Why is there a contraindication for using ticagrelor and simvastatin together?

The rationale for the contraindication of using ticagrelor and simvastatin together primarily revolves around the potential for increased plasma concentrations of simvastatin when co-administered with ticagrelor. Simvastatin is metabolized by a liver enzyme known as CYP3A4, and ticagrelor can influence the metabolic pathways of drugs that are substrates of this enzyme.

When ticagrelor is taken with simvastatin, especially in doses exceeding 40 mg, there is a significant risk of elevated levels of simvastatin in the bloodstream. This can lead to an increased likelihood of adverse effects, such as the risk of myopathy or rhabdomyolysis, due to the higher plasma concentration of simvastatin. Therefore, it is recommended that the dose of simvastatin not exceed 40 mg per day when it is used in conjunction with ticagrelor to mitigate these risks and ensure patient safety.

This context is crucial to understanding the interaction between these medications and why specific dosing guidelines exist when they are prescribed together.