Can atorvastatin (Lipitor) and diltiazem (Cardizem) be prescribed together?

Co-administration of Atorvastatin and Diltiazem

Atorvastatin and diltiazem can be prescribed together, but this combination results in a minor increase in statin exposure and requires monitoring for potential adverse effects. 1

Drug Interaction Mechanism

Diltiazem is a moderate inhibitor of CYP3A4, the enzyme system responsible for the metabolism of atorvastatin. When these medications are co-administered:

• Diltiazem increases atorvastatin plasma levels through inhibition of CYP3A4 enzymes and drug transporters 1
• This interaction is primarily a first-pass effect rather than a systemic event 2
• The increase in atorvastatin exposure is considered "minor" compared to other statin-diltiazem combinations 1

Clinical Recommendations

The American Heart Association provides specific guidance on this combination:

1. Combination therapy with atorvastatin and diltiazem is reasonable with appropriate monitoring 1
2. While non-CYP3A4-metabolized statins (rosuvastatin, pravastatin, pitavastatin, fluvastatin) are preferred when using diltiazem 1
3. If using atorvastatin with diltiazem:
   • Monitor for signs and symptoms of myopathy (muscle pain, weakness, tenderness)
   • Consider baseline and follow-up liver function tests
   • Watch for signs of rhabdomyolysis (severe muscle pain, dark urine, weakness)

Risk Factors for Adverse Events

Cases of rhabdomyolysis have been reported when atorvastatin and diltiazem are used together, particularly when additional risk factors are present:

• Higher doses of atorvastatin (≥40 mg daily) 3
• Genetic predisposition to impaired statin metabolism 4
• Advanced age
• Renal impairment
• Multiple medications that may interact with either drug

Important Precautions

1. Dose considerations:

   • Consider using lower doses of atorvastatin when combined with diltiazem
   • The FDA label for diltiazem specifically warns about the increased risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 5

2. Monitoring recommendations:

   • Inform patients about signs and symptoms of muscle injury to report
   • Consider more frequent monitoring of liver enzymes and creatine kinase in high-risk patients
   • Be particularly vigilant when initiating the combination or changing doses

Clinical Pitfalls to Avoid

• Don't ignore new symptoms: Rhabdomyolysis can develop even after months of stable therapy when diltiazem is added to atorvastatin 6
• Don't miss early warning signs: Elevated liver enzymes or mild muscle pain may precede more serious complications
• Don't overlook drug interactions: Both medications may interact with other drugs in complex regimens

In summary, while atorvastatin and diltiazem can be prescribed together, this combination requires appropriate patient selection, monitoring, and dose adjustment to minimize the risk of adverse effects.