Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents

  title={Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents},
  author={Lydia L. Benitez and Peggy L Carver},
Azole antifungals are first-line options in the prophylaxis and treatment of invasive fungal infections. They are often used for prolonged (weeks to months) periods of time, particularly in patients with hematologic malignancies, or in those who have received a solid organ or hematopoietic stem cell transplant. Long-term use of azoles is associated with hepatotoxicity and hormone-related effects, including gynecomastia, alopecia, decreased libido, oligospermia, azoospermia, impotence… 

Long-term use of systemic azole antifungals can result in hepatotoxicity and other serious adverse effects

Long-term use of systemic azole antifungals can result in serious adverse drug effects (ADEs), such as hepatotoxicity and cardiac effects, which may be managed with monitoring, adjusting dosages and switching azoles.

Case Report: Voriconazole induced refractory hyperkalemia and adrenal insufficiency

A 47-year-old male presented with worsening shortness of breath, requiring mechanical ventilation within 24 hours of presentation, and Voriconazole was added for anti-fungal coverage, causing treatment resistant hyperkalemia necessitating continuous renal replacement therapy (CRRT).

Antimycolytic agents: fungistatic and fungicide

  • Bereda Gudisa
  • Biology, Medicine
    Annals of Dermatological Research
  • 2022
The most routine adverse effects of fluconazole involve accelerated liver enzymes, gastrointestinal complaints, headache, and skin rash, and if antacids, PPIs, H2 blockers administered together with ketoconazole medicines; they will reduce the blood levels of ketoconzole by increasing gastric pH because ketoconAZole requires an acidic media for dissolution and systematic absorption.

Liposomal amphotericin B—the present

Liposomal amphotericin B is a suitable choice for the first-line empirical or pre-emptive treatment of suspected fungal infections in neutropenic haematology patients and is an excellent alternative for patients with documented fungal disease who can no longer tolerate or continue their first- line azole or echinocandin therapy, both in the haem atology setting and in the ICU.

PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections

In two lung transplant patients, PC945 treated an invasive pulmonary Aspergillus infection that had been unresponsive to multiple antifungal agents (systemic ± inhaled) without systemic side effects or detected drug–drug interactions.

Review of Pharmacologic Considerations in the Use of Azole Antifungals in Lung Transplant Recipients

Analysis of drug-interactions, adverse drug reactions, pharmacokinetic considerations, and the role of therapeutic drug monitoring with special emphasis on data from the post-lung transplant population is drawn.

How Long Do We Need to Treat an Invasive Mold Disease in Hematology Patients? Factors Influencing Duration of Therapy and Future Questions.

Validation of noninvasive biomarkers for monitoring treatment response, tests for quantifying the "net state of immunosuppression," and genetic polymorphisms associated with poor fungal immunity could lead to a personalized assessment for the continued need for antifungal therapy.

Possibly Appropriate Maintenance dose of Voriconazole in pediatric patients: a single center observational study

Pediatric patients especially those ≤12 years old might need a higher dosage regime to achieve therapeutic trough concentration and a high inter- and intra-individual variability of voriconazole in pediatric patients were observed.

How I perform hematopoietic stem cell transplantation on patients with a history of invasive fungal disease.

Critical evaluation of patient-, malignancy-, transplantation procedure-, antifungal treatment-, and fungus-specific issues affect the risk of IFD relapse and guidance for the complex decision making involved in the peri-HSCT management of these patients is provided.

The Use of Targeted Monoclonal Antibodies in the Treatment of ABPA—A Case Series

Two patients with severe relapsing ABPA were initially treated with corticosteroids and antifungal agents but had an incomplete response, and were switched to the anti-IL5R agent benralizumab and responded well to both agents.



Clinical hepatotoxicity associated with antifungal agents

The present article reviews incidence and severity of hepatotoxicity associated with different classes and agents to provide a better understanding of this specific end organ toxicity and safer use of antifungal agents.

The hepatotoxicity of antifungal medications in bone marrow transplant recipients.

In patients who developed hepatotoxicity and who continued receiving antifungal medication, one-third of those receiving liposomal amphotericin B had marked increases in bilirubin levels, as opposed to 8% of patients treated with fluconazole.

Alopecia Associated with Fluconazole Therapy

33 patients who developed reversible alopecia temporally associated with extended fluconazole use for fungal disease are reported on.

Adverse effects of voriconazole: Over a decade of use

Voriconazole use has increased since the drug's introduction in 2002, and new and unique adverse effects are emerging as patients undergo prolonged therapy. Most concerning is the increased risk of

An update on the safety and interactions of antifungal drugs in stem cell transplant recipients

The new triazole isavuconazole and the new tablet formulation of posaconazole will be probably increasingly used in the HSCT setting not only due to their efficacy but in particular for their interesting toxicity profile and pharmacokinetic characteristics.

Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections.

  • I. RaadJ. Graybill A. Ullmann
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2006
Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections and long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconzole.

Tolerability of long-term fluconazole therapy

A significant number of patients receiving long-term fluconazole therapy for coccidioidomycosis experienced adverse effects and required a therapeutic intervention such as dose reduction, discontinuation or switch to a new antifungal.

Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

Posaconazole tablets were generally well tolerated in high-risk neutropenic patients and identified the dose of posaconazoles that would provide exposure within a predefined range of exposures.