Can simvastatin (statin) and diltiazem (calcium channel blocker) be prescribed together?

Simvastatin and Diltiazem Should Not Be Prescribed Together

Simvastatin and diltiazem should not be prescribed together due to significant drug-drug interactions that increase the risk of myopathy and rhabdomyolysis. A non-CYP3A4-metabolized statin such as rosuvastatin, pravastatin, or pitavastatin is preferred when diltiazem therapy is required. 1

Mechanism of Interaction

The interaction between simvastatin and diltiazem occurs because:

• Diltiazem is an inhibitor of CYP3A4, the primary enzyme responsible for simvastatin metabolism 2
• This interaction significantly increases simvastatin exposure:
  • 5-fold increase in simvastatin AUC 3
  • 3.6-fold increase in peak serum concentration of simvastatin 3
  • 2.3-fold increase in elimination half-life 3

Evidence-Based Recommendations

The American Heart Association specifically recommends:

1. Doses of simvastatin >10 mg daily when used with diltiazem are not recommended 1
2. A non-CYP3A4-metabolized statin is preferred in combination with diltiazem 1
3. For patients on stable therapy with simvastatin, clinicians should change to a non-CYP3A4 statin if diltiazem therapy is initiated 1

Clinical Consequences of Co-administration

The consequences of this interaction can be serious:

• Increased risk of myopathy and rhabdomyolysis 4, 5
• Potential for hepatitis 5
• Case reports document CK elevations >8000 U/L and ALT elevations >200 IU/L 4

Safe Alternatives

When a patient requires both a statin and diltiazem, the following options are safer:

• Preferred options: Pravastatin, rosuvastatin, or pitavastatin 1, 6
• These statins are not significantly metabolized by CYP3A4 and have minimal interaction with diltiazem
• In a clinical study, diltiazem did not affect the pharmacokinetics of pravastatin 7

Special Considerations

• Asian patients may be at higher risk for statin-related adverse effects when combined with calcium channel blockers 1
• The interaction appears to be a first-pass rather than a systemic event 7
• Enhanced cholesterol reduction has been observed in patients taking both simvastatin and diltiazem (33.3% vs 24.7%), but this comes with increased risk 8

Monitoring Recommendations

If no alternative to the combination can be used (which is rarely the case):

• Limit simvastatin to ≤10 mg daily 1
• Monitor for signs and symptoms of myopathy (muscle pain, tenderness, or weakness)
• Check liver function tests and creatine kinase levels at baseline and periodically
• Educate patients to report any muscle symptoms immediately

In conclusion, the combination of simvastatin and diltiazem should be avoided whenever possible due to the well-documented risk of serious adverse effects. When both medications are indicated, switching to a non-CYP3A4-metabolized statin is the safest approach.