Posaconazole is the latest triazole antifungal drug approved by the FDA in 2006. It has the broadest antifungal spectrum of any azole, covering yeasts, molds and some opportunistic fungi. Its mechanism of action involves inhibiting the lanosterol 14α-demethylase enzyme, thereby blocking ergosterol biosynthesis in fungal cell membranes. It has favorable pharmacokinetics including high tissue penetration and minimal drug interactions or dose adjustments for renal/liver impairment. Studies have shown posaconazole's efficacy for prophylaxis and treatment of various invasive and refractory fungal infections.

1. POSACONAZOLE Dr.Sangeetha P

2. FUNGUS Yeasts Filamentous fungi/moulds - Dermatophytes - Opportunistic fungi Dimorphic fungi

3. MYCOSES – CLINICAL CLASSIFICATION Superficial Deep Opportunistic

4. ANTIFUNGAL AGENTS Antibiotics Polyenes Griseofulvin Azoles Imidazoles Triazoles Allylamines Antimetabolites Echinocandins

7. (-)Lanosterol demethylase (-)Ergosterol synthesis (-)The cell membrane (-)The cell membrane

9. WHY NEW AZOLES ? Broader spectrum Low toxicity Oral preparations

10. POSACONAZOLE Latest drug in triazole group Broadest spectrum azole Approved by FDA on 2006 “ Noxafil”

11. MECHANISM OF ACTION (-)Lanosterol demethylase (-)Ergosterol synthesis (-)The cell membrane

12. PHARMACOKINETICS Only as oral suspension Fatty food absorption High tissue penetration Low CSF penetration Potent inhibitor of CYP-3A4 Mainly excreted through bile No dose reduction in elderly, liver or renal ds

13. SPECTRUM - AZOLES Broad spectrum Covers yeasts, filamentous fungi (Dermatophytes) & dimorphic fungi weak against opportunistic fungi !(aspergillosis,mucor mycosis etc)

14. POSACONAZOLE SPECTRUM Broad spectrum like other azoles covers opportunistic fungi also

15. STUDIES 1: Posaconazole vs Fluconazole for prophylaxis of invasive fungal infections in transplant recepients 2: Posaconazole vs fluconazole in neutropenic patients

16. INDICATIONS Prophylaxis of invasive candidiasis (fluconazole/low dose polyene ) Rx of refractory oropharyngeal candidiasis ( fluconazole /itraconzole) Prophylaxis & Rx of invasive aspergillosis (secondary to voriconozle) Mucor mycosis –the only azole active against Mucor ! (high dose iv amph B)

17. DOSE Prophylaxis of invasive fungal infections-200mg TDS(40mg/ml) Oropharyngeal Candidiasis - 100mg BD Refractory cases – up to 400mg BD

18. CONTRAINDICATIONS Children 13 yrs Pregnancy Nursing mother

19. POSACONAZOLE ADR Gastrointestinal upset Hepatotoxicity Neutropenia Drug interactions (CYP3A4)

20. AZOLES-S/E Fluconazole Itraconzole voriconozle GI upset CCF,Dysrrythmias Visual disturbances

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