voriconazole
Sources réglementaires consultées
Indications approuvées
- Aspergillose invasive, candidémie et autres infections fongiques invasives sévères dues à des organismes sensibles.
Contre-indications
Absolues
- Hypersensibilité au voriconazole.
- Utilisation concomitante de rifampicine, carbamazépine, phénobarbital, sirolimus, dérivés de l’ergot, quinidine, pimozide, ivabradine ou autres associations CYP/QT expressément contre-indiquées.
Mises en garde cliniques
- Il peut provoquer une hépatotoxicité sévère ; surveiller le bilan hépatique avant et pendant le traitement. — CIMA/AEMPS, ficha técnica 02212015
- Il peut prolonger le QT et provoquer des torsades ; corriger potassium, magnésium et calcium et surveiller l’ECG chez les patients à risque. — CIMA/AEMPS, ficha técnica 02212015
- Mise en garde majeure · Surveiller les troubles visuels si le traitement dépasse 28 jours et protéger du soleil ; arrêter en cas de phototoxicité sévère, de SCAR ou de lésion suspecte de carcinome épidermoïde. — CIMA/AEMPS, ficha técnica 02212015
Interactions médicamenteuses
- ModéréeInducteurs puissants des CYP tels que rifampicine, carbamazépine ou phénobarbital
Mécanisme: Ils réduisent fortement l’exposition au voriconazole.
Recommandation: Ne pas associer.
CIMA/AEMPS, ficha técnica 02212015
- SévèreSubstrats du CYP2C19, CYP2C9 ou CYP3A4 à marge thérapeutique étroite
Mécanisme: Le voriconazole peut augmenter l’exposition et la toxicité.
Recommandation: Réévaluer chaque association, surveiller les concentrations ou la toxicité et adapter.
CIMA/AEMPS, ficha técnica 02212015
Effets indésirables
Communs (≥1%)
Troubles visuels, fièvre, éruption, nausées, vomissements, diarrhée et céphalées
Rares mais graves
Hépatotoxicité, torsades de pointes, SCAR et carcinome épidermoïde cutané
Grossesse et allaitement
Éviter pendant la grossesse sauf bénéfice vital et utiliser une contraception efficace. Décider de l’allaitement selon le risque et la nécessité du traitement.
Bibliographie récente (PubMed)
These European Society of Clinical Microbiology and Infectious Diseases guidelines are intended for clinicians involved in diagnosis and treatment of brain abscess in children and adults. Key questions were developed, and a systematic review was carried out of all studies published since 1 January 1996, using the search terms 'brain abscess' OR 'cerebral abscess' as Mesh terms or text in electronic databases of PubMed, Embase, and the Cochrane registry. The search was updated on 29 September 2022. Exclusion criteria were a sample size <10 patients or publication in non-English language. Extracted data was summarized as narrative reviews and tables. Meta-analysis was carried out using a random effects model and heterogeneity was examined by I2 tests as well as funnel and Galbraith plots. Risk of bias was assessed using Risk Of Bias in Non-randomised Studies - of Interventions (ROBINS-I) (observational studies) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (diagnostic studies). The Grading of Recommendations Assessment, Development and Evaluation approach was applied to classify strength of recommendations (strong or conditional) and quality of evidence (high, moderate, low, or very low). Magnetic resonance imaging is recommended for diagnosis of brain abscess (strong and high). Antimicrobials may be withheld until aspiration or excision of brain abscess in patients without severe disease if neurosurgery can be carried out within reasonable time, preferably within 24 hours (conditional and low). Molecular-based diagnostics are recommended, if available, in patients with negative cultures (conditional and moderate). Aspiration or excision of brain abscess is recommended whenever feasible, except for cases with toxoplasmosis (strong and low). Recommended empirical antimicrobial treatment for community-acquired brain abscess in immuno-competent individuals is a 3rd-generation cephalosporin and metronidazole (strong and moderate) with the addition of
Invasive aspergillosis (IA) is a severe fungal infection caused by Aspergillus species, particularly Aspergillus fumigatus, although new species, sometimes resistant to antifungals are becoming more common. IA predominantly affects immunocompromised patients, such as those with haematological malignancies, solid organ transplant recipients, and critically ill patients. However, new at-risk populations have emerged in recent years, such as IA associated with severe viral infections. Advanced diagnostic methods are crucial, especially considering the rising concern of antifungal resistance. Early detection is critical for successful treatment, typically involving antifungal medications like voriconazole or amphotericin B, but new antifungals are arriving to complete the therapeutic strategies. Despite advancements, mortality rates remain high, underscoring the importance of timely interventions and ongoing research. Healthcare providers should maintain a high index of suspicion, especially in immunocompromised patients and other new risk factors that are arising, to promptly diagnose and manage invasive aspergillosis. No information is available on the use of voriconazole during breastfeeding. If voriconazole is required by the mother, it is not a reason to discontinue breastfeeding. Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Fungal endocarditis accounts for 1% to 3% of all infective endocarditis cases, is associated with high morbidity and mortality (>70%), and presents numerous challenges during clinical care. Candida spp. are the most common causes of fungal endocarditis, implicated in over 50% of cases, followed by Aspergillus and Histoplasma spp. Important risk factors for fungal endocarditis include prosthetic valves, prior heart surgery, and injection drug use. The signs and symptoms of fungal endocarditis are nonspecific, and a high degree of clinical suspicion coupled with the judicious use of diagnostic tests is required for diagnosis. In addition to microbiological diagnostics (e.g., blood culture for Candida spp. or galactomannan testing and PCR for Aspergillus spp.), echocardiography remains critical for evaluation of potential infective endocarditis, although radionuclide imaging modalities such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography are increasingly being used. A multimodal treatment approach is necessary: surgery is usually required and should be accompanied by long-term systemic antifungal therapy, such as echinocandin therapy for Candida endocarditis or voriconazole therapy for Aspergillus endocarditis.
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.