Itraconazole for invasive fungal infection with pediatric malignancies

Ryoji Kobayashi1, Daisuke Suzuki, Kazue Yasuda

  • 1Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan. r-koba@jacls.jp

Abstract

Insights

Itraconazole oral solution (ITCZ-OS) shows promise in preventing invasive fungal infections (IFIs) in pediatric cancer patients. Careful administration is advised due to potential drug interactions and side effects.

Area of Science:

  • Pediatric Oncology
  • Infectious Diseases
  • Pharmacology

Background:

  • Invasive fungal infections (IFIs) pose a significant threat to children with hematological malignancies and solid tumors.
  • Early diagnosis of IFIs in this vulnerable population is challenging, underscoring the importance of prophylactic antifungal therapy.

Purpose of the Study:

  • To evaluate the efficacy and safety of itraconazole oral solution (ITCZ-OS) as a prophylactic agent against IFIs in children undergoing chemotherapy for hematological malignancies.

Main Methods:

  • A total of 22 children with hematological malignancies received 0.5 mL/kg/day of ITCZ-OS in divided doses.
  • The study monitored the prevention of IFIs, assessed side effects, and measured plasma levels of itraconazole.

Main Results:

  • Prophylactic ITCZ-OS was completed by 81.8% of patients, with no suspected IFIs. Four children discontinued treatment due to side effects, including liver dysfunction and syndrome of inappropriate anti-diuretic hormone secretion, often associated with concomitant use of vincristine sulfate or irinotecan hydrochloride.
  • Plasma levels of ITCZ were generally satisfactory, though slightly elevated in patients receiving vincristine sulfate, indicating a need for careful administration.

Conclusions:

  • ITCZ-OS demonstrated favorable plasma concentrations and suggested prophylactic effects against IFIs in pediatric cancer patients.
  • Potential drug interactions with agents like vincristine sulfate and irinotecan hydrochloride must be considered, as they may contribute to adverse events.

Related Concept Videos

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption01:23

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption

Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
231
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight,...
244
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
176
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
195
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
461
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K