From the Guidelines
It is not safe to co-administer itraconazole with rosuvastatin without careful consideration and potential dose adjustments. The provided evidence does not directly address the interaction between itraconazole and rosuvastatin, but based on the general principles of drug-drug interactions, itraconazole is a strong inhibitor of CYP3A4 and can also inhibit hepatic uptake transporters (OATP1B1) [not explicitly mentioned in 1, but based on general medical knowledge]. However, the study 1 discusses the management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease, which can be used as a guide for managing potential interactions. Given the potential for increased rosuvastatin plasma concentrations when co-administered with a strong inhibitor like itraconazole, the risk of statin-related adverse effects, including myopathy and rhabdomyolysis, is increased. If this combination cannot be avoided, the rosuvastatin dose should be temporarily reduced (by approximately 50-75%) during itraconazole treatment, and the patient should be closely monitored for muscle pain, tenderness, or weakness. Alternative antifungal medications with less potential for interaction might be considered if clinically appropriate. After discontinuation of itraconazole, rosuvastatin dosing can be gradually returned to the original dose with appropriate monitoring. Key considerations in managing this potential interaction include:
- Close monitoring of the patient for signs of muscle toxicity
- Potential dose adjustments of rosuvastatin during itraconazole treatment
- Consideration of alternative antifungal therapies with less potential for interaction.
From the Research
Co-administration of Itraconazole and Rosuvastatin
- The co-administration of itraconazole with rosuvastatin may lead to increased plasma concentrations of rosuvastatin, as itraconazole is a potent inhibitor of the liver enzyme CYP3A4, which plays a minor role in the metabolism of rosuvastatin 2.
- However, the increase in plasma concentrations of rosuvastatin is considered modest and unlikely to be of clinical relevance 2.
- A study found that after co-administration with itraconazole, the rosuvastatin geometric least-square mean for the treatment ratio was increased by 39% for AUC(0-ct) and by 28% for AUC(0-t), with the treatment ratio for maximum observed plasma drug concentration increased by 36% and 15% in two separate trials 2.
- It is essential to note that rosuvastatin is not significantly metabolized by CYP3A4, which reduces the risk of significant drug-drug interactions with itraconazole compared to other statins like simvastatin, atorvastatin, and lovastatin 3, 2.
- In general, when co-administering statins with other medications, it is crucial to consider the risk of muscle adverse effects, such as myopathy and rhabdomyolysis, especially in patients with factors that increase this risk, like advanced age, diabetes mellitus, and hypothyroidism 4, 5.
Clinical Considerations
- Clinicians should be aware of the potential for increased plasma concentrations of rosuvastatin when co-administered with itraconazole and monitor patients for signs of muscle toxicity 2, 4, 5.
- If muscle adverse effects occur, clinicians can consider alternative treatments, such as lowering the dose of rosuvastatin, switching to a different statin, or adding non-statin lipid-lowering agents 4, 5, 6.