Delavirdine versus Lovastatin or Simvastatin
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Study Design
The interaction between these agents has not been formally studied, but case reports such as that seen below have described potential related interactions. Report a patient who developed acute tubular necrosis caused by severe rhabdomyolysis, which was probably associated with the coadministration of atorvastatin and delavirdine. A 63-year-old man had well controlled hypercholesterolemia, for which he had been receiving atorvastatin (20 mg) administered daily for the last 5 years, and HIV infection, for which he was receiving treatment with indinavir, lamivudine, and stavudine for the previous 9 years. About 2 months before his hospital admission, indinavir was substituted with delavirdine (400 mg every 8 hours).
Study Results
Approximately 1 month after beginning the new regimen, he developed a generalized malaise, with muscle pain in legs and lower back, nausea, vomiting, and dark urine. He was found to have acute renal failure (serum urea nitrogen, 67 mg/dL; serum creatinine, 7.6 mg/dL) and rhabdomyolysis (creatine kinase, 9600 U/L; aspartate aminotransferase, 1575 IU/L; alanine aminotransferase, 948 IU/L; myoglobin in urine, 20 700 μg/L). All his medications were withheld. Ten days later, his enzymes levels improved (creatine kinase, 801 U/L; aspartate aminotransferase, 78 IU/L; alanine aminotransferase, 272 IU/L; serum urea nitrogen, 46 mg/dL; serum creatinine, 3.9 mg/dL), and were normal 1 month later.
Study Conclusions
Both lovastatin and simvastatin are CYP3A4 substrates and are especially sensitive to CYP3A4 inhibition; DLV may increase concentrations of these statins. The co-administration of lovastatin or simvastatin with DLV is not recommended due to the increased potential for serious reactions such as myopathy. Other statins such as atorvastatin or pravastatin are recommended. If concomitant use is deemed beneficial, careful monitoring is recommended for both safety and efficacy.
References
Castro JG, Gutierrez L. Rhabdomyolysis with acute renal failure probably related to the interaction of atorvastatin and delavirdine. The American Journal Of Medicine. 2002; 6: 505.
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