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Drug–Drug Interaction Between Itraconazole and the Protease Inhibitor Lopinavir/Ritonavir

HIV Clinical Pharmacist, Northern Alberta HIV Program and Regional Pharmacy Services, Alberta Health Services, Edmonton, AB, Canada

Christine A Hughes, BScPharm PharmD FCSHP

Associate Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton; Clinical Pharmacotherapy Practitioner–HIV, Northern Alberta HIV Program and Regional Pharmacy Services, Alberta Health Services

Stan Houston, MD FRCPC

Director, Northern Alberta HIV Program; Professor of Medicine and Public Health, Division of Infectious Diseases, Department of Medicine, University of Alberta

Stephen D Shafran, MD FRCPC

Professor of Medicine, Division of Infectious Diseases, Department of Medicine, University of Alberta

Reprints: Dr. Hughes, Faculty of Pharmacy and Pharmaceutical Sciences, 3126 Dentistry/Pharmacy Centre, University of Alberta, Edmonton, AB T6G 2N8, Canada, fax 780/492-1217, chughes{at}pharmacy.ualberta.ca

OBJECTIVE: To report the results of therapeutic drug monitoring of lopinavir/ritonavir and itraconazole concentrations in an HIV-infected male who was treated for histoplasmosis.

CASE SUMMARY: A 34-year-old HIV-infected man who had recently initiated efavirenz-based antiretroviral therapy was diagnosed with disseminated Histoplasma capsulatum infection. In the hospital, lopinavir/ritonavir 400 mg/100 mg twice daily replaced efavirenz to avoid efavirenz–itraconazole interactions. After 14 days of liposomal amphotericin B therapy, itraconazole solution was initiated at 150 mg twice daily for 3 days, followed by 200 mg daily. Prior to itraconazole initiation, lopinavir trough concentration was 7.4 mg/L. The lopinavir trough concentration 15 days later, after 14 days of itraconazole, was 6.8 mg/L. An itraconazole concentration measured 2 hours post-dose on day 15 of oral therapy was 1.9 µg/mL. After 2 weeks of liposomal amphotericin, urine Histoplasma antigen was 27.23 ng/mL; after 5 months of oral itraconazole therapy, it decreased to 5.24 ng/mL. Plasma HIV RNA decreased 4.26 log₁₀ in 5 months to less than 40 copies/mL. The patient has demonstrated marked clinical improvement.

DISCUSSION: In this case, dosing recommendations of itraconazole 200 mg daily with lopinavir/ritonavir were appropriate. Lopinavir trough concentrations were not significantly different following the addition of itraconazole and were above the minimum target of 1 mg/L in treatment-naïve patients. The itraconazole concentration was above the recommended concentration of at least 1 µg/mL.

CONCLUSIONS: The dose of itraconazole was reduced to 200 mg daily as recommended by current guidelines, and therapeutic drug monitoring of both itraconazole and lopinavir concentrations confirmed that no further dosage adjustments were necessary.

Key Words: drug interactions, itraconazole, lopinavir, protease inhibitors, ritonavir

Published Online, November 24, 2009. www.theannals.com, DOI 10.1345/aph.1M393