Long-Term Efficacy and Safety of TDM-Assisted Combination of Voriconazole plus Efavirenz in an AIDS Patient with Cryptococcosis and Liver Cirrhosis
| Autor: | Manuela Heichen, Paola Villani, Francesca Stano, Emanuela Ciracì, Maria Cusato, Mario Regazzi, Sergio Carbonara, Laura Monno |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Cyclopropanes Liver Cirrhosis Male medicine.medical_specialty Antifungal Agents Cirrhosis Efavirenz Anti-HIV Agents Meningitis Cryptococcal Pharmacology Gastroenterology chemistry.chemical_compound Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) Voriconazole Acquired Immunodeficiency Syndrome AIDS-Related Opportunistic Infections medicine.diagnostic_test business.industry Hepatitis C Triazoles medicine.disease Benzoxazines Pyrimidines chemistry Tolerability Therapeutic drug monitoring Alkynes Cryptococcosis Drug Therapy Combination Drug Monitoring business medicine.drug |
| Zdroj: | Annals of Pharmacotherapy. 43:978-984 |
| ISSN: | 1542-6270 1060-0280 |
| DOI: | 10.1345/aph.1l607 |
| Popis: | ObjectiveTo report the efficacy, tolerability, and pharmacokinetic effects of combined voriconazole and efavirenz treatment administered at therapeutic drug monitoring (TDM)–based adjusted doses to a patient with AIDS, cryptococcosis, and mild liver cirrhosis.Case SummaryA 40-year-old man with AIDS (hemophiliac, antiretroviral-naïve, plasma HIV-RNA = 290,000 copies/mL, CD4+ lymphocytes = 0), hepatitis C virus–related liver cirrhosis (Child-Pugh class A), and cryptococcal meningitis was failing standard antifungal therapies. He received an antifungal–antiretroviral combination treatment based on the association of voriconazole plus efavirenz. Doses of both drugs were serially adjusted based on their plasma concentrations, which were evaluated at steady-state of each dose combination at least once (week 3.1 or later) as full concentration–time profile (samples collected at 0, 1, 2, 3, 4, 6, 8, 12 h postdose). Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dose adjustment (voriconazole 200 mg twice daily plus efavirenz 300 mg once daily, both administered orally). The patient showed prompt and stable suppression of cryptococcosis and plasma viremia of HIV at long-term follow-up (66 wk), with no significant adverse events.DiscussionStandard therapies for cryptococcosis in patients with AIDS are often not effective. Voriconazole, despite its promising anticryptococcal efficacy, is currently not approved for cryptococcosis therapy in the US and Europe, nor is it recommended for combination with efavirenz due to the significant pharmacokinetic interactions between the 2 compounds. Thus far, published studies regarding the effects of voriconazole in human cryptococcosis are scarce and none has described the clinical and pharmacokinetic outcomes of a voriconazole/efavirenz combination in patients with AIDS, either with or without liver cirrhosis.ConlusionsThe combination of voriconazole and efavirenz at TDM-assisted doses may represent a valuable therapeutic option in AIDS patients with cryptococcosis and mild liver cirrhosis. |
| Databáze: | OpenAIRE |
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