TM is a 78 YOW with a history of hypertension, hypercholesterolemia and arthritis was admitted for proximal arterial fibrillation. While in the…

The patient is being started on diltiazem, a moderate inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme. Her home medication, simvastatin, is a substrate of CYP3A4. Co-administration of diltiazem significantly increases the plasma concentration of simvastatin, elevating the risk of myopathy and rhabdomyolysis. The maximum recommended dose of simvastatin with diltiazem is 10 mg daily. A more appropriate action is to switch to a statin with a less clinically significant interaction. While atorvastatin is also a CYP3A4 substrate, the interaction is less severe. The maximum recommended dose of atorvastatin with diltiazem is 40 mg daily. This change maintains the high-intensity statin therapy appropriate for the patient while mitigating the significant drug interaction risk.

A. Increasing simvastatin to 80mg would severely increase the risk of myopathy and rhabdomyolysis due to the drug interaction.

B. Keeping simvastatin at 40mg is inappropriate as it exceeds the maximum recommended dose of 10mg when used with diltiazem.

D. Changing to lovastatin 20mg is a low-intensity statin, which is a clinically inappropriate step-down from the patient's current high-intensity therapy.

E. Discontinuing statin therapy is not appropriate for a patient with hypercholesterolemia and cardiovascular risk factors.

1. U.S. Food and Drug Administration (FDA). ZOCOR (simvastatin) Prescribing Information. Revised: 08/2021. Section 7.1

Table 2: Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis with ZOCOR. The table specifies for Diltiazem: "Do not exceed 10 mg/day of ZOCOR." (Available at FDA Drugs@FDA database).

2. U.S. Food and Drug Administration (FDA). LIPITOR (atorvastatin calcium) Prescribing Information. Revised: 05/2022. Section 7.1

Table 2: Atorvastatin Drug Interactions. The table specifies for Diltiazem: "Atorvastatin dose should not exceed 40 mg daily." (Available at FDA Drugs@FDA database).

3. Grundy

S. M.

Stone

N. J.

Bailey

A. L.

et al. (2019). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation

139(25)

e1082–e1143. Table 3

"High-

Moderate-

and Low-Intensity Statin Therapy

" lists Atorvastatin 40-80 mg and Simvastatin 20-40 mg as high-intensity statins

and Lovastatin 20 mg as a low-intensity statin. (DOI: 10.1161/CIR.0000000000000625).

4. Wiggins

B. S.

Saseen

J. J.

Page

R. L.

et al. (2016). Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation

134(21)

e468–e495. Section 4.2.2

"Diltiazem and Verapamil

" discusses the interactions with simvastatin and atorvastatin

supporting the dose limitations cited in FDA labels. (DOI: 10.1161/CIR.0000000000000456).