Severe Rhabdomyolysis and Acute Renal Failure Secondary to Concomitant Use of Simvastatin, Amiodarone, and Atazanavir

Article Figures & Data

Table 1.

Summary of Published Case Reports Describing an Interaction Between Simvastatin and Miodarone

Details	Patient 1⁷	Patient 2⁸	Patient 3¹²	Patient 4¹⁶	Patient 5²¹	Current Patient
Age/sex	72/male	63/male	77/male	68/female	56/male	72/male
Simvastatin dose^*	80 mg	40 mg	80 mg	40 mg	40 mg	80 mg
Amiodarone dose^*	200 mg	200 mg	100 mg	Not reported	600 mg	200 mg
Other risk factors^†	Chronic renal insufficiency, age, diabetes, recent surgery	Age, diabetes, recent surgery	Chronic renal insufficiency, age, hypo-thyroidism	Age, verapamil	Recent surgery, clarithromycin	Age, atazanavir, delviradine
Reported adverse event	Rhabdomyolysis	Rhabdomyolysis	Rhabdomyolysis	Myopathy	Myositis	Rhabdomyolysis
Time to adverse event^‡	39 days	14 days	21 days	2 years	1 to 9 days	19 days
Peak creatine kinase (U/L)	19,620	40,392	28,523	48,000	>20,000	>70,000
Dialysis required	No	No	No	No	No	Yes
Outcome	Resolved	Resolved	Resolved	Resolved	Resolved	Resolved after 1 month of dialysis

* Dose at time of adverse event.
† Other risk factors include advanced age, chronic renal insufficiency, metabolic disorders such as diabetes or hypothyroidism, major surgery, alcohol abuse, and the use of concomitant medications (azole antifungals, macrolide antibiotics, HIV protease inhibitors, nefazodone, cyclosporine, danazol, verapamil, and amiodarone).
‡ Time to adverse event from the time that amiodarone and simvastatin were being administered concomitantly.

Table 2.

Summary of Manufacturer Recommendations for Statin and Protease Inhibitor Drug Interactions as Described in Prescribing Information

CYP3A4 Inhibitor	Simvastatin	Lovastatin	Atorvastatin	Pravastatin	Fluvastatin	Rosuvastatin
Atazanavir	Not recommended	Not recommended	Use with caution	Clinically significant DIs are not expected	Clinically significant DIs are not expected	N/A
Nelfinavir	Not recommended^*	Not recommended	Use with caution	Considered safe	Considered safe	N/A
Ritonavir	Not recommended^*	Not recommended	Use with caution	Considered safe	Considered safe	N/A
Indinavir	Not recommended	Not recommended	Use with caution	Considered safe	Considered safe	Considered safe
Saquinavir	Not recommended	Not recommended	Use with caution	Considered safe	Considered safe	Considered safe
Amprenavir	Not recommended	Not recommended	Use with caution	Considered safe	Considered safe	N/A
Fosamprenavir	Not recommended	Not recommended	Use with caution	Considered safe	Considered safe	Considered safe
Lopinavir/ritonavir	Not recommended	Not recommended	Use with caution^*	Considered safe	Considered safe	N/A
Tipranavir	Not recommended	Not recommended	Use with caution	N/A	N/A	N/A