posaconazole
Regulatory sources consulted
Approved indications
- Prophylaxis of invasive fungal infections in high-risk patients and treatment of selected invasive mycoses according to susceptibility and alternatives.
Contraindications
Absolute
- Hypersensitivity to posaconazole or other azoles.
- Concomitant sirolimus, QT-prolonging CYP3A4 substrates, simvastatin/lovastatin, ergot derivatives, and other expressly contraindicated combinations.
Clinical warnings
- It may cause hepatotoxicity; monitor liver tests and discontinue with severe injury. — CIMA/AEMPS, ficha técnica 105320002
- It may prolong QT; correct electrolytes and avoid high-risk combinations. Pseudoaldosteronism with hypertension and hypokalemia has been reported. — CIMA/AEMPS, ficha técnica 105320002
Drug interactions
- HighNarrow-therapeutic-index CYP3A4 substrates
Mechanism: Posaconazole strongly inhibits CYP3A4 and may increase concentrations.
Recommendation: Observe contraindications; reduce and monitor tacrolimus/cyclosporine and review venetoclax by treatment phase.
CIMA/AEMPS, ficha técnica 105320002
- HighRifabutin, rifampin, phenytoin, efavirenz, or other potent inducers
Mechanism: They reduce posaconazole exposure.
Recommendation: Avoid unless benefit is essential and monitor levels if used.
CIMA/AEMPS, ficha técnica 105320002
Adverse events
Common (≥1%)
Nausea, diarrhea, fever, headache, vomiting, and increased liver enzymes
Rare but serious
Severe hepatotoxicity, torsades de pointes, SCAR, and pseudoaldosteronism
Pregnancy and lactation
Avoid during pregnancy except for severe infection without an alternative. Do not breastfeed during treatment according to the label.
Recent literature (PubMed)
This review aims to summarize the epidemiology, etiology, pathogenesis, clinical manifestations, and current diagnostic and therapeutic approaches for mucormycosis. The goal is to improve understanding of mucormycosis and promote early diagnosis and treatment to reduce mortality. A comprehensive literature review was conducted, focusing on recent studies and data on mucormycosis. The review includes an analysis of the disease's epidemiology, etiology, and pathogenesis, as well as current diagnostic techniques and therapeutic strategies. Mucormycosis is increasingly prevalent due to the growing immunocompromised population, the COVID-19 pandemic, and advances in detection methods. The pathogenesis is closely associated with the host immune status, serum-free iron levels, and the virulence of Mucorales. However, the absence of typical clinical manifestations complicates diagnosis, leading to missed or delayed diagnoses and higher mortality. An enhanced understanding of the epidemiology, pathogenesis, and clinical presentation of mucormycosis, along with the adoption of improved diagnostic and therapeutic approaches, is essential for reducing mortality rates associated with this opportunistic fungal infection. Early diagnosis and prompt treatment are critical to improving patient outcomes. The incidence of mucormycosis has increased following the COVID-19 pandemic.The presence of the halo sign and reverse halo sign may indicate the onset of pulmonary mucormycosis.Early implementation of molecular diagnostic methods, such as mNGS and qPCR, may improve the early diagnosis rate of mucormycosis.Isavuconazole and posaconazole can also be considered as first-line treatments for the initial management of mucormycosis.
Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance.
Mucormycosis is an aggressive and frequently lethal disease. Most patients with mucormycosis have poorly controlled diabetes mellitus and rhino-orbito-cerebral disease. Patients with hematologic malignancy and transplant recipients mostly present with rhino-orbito-cerebral or pulmonary disease. Prompt recognition of clinical symptoms and radiographic features of mucormycosis is required to establish timely diagnosis and initiate targeted therapy. Diagnosis is, historically, made by direct microscopy, culture, and pathology of biopsy tissue, but molecular methods are increasingly playing a role in establishing an earlier diagnosis. Treatment is multidisciplinary, involving early surgical intervention, antifungal therapy, and correction of underlying immune compromising risk factors when possible.
Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific in these populations and the diagnostic work-up has considerably expanded. Computed tomography is key to assess the pulmonary lesions of aspergillosis, whose various features must be acknowledged. Positron-emission tomography can bring additional information for diagnosis and follow-up. The mycological argument for diagnosis is rarely fully conclusive, as biopsy from a sterile site is challenging in most clinical contexts. In patients with a risk and suggestive radiological findings, probable invasive aspergillosis is diagnosed through blood and bronchoalveolar lavage fluid samples by detecting galactomannan or DNA, or by direct microscopy and culture for the latter. Diagnosis is considered possible with mold infection in lack of mycological criterion. Nevertheless, the therapeutic decision should not be hindered by these research-oriented categories, that have been completed by better adapted ones in specific settings. Survival has been improved over the past decades with the development of relevant antifungals, including lipid formulations of amphotericin B and new azoles. New antifungals, including first-in-class molecules, are awaited.