Voriconazole: Pharmacokinetics, Role in Therapeutic Drug Monitoring and Clinical Outcomes

Andrea Angelini, MD (Editor)
University of Bologna, Istituto Ortopedico Rizzoli Department of Orthopaedics and Musculoskeletal Oncology, Bologna, Italy

Series: Pharmacology – Research, Safety Testing and Regulation
BISAC: MED071000

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In the last twenty years, the incidence of invasive fungal infections (IFI) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections and due to the increase of infection associated with travel. Moreover IFI in infants admitted to the neonatal intensive care unit are common and often fatal. Amphotericin B was for more than 40 years the gold standard for almost all IFI, but toxicity and resistance, especially of new and emerging pathogens remained important issues. Fluconazole and itraconazole have also the same disadvantage of resistance.

After a long period of relative inactivity in the introduction of new antifungals, more recently a few new drugs of already existing classes have been introduced as important agents in the treatment and prevention of IFI. These represent small or large advantages and differences compared with existing available alternative therapy for deep and systemic mycoses. Voriconazole is a second-generation triazole antifungal drug, often prescribed as first-line therapy for candidemia, in non-neutropenic hosts, for invasive pulmonary aspergillosis and as prophylaxis of many systemic mycoses.

In-vitro and in-vivo studies showed that voriconazole has broad-spectrum activity against most Candida species, Aspergillus species, fusariosis or scedosporiosis. Voriconazole has non-linear pharmacokinetics and, as substrate and inhibitor of cytochrome P450, it undergoes extensive hepatic metabolism that depends on age, genetic factors, and interactions with other drugs, which may lead to enhanced toxicity of the concomitant medication(s) or ineffective antifungal treatment. This book presents an update on voriconazole research, particularly its pharmacology, microbiology, toxicology, and clinical outcomes in order to optimize its use in daily clinical practice. (Imprint: Nova Biomedical)

Preface

List of Contributors

PART I

Chapter 1 - Voriconazole: Synthesis and Mechanism of Action (pp. 3-8)
Antonios Papadopoulos and Efthymia Giannitsioti (Fourth Department of Internal Medicine and Infectious Diseases, Athens University Medical School, ATTIKON University General Hospital, Athens, Greece)

Chapter 2 - Action of Voriconazole In Vitro and In Vivo (pp. 9-12)
Efthymia Giannitsioti, MD, PhD and Antonios Papadopoulos, MD, PhD (Fourth Department of Internal Medicine and Infectious Diseases, Athens University Medical School, ATTIKON University General Hospital, Athens, Greece)

Chapter 3 - Voriconazole: Pharmacokinetics, Dosage and Administration (pp. 13-28)
Rod Everett Quilitz (Department of Pharmacy, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA)

PART II

Chapter 4 - Antifungal Therapy with Voriconazole for Aspergillosis (pp. 29-40)
Malgorzata Mikulska, Paola Tatarelli and Claudio Viscoli (Division of Infectious Diseases, University of Genoa, IRCCS San Martino-IST, Genoa, Italy)

Chapter 5 - Voriconazole Treatment in Invasive Candidiasis (pp. 41-52)
Pierluigi Viale, MD, PhD, and Russell E. Lewis, MD, PhD (Department of Medical Sciences and Surgery, Infectious Diseases Unit- S. Orsola Malpighi Hospital, University of Bologna, Italy)

Chapter 6 - Antifungal Therapy with Voriconazole for Esophageal Candidiasis (pp. 53-58)
Jack D. Sobel, MD (Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI, USA)

Chapter 7 - Voriconazole in Orthopaedics: Osteomyelitis and Antifungal-Loaded Bone Cement (pp. 59-82)
Andrea Angelini, MD, Todd Bertrand, MD, Alessandra Maso and Pietro Ruggieri, MD PhD (University of Bologna, Rizzoli Orthopedic Institute, Department of Orthopedics, Bologna, Italy, and others)

Chapter 8 - Voriconazole for Endemic Fungal Infection (Disseminated Histoplasmosis, Blastomycosis, Coccidioidomycosis and Paracoccidioidomycosis) (pp. 83-94)
Antonios Papadopoulos, MD, PhD and Efthymia Giannitsioti, MD (Fourth Department of Internal Medicine and Infectious Diseases, Athens University Medical School, ATTIKON University General Hospital, Athens, Greece)

Chapter 9 - Use of Voriconazole As Antifungal Prophylaxis and Empirical Therapy During Chemotherapy in Immunodepressed Patients and in Solid Organ Transplantation (pp. 95-102)
Efthymia Giannitsioti, MD, PhD and Antonios Papadopoulos, MD, PhD (Fourth Department of Internal Medicine and Infectious Diseases, Athens University Medical School, ATTIKON University General Hospital, Athens, Greece)

Chapter 10 - Use of Voriconazole in Pediatric Patients with Cancer (pp. 103-110)
Pierluigi Brazzola, MD, and Mario Renato Rossi, MD (Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland)

PART III

Chapter 11 - Voriconazole: Contraindications, Warnings and Precautions, Adverse Reactions (pp. 113-128)
Antonios Papadopoulos, MD, PhD,, Andreas F. Mavrogenis, MD, PhD and Efthymia Giannitsioti, MD (Fourth Department of Internal Medicine and Infectious Diseases, Athens University Medical School, ATTIKON University General Hospital, Athens, Greece)

Chapter 12 - Drug Interactions with Voriconazole (pp. 129-140)
Russell E. Lewis, and Pierluigi Viale, MD, PhD (Department of Medical Sciences and Surgery, Infectious Diseases Unit- S. Orsola Malpighi Hospital, University of Bologna, Italy)

Chapter 13 - Drug Resistance Against Voriconazole (pp. 141-144)
Efthymia Giannitsioti, MD, PhD and Antonios Papadopoulos, MD, PhD (Fourth Department of Internal Medicine and Infectious Diseases, Athens University Medical School, ATTIKON University General Hospital, Athens, Greece)

Chapter 14 - Voriconazole Toxicology (pp. 145-154)
Russell E. Lewis, and Pierluigi Viale, MD, PhD (Department of Medical Sciences and Surgery, Infectious Diseases Unit- S. Orsola Malpighi Hospital, University of Bologna, Italy)

Chapter 15 - Therapeutic Drug Monitoring of Voriconazole (pp. 155-166)
Russell E. Lewis, and Pierluigi Viale, MD, PhD (Department of Medical Sciences and Surgery, Infectious Diseases Unit- S. Orsola Malpighi Hospital, University of Bologna, Italy)

Chapter 16 - Pharmacoeconomics of Voriconazole (pp. 167-184)
Daoud Al-Badriyeh (College of Pharmacy, Qatar University, Doha, Qatar)

Index

Audience: Infectious diseases physicians; Community ophthalmologists; Family physicians; General internists and other primary care professionals; Pneumologists; Pediatricians, Orthopaedic and General Surgeons, Dermatologists Physicians training or in practice in Occupational and Environmental Medicine (OEM); also useful to other professionals in occupational health including nurses, industrial hygienists, toxicologists, and safety professionals; Health Educators; Infection Control Professionals; HIV/ID.

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