Does Amlodipine Interfere with Simvastatin?
Yes, amlodipine does interact with simvastatin by increasing simvastatin exposure, but this combination can be safely used with a maximum simvastatin dose of 20 mg daily. 1
Key Interaction Mechanism
- Amlodipine increases simvastatin bioavailability by approximately 46% and decreases simvastatin clearance by 13% through CYP3A4 inhibition, primarily at the intestinal level 2
- The FDA drug label explicitly states that co-administration of simvastatin with amlodipine increases systemic exposure of simvastatin and requires dose limitation 1
- This is a minor to moderate pharmacokinetic interaction that is clinically manageable with appropriate dosing 3
Specific Dosing Recommendations
The maximum simvastatin dose when combined with amlodipine is 20 mg daily 3, 1
- Doses of simvastatin exceeding 20 mg daily are not recommended when coadministered with amlodipine 3
- This dose limitation is based on the increased risk of myopathy from elevated simvastatin levels 1
- Despite the pharmacokinetic interaction, combination therapy may be considered and is commonly prescribed 3
Clinical Safety Data
- Real-world analysis of 67,081 patients showed no increased incidence of muscular discomfort with amlodipine-simvastatin combination (6.20%) compared to amlodipine with other statins (6.60%) or simvastatin alone (8.04%) 4
- There is no convincing evidence that this combination increases cases of myopathy or rhabdomyolysis when dose limits are respected 5
- One case report documented severe rhabdomyolysis, but this occurred after adding ciprofloxacin (another CYP3A4 inhibitor) to a patient already on simvastatin-amlodipine, representing a triple drug interaction 6
Critical Distinction from Other Calcium Channel Blockers
Do not confuse amlodipine with diltiazem or verapamil - these non-dihydropyridine calcium channel blockers cause much more significant interactions 3, 7
- Diltiazem increases simvastatin AUC by 5-fold and requires a maximum simvastatin dose of only 10 mg daily 3, 7
- Amlodipine is a dihydropyridine with weaker CYP3A4 inhibition, allowing the higher 20 mg simvastatin dose limit 3
Monitoring Recommendations
Monitor for signs of statin-induced myopathy when using this combination 7:
- Check baseline and follow-up creatine phosphokinase (CPK) levels 7
- Monitor liver enzymes to rule out hepatotoxicity 7
- Educate patients to report muscle pain, weakness, or dark urine immediately
Alternative Management Strategy
If you need higher statin doses or want to avoid the interaction entirely, switch to a non-CYP3A4-metabolized statin 3:
- Atorvastatin, pitavastatin, rosuvastatin, fluvastatin, or pravastatin can be coadministered with amlodipine without dose restrictions 3, 7
- These statins show no evidence of significant interaction with amlodipine 3
- The combination pill of amlodipine/atorvastatin is FDA-approved and available, demonstrating the safety of this alternative 8
Common Pitfall to Avoid
The most common error is prescribing simvastatin 40 mg or 80 mg daily with amlodipine, which violates FDA dosing restrictions and unnecessarily increases myopathy risk 1. Always verify the simvastatin dose does not exceed 20 mg when amlodipine is coprescribed.