Comparison of oral antifungals

Availability in Hospital Keningau

• Cap Fluconazole 50mg & 200mg
• Tab Griseofulvin 125mg
• Cap Itraconazole 100mg
• Tab Ketoconazole 200mg 
• Suspension Nystatin 100 000 units/ml

Comparison of Oral Antifungals

Antifungal	Indication (FUKKM)	Pharmacokinetics
Ketoconazole 200mg (B)	Pityriasis Versicolor Systemic Mycoses (other skin mycosis) Nail infection	Absorption can be increased by administration with a cola beverage (requires acidic condition) Half life elimination is biphasic (initial 2 hours and terminal 8 hours)
Fluconazole 50mg Fluconazole 100mg (A)	Oropharyngeal candidiasis, atrophic oral candidiasis Tinea Pedis, corporis, cruris, versicolor and dermal candidiasis Invasive candida & cryptocococcal infections (includes meningitis) Prevention of relapse cryptococcal meningitis in AIDS after completion of primary therapy Prevention of fungal infections in immunocompromised patients	Oral bioavailability > 90% The long serum half-life (approximately 24 hours) allows once-daily dosing Good penetration into CSF Absorption is not affected by the presence of food or gastric pH.
Itraconazole 100mg (A/KK)	Dermatomycosis including pityriasis versicolor Oral candidiasis Palmar tinea manus and plantar tinea pedis Fingernail onychomycosis Toenail onychomycosis Vulvovaginal candidiasis	Capsule bioavailability of approximately 55% Relatively long half-life, approaching 25 to 50 hours thus allows OD dosing Absorption increased by concurrent ingestion of cola or cranberry juice
Voriconazole 200mg Voriconazole 50mg (A*)	Treatment of immunocompromised patients with progressive, possibly life-threatening infections such as invasive aspergillosis, fluconazole-resistant serious invasive candidiasis, candidiasis of the oesophagus, serious fungal infections caused by Scedosporium species and Fusarium species Prevention of breakthrough fungal infections in febrile high risk neutropenic patients	Oral biovailability >90% in adult and may vary with <12 year old Ability to penetrate CSF
Syr. Nystatin 500 000 (B)	Prevention and treatment of candidiasis of the skin and mucous membranes Protection against candidas overgrowth during antimicrobial /corticosteroid therapy and as selective decontamination regimens	Poorly absorbed Excreted unchanged at feces  Should be swished about the mouth and retained in the mouth for as long as possible (several minutes) before swallowing.
Griseofulvin (B)	Dermatophyte infection of the skin, scalp, hair and nails, where topical therapy has failed or inappropriate	Absorption is almost complete (ultramicrosize) Half life elimination is 9-24 hours
Flucytosine 500mg (A*)	Only for the treatment of fungal meningitis	Ability to penetrate CSF Bioavailability 78%-89% (decreased in neonates

Spectrum of activity

Imidazole (Ketoconazole)

• Ketoconazole causes more gastrointestinal disturbances compared to other azoles.
• Has been largely replaced by other triazoles due to favourable pharmacokinetic and safety profile
• Should not be used as first-line treatment for any fungal infection.
• It should be used for the treatment of endemic mycoses (eg, histoplasmosis, blastomycosis) only when alternative antifungal therapies are not available or tolerated.
• Contraindicated in acute or chronic liver disease.

Triazole (Itraconazole, Fluconazole, Voriconazole)

• The drugs in this class offer activity against many fungal pathogens without the serious nephrotoxic effects observed with amphotericin B 
• Due to its inotropic effects, itraconazole’s labeling includes a black box warning in patients with heart failure, particularly in patients receiving a total daily oral dose of 400 mg

Pyrimidine (Flucytosine)

• Flucytosine has limited clinical indication and is used primarily in combination with Amphotericin B as combination therapy for cryptococcal meningitis and selected life threatening Candida syndromes                 

References

• Uptodate
• https://mycology.adelaide.edu.au/docs/antifungals.pdf 
• https://www.uspharmacist.com/article/the-fungus-among-us-an-antifungal-review 
• Lexicomp 
• FUKKM