Fluconazole

Fluconazole - antifungal active against Candida albicans, Candida tropicalis, Candida parapsilosis and cryptococcus.Variable activity against Candida glabrata and poor activity for Candida krusei. It is rapidly and completely absorbed orally. Oral and IV therapy equally effective; IV for patients unable to take orally.Widely distributed in tissues and fluids. Excreted unchanged in urine.

Uses
• Local or systemic candidiasis
• Cryptococcal infections – usually follow-on therapy after amphotericin

Administration
• Oropharyngeal candidiasis
  Orally: 50–100 mg daily for 7–14 days
• Oesophageal candidiasis or candiduria
  Orally: 50–100 mg daily for 14–30 days
• Systemic candidiasis or cryptococcal infections
  IV infusion: 400 mg daily, consider higher doses for less susceptible
  Candida isolates
  Infusion rate 10–20 mg/min

Continued according to response (at least 6–8 weeks for cryptococcal meningitis; often longer)

In renal impairment:
>10 ml/min normal dose
<10 ml/min use 50% of normal dose

How not to use fluconazole
Avoid concurrent use with astemizole or terfenadine (arrhythmias)

Adverse effects
Rash
Pruritis
Nausea, vomiting, diarrhoea
Raised liver enzymes
Hypersensitivity

Cautions
Renal/hepatic impairment
May increase concentrations of ciclosporin, phenytoin,warfarin, midazolam, theophylline and tacrolimus.Possible increased risk of myopathy with simvastatin and atorvastatin

Organ failure
Renal: reduce dose

Renal replacement therapy
CVVH dialysed, no dose reduction needed, if high filtration rates are used or haemodiafiltration then higher doses may be needed, e.g. 600–800 mg daily. HD dialysed, dose as in CC < 10 ml/min, i.e. use half normal dose or 100% of dose three times per week after dialysis. PD dialysed, use 50% of normal dose.Three hours of HD have been shown to reduce fluconazole plasma levels by 50%.