Drug-Drug Interaction between Itraconazole and Efavirenz in a Patient with AIDS and Disseminated Histoplasmosis

Koo, Hoonmo L.; Hamill, Richard J.; Andrade, Roberto

doi:10.1086/520978

Cited by 32 publications

(18 citation statements)

References 9 publications

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“…10 The first case described an HIV-infected patient diagnosed with histoplasmosis who was receiving an efavirenz-based antiretroviral regimen. 9 The patient was initiated on itraconazole capsules at 200 mg daily for several months, but the urine Histoplasma antigen did not decrease below 4.28 U. A 12-hour plasma itraconazole concentration measured after more than 1 year of itraconazole therapy revealed undetectable levels.…”

Section: Discussionmentioning

confidence: 94%

“…5 In addition, this study did not include measurement of PI and NNRTI concentrations to determine the effects of itraconazole on antiretroviral therapy. 11 Because of the potential for low itraconazole concentrations reported with efavirenz, 9 we decided to substitute lopinavir/ritonavir for efavirenz in our patient. Lopinavir trough concentrations before and after initiation of itraconazole were essentially unchanged and were well above the suggested minimum trough concentrations of 1 mg/L recommended for antiretroviral-naïve patients.…”

Section: Discussionmentioning

confidence: 99%

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

Hills-Nieminen

Hughes

Houston³

et al. 2009

Ann Pharmacother

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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

Hills-Nieminen

Hughes

Houston³

et al. 2009

Ann Pharmacother

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“…The infection occurs more often in patients with a CD4 count <50 cells/mm 3 and is usually disseminated (Carme et al 1990). An extremely interesting study showed that the treatment of a patient with AIDS and disseminated histoplasmosis with a combined therapy of itraconazole and HIV peptidase inhibitors (atazanavir, 300 mg once daily, and ritonavir, 100 mg once daily) promoted an improvement in the desired urinary Histoplasma antigen level and plasma itraconazole concentration, leading to a mycological cure (Koo et al 2007). …”

Section: Histoplasma Capsulatummentioning

confidence: 99%

Aspartic Peptidase Inhibitors as Potential Bioactive Pharmacological Compounds Against Human Fungal Pathogens

Santos

2010

Combating Fungal Infections

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The development of novel antifungal drugs is becoming more demanding every day since existing drugs either have too many side-effects or they tend to lose effectiveness due to resistant fungal strains. In view of this, a number of new strategies to obstruct fungal biological processes have emerged; one of them is focused on peptidase inhibition. This particular class of hydrolytic enzymes cleaves peptide bond in proteinaceous substrates, a reaction extremely important in maintaining the physiology of all living cells. Interestingly, peptidases are also essential virulence factors for prokaryotic and eukaryote micro-organisms, including fungi, during all stages of the infection process. Consequently, peptidases are potential targets for the development of future antifungal drugs. This chapter will focus on the potential use of aspartic peptidase inhibitors against human fungal pathogens, showing the capability of these bioactive pharmacological compounds to arrest vital fungal processes such as growth, differentiation, nutrition, and interaction with host components.

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“…May increase plasma concentrations of PIs (such as indinavir, ritonavir and saquinavir) Caution [9] Nevirapine reduced exposure to itraconazole: Cmax 38%, AUC 61%, t 31% [74] Coadministration not recommended [9] Efavirenz reduced exposure to itraconazole in an AIDS patient [75] Voriconazole Voriconazole increased exposure to efavirenz: Cmax 37%, AUC 43%…”

Section: Pis Nrtis Nnrtismentioning

confidence: 99%

“…NNRTIs are CYP3A4 substrates, inhibitors, or CYP450 inducers; and PIs are CYP3A4 substrates and inhibitors. Table 3 summarizes the azoles' interactions with these drug classes [3,9,37,[72][73][74][75][76][77][78][79].…”

Section: Patients With Hiv Infectionmentioning

confidence: 99%

Drug-Drug Interactions of Triazole Antifungal Agents in Multimorbid Patients and Implications for Patient Care

Nivoix¹,

Ubeaud-Séquier²,

Engel³

et al. 2009

CDM

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Drug interactions occur frequently with triazole antifungal agents because of their properties as inhibitors of 1 or more phase 1 (cytochrome P450) biotransformation enzymes and, possibly, as inhibitors or substrates of a phase 2 biotransformation enzyme or transporter protein. Multimorbid patients, including those with hematologic malignancies or other cancers, hematopoietic stem cell or organ transplant recipients, patients infected with the human immunodeficiency virus, and those in the intensive care unit, are at increased risk for drug interactions because they typically require several concomitant medications. They may also be extremely vulnerable to the clinical signs and symptoms of drug interactions. This review describes clinically significant drug interactions most frequently seen in multimorbid patients who receive systemic therapy with triazole antifungals for the prophylaxis or treatment of invasive fungal infections; including interactions with corticosteroids, immunosuppressants, anti-infective drugs, benzodiazepines, opioid analgesics, statins, anticoagulants, anticonvulsants, and drugs affecting gastric pH. The review also describes recommendations concerning contraindications and dose-modification strategies. The azoles differ markedly in their pharmacokinetic and antifungal properties, safety and tolerability, and drug-interaction profiles. Many drug interactions can be prevented if clinicians are thoroughly familiar with the pharmacokinetic profiles of different azoles, follow contraindications and dose-modification recommendations, and switch azoles when possible to achieve the best combination of clinical efficacy and safety. Therapeutic drug monitoring can help optimize treatment and prevent underdosing or overdosing of drugs. Education of patients and their families about signs and symptoms of possible drug interactions is also beneficial.

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Drug-Drug Interaction between Itraconazole and Efavirenz in a Patient with AIDS and Disseminated Histoplasmosis

Cited by 32 publications

References 9 publications

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

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

Aspartic Peptidase Inhibitors as Potential Bioactive Pharmacological Compounds Against Human Fungal Pathogens

Drug-Drug Interactions of Triazole Antifungal Agents in Multimorbid Patients and Implications for Patient Care

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