Dementia-Like Symptoms Associated With Posaconazole

Area of Science:

• Pharmacology and Toxicology
• Transplant Medicine
• Infectious Diseases

Background:

• Posaconazole is a key antifungal agent for lung transplant recipients, often preferred over voriconazole due to concerns about squamous cell carcinoma (SCC) risk with long-term voriconazole use.
• Current understanding suggests posaconazole has a favorable safety profile with no identified dose-dependent toxicity in clinical trials or post-marketing surveillance.
• Lung transplant recipients are particularly vulnerable to invasive fungal infections, necessitating effective and safe prophylactic and therapeutic antifungal strategies.

Purpose of the Study:

• To report a rare adverse event associated with posaconazole use in a lung transplant recipient.
• To describe the clinical presentation, management, and outcome of a patient experiencing dementia-like symptoms potentially linked to posaconazole.
• To highlight the importance of considering posaconazole-induced neurotoxicity in patients presenting with cognitive decline.

Main Methods:

• Case report of a single lung transplant recipient.
• Detailed clinical history including duration of posaconazole therapy, dosage, and concurrent medications.
• Observation of symptom onset, resolution upon drug discontinuation, and recurrence upon re-challenge with posaconazole.

Main Results:

• A lung transplant recipient developed dementia-like symptoms approximately three years after initiating posaconazole for invasive fungal infections (Aspergillus fumigatus complex and Lomentospora prolificans).
• The patient's cognitive symptoms significantly improved after discontinuing posaconazole.
• Upon re-challenge with a lower dose of posaconazole over a year later, the dementia-like symptoms recurred, reinforcing the suspected association.

Conclusions:

• This case suggests a potential association between posaconazole and the development of dementia-like symptoms, even with long-term use.
• Clinicians should consider posaconazole-induced neurotoxicity in lung transplant recipients presenting with unexplained cognitive impairment.
• Further investigation into the potential neurological side effects of posaconazole is warranted, particularly in immunocompromised populations.