Symptomatic hyperbilirubinemia with indinavir/ritonavir-containing regimen.
OBJECTIVE
To report a case of symptomatic hyperbilirubinemia resulting from the addition of ritonavir to an indinavir-containing antiretroviral regimen.


METHODS
A 27-year-old white woman developed symptomatic hyperbilirubinemia and anemia while receiving an indinavir/ritonavir-containing antiretroviral (ARV) regimen that required disruption of therapy. Extensive laboratory examinations were performed including determination of indinavir and ritonavir concentrations. The findings were attributed to two independent processes, an unconjugated hyperbilirubinemia due to indinavir and anemia due to zidovudine.


CONCLUSIONS
Indinavir-induced hyperbilirubinemia is generally regarded as an adverse event with no clinical relevance that does not cause significant liver toxicity and does not necessitate discontinuing indinavir. It manifests primarily as an increase in unconjugated bilirubin and is reported to be dose related. We believe that the severe hyperbilirubinemia in this patient was a result of high indinavir concentrations that occurred due to metabolic inhibition caused by ritonavir. The anemia in this case was consistent with erythrocyte maturation arrest due to zidovudine rather than hemolysis.


CONCLUSIONS
Combination ARV therapy is the current standard of care for treating patients infected with HIV. It is important for providers to consider that, despite much improved pharmacokinetic profiles associated with pharmacokinetically enhanced protease inhibitor regimens, there may be undesirable effects that may differ in frequency or severity than when drugs are used individually.
Rayner
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CR
Department of Pharmacy Practice, Monash University, Parkville, Victoria, Australia. craig.rayner@vcp.monash.edu.au
Esch
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Wynn
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Eales
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D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced*; D019469:Indinavir / Q000009:adverse effects*; D019438:Ritonavir / Q000009:adverse effects*
D019380:Anti-HIV Agents; D004338:Drug Combinations; D019469:Indinavir; D019438:Ritonavir