Can fluconazole be given with simvastatin (statin)?

From the Guidelines

Fluconazole should not be given with simvastatin due to potential drug interactions, as indicated by the contraindication of itraconazole with simvastatin 1. When considering the use of fluconazole with simvastatin, it's crucial to understand the potential for increased simvastatin levels in the bloodstream due to fluconazole's inhibition of the CYP3A4 enzyme system in the liver. This interaction can lead to an increased risk of simvastatin-related side effects, including myopathy and rhabdomyolysis. Some key points to consider when managing patients on both medications include:

• Monitoring for muscle pain, tenderness, or weakness, especially during the initial weeks of combined therapy
• Considering alternative antifungal medications with less potential for interaction if appropriate for the infection being treated
• Informing healthcare providers about all medications being taken to effectively manage potential interactions However, the most recent and highest quality evidence regarding the specific interaction between fluconazole and simvastatin is limited, but given the similarity in mechanism with itraconazole, caution is advised 1. Additionally, guidelines for managing patients with chronic kidney disease suggest that statins, including simvastatin, can be used with caution in patients with reduced renal function, but the specific interaction with fluconazole is not addressed in this context 1. Given the potential risks, the safest approach is to avoid concomitant use of fluconazole and simvastatin whenever possible.

From the FDA Drug Label

HMG-CoA reductase inhibitors: The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin (decreased hepatic metabolism of the statin) If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatinine kinase should be monitored. HMG-CoA reductase inhibitors should be discontinued if a marked increase in creatinine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected. Dose reduction of statins may be needed Refer to the statin-specific prescribing information for details.

Strong CYP3A4 inhibitors Clinical Impact: Simvastatin is a substrate of CYP3A4. Concomitant use of strong CYP3A4 inhibitors with simvastatin increases simvastatin exposure and increases the risk of myopathy and rhabdomyolysis, particularly with higher simvastatin dosages Intervention: Concomitant use of strong CYP3A4 inhibitors with Simvastatin is contraindicated [see CONTRAINDICATIONS (4)] . If treatment with a CYP3A4 inhibitor is unavoidable, suspend simvastatin during the course of strong CYP3A4 inhibitor treatment.

Fluconazole and simvastatin can be given together but with caution. The risk of myopathy and rhabdomyolysis is increased when fluconazole is coadministered with simvastatin.

• Patients should be observed for symptoms of myopathy and rhabdomyolysis.
• Creatinine kinase should be monitored.
• HMG-CoA reductase inhibitors, such as simvastatin, should be discontinued if a marked increase in creatinine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected.
• Dose reduction of simvastatin may be needed.
• Refer to the simvastatin-specific prescribing information for details 2 3.

From the Research

Interaction between Fluconazole and Simvastatin

• The concomitant use of fluconazole and simvastatin can increase the risk of myopathy or rhabdomyolysis due to the inhibition of the cytochrome P450 3A4 enzyme by fluconazole 4, 5, 6, 7.
• This interaction can lead to elevated levels of simvastatin in the body, increasing the risk of muscle toxicity 4, 5, 6, 7.
• Several case reports have documented the development of rhabdomyolysis in patients taking simvastatin and fluconazole concurrently 4, 6, 7.
• The risk of myopathy or rhabdomyolysis can be minimized by closely monitoring patients for signs of muscle toxicity and adjusting the simvastatin dose or discontinuing the drug if necessary 5, 8.
• It is essential to be aware of this potential interaction and take steps to prevent it, especially in patients with a history of muscle disease or those taking other medications that can increase the risk of myopathy 5, 8.

Clinical Implications

• Patients receiving simvastatin should be closely monitored for signs of muscle toxicity, such as muscle weakness or pain, if fluconazole is added to their medication regimen 4, 5, 6, 7.
• The dose of simvastatin may need to be adjusted or the drug discontinued if signs of muscle toxicity occur 5, 8.
• Alternative antifungal medications that do not inhibit the cytochrome P450 3A4 enzyme may be considered in patients taking simvastatin 5.
• Interdisciplinary cooperation between healthcare professionals is crucial in preventing and managing potential drug interactions between simvastatin and fluconazole 5.