From the Guidelines
Itraconazole and rosuvastatin should not be used together due to a significant drug interaction that can increase the risk of serious side effects, such as muscle damage and rhabdomyolysis, as evidenced by the increased risk of muscle-related toxicity with a 7-fold increase in AUC of rosuvastatin when coadministered with certain immunosuppressants 1. When taken concurrently, itraconazole inhibits the CYP3A4 enzyme and the OATP1B1 transporter, which are involved in rosuvastatin metabolism and transport. This inhibition can lead to elevated rosuvastatin levels in the bloodstream, potentially increasing the risk of muscle damage (myopathy) and a rare but serious condition called rhabdomyolysis, where damaged muscle tissue releases proteins into the blood that can cause kidney damage. If you are prescribed itraconazole while on rosuvastatin, contact your healthcare provider immediately to discuss alternatives. Your doctor might temporarily discontinue rosuvastatin during itraconazole treatment, reduce the rosuvastatin dose, or consider an alternative antifungal medication depending on your specific situation. Some key points to consider:
- The combination of rosuvastatin with certain immunosuppressants, such as cyclosporine, tacrolimus, everolimus, or sirolimus, may increase the risk of muscle-related toxicity 1.
- The dose of rosuvastatin should be limited to 5 mg daily when coadministered with cyclosporine, tacrolimus, everolimus, or sirolimus 1.
- Patients receiving statin and immunosuppressant combination therapy should be monitored closely for muscle-related signs and symptoms 1. Never stop taking either medication without medical guidance, as both treat important conditions that require proper management.
From the Research
Potential Interactions between Itraconazole and Rosuvastatin
The potential interactions between itraconazole and rosuvastatin are a concern due to the risk of increased plasma concentrations of rosuvastatin.
- Itraconazole is known to inhibit cytochrome P450 (CYP) 3A4 and the transport protein P-glycoprotein, which can affect the metabolism of other drugs, including statins 2.
- A study found that itraconazole increased the plasma concentrations of rosuvastatin by 39% for AUC(0-ct) and 28% for AUC(0-t), with a 36% increase in maximum observed plasma drug concentration in one trial and a 15% increase in another trial 2.
- However, the study concluded that the increases in rosuvastatin plasma concentrations were unlikely to be of clinical relevance 2.
Clinical Relevance of the Interaction
The clinical relevance of the interaction between itraconazole and rosuvastatin is a concern due to the risk of increased toxicity.
- A case report described a patient who developed rhabdomyolysis after taking simvastatin and itraconazole, highlighting the potential risk of muscle toxicity when combining these drugs 3.
- Another study found that itraconazole greatly increased serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors, probably by inhibiting CYP3A-mediated metabolism 4.
- A review of the safety of rosuvastatin noted that the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney, and that clinicians should be cautious when rosuvastatin is co-administered with certain drugs, including antifungal azoles like itraconazole 5.
Recommendations for Clinicians
Clinicians should be aware of the potential interaction between itraconazole and rosuvastatin and take steps to minimize the risk of toxicity.
- If antifungal treatment is indicated in a patient using a CYP3A4-metabolised statin, it is recommended to use a non-CYP3A4-inhibiting antifungal drug or to temporarily discontinue statin treatment 3.
- Clinicians should monitor patients for signs of muscle toxicity and renal damage when co-administering itraconazole and rosuvastatin 3, 5.
- The combination of rosuvastatin with certain drugs, including antifungal azoles like itraconazole, should be used with caution and monitored closely for potential interactions 5.