Is it safe to use darolutamide and atorvastatin (Lipitor) together?

Darolutamide and Atorvastatin Combination Safety

Yes, darolutamide and atorvastatin can be used together, but atorvastatin dose must be limited to ≤10 mg daily due to a significant drug-drug interaction that increases statin exposure approximately 5-fold. 1

Mechanism of Interaction

• Darolutamide inhibits BCRP (breast cancer resistance protein), OATP1B1, and OATP1B3 transporters, which are critical for rosuvastatin clearance and also affect atorvastatin metabolism 1, 2
• When darolutamide was studied with rosuvastatin (a BCRP/OATP substrate similar to atorvastatin), it increased rosuvastatin exposure by approximately 5-fold 1, 2
• While the FDA label specifically studied rosuvastatin, atorvastatin is also a substrate for these same transporters, making clinically significant interaction highly likely 3

Critical Dosing Recommendations

For atorvastatin when combined with darolutamide:

• Limit atorvastatin to ≤10 mg daily maximum 3
• Doses above 10 mg daily are not recommended without close monitoring of creatinine kinase and muscle-related symptoms 3
• If patient is already on atorvastatin >10 mg daily, reduce dose before initiating darolutamide 4

Clinical Evidence of Risk

• A case report documented rhabdomyolysis in a patient receiving darolutamide with rosuvastatin 40 mg daily (8 times the recommended maximum dose of 5 mg for rosuvastatin with darolutamide) 4
• The patient developed lower extremity weakness, myalgia, and marked CPK elevation during week 11 of darolutamide treatment 4
• Symptoms resolved and CPK normalized after statin discontinuation 4
• Despite the pharmacokinetic interaction potential, the ARAMIS trial showed similar adverse event rates in statin users versus non-users, though specific statin doses were not reported 5

Monitoring Requirements

Essential monitoring when combining these medications:

• Baseline creatinine kinase (CK) before starting combination 3
• Monitor for muscle pain, tenderness, or weakness at each visit 3
• Check CK if any muscle symptoms develop 4
• Consider CK monitoring every 3-6 months in asymptomatic patients on combination therapy 3

Alternative Statin Options

Safer statin alternatives with darolutamide (though still require caution):

• Pravastatin ≤20 mg daily may be considered as it has less BCRP/OATP dependence 3
• Fluvastatin ≤40 mg daily may be considered 3
• All statins require dose limitation when combined with darolutamide due to transporter inhibition 1, 2

Common Pitfall to Avoid

• Do not continue pre-existing high-dose statins unchanged when initiating darolutamide - this is the exact scenario that led to the documented rhabdomyolysis case where a patient on rosuvastatin 40 mg was started on darolutamide without dose adjustment 4
• The 5-fold increase in statin exposure means a patient on atorvastatin 40 mg is effectively receiving a 200 mg equivalent dose 1, 2