Is it safe to switch a patient from pravastatin (pravastatin) 10 mg to rosuvastatin (rosuvastatin) 10 mg while taking ruxolitinib (ruxolitinib) 20 mg twice daily?

Safety of Switching from Pravastatin 10 mg to Rosuvastatin 10 mg in a Patient Taking Ruxolitinib

Switching from pravastatin 10 mg to rosuvastatin 10 mg is NOT safe in this patient taking ruxolitinib 20 mg twice daily without dose adjustment—rosuvastatin must be limited to a maximum of 5 mg daily when combined with ruxolitinib, or the patient should remain on pravastatin with appropriate dose limitations.

Critical Drug-Drug Interaction

Ruxolitinib significantly increases rosuvastatin exposure through multiple mechanisms, creating a severe drug-drug interaction that substantially elevates the risk of muscle-related toxicity, including rhabdomyolysis. 1

• Ruxolitinib, like other JAK inhibitors used in myeloproliferative disorders, shares similar interaction profiles with immunosuppressants (cyclosporine, tacrolimus, everolimus, sirolimus) that inhibit OATP1B1 and P-glycoprotein transporters 1
• Rosuvastatin exposure increases approximately 7-fold when combined with agents that inhibit these transporters 1
• This magnitude of interaction is classified as "severe" (≥5-fold increase in AUC) 1

Guideline-Based Recommendations

The American Heart Association and American College of Cardiology provide explicit guidance for managing statins with drugs that cause similar interactions to ruxolitinib:

• If rosuvastatin must be used with ruxolitinib, the dose must be limited to 5 mg daily maximum 1
• Switching to rosuvastatin 10 mg would double the recommended maximum safe dose, substantially increasing myopathy risk 1
• Pravastatin experiences a 5- to 10-fold increase in exposure with similar interacting agents, but can be used with a maximum dose of 40 mg daily 1

Safer Alternatives

The current pravastatin 10 mg regimen is actually a safer choice than switching to rosuvastatin 10 mg for this patient:

• Pravastatin 10 mg is well below the 40 mg daily maximum recommended when combined with drugs like ruxolitinib 1
• If greater LDL-C reduction is needed, pravastatin can be safely increased up to 40 mg daily 1
• Fluvastatin is another option with only a 2- to 4-fold increase in exposure, allowing doses up to 40 mg daily 1

Efficacy Considerations

While rosuvastatin is more potent than pravastatin milligram-for-milligram:

• Rosuvastatin 10 mg reduces LDL-C by approximately 49% versus pravastatin 20 mg at 28% 2
• However, rosuvastatin 5 mg (the maximum safe dose with ruxolitinib) reduces LDL-C by only 42% 2
• Pravastatin can be titrated to 40 mg (still within safe limits with ruxolitinib), potentially achieving similar or better LDL-C reduction than rosuvastatin 5 mg 1

Monitoring Requirements if Switch Proceeds

If the clinical decision is made to switch to rosuvastatin despite these concerns, the following is mandatory:

• Maximum rosuvastatin dose: 5 mg daily (not the proposed 10 mg) 1
• Monitor creatine kinase at baseline and with any unexplained muscle symptoms 1
• Educate patient to immediately report muscle pain, tenderness, weakness, or dark urine 1
• Monitor renal function, as rosuvastatin-associated proteinuria risk increases at higher exposures 3, 4

Common Pitfall to Avoid

The most critical error would be assuming that because rosuvastatin has minimal CYP3A4 metabolism, it is safe from drug interactions. 3 While rosuvastatin avoids CYP3A4-mediated interactions, it remains highly susceptible to transporter-mediated interactions through OATP1B1 and P-glycoprotein inhibition, which is precisely the mechanism by which ruxolitinib increases statin exposure 1, 4.

Recommended Action

Keep the patient on pravastatin 10 mg, or if inadequate LDL-C control, increase pravastatin up to 40 mg daily rather than switching to rosuvastatin. 1 This approach maintains safety while providing flexibility for dose optimization. If rosuvastatin is absolutely required for clinical reasons, use only 5 mg daily with close monitoring for myopathy.