POSACONAZOLE

Dr.Sangeetha P

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

MYCOSES – CLINICAL CLASSIFICATION

Superficial Deep Opportunistic

ANTIFUNGAL AGENTS

Antibiotics Polyenes Griseofulvin Azoles Imidazoles Triazoles Allylamines Antimetabolites Echinocandins

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

(-)The cell membrane

WHY NEW AZOLES ?

Broader spectrum

Low toxicity Oral preparations

POSACONAZOLE

Latest drug in triazole groupBroadest spectrum azoleApproved by FDA on 2006“Noxafil”

MECHANISM OF ACTION (-)Lanosterol demethylase

(-)Ergosterol synthesis

(-)The cell membrane

PHARMACOKINETICSOnly as oral suspensionFatty food absorptionHigh tissue penetrationLow CSF penetration Potent inhibitor of CYP-3A4Mainly excreted through bileNo dose reduction in elderly, liver or

renal ds

SPECTRUM - AZOLES Broad spectrumCovers yeasts, filamentous fungi (Dermatophytes) & dimorphic fungi

weak against opportunistic fungi !(aspergillosis,mucor mycosis etc)

POSACONAZOLE SPECTRUM

Broad spectrum like other azoles

covers opportunistic fungi also

STUDIES

1:Posaconazole vs Fluconazole for prophylaxis of invasive fungal infections

in transplant recepients

2:Posaconazole vs fluconazole in neutropenic patients

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)

DOSE Prophylaxis of invasive fungal infections-200mg TDS(40mg/ml)

Oropharyngeal Candidiasis - 100mg BD

Refractory cases – up to 400mg BD

CONTRAINDICATIONS

Children 13 yrsPregnancyNursing mother

POSACONAZOLE ADRGastrointestinal upset Hepatotoxicity Neutropenia Drug interactions (CYP3A4)

AZOLES-S/E

Fluconazole

Itraconzole

voriconozle

GI upset

CCF,Dysrrythmias

Visual disturbances

THANK YOU