The increasing use of ticagrelor for prevention of ischemic events in patients with acute coronary events raises the potential risk of adverse events caused by interactions with statins, leading to rhabdomyolysis. |
This interaction might be the result of CYP3A4 inhibition, but other pathways, such as competitive interaction with OATPs or P-glycoprotein, might be involved as well. |
Co-administration of statins and ticagrelor was found to be relatively safe in routinely prescribed doses. However, caution should be exercised, especially in elderly populations. |
1 Introduction
2 Statin-Induced Myopathy and Rhabdomyolysis
3 Influence of Ticagrelor on Renal Function
4 Underlying Mechanism of the Ticagrelor–Statin Interaction
4.1 Pharmacokinetic Interaction
4.2 CYP-450-Mediated Metabolism
4.3 Transport Mediated by OATPs
4.4 P-Glycoprotein System
4.5 Glucuronidation through UDP-Glucuronosyltransferase
5 Review of Reported Case Studies with a Possible Ticagrelor-Statin Interaction
Interaction through CYP3A4 | Other routes | |
---|---|---|
Inhibition | Induction | |
AmiodaroneS AmlodipineS CyclosporinS,A,R,T ClarithromycinS,A,T DanazolS DiltiazemT DronedaroneR ErythromycinS,A,T FluconazoleT Grapefruit juiceS,A,T Hepatitis C protease inhibitorsS,A HIV protease inhibitorsA,R,T ItraconazoleS,A,R,T KetoconazoleS,A,T VerapamilS,T VoriconazoleS | RifampicinA,T EfavirenzA PhenytoinS,A,R,T CarbamazepineT PhenobarbitalT DexamethasoneT | GemfibrozilS,R Warfarin (CYP2C9)R,T NiacinA Rifampicin (OATP1B1)A Fusidic acidA,R ColchicineA Eltrompobag (CYP450 substrate, UGT glucuronidation)R Cyclosporine (P-pg inhibition) Digoxin (P-gp substrate)A,T Clopidogrel (CYP450, P-gp substrate)R |
Statin | Dose of statin (mg) | Age (years) | Sex | Co-administered drugs |
---|---|---|---|---|
Simvastatin [59] | 20 | 72 | Male | Aspirin, ramipril, pantoprazole, tiotropium bromide, beclomethasone, formoterol |
Atorvastatin [60] | 80 | 62 | Female | Aspirin, metoprolol |
Atorvastatin [61] | 80 | 74 | Female | Amlodipine |
Atorvastatin [62] | 40 | 72 | Male | Aspirin, bisoprolol, enalapril, clarithromycin |
Rosuvastatin [64] | 40 | 78 | Male | Amlodipine, omeprazole, Perindopril, metoprolol, ezetimibe |
Rosuvastatin [65] | 20 | 49 | Female | Lisinopril, metformin, metoprolol, pantoprazole |