can lead to increased absorption and reduced clearance of one or both drugs, resulting in higher plasma concentrations.

Clinicians must be acutely aware of the potential for drug interactions involving colchicine, particularly with CYP3A4 and P-gp inhibitors like rivaroxaban, Periodic monitoring of liver function tets is advisable for patients on long-term colchicine therapy, especially those with identified risk factors.