Critical
Colchicine × ritonavir
Antigout agents×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Colchicine is a CYP3A4 and P-glycoprotein substrate with narrow therapeutic window. Ritonavir is the strongest CYP3A4 inhibitor and a notable P-glycoprotein inhibitor. Colchicine levels rise 4-fold or more. FDA carries a boxed warning.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain – first signs of toxicity. Pancytopenia (drop in leukocytes, erythrocytes, platelets), muscle weakness, peripheral neuropathy, hepatic and renal injury follow. Fatal cases have been reported.
Management
The combination is not prescribed. For acute gout in a patient on ritonavir, use glucocorticoids (intra-articular or short systemic) or NSAIDs. For long-term prophylaxis, allopurinol.