Ticagrelor-Simvastatin CYP3A4 Interaction — EECC MCQ

Correct answer: E — Ticagrelor is a moderate CYP3A4 inhibitor that increases simvastatin levels (a CYP3A4 substrate) — the risk of statin-related myopathy is increased; simvastatin dose should not exceed 40 mg with ticagrelor, or preferably switch to a statin less dependent on CYP3A4 (rosuvastatin or pravastatin)

Ticagrelor (unlike clopidogrel and prasugrel) is a moderate inhibitor of CYP3A4. Simvastatin and lovastatin are extensively metabolised by CYP3A4, and their plasma levels increase significantly when co-prescribed with CYP3A4 inhibitors — increasing the risk of myopathy and rhabdomyolysis. The BNF recommends simvastatin dose ≤40 mg with ticagrelor. However, pragmatically, switching to a statin with minimal CYP3A4 dependence is preferred: (1) rosuvastatin (predominantly CYP2C9, not significantly affected by CYP3A4 inhibitors — PREFERRED); (2) pravastatin (not significantly CYP metabolised). Atorvastatin is also CYP3A4-metabolised but to a lesser extent than simvastatin, with a wider therapeutic index. This interaction is commonly encountered in post-ACS patients and is an important medication safety issue.

Reference: BNF; ESC (2023): ACS Guidelines