role of antifungal drugs in leukemia

1. ANTIFUNGALS IN LEUKEMIA

2. Systemic fungal infections are relatively common in neutropenic
patients, and
empiric antifungal therapy should be considered in febrile patients if
empiric antibiotic therapy is not effective within 5 to 7 days
The high mortality rate of invasive fungal infections in neutropenic
patients makes their prevention extremely important

4. ANTIFUNGALS CLASSIFICATION
1.Altering Membrane Permeability:
a)Azoles
Triazoles- Flu-,Itra-,Vori-,Ter-,Posa-conazole
Imidazoles- Keto-,Mi-,E-,Buto-,oxi-,Serto-,Sul-conazole
b)Terbinafine,Butenafine,Naftifine
c)Polyenes:Amphotericin B,Nystatin,Hamycin
2.Block Nucleic Acid synthesis: Flucytosine
3.Disrupt Microtubule Fundtion:Griseofulvin
4.Inhibit Cell wall synthesis: Echinocandins,Nikkomycin

5. TRIAZOLES
In general Clinically useful activity against Candida albicans, Candida tropicalis,
Candida parapsilosis, Candida glabrata, Cryptococcus neoformans, Aspergillus spp.,
Candida krusei and the agents of mucormycosis are more resistant
Fluconazole less active against non-albicans Candida species, completely inactive
against Candida krusei, lacks activity against Aspergillus
Itraconazole - Spectrum similar to Fluconazole except slightest activity on
Aspergillus spp
Voriconazole- Spectrum similar to Itraconazole except it is the first-line therapy
against Aspergillus. intravenous and oral formulations
Posaconazole- primary use has been prophylactic, salvage therapy for invasive
aspergillosis, active against many species of mucormycosis
Isavuconazole-phase 3 trial efficacy comparable to voriconazole

6. TRIAZOLES DOSAGE
Fluconazole-400 mg daily decreases the incidence of deep candidiasis
in allogeneic bone marrow transplant recipients, the drug has been
used successfully as empirical treatment of febrile neutropenia in
patients not responding to antibacterial agents
Voriconazole initiated with an intravenous infusion of 6 mg/kg bd- 2
doses followed by 3-4 mg/kg every 12 hours no faster than 3 mg/kg/hr
As the patient improves oral administration is continued as 200 mg
every 12 hours
Posaconazole 100 mg bd on day 1 followed by 100mg od thereafter

7. POLYENE
Amphotericin B
Spectrum of activity covers candida,aspergillus,Mucor
4 formulations commercially available:
conventional amphotericin B (C-AMB),liposomal amphotericin B (L-
AMB),amphotericin B lipid complex (ABLC), and amphotericin B
colloidal dispersion (ABCD)
L-AMB empiric therapy 3mg/kg in 5D over 2 hours
ABLC 5mg/Kg in 5D over 2 hours

8. ECHINOCANDINS
Intravenous drugs that has activity against a wide variety of Candida
species as well as Aspergillus
Currently only caspofungin is approved for first-line empirical use in
febrile neutropenia(WILLIAMS HEMATOLOGY)
administered intravenously once daily over 1 hour
initial dose is 70 mg, followed by 50 mg daily
Micafungin 100 mg/day also approved for prophylaxis of deeply
invasive candidiasis in hematopoietic stem cell transplant
Recipients(GOODMAN & GILMAN).No loading dose needed