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.
Results
