Interaction between Lopinavir-ritonavir (Kaletra) and Rosuvastatin (Crestor) Reduces Drug's Lipid-lowering Effect

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By Liz Highleyman

During the HAART era, concern about the risk of cardiovascular disease among people with HIV has grown because the population is aging and antiretroviral therapy can cause metabolic side effects that may increase the risk of heart disease.

This has led to more HIV positive people using lipid-lowering medications such as statins. However, caution is needed when using these medications in conjunction with antiretroviral drugs, due to the potential for drug interactions and additive side effects.

Drug interactions, which may occur when 2 or more agents are processed by the same enzymes in the liver, can lead to drug levels that are too low (and therefore less effective) or too high (causing intensified side effects).

Kaletra Tablet

Crestor Tablet

As reported in the April 15, 2008 Journal of Acquired Immune Deficiency Syndromes, investigators designed an open-label, single-arm pharmacokinetic (PK) study of healthy HIV negative volunteers to evaluate whether levels of rosuvastatin (Crestor) and lopinavir/ritonavir (Kaletra) remained the same when administered alone and in combination. Tolerability and blood lipid changes were also assessed.

A total of 20 HIV negative participants took 20 mg of rosuvastatin alone for 7 days, then lopinavir/ritonavir alone for 10 days, and then the combination for 7 days. Intensive pharmacokinetic sampling was performed on days 7, 17, and 24, with data available for 15 subjects.

Results

• Geometric mean rosuvastatin areas under the concentration time curve (AUC, a measure of total drug concentration between doses) were 47.6 ng.h/mL when given alone versus 98.8 ng.h/mL when combined with lopinavir/ritonavir (P < 0.0001).

• The maximum rosuvastatin concentration (Cmax) was 4.34 ng/mL when administered alone, compared with 20.2 ng/mL when combined with lopinavir/ritonavir (P < 0.0001).

• The geometric mean ratio was 2.1 for rosuvastatin AUC and 4.7 for rosuvastatin Cmax with lopinavir/ritonavir versus rosuvastatin alone (P < 0.0001).

• 1 participant experienced an asymptomatic creatine phosphokinase elevation, 17 times the upper limit of normal (ULN), while taking both drugs.

• 1 experienced a liver function test elevation, between 1.1 and 2.5 times the ULN, while taking the combination.

Conclusion

The study authors concluded that, "Rosuvastatin low-density lipoprotein [LDL cholesterol] reduction was attenuated with lopinavir/ritonavir."

They added that, "Rosuvastatin AUC and Cmax were unexpectedly increased 2.1- and 4.7-fold in combination with lopinavir/ritonavir."

Based on these findings, they recommended that, "Rosuvastatin and lopinavir/ritonavir should be used with caution until the safety, efficacy, and appropriate dosing of this combination have been demonstrated in larger populations."

Department of Pharmaceutical Sciences, University of Colorado Denver, Denver, CO; Divisions of Pharmacology and Toxicology and Infectious Diseases, University of Colorado Denver, Denver, CO; Department of Preventive Medicine and Biometrics, University of Colorado Denver, Denver, CO; Department of Pharmacy, University of Colorado Hospital, Denver, CO.

5/13/08

Reference
J Kiser, J Gerber, J Predhomme, and others. Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. Journal of Acquired Immune Deficiency Syndromes. 47(5):570-578. April 15, 2008.