Atorvastatin and Caplyta (Lumateperone) Interaction
No clinically significant drug-drug interaction exists between atorvastatin and Caplyta (lumateperone), and these medications can be safely co-prescribed without dose adjustments for either agent.
Mechanism Analysis
- Atorvastatin is primarily metabolized by CYP3A4 and serves as a substrate for this enzyme system 1
- Caplyta (lumateperone) is also metabolized by CYP3A4 but functions as a substrate rather than an inhibitor or inducer of this pathway 2
- Since both medications are substrates (not inhibitors) of the same enzyme system, they do not interfere with each other's metabolism 2
- The FDA labeling for Caplyta specifically warns against CYP3A4 inducers (which decrease lumateperone levels) and CYP3A4 inhibitors (which increase lumateperone levels), but atorvastatin falls into neither category 2
Clinical Management
Standard dosing of both medications can be used without modification:
- Initiate atorvastatin at the clinically appropriate dose for cardiovascular risk reduction (typically 10-80 mg daily) 1
- Initiate Caplyta at the standard dose of 42 mg once daily 3
- No dose reduction is required for either medication when used together 2
Monitoring Recommendations
Apply routine statin safety monitoring only:
- Assess for unexplained muscle pain, tenderness, or weakness at each clinical visit 1
- Baseline creatine kinase (CK) is not mandatory but may be considered in high-risk patients 1
- Check CK only if muscle symptoms develop during therapy 1
- Monitor liver function tests as clinically indicated per standard statin protocols 1
Important Caveats
Be vigilant about third-party drug interactions:
- If adding a strong CYP3A4 inhibitor (e.g., itraconazole, ritonavir, clarithromycin), reduce Caplyta dose to 21 mg daily and consider limiting atorvastatin to ≤20 mg daily 1, 2
- If adding a moderate CYP3A4 inhibitor (e.g., diltiazem, verapamil, erythromycin), reduce Caplyta dose to 21 mg daily and use atorvastatin cautiously at lower doses 1, 2, 4
- Avoid CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort) entirely as they will reduce Caplyta efficacy 2
- Cyclosporine is contraindicated with atorvastatin due to 6-15 fold increases in statin exposure and rhabdomyolysis risk 1
Alternative Considerations
If concerns arise about polypharmacy or additional CYP3A4-interacting drugs:
- Consider switching to pravastatin (not metabolized by CYP3A4, limit to 20 mg daily with other interacting drugs) 1
- Consider switching to rosuvastatin (minimal CYP3A4 metabolism, limit to 5 mg daily with cyclosporine or similar agents) 1
- Consider switching to fluvastatin (metabolized by CYP2C9, not CYP3A4) 1, 5