What is the interaction between Atorvastatin (Lipitor) and Diltiazem (Cardizem)?

From the Guidelines

Atorvastatin and Diltiazem can be used together, but it is recommended to prefer a non-CYP3A4-metabolized statin, such as atorvastatin, in combination with diltiazem, as this combination results in only a minor increase in statin exposure. According to the American Heart Association scientific statement 1, combination therapy with atorvastatin and diltiazem is reasonable due to the minor increase in statin exposure. Some key points to consider when using this combination include:

• Diltiazem can increase blood levels of atorvastatin by inhibiting the CYP3A4 enzyme that metabolizes statins, potentially raising the risk of muscle-related side effects like myopathy or rhabdomyolysis 1.
• A lower starting dose of atorvastatin is not necessarily recommended, as the increase in statin exposure is minor, but careful monitoring is still necessary 1.
• Patients should promptly report any unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise.
• Regular liver function and creatine kinase monitoring may be necessary, particularly during the first few months of therapy.
• The benefits of this combination often outweigh the risks for patients with both hyperlipidemia and hypertension or certain cardiac conditions, as atorvastatin reduces cholesterol while diltiazem helps control blood pressure and heart rate 1. It is essential to manage this combination under the supervision of a healthcare provider who can assess individual risk factors and adjust dosing accordingly.

From the FDA Drug Label

Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased with concomitant use of diltiazem When possible, use a non-CYP3A4-metabolized statin together with diltiazem; otherwise, dose adjustments for both diltiazem and the statin should be considered along with close monitoring for signs and symptoms of any statin related adverse events In a healthy volunteer cross-over study (N=10), co-administration of a single 20 mg dose of simvastatin at the end of a 14 day regimen with 120 mg BID diltiazem SR resulted in a 5-fold increase in mean simvastatin AUC versus simvastatin alone. In a ten-subject randomized, open label, 4-way cross-over study, co-administration of diltiazem (120 mg BID diltiazem SR for 2 weeks) with a single 20 mg dose of lovastatin resulted in 3- to 4-fold increase in mean lovastatin AUC and Cmax versus lovastatin alone.

The interaction between Atorvastatin (Lipitor) and Diltiazem (Cardizem) is that Diltiazem, as a CYP3A4 inhibitor, may increase the AUC of Atorvastatin, which is a CYP3A4 substrate. This may increase the risk of myopathy and rhabdomyolysis.

• Key points:
  • Diltiazem increases the AUC of some statins, including Atorvastatin
  • The risk of myopathy and rhabdomyolysis may be increased with concomitant use
  • Dose adjustments and close monitoring may be necessary
  • Consider using a non-CYP3A4-metabolized statin with Diltiazem 2

From the Research

Interaction between Atorvastatin and Diltiazem

• The interaction between Atorvastatin (Lipitor) and Diltiazem (Cardizem) has been studied in various contexts, including their effects on endothelial function and exercise tolerance in patients with cardiac syndrome X 3.
• A case report describes a patient who developed rhabdomyolysis and acute hepatitis after initiating diltiazem while already taking atorvastatin, suggesting a potential drug interaction between the two medications 4.
• Diltiazem is a potent inhibitor of CYP3A4, which can affect the metabolism of other medications, including atorvastatin, and increase the risk of drug interactions 5.
• The safety and efficacy of diltiazem in patients with atrial fibrillation complicated by congestive heart failure have been reviewed, but the specific interaction between atorvastatin and diltiazem in this context is not well-studied 6.
• Combination therapy with a statin (fluvastatin) and a calcium channel blocker (diltiazem) has been shown to be more effective than monotherapy in improving endothelial function and exercise tolerance in patients with cardiac syndrome X 3.

Potential Risks and Considerations

• The concomitant use of atorvastatin and diltiazem may increase the risk of rhabdomyolysis and other adverse effects due to the potential drug interaction 4.
• Patients taking atorvastatin and diltiazem should be closely monitored for signs and symptoms of muscle injury and other adverse effects 4.
• The potential for drug interactions between atorvastatin and diltiazem should be considered when prescribing these medications, especially in patients with complex medication regimens or comorbidities 5.