What gout medications are contraindicated in patients taking Ribociclib (Cyclin-dependent kinase 4/6 inhibitor) and why?

Colchicine is Contraindicated with Ribociclib

Colchicine should not be co-prescribed with ribociclib because ribociclib is a strong CYP3A4 inhibitor, and this combination significantly increases the risk of life-threatening colchicine toxicity including neurotoxicity, muscular toxicity, and bone marrow suppression. 1

Mechanism of Drug Interaction

• Ribociclib functions as a potent CYP3A4 inhibitor, which is one of the primary metabolic pathways for colchicine elimination 1
• Colchicine is also a substrate of P-glycoprotein, and dual inhibition of both CYP3A4 and P-glycoprotein dramatically elevates colchicine plasma concentrations 1
• The EULAR guidelines explicitly state that colchicine should not be given to patients receiving strong P-glycoprotein and/or CYP3A4 inhibitors such as cyclosporin or clarithromycin 1
• This same contraindication applies to ribociclib given its strong CYP3A4 inhibitory properties 1

Alternative Gout Management Options

For Acute Gout Flares:

• NSAIDs (with proton pump inhibitors if appropriate) are recommended as first-line alternatives when colchicine is contraindicated 1
• Oral corticosteroids (30-35 mg/day prednisolone equivalent for 3-5 days) provide effective acute flare management 1
• Intra-articular corticosteroid injection following joint aspiration is another safe option 1
• IL-1 blockers should be considered for patients with frequent flares who have contraindications to colchicine, NSAIDs, and corticosteroids 1

For Gout Prophylaxis During Urate-Lowering Therapy:

• Low-dose NSAIDs can substitute for colchicine prophylaxis if not contraindicated 1
• Low-dose glucocorticoids represent another prophylactic alternative 1
• Prophylaxis is recommended during the first 6 months of urate-lowering therapy initiation 1

Urate-Lowering Therapy Considerations

• Allopurinol remains the first-line urate-lowering therapy and has no significant interaction with ribociclib 1
• Febuxostat is an appropriate alternative if allopurinol is not tolerated or fails to achieve target serum uric acid levels 1, 2, 3
• Uricosuric agents (probenecid, benzbromarone where available) can be used alone or in combination with xanthine oxidase inhibitors 1
• Target serum uric acid should be maintained below 6 mg/dL (360 μmol/L), with lower targets (<5 mg/dL) for severe gout with tophi 1

Critical Safety Considerations

• The risk of colchicine toxicity with strong CYP3A4 inhibitors includes potentially fatal complications such as pancytopenia, rhabdomyolysis, and multi-organ failure 1
• Patients with renal impairment face even higher toxicity risk, as both colchicine and its metabolites accumulate 1
• No other gout medications have absolute contraindications with ribociclib based on current evidence 1
• NSAIDs and corticosteroids should be selected based on individual patient comorbidities (renal function, cardiovascular disease, gastrointestinal risk, diabetes) rather than drug interactions with ribociclib 1