Fungal Infections: Their Diagnosis and Treatment in Transplant Recipients

Table 6

(a) Experience in patients with prexisting renal disease

Agent	Effects on the kidney	Dosing modifications for preexisting renal disease
(1) Amphotericin B	Nephrotoxic-elevation of BUN, creatinine	Sodium loading to ameliorate toxicity
(2) AmBisome	Nephrotoxic	Used in pt with pre-existing renal impairment
(3) ABCD	Nephrotoxic
(4) ABLC	Dose-limited renal toxicity
(5) Voriconazole	SBECD component of iv formulation	No adjustment for oral vori in pts with mild-to-severe renal impairment
	associated with renal toxicity	I.V. should be avoided if creatinine clearance <30 mL/min
(6) Fluconazole		50–400 mg creatinine clearance >50–100% creatinine clearance <50 (no dialysis)-adm.50% of dose
		regular dialysis-admin 100% of dose after each dialysis
(7) Itraconazole	SBECD component of iv formulation	I.V. should not be used if creatinine clearance <30 mL/min
	associated with renal toxicity
(8) Posaconazole		No dose adjustment for mild-to-moderate; severe-monitor for breakthrough IFI
(9) Anidulafungin	None	No dose adjustment, not dialyzable
(10) Caspofungin	None	No dose adjustment, not dialyzable
(11) Micafungin	None	No dose adjustment

(b) Experience in individuals with pre-existing hepatic disease

Antifungal	Normal Patients	Mild	Moderate	Severe	Effects on the liver
		(Child-Pugh 5-6)	(Child-Pugh 7–9)	(Child-Pugh >9)
Anidulafungin	200 mg loading dose on day 1 followed by 100 mg once/day	200 mg loading dose on day 1 followed by 100 mg once/day	200 mg loading dose on day 1 followed by 100 mg once/day	200 mg loading dose on day 1 followed by 100; mg once/day	None
Micafungin	100 mg once/day	100 mg once/day	100 mg once/day	Not studied	None
Caspofungin	70 mg loading dose on day 1 followed by 50 mg once/day	70 mg loading dose on day 1 followed by 50 mg once/day	70 mg loading dose on day 1 followed by 35 mg once/day	Not studied	None
Fluconazole	Loading dose of 2x the daily dose, then up to 400 mg daily	No dosage adjustments initially, monitor LFTs in patients for worsening hepatic function			Hepatotoxic
Itraconazole	200 mg q12 IV 100–200 mg q12 po-solution	No studies have been conducted looking at patients with hepatic impairment, use with caution			Hepatotoxic, prolonged elimination half-life in cirrhotic patients (meds metabolized by CYP3A4)
Voriconazole	6 mg/kg IV q12h for the first 24 hours loading dose followed by 3-4 mg/kg IV q12h maintenance dose then 200 mg q12h oral	6 mg/kg IV q12h for the first 24 hours loading dose followed by 1.5–2 mg/kg IV q12h maintenance dose	6 mg/kg IV q12h for the first 24 hours loading dose followed by 1.5–2 mg/kg IV q12h maintenance dose	Not studied	Hepatotoxic
Posaconazole	Oral Suspension 200 mg (5 mL) three times a day with a full meal or liquid nutritional supplement, monitoring of LFT's is recommended	Data was not sufficient to determine dosing, should be used with caution			Mild-to-moderate elevation of liver enzymes, bilirubin-generally reversible
Amphotericin B deoxycholate	0.6 to 1 mg/kg/day	Data was not sufficient to determine dosing			Elevation of liver enzymes
Ampho B lipid complex (Abelcet)	5 mg/kg/day	Data was not sufficient to determine dosing			Elevation of liver enzymes
Ampho B colloidal dispersion (Amphotec)	3-4 mg/kg/day can be increased up to 6 mg/kg/day	Data was not sufficient to determine dosing			Elevation of liver enzymes
Ampho B liposomal (AmBisome)	3-4 mg/kg/day can be increased up to 6 mg/kg/day	Data was not sufficient to determine dosing			Elevation of liver enzymes