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SYSTEMIC ANTIFUNGAL AGENTS SPECTRUM INDICATIONS PRECAUTIONS

SYSTEMIC ANTIFUNGAL AGENTS SPECTRUM INDICATIONS PRECAUTIONS. DR ALPAY AZAP Ankara University Medical School Infectious Diseases and Clinical Microbiology Dept. Anidulafungin. Caspofungin. Ravucon. XMP. Sordarins. Micafun. Voricon. Posacon. # of Antifungals. L-AmB ABCD

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SYSTEMIC ANTIFUNGAL AGENTS SPECTRUM INDICATIONS PRECAUTIONS

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  1. SYSTEMIC ANTIFUNGAL AGENTS SPECTRUM INDICATIONS PRECAUTIONS DR ALPAY AZAP Ankara University Medical School Infectious Diseases and Clinical Microbiology Dept

  2. Anidulafungin Caspofungin Ravucon XMP Sordarins Micafun Voricon Posacon # of Antifungals L-AmB ABCD ABLC Terbinafine Amphotericin B (1958) Itraconazole Griseofulvin Fluconazole Ketoconazole Miconazole Nystatin 5-FC

  3. ECHINOCANDINs POLYENs AZOLEs

  4. POLYENS NYSTATIN AMPHOTERICIN B Deoxycholate Lipid formulations AZOLES ITRACONAZOLE KETOCONAZOLE FLUCONAZOLE VORICONAZOLE POSACONAZOLE RAVUCONAZOLE ECHINOCANDINS CASPOFUNGIN ANIDULAFUNGIN MICAFUNGIN

  5. ECHINOCANDINS Candida spp. Aspergillus spp. SUSCEPTIBLE Cryptococcus neoformans Trichosporon spp. Fusarium spp. Zygomycetes Scedosporium spp. Pseudoallescheria spp. INHERENTLY RESISTANT

  6. CASPOFUNGIN Indications: Invasive candida infections Esophageal candidiasis Empirical antifungal tx of FEN IPA resistant or intolerant to OLAT Dosing regimen: IV, 70 mg loading dose, 50 mg/day maintenance Age; 3 months-17 years: 50 mg/m2/day Dose alteration: No dose alteration in renal dysfunction In moderate hepatic failure 35 mg/day maintenance

  7. CASPOFUNGIN Side effects: Fever (>%10), Raised LFTs (%1-10) Hypokalemia (%1-10) Nausea/vomiting (%1-10) Histamine mediated symptoms ? Drug interactions: No contraindicated concomitant drugs. Cyclosporine may increase caspo levels and increase LFTs Rifampicin caspo dose should be 70 mg/kg/day Phenytoin, Carbamazepine, Dexamethasone, Efavirenz, Nevirapine 70 mg/kg/day may be required

  8. ANIDULAFUNGIN Indications: Invasive candidiasis (Non-neutropenic patients) Esophageal candidiasis The single candin compared with fluconazole in candidemia Reboli C et al. New Engl J Med 2007;356:2472-82 Dosing regimen: Invasive candidiasis: 200 mg/d loading, 100 mg/d maintenance Esophageal candidiasis: 100 mg/d loading, 50 mg/d maintenance Not approved for use in children. Dose alteration: No dose alteration needed in renal/hepatic failure

  9. ANIDULAFUNGIN Side effects: Gastrointestinal (%3-26) Hypokalaemia (%1-10) Fever, rash (%1-10) Raised LFTs (%1-10) Drug interactions: No contraindicated concomitant drugs. No need for dose alteration of co-administered drugs Plasma level monitoring is not recommended

  10. MICAFUNGIN Indication: age≥16 y: Invasive candidiasis Esophageal candidiasis Prophylaxis in Allo HSCT/prolonged neutropenia IPA treatment in non-responsive/intolerant pts. age<16 y: Treatment of invasive candidiasis Prophylaxis in Allo HSCT/prolonged neutropenia Dosing regimen : IV, therapeutic dose in candidiasis: 100 mg/d prophylaxis: 50 mg/d Dose alteration: No dose alteration needed in renal/hepatic failure

  11. MICAFUNGIN Side effects: Nausea, vomiting (%1-10) Hypokalaemia (%1-10) Fever, rash (%1-10) Raised LFTs (%1-10) Anaphylactoid reactions (<%0.1) Intravascular haemolysis (rare) Drug interactions: No contraindicated concomitant drugs. Plasma level monitoring is not recommended Increase sirolimus, nifedipine and ıtraconazole levels

  12. AZOLES Triazoles: Fluconazole Itraconazole Voriconazole Posaconazole Ravuconazole Isavuconazole Different antifungal activity / indications for use Important drug interactions! Each has different formulations!

  13. ITRACONAZOLE Indications: Alternative option in treatment of IPA Alternative option in treatment of candidiasis (neutropenic host) Alternative option in treatment of oral/esophageal candidiasis First line treatment of ABPA and allergic aspergillus sinusitis First line treatment of chronic cavitary pulmonary aspergillosis Prophylaxis in neutropenic/allogeneic HSCT patients Dosing regimen: oral capsule, oral solution, IV solution Mucocutaneous candidiasis: 200mg/d oral solution Treatment or prophylaxis in Aspergillosis: 2x 200mg for first 2 days, 200mg/d maintenance Plasma level should be monitored weekly (target: >500ng/ml)

  14. ITRACONAZOLE Side effects: Nausea, vomiting (%10-28) Hypokalaemia (%1-10) Fever, rash (%1-10) Raised LFTs (%1-10) Drug interactions: Use with; Quinidine, dofetilide, pimozide, nidazolam, triazolam, cisapride, lovastatine, simvastatine is CONTRAINDICATED Raised Tacrolimus, sirolimus, cyclosporine levels! Macrolide antibiotics, indinavir, ritonavir increase ITRA levels

  15. VORICONAZOLE Indications: First line treatment of IPA Treatment of candidiasis (fluconazole resistant strains) Tx of Scedosporium apiospermum and Fusarium spp Dosing regimen: IV, oral tablets, oral suspension IV: 2 x 6 mg/kg first day, 2 x 4 mg/kg maintenance Oral: 2 x 400 mg first day, 2 x 200 mg maintenance Children: IV: 2 x 7mg/kg, oral: 2 x 200 mg

  16. VORICONAZOLE Dose alteration: Renal failure: No need for oral formulations IV formulation should not be given to pts with a creatinine clearence <50 ml/min Hepatic failure: Mild-moderate impairment one half maintenance dose Use not recommended in severe impairment Side effects: Transient visual disturbance: Photopsy (%20-30) Rash, photosensitivity (%7) Raised LFTs (%1-10) (should be monitored every 2 weeks) Headache, vomiting, diarrhoea, abdominal pain (%1-10) Hallucination (%5)

  17. VORICONAZOLE Drug interactions: Use with; Carbamazepine, phenobarbital, sirolimus, rifampicin, ritonavir, terfenadine, astemizole, cisapride, pimozide, quinidine, ergot alkaloids is CONTRAINDICATED Cyclosporine dose should be reduced to one half and its serum levels monitored Omeprazole dose should be reduced to one half Tacrolimus and methadone will require dose reduction If co-administered with phenytoin vori maintenance dose: 2 x 5 mg/kg Plasma level monitoring: In selected pts (serious and/or unresponsive IFI ) Target levels: 2-6 mg/L

  18. POSACONAZOLE Indications: Prophylaxis in AML/MDS pts receiving chemotherapy Prophylaxis in Allo HSCT pts with GVHD Treatment of severe oropharyngeal candidiasis Salvage therapy for IPA (EU) Alternative option in tx of IPA (IDSA) Dosing regimen: Oral suspension Prophylaxis: 3 x 200 mg with meals Salvage therapy: 2 x 400 mg or 4 x 200 mg with meals Children: should not be used in age <18 y (EU) can be used in age >13 y (USA)

  19. POSACONAZOLE Dose alterations: Renal failure: No dose adjustment, bevare of “breakthrough” infections Hepatic failure: Limited data available. Use with caution! Side effects: Nausea, vomiting, diarrhoea (%1-10) QT/QTc prolongation (%1-10) Headache, rash (%1-10) Hypokalaemia (%1-10)

  20. POSACONAZOLE Drug interactions: Use with; Terfenadine, astemizole, cisapride, pimozide, quinidine, ergot alkaloids is CONTRAINDICATED. Cyclosporine dose should be reduced to 3/4, Tacrolimus to 1/3, and drug levels should be monitored. Rifabutin, midazolam, phenytoin, vincristine levels are increased Cimetidine, rifabutin and phenytoin decrease POSA levels. Plasma level monitoring: Needed in selected pts (serious and/or unresponsive pts) Target levels: >1.5 mg/L (after 7 days therapy)

  21. Clin Infect Dis, 2008; 46:1401–8 271 pts, 407 neutropenic episodes, Placebo vs Liposomal Ampho B 2,5 ml of a 5 mg/ml solution 30 minutes inhaled, two consecutive days Halolite AAD veya ProDose AAD; Romedic/Medic-Aid. Particule size: 1.9 mikron

  22. L-AmfoB: 6 /139 (4%) IPA Placebo: 18 /132 (14%) IPA (p=.005)

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