Rosuvastatin and Grapefruit: No Clinically Significant Interaction
Rosuvastatin can be safely taken with grapefruit juice without dose adjustment or avoidance, as it is not metabolized by CYP3A4 and has minimal interaction with grapefruit. 1, 2
Why Rosuvastatin is Safe with Grapefruit
Rosuvastatin is primarily eliminated unchanged through active transport mechanisms (OATP1B1/3, breast cancer resistance protein, and OAT3) rather than through CYP3A4 metabolism, which is the enzyme inhibited by grapefruit juice. 1 This fundamental difference in metabolic pathway distinguishes rosuvastatin from statins like simvastatin, lovastatin, and atorvastatin that are significantly affected by grapefruit. 1, 2
- Grapefruit juice inhibits CYP3A4 enzymes and P-glycoprotein in the intestine, which dramatically increases blood levels of CYP3A4-metabolized statins 2
- Pravastatin, rosuvastatin, fluvastatin, and pitavastatin are not significantly metabolized by CYP3A4 and have minimal interaction with grapefruit juice 1
- Rosuvastatin is metabolized primarily by CYP2C9, not CYP3A4 1
Statins That DO Interact with Grapefruit
For context, you should be aware of which statins require grapefruit avoidance:
- Simvastatin and lovastatin: Complete avoidance of grapefruit is recommended, as grapefruit increases their blood levels 9-16 fold 2, 3, 4
- Atorvastatin: Grapefruit increases blood levels by approximately 80% and should be limited or the dose adjusted 1, 5
Clinical Recommendations for Rosuvastatin
Patients taking rosuvastatin do not need to avoid or limit grapefruit consumption. 1 This makes rosuvastatin an excellent alternative for patients who regularly consume grapefruit and require statin therapy. 1
- When patients cannot avoid grapefruit consumption, consider using pravastatin, rosuvastatin, fluvastatin, or pitavastatin as alternatives 1
- Rosuvastatin is specifically recommended as an alternative for patients who consume grapefruit while needing statin therapy 1
Important Caveat: Pomegranate Juice
While grapefruit is safe with rosuvastatin, one case report documented rhabdomyolysis associated with pomegranate juice consumption during rosuvastatin treatment 6, suggesting that pomegranate juice (not grapefruit) may pose a risk despite rosuvastatin's lack of CYP3A4 metabolism. This remains a single case report and the mechanism is unclear. 6
Special Populations
In patients with impaired renal or hepatic function taking rosuvastatin, grapefruit consumption remains safe as the interaction mechanism (CYP3A4 inhibition) does not apply to rosuvastatin's elimination pathway. 1 However, note that rosuvastatin itself may require dose adjustment in severe renal impairment based on kidney function, independent of any grapefruit interaction. 7